Occurrence of pituitary dysfunction following traumatic brain injury.

PubMed

Bondanelli, Marta; De Marinis, Laura; Ambrosio, Maria Rosaria; Monesi, Marcello; Valle, Domenico; Zatelli, Maria Chiara; Fusco, Alessandra; Bianchi, Antonio; Farneti, Marco; degli Uberti, Ettore C I

2004-06-01

Traumatic brain injury (TBI) may be associated with impairment of pituitary hormone secretion, which may contribute to long-term physical, cognitive, and psychological disability. We studied the occurrence and risk factors of pituitary dysfunction, including growth hormone deficiency (GHD) in 50 patients (mean age 37.6 +/- 2.4 years; 40 males, age 20-60 years; 10 females, age 23-87 years) with TBI over 5 years. Cranial or facial fractures were documented in 12 patients, and neurosurgery was performed in 14. According to the Glasgow Coma Scale (GCS), 16 patients had suffered from mild, 7 moderate, and 27 severe TBI. Glasgow Outcome Scale (GOS) indicated severe disability in 5, moderate disability in 11, and good recovery in 34 cases. Basal pituitary hormone evaluation, performed once at times variable from 12 to 64 months after TBI, showed hypogonadotrophic hypogonadism in 7 (14%), central hypothyroidism in 5 (10%), low prolactin (PRL) levels in 4 (8%), and high PRL levels in 4 (8%) cases. All subjects had normal corticotrophic and posterior pituitary function. Seven patients showed low insulin-like growth factor-I (IGF-I) levels for age and sex. Results of GHRH plus arginine testing indicated partial GHD in 10 (20%) and severe GHD in 4 (8%) cases. Patients with GHD were older (p <0.05) than patients with normal GH secretion. Magnetic resonance imaging demonstrated pituitary abnormalities in 2 patients; altogether pituitary dysfunction was observed in 27 (54%) patients. Six patients (12%) showed a combination of multiple abnormalities. Occurrence of pituitary dysfunction was 37.5%, 57.1%, and 59.3% in the patients with mild, moderate, and severe TBI, respectively. GCS scores were significantly (p <0.02) lower in patients with pituitary dysfunction compared to those with normal pituitary function (8.3 +/- 0.5 vs. 10.2 +/- 0.6). No relationship was detected between pituitary dysfunction and years since TBI, type of injury, and outcome from TBI. In conclusion, subjects with a history of TBI frequently develop pituitary dysfunction, especially GHD. Therefore, evaluation of pituitary hormone secretion, including GH, should be included in the long-term follow-up of all TBI patients so that adequate hormone replacement therapy may be administered.

Variations of pituitary function over time after brain injuries: the lesson from a prospective study.

PubMed

Giordano, Giulio; Aimaretti, Gianluca; Ghigo, Ezio

2005-01-01

Traumatic Brain Injury (TBI) and Subarachnoid Haemorrhage (SAH) are conditions at high risk to develop hypopituitarism as pointed out by many papers in scientific literature. But most of the papers were referred to retrospective evaluations, not considering the possible evolution of the pituitary function over time. Aim of our studies was to clarify whether pituitary deficiencies and normal pituitary function recorded at short term follow-up (3 months), would improve or worsen, respectively, at long term (12 months after the brain injury). In a multicenter study protocol, in patients who suffered TBI (n = 70; 50 Males, 20 Females; age 39.31 +/- 2.4 years; BMI 23.8 +/- 0.4 kg/m(2)) or SAH (n = 32; 12M, 20F; age: 51.9 +/- 2.2 year; BMI: 24.7 +/- 0.6 kg/m(2)) we tested 3 and 12 months after the pathological events the pituitary function. In TBI patients, the 3 month evaluation had shown some degree of hypopituitarism in 32.8% and the 12 months retesting demonstrated some degree of hypopituitarism in 22.7%. Total hypopituitarism was always confirmed at 12 months while Multiple and Isolated deficits recorded at 3 months was confirmed in nearly 25% only of the patients. On the other hand, in 5.5% of TBI with normal pituitary function at 3 months Isolated deficits were recorded at 12 months testing. Moreover, in 13.3% of TBI with Isolated deficit at 3 months Multiple hypopituitarism was demonstrated at 12 months retesting. In SAH patients, the 3 months evaluation had shown some degree of hypopituitarism in 46.8% and the 12 month retesting demonstrated some degree of hypopituitarism in 37.5%. No multiple hypopituitarism recorded at 3 months was confirmed at 12 months, but 2 patients with isolated deficits at 3 months showed multiple hypopituitarism at 12 month retesting. At 12 as well as at 3 months, both in TBI and SAH patients, the most common deficit was severe GHD (>20%) followed by secondary hypogonadism and then hypoadrenalism and hypothyroidism. In all, in patients who experienced TBI or SAH the risk to develop hypopituitarism is very high; early diagnosis of total hypopituitarism is always confirmed at the long term follow-up; however pituitary function in brain injured patients may improve over time, because, isolated and even multiple pituitary insufficiencies recorded at short term can be transient; on the other hand normal pituitary function recorder at short term may, become impaired 12 months after the injury. Thus, brain injured patients must undergo neuroendocrine follow-up over time in order to monitoring pituitary function and eventually providing appropriate placement.

Melatonin regulates somatotrope and lactotrope function through common and distinct signaling pathways in cultured primary pituitary cells from female primates.

PubMed

Ibáñez-Costa, Alejandro; Córdoba-Chacón, José; Gahete, Manuel D; Kineman, Rhonda D; Castaño, Justo P; Luque, Raúl M

2015-03-01

Melatonin (MT) is secreted by the pineal gland and exhibits a striking circadian rhythm in its release. Depending on the species studied, some pituitary hormones also display marked circadian/seasonal patterns and rhythms of secretion. However, the precise relationship between MT and pituitary function remains controversial, and studies focusing on the direct role of MT in normal pituitary cells are limited to nonprimate species. Here, adult normal primate (baboons) primary pituitary cell cultures were used to determine the direct impact of MT on the functioning of all pituitary cell types from the pars distalis. MT increased GH and prolactin (PRL) expression/release in a dose- and time-dependent fashion, a response that was blocked by somatostatin. However, MT did not significantly affect ACTH, FSH, LH, or TSH expression/release. MT did not alter GHRH- or ghrelin-induced GH and/or PRL secretions, suggesting that MT may activate similar signaling pathways as ghrelin/GHRH. The effects of MT on GH/PRL release, which are likely mediated through MT1 receptor, involve both common (adenylyl cyclase/protein kinase A/extracellular calcium-channels) and distinct (phospholipase C/intracellular calcium-channels) signaling pathways. Actions of MT on pituitary cells also included regulation of the expression of other key components for the control of somatotrope/lactotrope function (GHRH, ghrelin, and somatostatin receptors). These results show, for the first time in a primate model, that MT directly regulates somatotrope/lactotrope function, thereby lending support to the notion that the actions of MT on these cells might substantially contribute to the define daily patterns of GH and PRL observed in primates and perhaps in humans.

An unusual case of hypopituitarism and transient thyrotoxicosis following asymptomatic pituitary apoplexy.

PubMed

Yoshida, Masanori; Murakami, Miho; Ueda, Harumi; Miyata, Misaki; Takahashi, Norio; Oiso, Yutaka

2014-01-01

Although pituitary function is often impaired in pituitary apoplexy, the development of thyrotoxicosis is rare. We describe an unusual case of hypopituitarism due to pituitary apoplexy coexisting with transient hyperthyroidism. A 74-year-old woman presented with severe fatigue, palpitation, appetite loss, hypotension, and hyponatremia. Endocrine studies showed hyperthyroidism and anterior pituitary hormone deficiencies. A magnetic resonance imaging suggested recent-onset pituitary apoplexy in a pituitary tumor, although the patient had no apoplectic symptoms such as headache and visual disturbance. Thyrotoxicosis and adrenal insufficiency worsened her general condition. Glucocorticoid supplementation improved her clinical symptoms and hyponatremia. Serum anti-thyrotropin receptor and thyroid-stimulating antibody titers were negative, and her thyroid function was spontaneously normalized without antithyroid medication, suggesting painless thyroiditis. Thereafter, her thyroid function decreased because of central hypothyroidism and 75 µg of levothyroxine was needed to maintain thyroid function at the euthyroid stage. The pituitary mass was surgically removed and an old hematoma was detected in the specimen. Considering that painless thyroiditis develops as a result of an autoimmune process, an immune rebound mechanism due to adrenal insufficiency probably caused painless thyroiditis. Although the most common type of thyroid disorder in pituitary apoplexy is central hypothyroidism, thyrotoxicosis caused by painless thyroiditis should be considered even if the patient has pituitary deficiencies. Because thyrotoxicosis with adrenal insufficiency poses a high risk for a life-threatening adrenal crisis, prompt diagnosis and treatment are critical.

Neuronal M3 muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth.

PubMed

Gautam, Dinesh; Jeon, Jongrye; Starost, Matthew F; Han, Sung-Jun; Hamdan, Fadi F; Cui, Yinghong; Parlow, Albert F; Gavrilova, Oksana; Szalayova, Ildiko; Mezey, Eva; Wess, Jürgen

2009-04-14

The molecular pathways that promote the proliferation and maintenance of pituitary somatotrophs and other cell types of the anterior pituitary gland are not well understood at present. However, such knowledge is likely to lead to the development of novel drugs useful for the treatment of various human growth disorders. Although muscarinic cholinergic pathways have been implicated in regulating somatotroph function, the physiological relevance of this effect and the localization and nature of the receptor subtypes involved in this activity remain unclear. We report the surprising observation that mutant mice that selectively lack the M(3) muscarinic acetylcholine receptor subtype in the brain (neurons and glial cells; Br-M3-KO mice) showed a dwarf phenotype associated with a pronounced hypoplasia of the anterior pituitary gland and a marked decrease in pituitary and serum growth hormone (GH) and prolactin. Remarkably, treatment of Br-M3-KO mice with CJC-1295, a synthetic GH-releasing hormone (GHRH) analog, rescued the growth deficit displayed by Br-M3-KO mice by restoring normal pituitary size and normal serum GH and IGF-1 levels. These findings, together with results from M(3) receptor/GHRH colocalization studies and hypothalamic hormone measurements, support a model in which central (hypothalamic) M(3) receptors are required for the proper function of hypothalamic GHRH neurons. Our data reveal an unexpected and critical role for central M(3) receptors in regulating longitudinal growth by promoting the proliferation of pituitary somatotroph cells.

[Influence of hyperprolactinemia and tumoral size in the postoperative pituitary function in clinically nonfunctioning pituitary macroadenomas].

PubMed

Fonseca, Ana Luiza Vidal; Chimelli, Leila; Santos, Mario José C Felippe; Santos, Alair Augusto S M Damas dos; Violante, Alice Helena Dutra

2002-09-01

To study the influence of hyperprolactinemia and tumoral size in the pituitary function in clinically nonfunctioning pituitary macroadenomas. Twenty three patients with clinically nonfunctioning pituitary macroadenomas were evaluated by image studies (computed tomography or magnetic resonance) and basal hormonal level; 16 had preoperative hypothalamus-hypophysial function tests (megatests). All tumors had histological diagnosis and in seventeen immunohistochemical study for adenohypophysial hormones was also performed. Student's t test, chi square test, exact test of Fisher and Mc Neman test were used for the statistics analysis. The level of significance adopted was 5% (p<0.05). Tumoral diameter varied of 1.1 to 4.7 cm (average=2.99 cm +/- 1.04). In the preoperative, 5 (21.7%) patients did not show laboratorial hormonal deficit, 9 (39.1%) developed hyperprolactinemia, 13 (56,5%) normal levels of prolactin (PRL) and 1 (4.3%) subnormal; 18 (78.3%) patients developed hypopituitarism (4 pan-hypopituitarism). Nineteen patients (82.6%) underwent transsfenoidal approach, 3 (13%) craniotomy and 1 (4.4%) combined access. Only 6 patients had total tumoral resection. Of the 17 immunohistochemical studies, 5 tumours were immunonegatives, 1 compound, 1 LH+, 1 FSH +, 1 alpha sub-unit and 8 focal or isolated immunorreactivity for one of the pituitary hormones or sub-units; of the other six tumours, 5 were chromophobe and 1 chromophobe/acidophile. No significant statistic difference was noted between tumoral size and preoperative PRL levels (p=0.82), nor between tumoral size and postoperative hormonal state, except in the GH and gonadal axis. Significant statistic was noted: between tumoral size and preoperative hormonal state (except in the gonadal axis); between normal PRL levels, associated to none or little preoperative hypophysial disfunction, and recovery of postoperative pituitary function. Isolated preoperative hyperprolactinemia and tumoral size have not been predictable for the recovery of postoperative pituitary function.

cAMP-specific PDE4 Phosphodiesterases and AIP in the Pathogenesis of Pituitary Tumors

PubMed Central

Bolger, Graeme B.; Bizzi, Mariana Ferreira; Brant Pinheiro, Sergio Veloso; Trivellin, Giampaolo; Smoot, Lisa; Accavitti, Mary-Ann; Korbonits, Márta; Ribeiro-Oliveira, Antonio

2016-01-01

PDE4 cyclic nucleotide phosphodiesterases regulate cAMP abundance in cells and thereby regulate numerous processes, including cell growth and differentiation. The rat PDE4A5 isoform (human homologue PDE4A4) interacts with the AIP protein (also called XAP2 or ARA-9). Germline mutations in AIP occur in approximately 20% of patients with Familial Isolated Pituitary Adenoma (FIPA) and 20% of childhood-onset simplex somatotroph adenomas. We therefore examined the protein expression of PDE4A4 and the closely-related isoform PDE4A8 in normal human pituitary tissue and in pituitary adenomas. PDE4A4 had low expression in normal pituitary, but was significantly over-expressed in somatotroph, lactotroph, corticotroph and clinically non-functioning gonadotroph adenomas (P<0.0001 for all subtypes). Likewise, PDE4A8 was expressed in normal pituitary and was also significantly over-expressed in the adenoma subtypes (P<0.0001 for all). Among the different adenoma subtypes, corticotroph and lactotroph adenomas were the highest and lowest expressed for PDE4A4, respectively, whereas the opposite was observed for PDE4A8. Naturally occurring oncogenic variants in AIP were shown by a two-hybrid assay to disrupt the ability of AIP to interact with PDE4A5. A reverse-two-hybrid screen identified numerous additional variants in the TPR region of AIP that also disrupted its ability to interact with PDE4A5. The expression of PDE4A4 and PDE4A8 in normal pituitary, their increased expression in adenomatous pituitary cells where AIP is meant to participate, and the disruption of the PDE4A4-AIP interaction by AIP mutants may play a role in pituitary tumorigenesis. PMID:27267386

Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

PubMed

Warren, W B; Gurewitsch, E D; Goland, R S

1995-02-01

We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

Spontaneous endocrine cure of gigantism due to pituitary apoplexy.

PubMed

Arisaka, O; Hall, R; Hughes, I A

1983-10-08

An 11 year old, tall boy presented with symptoms typical of pituitary apoplexy. A large necrotic and haemorrhagic tumour was removed, which was shown to be an adenoma secreting growth hormone and prolactin. Subsequent treatment comprised cranial irradiation and hormone replacement. Eighteen months after operation growth was static and plasma growth hormone and prolactin concentrations were undetectable. Treatment of pituitary apoplexy should comprise excision of the tumour and postoperative irradiation; such treatment after early recognition of the condition offers the best chance of preserving normal pituitary function in children with gigantism.

Spontaneous endocrine cure of gigantism due to pituitary apoplexy.

PubMed Central

Arisaka, O; Hall, R; Hughes, I A

1983-01-01

An 11 year old, tall boy presented with symptoms typical of pituitary apoplexy. A large necrotic and haemorrhagic tumour was removed, which was shown to be an adenoma secreting growth hormone and prolactin. Subsequent treatment comprised cranial irradiation and hormone replacement. Eighteen months after operation growth was static and plasma growth hormone and prolactin concentrations were undetectable. Treatment of pituitary apoplexy should comprise excision of the tumour and postoperative irradiation; such treatment after early recognition of the condition offers the best chance of preserving normal pituitary function in children with gigantism. PMID:6311318

In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features.

PubMed

Ibáñez-Costa, Alejandro; Gahete, Manuel D; Rivero-Cortés, Esther; Rincón-Fernández, David; Nelson, Richard; Beltrán, Manuel; de la Riva, Andrés; Japón, Miguel A; Venegas-Moreno, Eva; Gálvez, Ma Ángeles; García-Arnés, Juan A; Soto-Moreno, Alfonso; Morgan, Jennifer; Tsomaia, Natia; Culler, Michael D; Dieguez, Carlos; Castaño, Justo P; Luque, Raúl M

2015-03-04

Pituitary adenomas comprise a heterogeneous subset of pathologies causing serious comorbidities, which would benefit from identification of novel, common molecular/cellular biomarkers and therapeutic targets. The ghrelin system has been linked to development of certain endocrine-related cancers. Systematic analysis of the presence and functional implications of some components of the ghrelin system, including native ghrelin, receptors and the recently discovered splicing variant In1-ghrelin, in human normal pituitaries (n = 11) and pituitary adenomas (n = 169) revealed that expression pattern of ghrelin system suffers a clear alteration in pituitary adenomasas compared with normal pituitary, where In1-ghrelin is markedly overexpressed. Interestingly, in cultured pituitary adenoma cells In1-ghrelin treatment (acylated peptides at 100 nM; 24-72 h) increased GH and ACTH secretion, Ca(2+) and ERK1/2 signaling and cell viability, whereas In1-ghrelin silencing (using a specific siRNA; 100 nM) reduced cell viability. These results indicate that an alteration of the ghrelin system, specially its In1-ghrelin variant, could contribute to pathogenesis of different pituitary adenomas types, and suggest that this variant and its related ghrelin system could provide new tools to identify novel, more general diagnostic, prognostic and potential therapeutic targets in pituitary tumors.

In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features

PubMed Central

Ibáñez-Costa, Alejandro; Gahete, Manuel D.; Rivero-Cortés, Esther; Rincón-Fernández, David; Nelson, Richard; Beltrán, Manuel; de la Riva, Andrés; Japón, Miguel A.; Venegas-Moreno, Eva; Gálvez, Ma Ángeles; García-Arnés, Juan A.; Soto-Moreno, Alfonso; Morgan, Jennifer; Tsomaia, Natia; Culler, Michael D.; Dieguez, Carlos; Castaño, Justo P.; Luque, Raúl M.

2015-01-01

Pituitary adenomas comprise a heterogeneous subset of pathologies causing serious comorbidities, which would benefit from identification of novel, common molecular/cellular biomarkers and therapeutic targets. The ghrelin system has been linked to development of certain endocrine-related cancers. Systematic analysis of the presence and functional implications of some components of the ghrelin system, including native ghrelin, receptors and the recently discovered splicing variant In1-ghrelin, in human normal pituitaries (n = 11) and pituitary adenomas (n = 169) revealed that expression pattern of ghrelin system suffers a clear alteration in pituitary adenomasas comparedwith normal pituitary, where In1-ghrelin is markedly overexpressed. Interestingly, in cultured pituitary adenoma cells In1-ghrelin treatment (acylated peptides at 100 nM; 24–72 h) increased GH and ACTH secretion, Ca2+ and ERK1/2 signaling and cell viability, whereas In1-ghrelin silencing (using a specific siRNA; 100 nM) reduced cell viability. These results indicate that an alteration of the ghrelin system, specially its In1-ghrelin variant, could contribute to pathogenesis of different pituitary adenomas types, and suggest that this variant and its related ghrelin system could provide new tools to identify novel, more general diagnostic, prognostic and potential therapeutic targets in pituitary tumors. PMID:25737012

Extreme elevation of intrasellar pressure in patients with pituitary tumor apoplexy: relation to pituitary function.

PubMed

Zayour, Dany H; Selman, Warren R; Arafah, Baha M

2004-11-01

The dominant mechanism for hypopituitarism and hyperprolactinemia commonly observed in patients with pituitary macroadenomas was postulated to be increased intrasellar pressure (ISP) caused by the slow and gradual expansion of adenomas within the sella turcica. Hemorrhagic infarction of adenomas (pituitary tumor apoplexy) is associated with a rapid, rather than gradual, increase in intrasellar contents. The impacts of the sudden increase in intrasellar contents on ISP and pituitary function are unknown. ISP and pituitary function were determined in 13 patients with pituitary tumor apoplexy who had surgical decompression within 1 wk of symptoms' onset. ISP measurements were remarkably high (median, 47 mm Hg), whereas serum prolactin (PRL) concentrations were generally low (median, 3.5 microg/liter). There was an inverse correlation (r = -0.76; P < 0.01) between ISP measurements and serum PRL concentrations. Postoperatively, partial recovery or maintenance of pituitary function was noted in seven of 13 patients. These seven patients had higher (P = 0.013) serum PRL levels (9.3 +/- 7.4 microg/liter) and lower (P < 0.001) ISP measurements (35.9 +/- 7.3 mm Hg) than the respective values in the remaining six with persistent postoperative hypopituitarism (1.6 +/- 0.6 microg/liter and 55.9 +/- 2.4 mm Hg, respectively). The low serum PRL levels in patients with tumor apoplexy suggested that ischemic necrosis of the anterior pituitary resulting from sudden and extreme elevation of ISP was commonly observed in this setting. A normal or elevated serum PRL level in patients with non-PRL-secreting macroadenomas indicates the presence of viable pituitary cells and the high likelihood of postoperative recovery of pituitary function.

Effect of Chlorotriazine Pesticides on Gonadotrophin Releasing Hormone in the Neuronal GT1-7 Cell Line and Hypothalamic Explants

EPA Science Inventory

Gonadotrophin releasing hormone (GnRH) stimulates the release of pituitary luteinizing hormone (LH) and follicle stimulating hormone. These pituitary hormones are necessary for normal reproductive function in both males and females. It is well recognized that disruption of nor...

Radioimmunoassay of human homologous prolactin in serum with commercially available reagents. [/sup 125/I tracer technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kao, P.C.; Jiang, N.S.; Abboud, C.F.

A clinically useful and reproducible radioimmunoassay for human homologous prolactin, established with commercially available reagents, was studied and validated. We present detailed conditions for iodination and purification of labeled prolactin and the optimal conditions for the assay. By the method, we found values (..mu..g/liter) as follows for serum prolactin: normal men, 8.9 +- 5.2 (mean +- SD); normal women, 11.8 +- 5.5; normal women taking contraceptive pills, 9.2 +- 5.0; pregnant women in the third trimester, 188 +- 69.5; patients with various diseases other than of the hypothalamic-pituitary axis, 9.3 +- 6.3; in some patients with amenorrhea and galactorrhea ofmore » diverse origin, 78.2 +- 87.4; and in some patients with surgically proven pituitary tumor, 1414 +- 1980. Results under provocative testing are also presented for a patient with normal hypothalamic-pituitary function.« less

Magnetic resonance imaging validation of pituitary gland compression and distortion by typical sellar pathology.

PubMed

Cho, Charles H; Barkhoudarian, Garni; Hsu, Liangge; Bi, Wenya Linda; Zamani, Amir A; Laws, Edward R

2013-12-01

Identification of the normal pituitary gland is an important component of presurgical planning, defining many aspects of the surgical approach and facilitating normal gland preservation. Magnetic resonance imaging is a proven imaging modality for optimal soft-tissue contrast discrimination in the brain. This study is designed to validate the accuracy of localization of the normal pituitary gland with MRI in a cohort of surgical patients with pituitary mass lesions, and to evaluate for correlation between presurgical pituitary hormone values and pituitary gland characteristics on neuroimaging. Fifty-eight consecutive patients with pituitary mass lesions were included in the study. Anterior pituitary hormone levels were measured preoperatively in all patients. Video recordings from the endoscopic or microscopic surgical procedures were available for evaluation in 47 cases. Intraoperative identification of the normal gland was possible in 43 of 58 cases. Retrospective MR images were reviewed in a blinded fashion for the 43 cases, emphasizing the position of the normal gland and the extent of compression and displacement by the lesion. There was excellent agreement between imaging and surgery in 84% of the cases for normal gland localization, and in 70% for compression or noncompression of the normal gland. There was no consistent correlation between preoperative pituitary dysfunction and pituitary gland localization on imaging, gland identification during surgery, or pituitary gland compression. Magnetic resonance imaging proved to be accurate in identifying the normal gland in patients with pituitary mass lesions, and was useful for preoperative surgical planning.

Investigation of pituitary functions in patients with acute meningitis: a pilot study.

PubMed

Tanriverdi, F; Alp, E; Demiraslan, H; Dokmetas, H S; Unluhizarci, K; Doganay, M; Casanueva, F F; Kelestimur, F

2008-06-01

Although long-term pituitary consequences of tuberculous meningitis are well documented in the literature, there have been few case reports of pituitary dysfunction after acute bacterial or viral meningitis. In this preliminary study, we have assessed the pituitary functions in adult patients who had acute bacterial or viral meningitis. Fourteen patients (8 men, 6 women; mean age 35.3+/-13.3) were included in the study. The diagnosis of bacterial and viral meningitis was proven by clinical findings, cerebrospinal fluid (CSF) examination, gram staining, and blood and CSF cultures. Pituitary functions were evaluated ranging from 6 to 48 months (mean 20 months) after acute meningitis. GH deficiency was investigated by the GHRH+arginine stimulation test. Four of 14 patients (28.6%) had isolated GH deficiency. In GH-deficient patients, the earliest duration was 6 months and the latest duration was 48 months after the diagnosis of acute meningitis. Three of the GH-deficient patients had acute bacterial meningitis and 1 patient had acute viral meningitis. Pituitary magnetic resonance imaging revealed normal pituitary gland in the patients with GH deficiency. This is the first systematic study evaluating the anterior pituitary function long term after the diagnosis of acute meningitis. Based on the present study, it is tempting to speculate that pituitary dysfunction is a more common sequel of acute bacterial or viral meningitis than hitherto reported. Studies with high numbers of patients are warranted to ascertain the prevalence of meningitis-induced hypopituitarism.

Normal dimensions of the posterior pituitary bright spot on magnetic resonance imaging.

PubMed

Côté, Martin; Salzman, Karen L; Sorour, Mohammad; Couldwell, William T

2014-02-01

The normal pituitary bright spot seen on unenhanced T1-weighted MRI is thought to result from the T1-shortening effect of the vasopressin stored in the posterior pituitary. Individual variations in its size may be difficult to differentiate from pathological conditions resulting in either absence of the pituitary bright spot or in T1-hyperintense lesions of the sella. The objective of this paper was to define a range of normal dimensions of the pituitary bright spot and to illustrate some of the most commonly encountered pathologies that result in absence or enlargement of the pituitary bright spot. The authors selected normal pituitary MRI studies from 106 patients with no pituitary abnormality. The size of each pituitary bright spot was measured in the longest axis and in the dimension perpendicular to this axis to describe the typical dimensions. The authors also present cases of patients with pituitary abnormalities to highlight the differences and potential overlap between normal and pathological pituitary imaging. All of the studies evaluated were found to have pituitary bright spots, and the mean dimensions were 4.8 mm in the long axis and 2.4 mm in the short axis. The dimension of the pituitary bright spot in the long axis decreased with patient age. The distribution of dimensions of the pituitary bright spot was normal, indicating that 99.7% of patients should have a pituitary bright spot measuring between 1.2 and 8.5 mm in its long axis and between 0.4 and 4.4 mm in its short axis, an interval corresponding to 3 standard deviations below and above the mean. In cases where the dimension of the pituitary bright spot is outside this range, pathological conditions should be considered. The pituitary bright spot should always be demonstrated on T1-weighted MRI, and its dimensions should be within the identified normal range in most patients. Outside of this range, pathological conditions affecting the pituitary bright spot should be considered.

Characterization of pituitary cells targeted by antipituitary antibodies in patients with isolated autoimmune diseases without pituitary insufficiency may help to foresee the kind of future hypopituitarism.

PubMed

De Bellis, A; Dello Iacovo, A; Bellastella, G; Savoia, A; Cozzolino, D; Sinisi, A A; Bizzarro, A; Bellastella, A; Giugliano, D

2014-10-01

Detection of antipituitary antibodies (APA) at high levels and with a particular immunofluorescence pattern in patients with autoimmune polyendocrine syndromes may indicate a possible future autoimmune pituitary involvement. This longitudinal study was aimed at characterizing in patients with a single organ-specific autoimmune disease the pituitary cells targeted by APA at start, verifying whether this characterization allows to foresee the kind of possible subsequent hypopituitarism. Thirty-six APA positive and 40 APA negative patients with isolated autoimmune diseases participated in the study. None of them had pituitary dysfunction at entry. Characterization by four-layer immunofluorescence of pituitary cells targeted by APA in APA positive patients at entry and study of pituitary function in all patients were performed every 6 months during a 5 year follow-up. Antipituitary antibodies immunostained selectively one type of pituitary-secreting cells in 21 patients (58.3 %, group 1), and several types of pituitary cells in the remaining 15 (41.7 %, group 2). All patients in group 1 showed subsequently a pituitary insufficiency, corresponding to the type of cells targeted by APA in 18 of them (85.7 %). Only 8 out of 15 patients in group 2 (53.3 %) showed a hypopituitarism, isolated in 7 and combined in the other one. None of APA negative patients showed hypopituitarism. The characterization of pituitary cells targeted by APA in patients with isolated autoimmune diseases, when the pituitary function is still normal, may help to foresee the kind of subsequent hypopituitarism, especially when APA immunostained selectively only one type of pituitary cells. A careful follow-up of pituitary function in these patients is advisable to allow an early diagnosis of hypopituitarism, even in subclinical phase and a consequent timely replacement therapy.

Lack of normal MR enhancement of the pituitary gland: findings in three siblings with combined pituitary hormone deficiency.

PubMed

Falcone, S; Sanchez, J; Quencer, R M

1998-02-01

We present the MR appearance of the sella turcica in three sibling dwarfs with combined pituitary hormone deficiency in which MR images revealed a peripheral curvilinear band of enhancement about the pituitary gland in all three patients, a normal-size pituitary gland in two siblings, a mildly enlarged pituitary gland in one sibling, and a thin infundibulum and a normal posterior pituitary bright spot in all three siblings. Possible antecedents include an abnormal vascular supply, pituitary gland replacement by a nonfunctioning adenoma, a proteinaceous cyst, or a hamartoma.

Neuroendocrine abnormalities in patients with traumatic brain injury

NASA Technical Reports Server (NTRS)

Yuan, X. Q.; Wade, C. E.

1991-01-01

This article provides an overview of hypothalamic and pituitary alterations in brain trauma, including the incidence of hypothalamic-pituitary damage, injury mechanisms, features of the hypothalamic-pituitary defects, and major hypothalamic-pituitary disturbances in brain trauma. While hypothalamic-pituitary lesions have been commonly described at postmortem examination, only a limited number of clinical cases of traumatic hypothalamic-pituitary dysfunction have been reported, probably because head injury of sufficient severity to cause hypothalamic and pituitary damage usually leads to early death. With the improvement in rescue measures, an increasing number of severely head-injured patients with hypothalamic-pituitary dysfunction will survive to be seen by clinicians. Patterns of endocrine abnormalities following brain trauma vary depending on whether the injury site is in the hypothalamus, the anterior or posterior pituitary, or the upper or lower portion of the pituitary stalk. Injury predominantly to the hypothalamus can produce dissociated ACTH-cortisol levels with no response to insulin-induced hypoglycemia and a limited or failed metopirone test, hypothyroxinemia with a preserved thyroid-stimulating hormone response to thyrotropin-releasing hormone, low gonadotropin levels with a normal response to gonadotropin-releasing hormone, a variable growth hormone (GH) level with a paradoxical rise in GH after glucose loading, hyperprolactinemia, the syndrome of inappropriate ADH secretion (SIADH), temporary or permanent diabetes insipidus (DI), disturbed glucose metabolism, and loss of body temperature control. Severe damage to the lower pituitary stalk or anterior lobe can cause low basal levels of all anterior pituitary hormones and eliminate responses to their releasing factors. Only a few cases showed typical features of hypothalamic or pituitary dysfunction. Most severe injuries are sufficient to damage both structures and produce a mixed endocrine picture. Increased intracranial pressure, which releases vasopressin by altering normal hypothalamic anatomy, may represent a unique type of stress to neuroendocrine systems and may contribute to adrenal secretion by a mechanism that requires intact brainstem function. Endocrine function should be monitored in brain-injured patients with basilar skull fractures and protracted posttraumatic amnesia, and patients with SIADH or DI should be closely monitored for other endocrine abnormalities.

In vivo and in vitro effects of chromium VI on anterior pituitary hormone release and cell viability.

PubMed

Quinteros, Fernanda A; Poliandri, Ariel H B; Machiavelli, Leticia I; Cabilla, Jimena P; Duvilanski, Beatriz H

2007-01-01

Hexavalent chromium (Cr VI) is a highly toxic metal and an environmental pollutant. Different studies indicate that Cr VI exposure adversely affects reproductive functions. This metal has been shown to affect several tissues and organs but Cr VI effects on pituitary gland have not been reported. Anterior pituitary hormones are central for the body homeostasis and have a fundamental role in reproductive physiology. The aim of this study was to evaluate the effect of Cr VI at the pituitary level both in vivo and in vitro. We showed that Cr VI accumulates in the pituitary and hypothalamus, and decreases serum prolactin levels in vivo but observed no effects on LH levels. In anterior pituitary cells in culture, the effect of Cr VI on hormone secretion followed the same differential pattern. Besides, lactotrophs were more sensitive to the toxicity of the metal. As a result of oxidative stress generation, Cr VI induced apoptosis evidenced by nuclear fragmentation and caspase 3 activation. Our results indicate that the anterior pituitary gland can be a target of Cr VI toxicity in vivo and in vitro, thus producing a negative impact on the hypothalamic-pituitary-gonadal axis and affecting the normal endocrine function.

A unique case of combined pituitary hormone deficiency caused by a PROP1 gene mutation (R120C) associated with normal height and absent puberty

PubMed Central

Arroyo, Armando; Pernasetti, Flavia; Vasilyev, Vyacheslav V.; Amato, Paula; Yen, Samuel S. C.; Mellon, Pamela L.

2010-01-01

Summary We report a 28-year-old-female who presented with primary amenorrhoea, absence of puberty, obesity and normal stature. The subject was clearly short as a child, with a height more than 2 SD below normal until the age of 15 years. The pubertal growth spurt failed to develop. She continued growing at a prepubertal rate until growth ceased at the age of 20 years, reaching her final adult height of 157 cm (SDS −0.86) without hormonal treatment. A combined pituitary hormone stimulation test of anterior pituitary function showed deficiencies of GH, LH and FSH, and low normal serum levels of TSH and PRL. Magnetic resonance imaging revealed a hypoplastic pituitary with markedly reduced pituitary height. In addition, a whole body dual energy X-ray absorptiometry scan showed high levels of body fat (54%). Combined pituitary hormone deficiencies with a hypoplastic pituitary suggested the diagnosis of a Prophet of Pit-1 (PROP1) gene mutation. Normal stature in this case, however, confounded this diagnosis. Sequencing of PROP1 revealed homozygosity for a single base-pair substitution (C to T), resulting in the replacement of an Arg by a Cys at codon 120 (R120C) in the third helix of the homeodomain of the Prop-1 protein. To our knowledge, this is the first report of a patient with a mutation in the PROP1 gene that attained normal height without hormonal treatment, indicating a new variability in the PROP1 phenotype, with important implications for the diagnosis of these patients. We suggest that this can be explained by (i) the presence of low levels of GH in the circulation during childhood and adolescence; (ii) the lack of circulating oestrogen delaying epiphyseal fusion, resulting in growth beyond the period of normal growth; and (iii) fusion of the epiphyseal plates, possibly as a result of circulating oestrogens originating from peripheral conversion of androgens by adipose tissue. PMID:12153609

Pituitary function in patients with hereditary haemochromatosis.

PubMed

Uitz, P M; Hartleb, S; Schaefer, S; Al-Fakhri, N; Kann, P H

2013-01-01

Haemochromatosis may impair the function of endocrine organs, amongst others the pituitary gland. It was the aim of this study to determine pituitary function in adult patients with genetically defined hereditary haemochromatosis in a prospective diagnostic study using a standardised stimulation test. Therefore, 22 patients (7 females, 15 males; age at diagnosis of haemochromatosis 48.1 ± 7.9 years; age at study inclusion 50.7 ± 7.7 years) with genetically defined hereditary haemochromatosis were investigated by a combined pituitary stimulation test (CRH, GHRH/arginine, GnRH, TRH). In 11 patients (50% of the study population; 2 females, 9 males), pituitary insufficiencies were detected [isolated corticotrophic insufficiency (peak cortisol < 181.25 μg/l/500 nmol/l) n=10 (2 females, 8 males); combined corticotrophic and borderline gonadotrophic insufficiency (basal testosterone 2.4-3.0 μg/l without basal LH-elevation) in 1 male]. Somatotrophic pituitary insufficiencies were not found. IFG-1 concentrations below -2 standard deviations in 7 patients (32%) may be attributed to impaired hepatic IGF-1 synthesis. Hypopituitarism, particularly corticotrophic insufficiency, seems to be prevalent in a considerable number of middle-aged patients with hereditary haemochromatosis. Despite normal somatotrophic function, low IGF-1 serum concentrations may be found in a subgroup of haemochromatosis patients. © Georg Thieme Verlag KG Stuttgart · New York.

Cocaine-and Amphetamine Regulated Transcript (CART) Peptide Is Expressed in Precursor Cells and Somatotropes of the Mouse Pituitary Gland

PubMed Central

Mortensen, Amanda H.

2016-01-01

Cocaine-and Amphetamine Regulated Transcript (CART) peptide is expressed in the brain, endocrine and neuroendocrine systems and secreted into the serum. It is thought to play a role in regulation of hypothalamic pituitary functions. Here we report a spatial and temporal analysis of Cart expression in the pituitaries of adult and developing normal and mutant mice with hypopituitarism. We found that Prop1 is not necessary for initiation of Cart expression in the fetal pituitary at e14.5, but it is required indirectly for maintenance of Cart expression in the postnatal anterior pituitary gland. Pou1f1 deficiency has no effect on Cart expression before or after birth. There is no 1:1 correspondence between CART and any particular cell type. In neonates, CART is detected primarily in non-proliferating, POU1F1-positive cells. CART is also found in some cells that express TSH and GH suggesting a correspondence with committed progenitors of the POU1F1 lineage. In summary, we have characterized the normal temporal and cell specific expression of CART in mouse development and demonstrate that postnatal CART expression in the pituitary gland requires PROP1. PMID:27685990

Male acquired hypogonadotropic hypogonadism: diagnosis and treatment.

PubMed

Salenave, Sylvie; Trabado, Sévérine; Maione, Luigi; Brailly-Tabard, Sylvie; Young, Jacques

2012-04-01

Acquired hypogonadotropic hypogonadism (AHH), contrary to congenital hypogonadotropic hypogonadism (CHH) is characterized by postnatal onset of disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. AHH thus prevents the establishment of gonadotropin secretion at puberty, or its post-pubertal maintenance. Thus, postnatal AHH may prevent the onset of puberty or appear during pubertal development, but it usually emerges after the normal age of puberty. Although pituitary tumors, particularly prolactinoma, are the most common cause, sellar tumors or cyst of the hypothalamus or infundibulum, infiltrative, vascular, iron overload and other disorders may also cause AHH. Pituitary surgery and head trauma or cranial/pituitary radiation therapy are also usual causes of AHH. The clinical manifestations of AHH depend on age of onset, the degree of gonadotropin deficiency, the rapidity of its onset and the association to other pituitary function deficiencies or excess. Men with AHH have less stamina, decreased libido, erectile dysfunction and strength, and a worsened sense of well being leading to degraded quality of life. The physical examination is usually normal if hypogonadism is of recent onset. Diminished facial, body hair and muscle mass, fine facial wrinkles, gynecomastia, and hypotrophic testes are observed in long-standing and complete AHH. Spermatogenesis is impaired and the volume of ejaculate is decreased only when gonadotropins and testosterone levels are very low. Men with AHH may have normal or low serum LH and FSH concentrations, but normal gonadotropin values are inappropriate when associated with low serum testosterone. In the majority of AHH patients, serum inhibin B is "normal". The decrease of this sertolian hormone indicates a long-standing and severe gonadotropin deficiency. Symptoms, usually associated with significant testosterone deficiency in men with AHH, improve with testosterone replacement therapy. Replacement therapy is often simple, using an injectable testosterone ester as first line treatment. Fertility can be restored rather quickly, provided there is no independent primary testicular damage and the partner is fertile. Copyright © 2012. Published by Elsevier Masson SAS.

Xanthomatous Hypophysitis Presenting with Diabetes Insipidus Completely Cured Through Transsphenoidal Surgery: Case Report and Literature Review.

PubMed

Lin, Wei; Gao, Lu; Guo, Xiaopeng; Wang, Wenze; Xing, Bing

2017-08-01

Xanthomatous hypophysitis (XH) is extremely rare. Only 27 cases have been reported in the literature. No XH patient presenting with diabetes insipidus (DI) has been completely cured through surgery. Here, we describe the first XH case of a DI patient whose pituitary function was normalized postoperatively, without hormone replacement therapy. A 41-year-old woman suffered from polydipsia, DI, headache, and breast discharge. Laboratory investigation revealed hyperprolactinemia. Pituitary magnetic resonance imaging showed a 2.0-cm × 1.4-cm × 1.6-cm lesion that demonstrated heterogeneous intensity on T1-weighted imaging and peripheral ring enhancement following contrast; the lesion was totally removed through transsphenoidal surgery. Histopathologic and immunohistochemical examinations confirmed the diagnosis of XH. At the 4- and 15-month follow-up visits, all pituitary-related hormones were normal, and the patient was not taking medication. A repeat pituitary magnetic resonance imaging showed no evidence of recurrence. To the best of our knowledge, this case is the first documented occurrence of XH with DI completely cured through surgery. If XH is suspected, total surgical resection of the lesion is recommended and normal pituitary tissue should be carefully protected intraoperatively. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamic enhancement MRI of anterior lobe in pituitary dwarfism.

PubMed

Liu, H M; Li, Y W; Tsai, W Y; Su, C T

1995-08-01

We examined 23 patients with pituitary dwarfism by dynamic MRI; with a repetition time of 150 or 50 ms. The time-enhancement difference curves of selected regions in the anterior lobes were plotted. Another 48 patients with no definite clinical pituitary disfunction were examined with the same technique. We found that the intensity of maximum enhancement in both groups was similar, but the time to achieve maximum enhancement was delayed in pituitary dwarfism with or without stalk transection; the time seemed longest with stalk transection. There was little difference in enhancement between patients with multiple hormone deficiency or isolated growth hormone deficiency. Dynamic MRI of the anterior lobes may be an important functional imaging study, and our results imply that poor perfusion is a useful finding in pituitary dwarfism, especially in patients without stalk transection and normal pituitary height.

Thyrotropin secreting pituitary adenoma accompanying a silent somatotropinoma.

PubMed

Berker, Dilek; Isik, Serhat; Aydin, Yusuf; Tutuncu, Yasemin; Akdemir, Gokhan; Ozcan, Hatice Nursun; Guler, Serdar

2011-01-01

Thyroid stimulating hormone (TSH) secreting pituitary adenomas are rare tumors manifested as hyperthyroidism with goiter in the presence of elevated TSH. We present a case with pituitary adenoma secreting both TSH and growth hormone (GH) with the prominent clinical findings of hyperthyroidism but without clinical findings of acromegaly. Pituitary magnetic resonance imaging revealed a macroadenoma. Transsphenoidal surgery was performed twice. The immunohistochemical staining showed that tumor cells were strongly reactive to GH and relatively mildly reactive to TSH. Control pituitary imaging revealed a residual macroadenoma, and long acting octreotide treatment was administered. After two years of the treatment, tumor size remained the same while thyroid function tests and insulin-like growth factor 1 (IGF-I) values returned to normal ranges. In conclusion, we always recommend hormonal examinations for all patients who have pituitary adenoma without signs and symptoms of acromegaly.

Oxidative stress and mitochondrial adaptive shift during pituitary tumoral growth.

PubMed

Sabatino, Maria Eugenia; Grondona, Ezequiel; Sosa, Liliana D V; Mongi Bragato, Bethania; Carreño, Lucia; Juarez, Virginia; da Silva, Rodrigo A; Remor, Aline; de Bortoli, Lucila; de Paula Martins, Roberta; Pérez, Pablo A; Petiti, Juan Pablo; Gutiérrez, Silvina; Torres, Alicia I; Latini, Alexandra; De Paul, Ana L

2018-05-20

The cellular transformation of normal functional cells to neoplastic ones implies alterations in the cellular metabolism and mitochondrial function in order to provide the bioenergetics and growth requirements for tumour growth progression. Currently, the mitochondrial physiology and dynamic shift during pituitary tumour development are not well understood. Pituitary tumours present endocrine neoplastic benign growth which, in previous reports, we had shown that in addition to increased proliferation, these tumours were also characterized by cellular senescence signs with no indication of apoptosis. Here, we show clear evidence of oxidative stress in pituitary cells, accompanied by bigger and round mitochondria during tumour development, associated with augmented biogenesis and an increased fusion process. An activation of the Nrf2 stress response pathway together with the attenuation of the oxidative damage signs occurring during tumour development were also observed which will probably provide survival advantages to the pituitary cells. These neoplasms also presented a progressive increase in lactate production, suggesting a metabolic shift towards glycolysis metabolism. These findings might imply an oxidative stress state that could impact on the pathogenesis of pituitary tumours. These data may also reflect that pituitary cells can modulate their metabolism to adapt to different energy requirements and signalling events in a pathophysiological situation to obtain protection from damage and enhance their survival chances. Thus, we suggest that mitochondria function, oxidative stress or damage might play a critical role in pituitary tumour progression. Copyright © 2018 Elsevier Inc. All rights reserved.

Pituitary iron and volume predict hypogonadism in transfusional iron overload.

PubMed

Noetzli, Leila J; Panigrahy, Ashok; Mittelman, Steven D; Hyderi, Aleya; Dongelyan, Ani; Coates, Thomas D; Wood, John C

2012-02-01

Hypogonadism is the most common morbidity in patients with transfusion-dependent anemias such as thalassemia major. We used magnetic resonance imaging (MRI) to measure pituitary R2 (iron) and volume to determine at what age these patients develop pituitary iron overload and volume loss. We recruited 56 patients (47 with thalassemia major, five with chronically transfused thalassemia intermedia and four with Blackfan-Diamond syndrome) to have pituitary MRIs to measure pituitary R2 and volume. Hypogonadism was defined clinically based on the timing of secondary sexual characteristics or the need for sex hormone replacement therapy. Patients with transfusional iron overload begin to develop pituitary iron overload in the first decade of life; however, clinically significant volume loss was not observed until the second decade of life. Severe pituitary iron deposition (Z > 5) and volume loss (Z < -2.5) were independently predictive of hypogonadism. Pituitary R2 correlated significantly with serum ferritin as well as liver, pancreatic, and cardiac iron deposition by MRI. Log pancreas R2* was the best single predictor for pituitary iron, with an area under the receiving operator characteristic curve of 0.88, but log cardiac R2* and ferritin were retained on multivariate regression with a combined r(2) of 0.71. Pituitary iron overload and volume loss were independently predictive of hypogonadism. Many patients with moderate-to-severe pituitary iron overload retained normal gland volume and function, representing a potential therapeutic window. The subset of hypogonadal patients having preserved gland volumes may also explain improvements in pituitary function observed following intensive chelation therapy. Copyright © 2011 Wiley Periodicals, Inc.

ACTH Antibodies in Patients Receiving Depot Porcine ACTH to Hasten Recovery from Pituitary-Adrenal Suppression*

PubMed Central

Fleischer, Norman; Abe, Kaoru; Liddle, Grant W.; Orth, David N.; Nicholson, Wendell E.

1967-01-01

Six patients who had experienced prolonged steroid-induced pituitary-adrenal suppression were treated with 100 U of depot procine ACTH every 2 to 4 days for several months. Such treatment did not hasten the recovery of normal pituitary-adrenal function compared with the rate of recovery of a group of similarly suppressed patients who received no depot ACTH. Eight of nine patients who received prolonged courses of depot porcine ACTH developed antibodies to ACTH that cross-reacted with endogenous ACTH, binding it in the circulation in inactive form and retarding its removal from the circulation. The presence of such antibodies did not in itself grossly alter pituitary-adrenal interrelationships. Images PMID:4289551

Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.

PubMed

Zheng, Junjie; Mao, Jiangfeng; Xu, Hongli; Wang, Xi; Huang, Bingkun; Liu, Zhaoxiang; Cui, Mingxuan; Xiong, Shuyu; Ma, Wanlu; Min, Le; Kaiser, Ursula B; Nie, Min; Wu, Xueyan

2017-07-01

The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH. To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD. Prospective, self-controlled, 3-month clinical trial. University endocrine clinic. Men with hypogonadotropic hypogonadism caused by CCPHD. Pulsatile GnRH was administered subcutaneously for 3 months. Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis. A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk. This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice. Copyright © 2017 Endocrine Society

Panhypopituitarism after multisystem trauma.

PubMed

Wiechecka, Joanna; Krzewska, Aleksandra; Droń, Izabela; Beń-Skowronek, Iwona

2013-01-01

The pituitary gland plays a key role in hormonal regulation in the organism, contributing to maintenance of balance of basic vital functions. To emphasise the need for assessment of pituitary function after head injury, as correct diagnosis and hormone replacement therapy prove to be a life-saving therapy accelerating the recovery process. A healthy, normally developing 9-year-old girl, a child of young and healthy parents, was struck by a falling tree. The results of severe head trauma included adrenal crisis, hypothyroidism, and diabetes insipidus as manifestations of damage to the anterior and posterior pituitary gland. Administration of hormone replacement therapy, i.e. hydrocortisone, L-thyroxine, and desmopressin greatly improved the patient´s condition and facilitated effective rehabilitation. Determination of pituitary hormones in children after severe head injury should be an important part of diagnosis allowing identification of an early stage of acute hypopituitarism and acceleration of recovery through hormone replacement therapy.

Decreased apparent diffusion coefficient in the pituitary and correlation with hypopituitarism in patients with traumatic brain injury.

PubMed

Zheng, Ping; He, Bin; Guo, Yijun; Zeng, Jingsong; Tong, Wusong

2015-07-01

The relationship between microstructural abnormality in patients with traumatic brain injury (TBI) and hormone-secreting status remains unknown. In this study, the authors aimed to identify the role of the apparent diffusion coefficient (ADC) using a diffusion-weighted imaging (DWI) technique and to evaluate the association of such changes with hypopituitarism in patients with TBI. Diffusion-weighted images were obtained in 164 consecutive patients with TBI within 2 weeks after injury to generate the pituitary ADC as a measure of microstructural change. Patients with TBI were further grouped into those with and those without hypopituitarism based on the secretion status of pituitary hormones at 6 months postinjury. Thirty healthy individuals were enrolled in the study and underwent MRI examinations for comparison. Mean ADC values were compared between this control group, the patients with TBI and hypopituitarism, and the patients with TBI without hypopituitarism; correlational studies were also performed. Neurological outcome was assessed with the Glasgow Outcome Scale (GOS) for all TBI patients 6 months postinjury. In the TBI group, 84 patients had hypopituitarism and 80 had normal pituitary function. The pituitary ADC in TBI patients was significantly less than that in controls (1.83 ± 0.16 vs 4.13 ± 0.33, p < 0.01). Furthermore, the mean ADC was much lower in TBI patients with hypopituitarism than in those without pituitary dysfunction (1.32 ± 0.09 vs 2.28 ± 0.17, p < 0.05). There was also a significant difference in ADC values between patients with hyperprolactinemia and those with normal prolactin levels (p < 0.05). Additionally, the receiver operating characteristic curve analysis showed that the pituitary ADC could predict hypopituitarism with a sensitivity of 90.0% and a specificity of 90.1% at the level of 1.720 (ADC value). Finally, the ADC value was positively correlated with neurological outcome at 6 months following TBI (r = 0.602, p < 0.05). Use of DWI demonstrated that the pituitary ADC is correlated with hormone-secreting status in TBI patients. The authors suggest that pituitary ADC may be a useful biomarker to predict pituitary function in patients with TBI.

Lhx4 and Prop1 are required for cell survival and expansion of the pituitary primordia.

PubMed

Raetzman, Lori T; Ward, Robert; Camper, Sally A

2002-09-01

Deficiencies in the homeobox transcription factors LHX4 and PROP1 cause pituitary hormone deficiency in both humans and mice. Lhx4 and Prop1 mutants exhibit severe anterior pituitary hypoplasia resulting from limited differentiation and expansion of most specialized cell types. Little is known about the mechanism through which these genes promote pituitary development. In this study we determined that the hypoplasia in Lhx4 mutants results from increased cell death and that the reduced differentiation is attributable to a temporal shift in Lhx3 activation. In contrast, Prop1 mutants exhibit normal cell proliferation and cell survival but show evidence of defective dorsal-ventral patterning. Molecular genetic analyses reveal that Lhx4 and Prop1 have overlapping functions in early pituitary development. Double mutants exhibit delayed corticotrope specification and complete failure of all other anterior pituitary cell types to differentiate. Thus, Lhx4 and Prop1 have critical, but mechanistically different roles in specification and expansion of specialized anterior pituitary cells.

Effect of hypothyroidism on the hypothalamic-pituitary-ovarian axis and reproductive function of pregnant rats.

PubMed

Sun, Jianran; Hui, Cancan; Xia, Tongjia; Xu, Min; Deng, Datong; Pan, Faming; Wang, Youmin

2018-05-24

This study aimed to detect changes in hormone levels in the hypothalamic-pituitary-ovarian axis in Sprague-Dawley (SD) rats with hypothyroidism, and identify differences in the pregnancy and abortion rates of female adult rats. The potential role of gonadotropin releasing hormone (GnRH) as the link between the hypothalamic-pituitary-ovarian axis and reproductive function regulated by thyroid hormones was also investigated. Female SD rats (n = 136) were causally classified into two groups: the normal-drinking-water group (n = 60) and the 0.05% propylthiouracil-drinking-water group (PTU 2 mg/kg/day, n = 76) to establish an adult rat model of hypothyroidism (6 weeks). Female and male rats at a ratio of 1:2 were used to establish a hypothyroidism pregnancy model. GnRH mRNA and GnRH receptor (GnRHR) expression in rats was detected using real time quantitative PCR(qRT-PCR) and immunohistochemistry, respectively. The abortion rate differed significantly between the hypothyroidism pregnancy group and the normal pregnancy group (P < 0.05). No significant differences were found in the distribution of the GnRHR among the five nuclei (hypothalamic arcuate nucleus, hypothalamic ventromedial nucleus, hypothalamic anterior nucleus, paraventricular nucleus of the hypothalamus, and ventral premammillary nucleus) of the hypothalamus and ovary (P > 0.05). Hypothyroidism had no significant effect on GnRH mRNA expression in the hypothalamic-pituitary-ovarian axis in the four groups (normal control group, normal pregnancy group, hypothyroidism pregnancy group, and hypothyroidism group) (P > 0.05). Hypothyroidism had an adverse impact on pregnancy in rats and may affect the distribution of pituitary GnRHR, whereas it did not obviously affect the distribution of GnRHR in the nuclei of the hypothalamus and ovary. Hypothyroidism had no effect on GnRH mRNA expression.

Early effects of cranial irradiation on hypothalamic-pituitary function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lam, K.S.; Tse, V.K.; Wang, C.

1987-03-01

Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordantmore » changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.« less

Endocrinology Update: Hypopituitarism.

PubMed

Heidelbaugh, Joel J

2016-12-01

Hypopituitarism is defined as a deficiency of one or more pituitary hormones due to a decline in function of the pituitary gland and/or hypothalamus, which can result in higher risks of morbidity and mortality and decreased quality of life. Although hypopituitarism is a rare condition, it commonly develops after traumatic brain injury and in the setting of functioning and nonfunctioning pituitary adenomas. The diagnosis is based on detailed investigation of symptoms of target endocrine gland function relative to the corresponding pituitary hormone deficiency. The clinical manifestations of hypopituitarism result from the degree of the specific hormone deficiency. A thorough and longitudinal history and physical examination, including visual field testing, are paramount. Management consists of prompt pharmacotherapy, surgery, and/or radiotherapy to restore normal endocrine function and quality of life. In most patients with anterior and posterior pituitary hormone deficiency, corresponding hormone replacement is the mainstay of therapy. The prognosis for patients with hypopituitarism depends on the manner of and age at presentation, degree and severity of hormonal impairment, and response to medical and surgical therapies. Patients with hypopituitarism require lifelong monitoring of serum hormone levels and symptoms of hormone deficiency or excess. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma

PubMed Central

Pozzi, Sara; Carreno, Gabriela; Manshaei, Saba; Panousopoulos, Leonidas; Gonzalez-Meljem, Jose Mario; Apps, John R.; Virasami, Alex; Thavaraj, Selvam; Gutteridge, Alice; Forshew, Tim; Marais, Richard; Brandner, Sebastian; Jacques, Thomas S.; Andoniadou, Cynthia L.

2017-01-01

Despite the importance of the RAS-RAF-MAPK pathway in normal physiology and disease of numerous organs, its role during pituitary development and tumourigenesis remains largely unknown. Here, we show that the over-activation of the MAPK pathway, through conditional expression of the gain-of-function alleles BrafV600E and KrasG12D in the developing mouse pituitary, results in severe hyperplasia and abnormal morphogenesis of the gland by the end of gestation. Cell-lineage commitment and terminal differentiation are disrupted, leading to a significant reduction in numbers of most of the hormone-producing cells before birth, with the exception of corticotrophs. Of note, Sox2+ stem cells and clonogenic potential are drastically increased in the mutant pituitaries. Finally, we reveal that papillary craniopharyngioma (PCP), a benign human pituitary tumour harbouring BRAF p.V600E also contains Sox2+ cells with sustained proliferative capacity and disrupted pituitary differentiation. Together, our data demonstrate a crucial function of the MAPK pathway in controlling the balance between proliferation and differentiation of Sox2+ cells and suggest that persistent proliferative capacity of Sox2+ cells may underlie the pathogenesis of PCP. PMID:28506993

Craniopharyngiomas express embryonic stem cell markers (SOX2, OCT4, KLF4, and SOX9) as pituitary stem cells but do not coexpress RET/GFRA3 receptors.

PubMed

Garcia-Lavandeira, Montserrat; Saez, Carmen; Diaz-Rodriguez, Esther; Perez-Romero, Sihara; Senra, Ana; Dieguez, Carlos; Japon, Miguel A; Alvarez, Clara V

2012-01-01

Adult stem cells maintain some markers expressed by embryonic stem cells and express other specific markers depending on the organ where they reside. Recently, stem/progenitor cells in the rodent and human pituitary have been characterized as expressing GFRA2/RET, PROP1, and stem cell markers such as SOX2 and OCT4 (GPS cells). Our objective was to detect other specific markers of the pituitary stem cells and to investigate whether craniopharyngiomas (CRF), a tumor potentially derived from Rathke's pouch remnants, express similar markers as normal pituitary stem cells. We conducted mRNA and Western blot studies in pituitary extracts, and immunohistochemistry and immunofluorescence on sections from normal rat and human pituitaries and 20 CRF (18 adamantinomatous and two papillary). Normal pituitary GPS stem cells localized in the marginal zone (MZ) express three key embryonic stem cell markers, SOX2, OCT4, and KLF4, in addition to SOX9 and PROP1 and β-catenin overexpression. They express the RET receptor and its GFRA2 coreceptor but also express the coreceptor GFRA3 that could be detected in the MZ of paraffin pituitary sections. CRF maintain the expression of SOX2, OCT4, KLF4, SOX9, and β-catenin. However, RET and GFRA3 expression was altered in CRF. In 25% (five of 20), both RET and GFRA3 were detected but not colocalized in the same cells. The other 75% (15 of 20) lose the expression of RET, GFRA3, or both proteins simultaneously. Human pituitary adult stem/progenitor cells (GPS) located in the MZ are characterized by expression of embryonic stem cell markers SOX2, OCT4, and KLF4 plus the specific pituitary embryonic factor PROP1 and the RET system. Redundancy in RET coreceptor expression (GFRA2 and GFRA3) suggest an important systematic function in their physiological behavior. CRF share the stem cell markers suggesting a common origin with GPS. However, the lack of expression of the RET/GFRA system could be related to the cell mislocation and deregulated growth of CRF.

Role of stromal cell-derived factor 1 (SDF1/CXCL12) in regulating anterior pituitary function.

PubMed

Barbieri, Federica; Bajetto, Adriana; Porcile, Carola; Pattarozzi, Alessandra; Schettini, Gennaro; Florio, Tullio

2007-03-01

Chemokines are key factors involved in the regulation of immune response, through the activation and control of leukocyte traffic, lymphopoiesis and immune surveillance. However, a large number of chemokines and their receptors are expressed in central nervous system (CNS) cells, either constitutively or induced by inflammatory stimuli, playing a role in many neuropathological processes. Stromal cell-derived factor 1 (SDF1) is a chemokine whose extra-immunological localization and functions have been extensively studied. SDF1 and its receptor CXCR4 were identified in both neurons and glia of many brain areas, including the hypothalamus, as well as at the pituitary level. Importantly, SDF1 and CXCR4 expression is increased in brain tumors in which their activity induced tumor cell proliferation and brain parenchyma invasion. Despite their localization, to date very few reports addressed the role of CXCR4 and SDF1 in the modulation of the hypothalamus/pituitary axis and their possible involvement in the development of pituitary adenomas. In this review, we discuss previous literature data on the role of chemokines in normal and adenomatous pituitary cells, focusing on recent data from our group showing that CXCR4 activation controls proliferation and both prolactin and GH release in the pituitary adenoma cell line GH4C1 through a complex network of intracellular signals. Thus, the SDF1/CXCR4 system together with other chemokinergic ligand-receptor pairs, may represent a novel regulatory pathway for pituitary function and, possibly, be involved in pituitary adenoma development. These lines of evidence suggest that the inhibition of chemokine receptors may represent a novel pharmacological target for the treatment of pituitary adenomas.

[Effect of combined oral contraceptives on the hypophyseo-thyroid and hypophyseo-adrenal systems in women with various anatomy of the thyroid gland].

PubMed

Zigizmund, V A; Sadykova, M Sh; Samoĭlova, O N; Moiseeva, O M

1988-11-01

Potential therapeutic effects of combined oral contraceptives (COC) rigevidon and ovidon (estrogen:gestagen ratio of 1:5) were studied in 97 women aged 19-35 years. With respect to the anatomical state of the thyroid, the patients were divided into two groups: group 1 included 42 women with normal thyroid function and group 2 included 55 women with euthyroid hyperplasia of the thyroid gland of stage I-II (the anatomical state of the thyroid gland was ranked according to the five-point Swiss scale adopted by WHO in 1975). All patients had a history of pregnancy, normal delivery, or abortion. The state of the pituitary-thyroid system was estimated by absorption of iodine isotopes in the thyroid tissue, and by the blood levels of thyrotropic hormone, thyroxine-binding globulin, thyroxine, and triiodothyronine. Activity of the pituitary- adrenal system was estimated by the blood levels of adrenocorticotropic hormone (ACTH) and cortisol. Blood samples were withdrawn 9 and 10 hours prior to the onset of COC administration, and after 24 and 48 weeks of COC use. The changes in the functional state of the pituitary- thyroid system in groups 1 and 2 were identical throughout the entire period of COC administration. Progressive increase in the levels of thyroxine and triiodothyronine was associated with inhibition of the thyrotropic function of the pituitary seen as decrease in thyrotropin levels. COC administration caused decrease in size of hyperplastic tyroid gland. Prior to COC administration, women in group 2 showed significant elevation of ACTH levels and marked decrease in ACTH levels and increase in cortisol levels in both groups. Normalization of the size of thyroid gland indicated that COC be used therapeutically in patients with thyroid hyperplasia.

Clinical and diagnostic approach to patients with hypopituitarism due to traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and ischemic stroke (IS).

PubMed

Karamouzis, Ioannis; Pagano, Loredana; Prodam, Flavia; Mele, Chiara; Zavattaro, Marco; Busti, Arianna; Marzullo, Paolo; Aimaretti, Gianluca

2016-06-01

The hypothalamic-pituitary dysfunction attributable to traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (SAH), and ischemic stroke (IS) has been lately highlighted. The diagnosis of TBI-induced-hypopituitarism, defined as a deficient secretion of one or more pituitary hormones, is made similarly to the diagnosis of classical hypopituitarism because of hypothalamic/pituitary diseases. Hypopituitarism is believed to contribute to TBI-associated morbidity and to functional and cognitive final outcome, and quality-of-life impairment. Each pituitary hormone must be tested separately, since there is a variable pattern of hormone deficiency among patients with TBI-induced-hypopituitarism. Similarly, the SAH and IS may lead to pituitary dysfunction although the literature in this field is limited. The drive to diagnose hypopituitarism is the suspect that the secretion of one/more pituitary hormone may be subnormal. This suspicion can be based upon the knowledge that the patient has an appropriate clinical context in which hypopituitarism can be present, or a symptom known as caused by hypopituitarism. Hypopituitarism should be diagnosed as a combination of low peripheral and inappropriately normal/low pituitary hormones although their basal evaluation may be not distinctive due to pulsatile, circadian, or situational secretion of some hormones. Evaluation of the somatotroph and corticotroph axes require dynamic stimulation test (ITT for both axes, GHRH + arginine test for somatotroph axis) in order to clearly separate normal from deficient responses.

Outcomes of Pituitary Radiation for Cushing's Disease.

PubMed

Ironside, Natasha; Chen, Ching-Jen; Lee, Cheng-Chia; Trifiletti, Daniel M; Vance, Mary Lee; Sheehan, Jason P

2018-06-01

Achievement of biochemical remission with preservation of normal pituitary function is the goal of treatment for Cushing's disease. For patients with persistent or recurrent Cushing's disease after transsphenoidal resection, radiation therapy may be a safe and effective treatment. Stereotactic radiosurgery is favored over conventional fractionated external beam radiation. Hormonal recurrence rates range from 0% to 36% at 8 years after treatment. Tumor control rates are high. New pituitary hormone deficiency is the most common adverse effect after stereotactic radiosurgery and external beam radiation. The effects of radiation planning optimization and use of adjuvant medication on endocrine remission rates warrant investigation. Copyright © 2018 Elsevier Inc. All rights reserved.

Tissue interactions in the induction of anterior pituitary: role of the ventral diencephalon, mesenchyme, and notochord.

PubMed

Gleiberman, A S; Fedtsova, N G; Rosenfeld, M G

1999-09-15

Rathke's pouch, the epithelial primordium of the anterior pituitary, differentiates in close topographical and functional association with the ventral diencephalon. It is still not known whether the ventral diencephalon acts as the initial inducer of pituitary development. The roles of the adjacent mesenchyme and notochord, two other tissues located in close proximity to Rathke's pouch, in this process are even less clear. In this report we describe an in vitro experimental system that reproduces the earliest steps of anterior pituitary development. We provide evidence that the ventral diencephalon from 2- to 4-day-old chick embryos is able to function as an inducer of pituitary development and can convert early chick embryonic head ectoderm, which is not involved normally in pituitary development, into typical anterior pituitary tissue. This induction is contact-dependent. In our experimental system, there is a requirement for the supporting action of mesenchyme, which is independent of the mesenchyme source. Transplantation of the notochord into the lateral head region of a six-somite chick embryo induces an epithelial invagination, suggesting that the notochord induces the outpouching of the roof of the stomodeal ectoderm that results in formation of Rathke's pouch and causes the close contact between this ectoderm and the ventral diencephalon. Finally, we demonstrate that the ventral diencephalon from e9.5-e11.5 mouse embryos is also an efficient inducer of anterior pituitary differentiation in chick embryonic lateral head ectoderm, suggesting that the mechanism of anterior pituitary induction is conserved between mammals and birds, using the same, or similar, signaling pathways. Copyright 1999 Academic Press.

Clinical and endocrine responses to pituitary radiotherapy in pediatric Cushing's disease: an effective second-line treatment.

PubMed

Storr, Helen L; Plowman, P Nicholas; Carroll, Paul V; François, Inge; Krassas, Gerasimos E; Afshar, Farhad; Besser, G Michael; Grossman, Ashley B; Savage, Martin O

2003-01-01

Transsphenoidal surgery (TSS) is considered first-line treatment for Cushing's disease (CD). Options for treatment of postoperative persisting hypercortisolemia are pituitary radiotherapy (RT), repeat TSS, or bilateral adrenalectomy. From 1983 to 2001, we treated 18 pediatric patients (age, 6.4-17.8 yr) with CD. All underwent TSS, and 11 were cured (postoperative serum cortisol, <50 nM). Seven (39%) had 0900-h serum cortisol of 269-900 nM during the immediate postoperative period (2-20 d), indicating lack of cure. These patients (6 males and 1 female; mean age, 12.8 yr; range, 6.4-17.8 yr; 4 prepubertal; 3 pubertal) received external beam RT to the pituitary gland, using a 6-MV linear accelerator, with a dose of 45 Gy in 25 fractions over 35 d. Until the RT became effective, hypercortisolemia was controlled with ketoconazole (dose, 200-600 mg/d) (n = 4) and metyrapone (750 mg-3 g/d) +/- aminoglutethimide (1 g/d) or o'p'DDD (mitotane, 3 mg/d) (n = 3). All patients were cured after pituitary RT. The mean interval from RT to cure (mean serum cortisol on 5-point day curve, <150 nM) was 0.94 yr (0.25-2.86 yr). Recovery of pituitary-adrenal function (mean cortisol, 150-300 nM) occurred at mean 1.16 yr (0.40-2.86 yr) post RT. At 2 yr post RT, puberty occurred early in one male patient (age, 9.8 yr) but was normal in the others. GH secretion was assessed at 0.6-2.5 yr post RT in all patients: six had GH deficiency (peak on glucagon/insulin provocation, <1.0-17.9 mU/liter) and received human GH replacement. Follow-up of pituitary function 7.6 and 9.5 yr post RT in two patients showed normal gonadotropin secretion and recovery of GH peak to 29.7 and 19.2 mU/liter. The seven patients were followed for mean 6.9 yr (1.4-12.0 yr), with no evidence of recurrence of CD. In conclusion, pituitary RT is an effective and relatively rapid-onset treatment for pediatric CD after failure of TSS. GH deficiency occurred in 86% patients. Long-term follow-up suggests some recovery of GH secretion and preservation of other anterior pituitary function.

MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma.

PubMed

Haston, Scott; Pozzi, Sara; Carreno, Gabriela; Manshaei, Saba; Panousopoulos, Leonidas; Gonzalez-Meljem, Jose Mario; Apps, John R; Virasami, Alex; Thavaraj, Selvam; Gutteridge, Alice; Forshew, Tim; Marais, Richard; Brandner, Sebastian; Jacques, Thomas S; Andoniadou, Cynthia L; Martinez-Barbera, Juan Pedro

2017-06-15

Despite the importance of the RAS-RAF-MAPK pathway in normal physiology and disease of numerous organs, its role during pituitary development and tumourigenesis remains largely unknown. Here, we show that the over-activation of the MAPK pathway, through conditional expression of the gain-of-function alleles BrafV600E and KrasG12D in the developing mouse pituitary, results in severe hyperplasia and abnormal morphogenesis of the gland by the end of gestation. Cell-lineage commitment and terminal differentiation are disrupted, leading to a significant reduction in numbers of most of the hormone-producing cells before birth, with the exception of corticotrophs. Of note, Sox2 + stem cells and clonogenic potential are drastically increased in the mutant pituitaries. Finally, we reveal that papillary craniopharyngioma (PCP), a benign human pituitary tumour harbouring BRAF p.V600E also contains Sox2 + cells with sustained proliferative capacity and disrupted pituitary differentiation. Together, our data demonstrate a crucial function of the MAPK pathway in controlling the balance between proliferation and differentiation of Sox2 + cells and suggest that persistent proliferative capacity of Sox2 + cells may underlie the pathogenesis of PCP. © 2017. Published by The Company of Biologists Ltd.

Identification of M2 macrophages in anterior pituitary glands of normal rats and rats with estrogen-induced prolactinoma.

PubMed

Fujiwara, Ken; Yatabe, Megumi; Tofrizal, Alimuddin; Jindatip, Depicha; Yashiro, Takashi; Nagai, Ryozo

2017-05-01

Macrophages are present throughout the anterior pituitary gland. However, the features and function of macrophages in the gland are poorly understood. Recent studies have indicated that there are two main macrophage classes: M1 (classically activated) and M2 (alternatively activated). In this study, we examine whether both M1 and M2 macrophages are present in the anterior pituitary gland of rats. Our findings indicate that macrophages that are positive for CD68 (a pan-macrophage marker) were localized near capillaries in rat anterior pituitary gland. These macrophages were positive for iNOS or mannose receptor (MR), which are markers of M1 and M2 macrophages, respectively. To determine the morphological characteristics of M2 macrophages under pathological conditions, diethylstilbestrol (DES)-treated rats were used as an animal model of prolactinoma. After 2 weeks of DES treatment, a number of MR-immunopositive cells were present in the gland. Immunoelectron microscopy revealed that MR-immunopositive M2 macrophages had many small vesicles and moderately large vacuoles in cytoplasm. Phagosomes were sometimes present in cytoplasm. Interestingly, M2 macrophages in prolactinoma tissues did not usually exhibit distinct changes or differences during the normal, hyperplasia and adenoma stages. This study is the first to confirm that both M1 and M2 macrophages are present in the anterior pituitary gland of rats. Moreover, the number of M2 macrophages was greatly increased in rats with DES-induced prolactinoma. Future studies should attempt to characterize the functional role of M2 macrophages in the gland.

Glial-derived neurotropic factor and RET gene expression in normal human anterior pituitary cell types and in pituitary tumors.

PubMed

Japón, Miguel A; Urbano, Angel G; Sáez, Carmen; Segura, Dolores I; Cerro, Alfonso Leal; Diéguez, Carlos; Alvarez, Clara V

2002-04-01

Glial-derived neurotropic factor (GDNF) signaling is mediated through a 2-component system consisting of the so-called GDNF receptor-alpha (GFRalpha1), which binds to GDNF. This complex activates the tyrosine kinase receptor RET. In this paper we demonstrate GDNF, GFRalpha1, and RET mRNA and protein expression in the human anterior pituitary gland. Double immunohistochemistry of anterior pituitary sections showed GDNF immunoreactivity in more than 95% of somatotrophs and to a lesser extent in corticotrophs (20%); it was almost absent in the remaining cell types. Also, although more than 95% of somatotrophs were stained for RET, no positive immunostaining could be detected in other cell types. Furthermore, we have looked for GDNF and RET in human pituitary adenomas of various hormonal phenotypes. Strong positive immunostaining was found for c-RET in all of the GH-secreting adenomas screened as well as in 50% of ACTH-producing adenomas. Positive immunostaining for GDNF was found in all of the GH-secreting adenomas and in 10% of the corticotropinomas. Lastly, we found strong positive immunostaining for GFRalpha1 in 90% of the somatotropinomas and 50% of the corticotropinomas as well as in 1 of 8 prolactinomas and 1 of 13 nonfunctioning adenomas. All of the remaining pituitary tumors screened were negative for RET, GDNF, and GFRalpha1. This study indicates that GDNF may well be acting in the regulation of somatotroph cell growth and/or cell function in the normal human anterior pituitary gland. The expression of RET in all of the somatotropinomas and in 50% of the ACTH-producing tumors implies that GDNF and RET could be involved in the pathogenesis of pituitary tumors.

Candidate genes for panhypopituitarism identified by gene expression profiling

PubMed Central

Mortensen, Amanda H.; MacDonald, James W.; Ghosh, Debashis

2011-01-01

Mutations in the transcription factors PROP1 and PIT1 (POU1F1) lead to pituitary hormone deficiency and hypopituitarism in mice and humans. The dysmorphology of developing Prop1 mutant pituitaries readily distinguishes them from those of Pit1 mutants and normal mice. This and other features suggest that Prop1 controls the expression of genes besides Pit1 that are important for pituitary cell migration, survival, and differentiation. To identify genes involved in these processes we used microarray analysis of gene expression to compare pituitary RNA from newborn Prop1 and Pit1 mutants and wild-type littermates. Significant differences in gene expression were noted between each mutant and their normal littermates, as well as between Prop1 and Pit1 mutants. Otx2, a gene critical for normal eye and pituitary development in humans and mice, exhibited elevated expression specifically in Prop1 mutant pituitaries. We report the spatial and temporal regulation of Otx2 in normal mice and Prop1 mutants, and the results suggest Otx2 could influence pituitary development by affecting signaling from the ventral diencephalon and regulation of gene expression in Rathke's pouch. The discovery that Otx2 expression is affected by Prop1 deficiency provides support for our hypothesis that identifying molecular differences in mutants will contribute to understanding the molecular mechanisms that control pituitary organogenesis and lead to human pituitary disease. PMID:21828248

Bone morphogenetic protein 4 and bone morphogenetic protein receptor expression in the pituitary gland of adult dogs in healthy condition and with ACTH-secreting pituitary adenoma.

PubMed

Sato, A; Ochi, H; Harada, Y; Yogo, T; Kanno, N; Hara, Y

2017-01-01

The purpose of this study was to investigate the expression of bone morphogenetic protein 4 (BMP4) and its receptors, bone morphogenetic protein receptor I (BMPRI) and BMPRII, in the pituitary gland of healthy adult dogs and in those with ACTH-secreting pituitary adenoma. Quantitative polymerase chain reaction analysis showed that the BMP4 messenger RNA expression level in the ACTH-secreting pituitary adenoma samples was significantly lower than that in the normal pituitary gland samples (P = 0.03). However, there were no statistically significant differences between samples with respect to the messenger RNA expression levels of the receptors BMPRIA, BMPRIB, and BMPRII. Double-immunofluorescence analysis of the normal canine pituitary showed that BMP4 was localized in the thyrotroph (51.3 ± 7.3%) and not the corticotroph cells. By contrast, BMPRII was widely expressed in the thyrotroph (19.9 ± 5.2%) and somatotroph cells (94.7 ± 3.6%) but not in the corticotroph cells (P < 0.001, thyrotroph cells vs somatotroph cells). Similarly, in ACTH-secreting pituitary adenoma, BMP4 and BMPRII were not expressed in the corticotroph cells. Moreover, the percentage of BMP4-positive cells was also significantly reduced in the thyrotroph cells of the surrounding normal pituitary tissue obtained from the resected ACTH-secreting pituitary adenoma (8.3 ± 7.9%) compared with that in normal canine pituitary (P < 0.001). BMP4 has been reported to be expressed in corticotroph cells in the human pituitary gland. Therefore, the results of this study reveal a difference in the cellular pattern of BMP4-positive staining in the pituitary gland between humans and dogs and further revealed the pattern of BMPRII-positive staining in the dog pituitary gland. These species-specific differences regarding BMP4 should be considered when using dogs as an animal model for Cushing's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Reversible Hypopituitarism Associated with Intravascular Large B-Cell Lymphoma: Case Report of Successful Immunochemotherapy.

PubMed

Sawada, Yusuke; Ishii, Sumiyasu; Koga, Yasuhiko; Tomizawa, Taku; Matsui, Ayako; Tomaru, Takuya; Ozawa, Atsushi; Shibusawa, Nobuyuki; Satoh, Tetsurou; Shimizu, Hiroaki; Hirato, Junko; Yamada, Masanobu

2016-03-01

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma. There have been only a limited number of reports regarding pituitary dysfunction associated with IVLBCL. We present a 71-year-old woman with hypopituitarism without any hypothalamic/pituitary abnormalities as assessed by magnetic resonance imaging. She presented with edema, abducens palsy, and elevated levels of lactate dehydrogenase and soluble interleukin-2 receptor. Provocative testing showed that the peaks of luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone and adrenocorticotropic hormone were evoked to normal levels by simultaneous administration of luteinizing hormone-releasing hormone, thyrotropin-releasing hormone and corticotropin-releasing hormone, but the responses of these four pituitary hormones showed a delayed pattern. She was diagnosed with IVLBCL with cerebrospinal invasion by pathological findings of the bone marrow, skin, and cerebrospinal fluid. She achieved hematological remission after immunochemotherapy. Pituitary function was also restored without hormonal replacement, and the improvement of the pituitary function was confirmed by dynamic testing. We reviewed the literature with respect to hypopituitarism associated with IVLBCL. There were less than 20 case reports and most of the patients died. Endocrinological course was described in only two cases, and both of them required hormonal supplementation. To our knowledge, this is the first case of hypopituitarism induced by IVLBCL that was successfully managed by immunochemotherapy alone. This case suggests that early diagnosis and treatment of IVLBCL might improve anterior pituitary function and enable patients to avoid hormone replacement therapy.

Pathophysiology of Cushing's disease.

PubMed

Fehm, H L; Voigt, K H

1979-01-01

The term Cushing's disease is applied to those cases of Cushing's syndrome in which hypercortisolism is secondary to inappropriate secretion of ACTH by the pituitary. Studies on control of ACTH secretion in these patients reveal: (a) that the episodic secretion of ACTH is similar to the normal; however, frequency and amplitude of the secretory episodes lack the normal circadian rhythm; (b) that ACTH release can be stimulated by vasopressin and metyrapone in a normal or above-normal manner; and (c) that it can be suppressed by large doses of corticosteroids. When the dynamic aspects of the ACTH response to corticosteroid administration are studied, it appears that the normally negative differential feedback mechanism is converted into a positive one, whereas the delayed, integral mechanism is undisturbed. Patients with Cushing's disease in the presence of obvious pituitary tumors cannot be distinguished from those without pituitary tumors by studying only the pituitary function. All these and other well-known facts would favor the concept that ACTH secretion in Cushing's disease is under hypothalamic control whether or not a pituitary tumor is present. Moreover, there are observations that suggest that brain centers superior to the hypophysiotropic area of the hypothalamus are involved in the pathophysiology of Cushing's disease. This concept has led to the discovery of neurotropic drugs that are able to induce complete remission of Cushing's syndrome in a cerain percentage of patients. In some patients with severe psychiatric diseases, neuroendocrine abnormalities are present that resemble closely those characteristic for Cushing's disease. With the most refined neuroradiological methods, pituitary microadenomas are demonstrable in approximately 70% of patients with Cushing's disease, and this number compares well with those of earlier autopsy findings (70 to 80%). In a small number of patients (4 to 10%), these tumors are large and can easily be detected by standard roentgenograms of the head. Recent studies on the frequency of these large tumors do not support the hypothesis that adrenalectomy accelerates the progression of these tumors. In this case the term "Nelson's syndrome" would be uncessary. It is established that complete cure of Cushing's disease can be obtained in most patients with selective removal of a microadenoma from the pituitary gland. The current experience with this microsurgical procedure caused a renewed interest in Cushing's original suggestion that the disease is primarily a pituitary disorder. However, there are already a number of enigmatic observations. Possibly, the recent ultrastructural studies using immunocytochemical methods will resolve some of these problems. At this moment it is impossible to decide whether Cushing's disease is primarily a CNS or a pituitary disorder, when all arguments for one or the other hypothesis are taken into account...

Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene.

PubMed

Mantovani, Giovanna; Maghnie, Mohamad; Weber, Giovanna; De Menis, Ernesto; Brunelli, Valeria; Cappa, Marco; Loli, Paola; Beck-Peccoz, Paolo; Spada, Anna

2003-09-01

Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteodystrophy. Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action [pseudohypoparathyroidism type Ia (PHP Ia)], recent studies provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad, and pituitary. The aim of this study was to investigate the presence of pituitary resistance to hypothalamic hormones acting via Gs alpha-coupled receptors in patients with PHP Ia. Six of nine patients showed an impaired GH responsiveness to GHRH plus arginine, consistent with a complete GH deficiency (GH peak from 2.6-8.6 microg/liter, normal > 16.5), and partial (GH peak 13.9 and 13.6 microg/liter) and normal responses were found in two and one patient, respectively. Accordingly, IGF-I levels were below and in the low-normal range in seven and two patients. All patients had a normal cortisol response to 1 microg ACTH test, suggesting a normal corticotroph function that was confirmed by a normal ACTH and cortisol response to CRH test in three patients. In conclusion, we report that in addition to PTH and TSH resistance, patients with PHP Ia display variable degrees of GHRH resistance, consistent with Gs alpha imprinting in human pituitary.

Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sabatino, María Eugenia; Sosa, Liliana del Valle; Petiti, Juan Pablo

Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophsmore » taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K-Akt and NF-κB signaling pathways. - Highlights: • In hyperplastic pituitaries, LPS triggered the lactotroph cell proliferation and IL-6 release. • Functional Toll-like receptor 4 (TLR4) is expressed at the plasma membrane of tumoral lactotrophs. • Increases in TLR4 and CD14 intracellular expression levels were detected after an LPS challenge. • The proliferative stimulation and IL-6 release involved the PI3K-Akt pathway and NF-κB activation. • 17β-estradiol attenuated the LPS-evoked tumoral lactotroph proliferation and IL-6 secretion.« less

Tracing of Zinc Nanocrystals in the Anterior Pituitary of Zinc-Deficient Wistar Rats.

PubMed

Kuldeep, Anjana; Nair, Neena; Bedwal, Ranveer Singh

2017-06-01

The aim of this study was to trace zinc nanocrystals in the anterior pituitary of zinc-deficient Wistar rats by using autometallographic technique. Male Wistar rats (30-40 days of age, pre-pubertal period) of 40-50 g body weight were divided into the following: the ZC (zinc control) group-fed with 100 ppm zinc in diet, the ZD (zinc-deficient) group-fed with zinc-deficient (1.00 ppm) diet and the PF (pair-fed) group-received 100 ppm zinc in diet. The experiments were set for 2 and 4 weeks. Pituitary was removed and processed for the autometallographic technique. The control and pair-fed groups retained their normal morphological features. However, male Wistar rats fed on zinc-deficient diet for 2 and 4 weeks displayed a wide range of symptoms such as significant (P < 0.05) decrease in diet consumption, body weight and pituitary weight and decrease in gradation of intensity of zinc nanocrystals in the nuclei. The present findings suggest that the dietary zinc deficiency causes decreased intensity of zinc nanocrystals localization and their distribution in the pituitary thereby contributing to the dysfunction of the pituitary of the male Wistar rats. The severity of zinc deficiency symptoms progressed after the second week of the experiment. Decreased intensity of zinc nanocrystals attenuates the pituitary function which would exert its affect on other endocrine organs impairing their functions indicating that the metabolic regulation of pituitary is mediated to a certain extent by zinc and/or hypothalamus-hypophysial system which also reflects its essentiality during the period of growth.

Governor Pio Pico, the monster of California...no more: lessons in neuroendocrinology.

PubMed

Login, Ivan S; Login, Jessica

2010-01-01

We hypothesize that Pio Pico, the last Mexican Governor of California, had acromegaly between at least ages 43 to 57, from 1844 to 1858, before Pierre Marie published the clinical description of acromegaly in 1886. Pico's probable growth hormone-secreting pituitary tumor likely infarcted spontaneously after 1858. The tumor infarction resulted in burnt-out acromegaly and probably restored normal pituitary function. Pearce Bailey published the first account of pituitary tumor infarction only in 1898. Pico's undiagnosed, misunderstood, profoundly acromegalic appearance was widely misinterpreted, leading to pervasive, degrading, and highly prejudicial comments. This landmark case study in neuroendocrinology provides the opportunity to re-examine elements of 19th century California and American history.

Glucocorticoids, stress, and fertility.

PubMed

Whirledge, S; Cidlowski, J A

2010-06-01

Modifications of the hypothalamo-pituitary-adrenal axis and associated changes in circulating levels of glucocorticoids form a key component of the response of an organism to stressful challenges. Increased levels of glucocorticoids promote gluconeogenesis, mobilization of amino acids, and stimulation of fat breakdown to maintain circulating levels of glucose necessary to mount a stress response. In addition to profound changes in the physiology and function of multiple tissues, stress and elevated glucocorticoids can also inhibit reproduction, a logical effect for the survival of self. Precise levels of glucocorticoids are required for proper gonadal function; where the balance is disrupted, so is fertility. Glucocorticoids affect gonadal function at multiple levels in hypothalamo-pituitary-gonadal axis: 1) the hypothalamus (to decrease the synthesis and release of gonadotropin-releasing hormone [GnRH]); 2) the pituitary gland (to inhibit the synthesis and release of luteinizing hormone [LH] and follicle stimulating hormone [FSH]); 3) the testis/ovary (to modulate steroidogenesis and/or gametogenesis directly). Furthermore, maternal exposure to prenatal stress or exogenous glucocorticoids can lead to permanent modification of hypothalamo-pituitary-adrenal function and stress-related behaviors in offspring. Glucocorticoids are vital to many aspects of normal brain development, but fetal exposure to superabundant glucocorticoids can result in life-long effects on neuroendocrine function. This review focuses on the molecular mechanisms believed to mediate glucocorticoid inhibition of reproductive functions and the anatomical sites at which these effects take place.

Overexpression of vasopressin (V3) and corticotrophin-releasing hormone receptor genes in corticotroph tumours.

PubMed

de Keyzer, Y; René, P; Beldjord, C; Lenne, F; Bertagna, X

1998-10-01

The molecular mechanisms underlying ACTH-secreting tumour formation remain unknown. Transmembrane signalling pathways play an important role in several endocrine disorders including pituitary tumours. To investigate the role of the pituitary vasopressin (V3) receptor (R) in ACTH-secreting tumours we have qualitatively and quantitatively analysed its mRNA. RT-PCR, denaturing gradient gel electrophoresis and S1 nuclease protection experiments were used to analyse V3 mRNA structure in ACTH-secreting tumours. We also developed a competitive RT-PCR system to compare the levels of expression of POMC, V3 and CRH-R genes. This system used as competitor a single mutant template (termed multi-mutant) containing primers for the three genes flanking an unrelated core sequence allowing multiple quantifications from the same cDNA preparations. We analysed 12 normal pituitaries, 15 corticotroph pituitary adenomas and 6 ACTH-secreting bronchial carcinoids. The V3 mRNA structure and sequence were found to be identical in normal and tumoural pituitary indicating that the tumoural Vs mRNA codes for a normal receptor. POMC RT-PCR signals in the pituitary tumour group were approximately 7-fold higher than in the normal pituitary group. Similarly, V3 and CRH-R signal were increased in pituitary tumors (mean +/- SEM: 5.87 x 10(-6) +/- 1.73 x 10(-6), and 2.33 x 10(-4) +/- 1.4 x 10(-4), respectively), when compared to normal pituitaries (1.19 x 10(-7) +/- 2.39 x 10(-8), and 1.7 x 10(-6) +/- 4.65 x 10(-7), respectively) suggesting that these two genes are expressed at very high levels in corticotroph tumours. When expressed relative to the corresponding POMC signals, increases in V3 and CRH-R signals reached 49-fold and 137-fold, respectively, in pituitary tumours. In ACTH-secreting bronchial carcinoids V3 gene expression level was also higher than in normal pituitary, whereas CRH-R signals were detected in only 4 of the 6 tumours with wide variations. Our results show that both vasopressin and CRH receptor genes are overexpressed in ACTH-secreting pituitary tumours. They suggest that overexpression of G protein-coupled receptors may be an additional mechanism through which membrane receptors may play a role in human tumours.

miR-133 inhibits pituitary tumor cell migration and invasion via down-regulating FOXC1 expression.

PubMed

Wang, D S; Zhang, H Q; Zhang, B; Yuan, Z B; Yu, Z K; Yang, T; Zhang, S Q; Liu, Y; Jia, X X

2016-03-24

Many studies have shown that microRNA (miR)-133 functions as a tumor suppressor in a variety of metastatic cancers, including breast cancer, gastric cancer, and liver fibrosis. However, the influence of miR-133 on pituitary tumor malignancy has not yet been reported. The purpose of this study was to explore the role of miR-133 in pituitary tumor cell migration and invasive ability and the molecular mechanisms involved. Our findings suggest that in pituitary adenoma cell lines, through direct targeting and negative control of forkhead box C1 (FOXC1), miR-133 can inhibit pituitary adenoma cell migration and invasion. In addition, epithelial-to-mesenchymal transition can be induced by miR-133. Additionally, a negative correlation was found between FOXC1 and miR-133 expression when comparing their expression levels between cancerous tissue and adjacent normal tissue. This suggests that miR-133 can inhibit cell migration and invasion by directly targeting FOXC1, implying that miR-133 could be a potential therapeutic target for treatment of invasive pituitary adenoma.

Impact of selective pituitary gland incision or resection on hormonal function after adenoma or cyst resection.

PubMed

Barkhoudarian, Garni; Cutler, Aaron R; Yost, Sam; Lobo, Bjorn; Eisenberg, Amalia; Kelly, Daniel F

2015-12-01

With the resection of pituitary lesions, the anterior pituitary gland often obstructs transsphenoidal access to the lesion. In such cases, a gland incision and/or partial gland resection may be required to obtain adequate exposure. We investigate this technique and determine the associated risk of post-operative hypopituitarism. All patients who underwent surgical resection of a pituitary adenoma or Rathke cleft cyst (RCC) between July 2007 and January 2013 were analyzed for pre- and post-operative hormone function. The cohort of patients with gland incision/resection were compared to a case-matched control cohort of pituitary surgery patients. Total hypophysectomy patients were excluded from outcome analysis. Of 372 operations over this period, an anterior pituitary gland incision or partial gland resection was performed in 79 cases (21.2 %). These include 53 gland incisions, 12 partial hemi-hypophysectomies and 14 resections of thinned/attenuated anterior gland. Diagnoses included 64 adenomas and 15 RCCs. New permanent hypopituitarism occurred in three patients (3.8 %), including permanent DI (3) and growth hormone deficiency (1). There was no significant difference in the rate of worsening gland dysfunction nor gain of function. Compared to a control cohort, there was a significantly lower incidence of transient DI (1.25 vs. 11.1 %, p = 0.009) but no significant difference in permanent DI (3.8 vs. 4.0 %) in the gland incision group. Selective gland incisions and gland resections were performed in over 20 % of our cases. This technique appears to minimize traction on compressed normal pituitary gland during removal of large lesions and facilitates better visualization and removal of cysts, microadenomas and macroadenomas.

The postoperative cortisol stress response following transsphenoidal pituitary surgery: a potential screening method for assessing preserved pituitary function.

PubMed

Zada, Gabriel; Tirosh, Amir; Huang, Abel P; Laws, Edward R; Woodmansee, Whitney W

2013-09-01

The ability to reliably identify patients with new hypocortisolemia acutely following pituitary surgery is critical. We aimed to quantify the postoperative cortisol stress response following selective transsphenoidal adenomectomy, as a marker for postoperative preservation of functional pituitary gland. Records of 208 patients undergoing transsphenoidal operations for pituitary lesions were reviewed. Patients with Cushing's Disease, preoperative adrenal insufficiency, and those receiving intraoperative steroids were excluded. To quantify the postoperative stress response, the ∆ cortisol index was defined as the postoperative day (POD) 1 morning cortisol minus the preoperative morning cortisol level. The incidence of new hypocortisolemia requiring glucocorticoid replacement upon hospital discharge was also recorded. Fifty-two patients met inclusion criteria. The mean preoperative, POD1, and POD2 cortisol levels were 16.5, 29.2, and 21.8 μg/dL, respectively. Morning fasting cortisol levels on POD1 ranged from 4.2 to 73.0 μg/dL. The ∆ cortisol index ranged from -19.0 to +56.2 (mean +12.7 μg/dL). Five patients (9.6%) developed new hypocortisolemia on POD 1-3 requiring glucocorticoid replacement; only one required long-term replacement. The mean ∆ cortisol in patients requiring postoperative glucocorticoids was -2.8 μg/dL, compared with +14.4 μg/dL in patients without evidence of adrenal insufficiency (p = 0.005). Of the 32 patients (61.5%) with a ∆cortisol >25 μg/dL, none developed postoperative adrenal insufficiency. The postoperative cortisol stress response, as quantified by the ∆ cortisol index, holds potential as a novel and complimentary screening method to predict preservation of normal pituitary function and acute development of new ACTH deficiency following transsphenoidal pituitary surgery.

Two novel mutations in the POU1F1 gene generate null alleles through different mechanisms leading to combined pituitary hormone deficiency.

PubMed

Turton, J P; Strom, M; Langham, S; Dattani, M T; Le Tissier, P

2012-03-01

  Mutations in the POU1F1 gene severely affect the development and function of the anterior pituitary gland and lead to combined pituitary hormone deficiency (CPHD).   The clinical and genetic analysis of a patient presenting with CPHD and functional characterization of identified mutations.   We describe a male patient with extreme short stature, learning difficulties, anterior pituitary hypoplasia, secondary hypothyroidism and undetectable prolactin, growth hormone (GH) and insulin-like growth factor 1 (IGF1), with normal random cortisol.   The POU1F1 coding region was amplified by PCR and sequenced; the functional consequence of the mutations was analysed by cell transfection and in vitro assays.   Genetic analysis revealed compound heterozygosity for two novel putative loss of function mutations in POU1F1: a transition at position +3 of intron 1 [IVS1+3nt(A>G)] and a point mutation in exon 6 resulting in a substitution of arginine by tryptophan (R265W). Functional analysis revealed that IVS1+3nt(A>G) results in a reduction in the correctly spliced POU1F1 mRNA, which could be corrected by mutations of the +4, +5 and +6 nucleotides. Analysis of POU1F1(R265W) revealed complete loss of function resulting from severely reduced protein stability.   Combined pituitary hormone deficiency in this patient is caused by loss of POU1F1 function by two novel mechanisms, namely aberrant splicing (IVS1+3nt (A>G) and protein instability (R265W). Identification of the genetic basis of CPHD enabled the cessation of hydrocortisone therapy without the need for further assessment for evolving endocrinopathy. © 2012 Blackwell Publishing Ltd.

Chromium VI administration induces oxidative stress in hypothalamus and anterior pituitary gland from male rats.

PubMed

Nudler, Silvana I; Quinteros, Fernanda A; Miler, Eliana A; Cabilla, Jimena P; Ronchetti, Sonia A; Duvilanski, Beatriz H

2009-03-28

Hexavalent chromium (Cr VI)-containing compounds are known carcinogens which are present in industrial settings and in the environment. The major route of chromium exposure for the general population is oral intake. Previously we have observed that Cr VI affects anterior pituitary secretion and causes oxidative stress in vitro. The aim of the present work was to investigate if in vivo Cr VI treatment (100 ppm of Cr VI in drinking water for up 30 days) causes oxidative stress in hypothalamus and anterior pituitary gland from male rats. This treatment produced a 4-fold increase of chromium content in hypothalamus and 10-fold increase in anterior pituitary gland. Lipid peroxidation showed a significant increase in hypothalamus and anterior pituitary. Cr VI augmented superoxide dismutase activity in anterior pituitary gland and glutathione reductase activity in hypothalamus, but glutathione peroxidase and catalase activities remained unchanged in both tissues. Heme oxygenase-1 mRNA expression significantly rose in both tissues. Metallothionein 1 mRNA content increased in anterior pituitary and metallothionein 3 mRNA increased in hypothalamus. These results show, for the first time, that oral chronic administration of Cr VI produces oxidative stress on the hypothalamus and anterior pituitary gland which may affect normal endocrine function.

Empty sella syndrome secondary to intrasellar cyst in adolescence.

PubMed

Raiti, S; Albrink, M J; Maclaren, N K; Chadduck, W M; Gabriele, O F; Chou, S M

1976-09-01

A 15-year-old boy had growth failure and failure of sexual development. The probable onset was at age 10. Endocrine studies showed hypopituitarism with deficiency of growth hormone and follicle-stimulating hormone, an abnormal response to metyrapone, and deficiency of thyroid function. Luteinizing hormone level was in the low-normal range. Posterior pituitary function was normal. Roentgenogram showed a large sella with some destruction of the posterior clinoids. Transsphenoidal exploration was carried out. The sella was empty except for a whitish membrane; no pituitary tissue was seen. The sella was packed with muscle. Recovery was uneventful, and the patient was given replacement therapy. On histologic examination,the cyst wall showed low pseudostratified cuboidal epithelium and occasional squamous metaplasia. Hemosiderin-filled phagocytes and acinar structures were also seen. The diagnosis was probable rupture of an intrasellar epithelial cyst, leading to empty sella syndrome.

A novel mutation of LHX3 is associated with combined pituitary hormone deficiency including ACTH deficiency, sensorineural hearing loss, and short neck-a case report and review of the literature.

PubMed

Bonfig, Walter; Krude, Heiko; Schmidt, Heinrich

2011-08-01

The LHX3 LIM-homeodomain transcription factor gene is required for normal pituitary and motoneuron development. LHX3 mutations are associated with growth hormone, prolactin, gonadotropin, and TSH deficiency; abnormal pituitary morphology; and may be accompanied with limited neck rotation and sensorineural hearing loss. We report on a boy, who presented with hypoglycemia in the newborn period. He is the second child of healthy unrelated parents. Short neck, growth hormone deficiency, and central hypothyroidism were diagnosed at a general pediatric hospital. Growth hormone and levothyroxine treatment were started, and blood sugar normalized with this treatment. On cerebral MRI, the anterior pituitary gland was hypoplastic. Sensorineural hearing loss was diagnosed by auditory testing. During follow-up, six repeatedly low morning cortisol levels (<1 μg/dl) and low ACTH levels (<10 pg/ml) were documented, so ACTH deficiency had developed over time and therefore hydrocortisone replacement was started at 1.5 years of age. Mutation analysis of the LHX3 gene revealed a homozygous stop mutation in exon 2: c.229C>T (CGA > TGA), Arg77stop (R77X). A complete loss of function is assumed with this homozygous stop mutation. We report a novel LHX3 mutation, which is associated with combined pituitary hormone deficiency including ACTH deficiency, short neck, and sensorineural hearing loss. All patients with LHX3 defects should undergo longitudinal screening for ACTH deficiency, since corticotrope function may decline over time. All patients should have auditory testing to allow for regular speech development.

[Dwarfism due to familial panhypopituitarism].

PubMed

Cos Welsh, J; Espinosa de los Monteros, A; de la Luz Ajuria, M; Morillo Almao, E

1977-01-01

Three sisters of 27 7/12, 13 8/12 and 9 1/12 years of age, respectively, with proportionate dwarfism, high pitched voice and lack of sexual development are described. All the patients had very low serum levels of immunoreactive growth hormone (GH), as well as of LH and FSH. Hypoglycemia induced by insulin and arginine infusion failed to increase GH levels, and the administration of the hypothalamic LH-FSH releasing hormone (LH-RH) did not elicit any response in the secretion of gonadotropins. The oldest sister developed hypothyroidism in recent years, since the I131 thyroid uptake was normal ten years before; her serum TSH was low and did not change with TRH stimulation. In addition, a low pituitary ACTH reserve was demonstrated by the hypoglycemia and metirapone tests. Case 2 showed partial pituitary TSH and ACTH reserve, whereas the youngest child only had low TSH pituitary reserve. These patients had all the clinical and laboratory characteristics of familial panhypopituitarism, with normal sella turcica. Genetic transmission in this cases is consistent with the autosomal recessive form, which is the most frequent type of inheritance of this entity. Consanguinity can not be ruled out. The results of the hypothalamic-pituitary functional tests apparently suggest that the primary defect could be located at the pituitary level. It is also possible that the pathological process may have a progressive evolution.

Is IGSF1 involved in human pituitary tumor formation?

PubMed

Faucz, Fabio R; Horvath, Anelia D; Azevedo, Monalisa F; Levy, Isaac; Bak, Beata; Wang, Ying; Xekouki, Paraskevi; Szarek, Eva; Gourgari, Evgenia; Manning, Allison D; de Alexandre, Rodrigo Bertollo; Saloustros, Emmanouil; Trivellin, Giampaolo; Lodish, Maya; Hofman, Paul; Anderson, Yvonne C; Holdaway, Ian; Oldfield, Edward; Chittiboina, Prashant; Nesterova, Maria; Biermasz, Nienke R; Wit, Jan M; Bernard, Daniel J; Stratakis, Constantine A

2015-02-01

IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary. Pathogenic mutations in the IGSF1 gene (on Xq26.2) are associated with X-linked central hypothyroidism and testicular enlargement in males. In this study, we tested the hypothesis that IGSF1 is involved in the development of pituitary tumors, especially those that produce growth hormone (GH). IGSF1 was sequenced in 21 patients with gigantism or acromegaly and 92 healthy individuals. Expression studies with a candidate pathogenic IGSF1 variant were carried out in transfected cells and immunohistochemistry for IGSF1 was performed in the sections of GH-producing adenomas, familial somatomammotroph hyperplasia, and in normal pituitary. We identified the sequence variant p.N604T, which in silico analysis suggested could affect IGSF1 function, in two male patients and one female with somatomammotroph hyperplasia from the same family. Of 60 female controls, two carried the same variant and seven were heterozygous for other variants. Immunohistochemistry showed increased IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 p.N604T variant compared with a GH-producing adenoma from a patient negative for any IGSF1 variants and with normal control pituitary tissue. The IGSF1 gene appears polymorphic in the general population. A potentially pathogenic variant identified in the germline of three patients with gigantism from the same family (segregating with the disease) was also detected in two healthy female controls. Variations in IGSF1 expression in pituitary tissue in patients with or without IGSF1 germline mutations point to the need for further studies of IGSF1 action in pituitary adenoma formation. © 2015 Society for Endocrinology.

Is IGSF1 involved in human pituitary tumor formation?

PubMed Central

Faucz, Fabio R.; Horvath, Anelia D.; Azevedo, Monalisa F.; Levy, Isaac; Bak, Beata; Wang, Ying; Xekouki, Paraskevi; Szarek, Eva; Gourgari, Evgenia; Manning, Allison D.; de Alexandre, Rodrigo Bertollo; Saloustros, Emmanouil; Trivellin, Giampaolo; Lodish, Maya; Hofman, Paul; Anderson, Yvonne C; Holdaway, Ian; Oldfield, Edward; Chittiboina, Prashant; Nesterova, Maria; Biermasz, Nienke R.; Wit, Jan M.; Bernard, Daniel J.; Stratakis, Constantine A.

2014-01-01

IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary. Pathogenic mutations in the IGSF1 gene (on Xq26.2) are associated with X-linked central hypothyroidism and testicular enlargement in males. In this study we tested the hypothesis that IGSF1 is involved in the development of pituitary tumors, especially those that produce growth hormone (GH). IGSF1 was sequenced in 21 patients with gigantism or acromegaly and 92 healthy individuals. Expression studies with a candidate pathogenic IGSF1 variant were carried out in transfected cells and immunohistochemistry for IGSF1 was performed in sections from GH-producing adenomas, familial somatomammotroph hyperplasia and in normal pituitary. In two male patients, and in one female, with somatomammotroph hyperplasia from the same family, we identified the sequence variant p.N604T, which in silico analysis suggested could affect IGSF1 function. Of 60 female controls, two carried the same variant, and seven were heterozygous for other variants. Immunohistochemistry showed increase IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 p.N604T variant compared to a GH-producing adenoma from a patient negative for any IGSF1 variants and to normal control pituitary tissue. The IGSF1 gene appears polymorphic in the general population. A potentially pathogenic variant identified in the germline of three patients with gigantism from the same family (segregating with the disease) was also detected in two healthy female controls. Variations in IGSF1 expression in pituitary tissue in patients with or without IGSF1 germline mutations point to the need for further studies of IGSF1 action in pituitary adenoma formation. PMID:25527509

Altered neuroendocrine regulation of gonadotropin secretion in women distance runners.

PubMed

Veldhuis, J D; Evans, W S; Demers, L M; Thorner, M O; Wakat, D; Rogol, A D

1985-09-01

We tested the hypothesis that the neuroendocrine control of gonadotropin secretion is altered in certain women distance runners with secondary amenorrhea. To this end, we quantitated the frequency and amplitude of spontaneous pulsatile LH secretion during a 24-h interval in nine such women. The ability of the pituitary gland to release LH normally was assessed by administration of graded bolus doses of GnRH during the subsequent 8 h. Compared to normally menstruating women, six of nine amenorrheic distance runners had a distinct reduction in spontaneous LH pulse frequency, with one, three, six, five, four, or two pulses per 24 h (normal, 8-15 pulses/24 h). This reduction in LH pulse frequency occurred without any significant alterations in plasma concentrations of estradiol and free testosterone or 24-h integrated serum concentrations of LH, FSH, or PRL. Moreover, in long-distance runners, the capacity of the pituitary gland to release LH was normal or accentuated in response to exogenous pulses of GnRH. In the six women athletes with diminished spontaneous LH pulsatility, acute ovarian responsiveness also was normal, since serum estradiol concentrations increased normally in response to the GnRH-induced LH pulses. Although long-distance runners had significantly lower estimated percent body fat compared to control women, specific changes in pulsatile gonadotropin release did not correlate with degree of body leanness. In summary, certain long-distance runners with secondary amenorrhea or severe oligomenorrhea have unambiguously decreased spontaneous LH pulse frequency with intact pituitary responsiveness to GnRH. This neuroendocrine disturbance may be relevant to exercise-associated amenorrhea, since pulsatile LH release is a prerequisite for cyclic ovarian function. We speculate that such alterations in pulsatile LH release in exercising women reflect an adaptive response of the hypothalamic pulse generator controlling the intermittent GnRH signal to the pituitary gland. The basis for amenorrhea in the remaining runners who have normal pulsatile properties of LH release is not known.

[Identification and management of intra-operative suspicious tissues in 20 transsphenoidal surgery cases].

PubMed

Liu, Jun-Feng; Ke, Chang-Shu; Chen, Xi; Xu, Yu; Zhang, Hua-Qiu; Chen, Juan; Gan, Chao; Li, Chao-Xi; Lei, Ting

2013-05-01

To determine appropriate protocols for the identification and management of intra operative suspicious tissues during transsphenoidal surgery. Clinical data and pathological reports of 20 patients with intra-operative suspicious tissues during transsphenoidal surgeries were analyzed retrospectively. The methods for discriminating between adenoma and normal pituitary tissues were reviewed. The postoperative pathological reports revealed that adenoma and normal pituitary tissues coexisted in 9 samples, while 5 samples were identified as normal pituitary tissues, 2 as adenoma tissues, and 4 as other tissues. Adenomas were distinguished from normal pituitary tissues on the basis of intra-operative appearance, texture, blood supply and possible existence of boundary. If decisions are difficult to made during surgeries from the appearance of the suspicious tissues, pathological examinations are advised as a guidance for the next steps.

Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism: Case Report and Review.

PubMed

Wang, Yi; Zhang, Qiongyue; Yang, Jianzhi; Zhao, Xiaolong; He, Min; Shou, Xuefei; Li, Shiqi; Li, Yiming; Wang, Yongfei; Ye, Hongying

2015-09-01

Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered after pregnancy and delivery. In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery. The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 μg daily and readjusted to 150 μg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 μg daily after delivery. During follow-up, her hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered. The peak serum cortisol level could increase to 19.08 μg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation. Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary cooperation during the pregnancy of patients with hypopituitarism. This case indicates that the pituitary function may partially recover after pregnancy in panhypopituitarism patients.

[MR findings in patients with idiopathic panhypopituitarism].

PubMed

Fahrendorf, G; Brämswig, J; Bals-Pratsch, M

1990-05-01

High-resolution MR imaging was performed in seven patients with pituitary dwarfism and panhypopituitarism. In five cases MR-findings included absence of the infundibulum and of the normal intrasellar posterior pituitary bright spot, and the presence of a small nodule at the median eminence. The absence of diabetes insipidus in these patients and the signal characteristics of the nodule at the median eminence suggest that the latter may represent a functioning ectopic posterior pituitary lobe. This complex of findings was only observed in patients with complications in the perinatal period (breech delivery) and appears to be the end result of an ischemic or traumatic injury of the infundibular stem. The infundibular defect would explain both the permanent hormone deficiency of the anterior pituitary gland through a disruption of the hypothalamic-hypophyseal portal system and the absence of diabetes insipidus through an ectopic regeneration of the neurohypophysis at the median eminence.

Spontaneous remission of acromegaly or gigantism due to subclinical apoplexy of pituitary growth hormone adenoma.

PubMed

Wang, Xian-Ling; Dou, Jing-Tao; Lü, Zhao-Hui; Zhong, Wen-Wen; Ba, Jian-Ming; Jin, Du; Lu, Ju-Ming; Pan, Chang-Yu; Mu, Yi-Ming

2011-11-01

Subclinical apoplexy of pituitary functional adenoma can cause spontaneous remission of hormone hypersecretion. The typical presence of pituitary growth hormone (GH) adenoma is gigantism and/or acromegaly. We investigated the clinical characteristics of patients with spontaneous partial remission of acromegaly or gigantism due to subclinical apoplexy of GH adenoma. Six patients with spontaneous remission of acromegaly or gigantism were enrolled. The clinical characteristics, endocrinological evaluation and imageological characteristics were retrospectively analyzed. In these cases, the initial clinical presences were diabetes mellitus or hypogonadism. No abrupt headache, vomiting, visual function impairment, or conscious disturbance had ever been complained of. The base levels of GH and insulin growth factor-1 (IGF-1) were normal or higher, but nadir GH levels were all still > 1 µg/L in 75 g oral glucose tolerance test. Magnetic resonance imaging detected enlarged sella, partial empty sella and compressed pituitary. The transsphenoidal surgery was performed in 2 cases, and the other patients were conservatively managed. All the patients were in clinical remission. When the clinical presences, endocrine evaluation, biochemical examination and imageology indicate spontaneous remission of GH hypersecretion in patients with gigantism or acromegaly, the diagnosis of subclinical apoplexy of pituitary GH adenoma should be presumed. To these patients, conservative therapy may be appropriate.

Male hypogonadism: an extended classification based on a developmental, endocrine physiology-based approach.

PubMed

Rey, R A; Grinspon, R P; Gottlieb, S; Pasqualini, T; Knoblovits, P; Aszpis, S; Pacenza, N; Stewart Usher, J; Bergadá, I; Campo, S M

2013-01-01

Normal testicular physiology results from the integrated function of the tubular and interstitial compartments. Serum markers of interstitial tissue function are testosterone and insulin-like factor 3 (INSL3), whereas tubular function can be assessed by sperm count, morphology and motility, and serum anti-Müllerian hormone (AMH) and inhibin B. The classical definition of male hypogonadism refers to testicular failure associated with androgen deficiency, without considering potential deficiencies in germ and Sertoli cells. Furthermore, the classical definition does not consider the fact that low basal serum testosterone cannot be equated to hypogonadism in childhood, because Leydig cells are normally quiescent. A broader clinical definition of hypogonadism that could be applied to male patients in different periods of life requires a comprehensive consideration of the physiology of the hypothalamic-pituitary-testicular axis and its disturbances along development. Here we propose an extended classification of male hypogonadism based on the pathophysiology of the hypothalamic-pituitary-testicular axis in different periods of life. The clinical and biochemical features of male hypogonadism vary according to the following: (i) the level of the hypothalamic-pituitary-testicular axis primarily affected: central, primary or combined; (ii) the testicular cell population initially impaired: whole testis dysfunction or dissociated testicular dysfunction, and: (iii) the period of life when the gonadal function begins to fail: foetal-onset or postnatal-onset. The evaluation of basal testicular function in infancy and childhood relies mainly on the assessment of Sertoli cell markers (AMH and inhibin B). Hypergonadotropism should not be considered a sine qua non condition for the diagnosis of primary hypogonadism in childhood. Finally, the lack of elevation of gonadotropins in adolescents or adults with primary gonadal failure is indicative of a combined hypogonadism involving the gonads and the hypothalamic-pituitary axis. © 2012 American Society of Andrology and European Academy of Andrology.

The Forkhead Transcription Factor, Foxd1, Is Necessary for Pituitary Luteinizing Hormone Expression in Mice

PubMed Central

Gumbel, Jason H.; Patterson, Elizabeth M.; Owusu, Sarah A.; Kabat, Brock E.; Jung, Deborah O.; Simmons, Jasmine; Hopkins, Torin; Ellsworth, Buffy S.

2012-01-01

The pituitary gland regulates numerous physiological functions including growth, reproduction, temperature and metabolic homeostasis, lactation, and response to stress. Pituitary organogenesis is dependent on signaling factors that are produced in and around the developing pituitary. The studies described in this report reveal that the forkhead transcription factor, Foxd1, is not expressed in the developing mouse pituitary gland, but rather in the mesenchyme surrounding the pituitary gland, which is an essential source of signaling factors that regulate pituitary organogenesis. Loss of Foxd1 causes a morphological defect in which the anterior lobe of the pituitary gland protrudes through the cartilage plate that is developing ventral to the pituitary at embryonic days (e)14.5, e16.5, and e18.5. The number of proliferating pituitary cells is increased at e14.5 and e16.5. Loss of Foxd1 also results in significantly decreased levels of Lhb expression at e18.5. This decrease in Lhb expression does not appear to be due to a change in the number of gonadotrope cells in the pituitary gland. Previous studies have shown that loss of the LIM homeodomain factor, Lhx3, which is activated by the FGF signaling pathway, results in loss of LH production. Although there is a difference in Lhb expression in Foxd1 null mice, the expression pattern of LHX3 is not altered in Foxd1 null mice. These studies suggest that Foxd1 is indirectly required for normal Lhb expression and cartilage formation. PMID:23284914

Pituitary imaging findings in male patients with hypogonadotrophic hypogonadism.

PubMed

Hirsch, Dania; Benbassat, Carlos; Toledano, Yoel; S'chigol, Irena; Tsvetov, Gloria; Shraga-Slutzky, Ilana; Eizenberg, Yoav; Shimon, Ilan

2015-08-01

Data on pituitary imaging in adult male patients presenting with hypogonadotrophic hypogonadism (HH) and no known pituitary disease are scarce. To assess the usefulness of pituitary imaging in the evaluation of men presenting with HH after excluding known pituitary disorders and hyperprolactinemia. A historical prospective cohort of males with HH. Men who presented for endocrine evaluation from 2011 to 2014 with testosterone levels <10.4 nmol/L (300 ng/mL), normal LH and FSH levels and no known pituitary disease. Seventy-five men were included in the analysis. Their mean age and BMI were 53.4 ± 14.8 years and 30.7 ± 5.2 kg/m2, respectively. Mean total testosterone, LH, and FSH were 6.2 ± 1.7 nmol/L, 3.4 ± 2 and 4.7 ± 3.1 mIU/L, respectively. Prolactin level within the normal range was obtained in all men (mean 161 ± 61, range 41-347 mIU/L). Sixty-two men had pituitary MRI and 13 performed CT. In 61 (81.3%) men pituitary imaging was normal. Microadenoma was found in 8 (10.7%), empty sella and thickened pituitary stalk in one patient (1.3%) each. In other four patients (5.3%) a small or mildly asymmetric pituitary gland was noted. No correlation was found between testosterone level and the presence of pituitary anomalies. This study suggests that the use of routine hypothalamic-pituitary imaging in the evaluation of IHH, in the absence of clinical characteristics of other hormonal loss or sellar compression symptoms, will not increase the diagnostic yield of sellar structural abnormalities over that reported in the general population.

Mice with Inactivation of Aryl Hydrocarbon Receptor-Interacting Protein (Aip) Display Complete Penetrance of Pituitary Adenomas with Aberrant ARNT Expression

PubMed Central

Raitila, Anniina; Lehtonen, Heli J.; Arola, Johanna; Heliövaara, Elina; Ahlsten, Manuel; Georgitsi, Marianthi; Jalanko, Anu; Paetau, Anders; Aaltonen, Lauri A.; Karhu, Auli

2010-01-01

Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been shown to predispose to pituitary adenoma predisposition, a condition characterized by growth hormone (GH)-secreting pituitary tumors. To study AIP-mediated tumorigenesis, we generated an Aip mouse model. Heterozygous mice developed normally but were prone to pituitary adenomas, in particular to those secreting GH. A complete loss of AIP was detected in these lesions, and full penetrance was reached at the age of 15 months. No excess of any other tumor type was found. Ki-67 analysis indicated that Aip-deficient tumors have higher proliferation rates compared with Aip-proficient tumors, suggesting a more aggressive disease. Similar to human AIP-deficient pituitary adenomas, immunohistochemical studies showed that expression of aryl hydrocarbon receptor nuclear translocator 1 or 2 (ARNT or ARNT2) protein was lost in the mouse tumors, suggesting that mechanisms of AIP-related tumorigenesis involve aberrant ARNT function. The Aip+/− mouse appears to be an excellent model for the respective human disease phenotype. This model constitutes a tool to further study AIP-associated pituitary tumorigenesis and may be potentially valuable in efforts to develop therapeutic strategies to treat pituitary adenomas. PMID:20709796

Loss of microRNA-7a2 induces hypogonadotropic hypogonadism and infertility

PubMed Central

Ahmed, Kashan; LaPierre, Mary P.; Denzler, Rémy; Yang, Yinjie; Rülicke, Thomas; Latreille, Mathieu

2017-01-01

MicroRNAs (miRNAs) are negative modulators of gene expression that fine-tune numerous biological processes. miRNA loss-of-function rarely results in highly penetrant phenotypes, but rather, influences cellular responses to physiologic and pathophysiologic stresses. Here, we have reported that a single member of the evolutionarily conserved miR-7 family, miR-7a2, is essential for normal pituitary development and hypothalamic-pituitary-gonadal (HPG) function in adulthood. Genetic deletion of mir-7a2 causes infertility, with low levels of gonadotropic and sex steroid hormones, small testes or ovaries, impaired spermatogenesis, and lack of ovulation in male and female mice, respectively. We found that miR-7a2 is highly expressed in the pituitary, where it suppresses golgi glycoprotein 1 (GLG1) expression and downstream bone morphogenetic protein 4 (BMP4) signaling and also reduces expression of the prostaglandin F2a receptor negative regulator (PTGFRN), an inhibitor of prostaglandin signaling and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion. Our results reveal that miR-7a2 critically regulates sexual maturation and reproductive function by interconnecting miR-7 genomic circuits that regulate FSH and LH synthesis and secretion through their effects on pituitary prostaglandin and BMP4 signaling. PMID:28218624

Transsphenoidal microsurgery in the treatment of acromegaly and gigantism.

PubMed

Arafah, B U; Brodkey, J S; Kaufman, B; Velasco, M; Manni, A; Pearson, O H

1980-03-01

Twenty-five patients with acromegaly and 3 patients with gigantism underwent transsphenoidal microsurgery in an attempt to remove the tumor and preserve normal pituitary function whenever possible. An adenoma was identified and removed in 27 of 28 patients. Evaluation 3--6 months postoperatively revealed a GH level less than 5 ng/ml in 29 patients, 5--10 ng/ml in 4 patients and 11--29 ng/ml in 4 other patients. Dynamics of GH secretion were normal in 11 patients who had normal pituitary function and are considered cured. Two patients with low or undetectable GH levels are also considered cured at the expense of being hypopituitary. Three of 7 patients with normal basal GH levels but abnormal dynamics of GH secretion relapsed within 1 yr. Eleven of the 13 patients considered cured did not have extrasellar extension, while 14 of the 15 patients not cured had extrasellar extension. Five patients who were not cured with surgery received radiation therapy. Three patients were treated with an ergot derivative, Lergotrile mesylate, after surgery and radiation therapy failed to normalize GH levels. Transsphenoidal microsurgery is an optimal form of therapy for patients with acromegaly or gigantism, especially those with no extrasellar extension. Dynamics of GH secretion are very useful in evaluating the completeness of adenoma removal.

Dopamine D2 receptor expression in the corticotroph cells of the human normal pituitary gland.

PubMed

Pivonello, Rosario; Waaijers, Marlijn; Kros, Johan M; Pivonello, Claudia; de Angelis, Cristina; Cozzolino, Alessia; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J

2017-08-01

The dopamine D 2 receptor is the main dopamine receptor expressed in the human normal pituitary gland. The aim of the current study was to evaluate dopamine D 2 receptor expression in the corticotroph cell populations of the anterior lobe and pars intermedia, as well as posterior lobe of the human normal pituitary gland by immunohistochemistry. Human normal pituitary gland samples obtained from routine autopsies were used for the study. In all cases, histology together with immunostaining for adrenocorticotropic hormone, melanocyte-stimulating hormone, prolactin, and neurofilaments were performed and compared to the immunostaining for D 2 receptor. D 2 receptor was heterogeneously expressed in the majority of the cell populations of the anterior and posterior lobe as well as in the area localized between the anterior and posterior lobe, and arbitrary defined as "intermediate zone". This zone, characterized by the presence of nerve fibers included the residual pars intermedia represented by the colloid-filled cysts lined by the remnant melanotroph cells strongly expressing D 2 receptors, and clusters of corticotroph cells, belonging to the anterior lobe but localized within the cysts and adjacent to the posterior lobe, variably expressing D 2 receptors. D 2 dopamine receptor is expressed in the majority of the cell populations of the human normal pituitary gland, and particularly, in the different corticotroph cell populations localized in the anterior lobe and the intermediate zone of the pituitary gland.

Antiapoptotic Factor Humanin Is Expressed in Normal and Tumoral Pituitary Cells and Protects Them from TNF-α-Induced Apoptosis

PubMed Central

Magri, María Laura; Zárate, Sandra; Moreno Ayala, Mariela; Ferraris, Jimena; Eijo, Guadalupe; Pisera, Daniel; Candolfi, Marianela; Seilicovich, Adriana

2014-01-01

Humanin (HN) is a 24-amino acid peptide with cytoprotective action in several cell types such as neurons and testicular germ cells. Rattin (HNr), a homologous peptide of HN expressed in several adult rat tissues, also has antiapoptotic action. In the present work, we demonstrated by immunocytochemical analysis and flow cytometry the expression of HNr in the anterior pituitary of female and male adult rats as well as in pituitary tumor GH3 cells. HNr was localized in lactotropes and somatotropes. The expression of HNr was lower in females than in males, and was inhibited by estrogens in pituitary cells from both ovariectomized female and orquidectomized male rats. However, the expression of HNr in pituitary tumor cells was not regulated by estrogens. We also evaluated HN action on the proapoptotic effect of TNF-α in anterior pituitary cells assessed by the TUNEL method. HN (5 µM) per se did not modify basal apoptosis of anterior pituitary cells but completely blocked the proapoptotic effect of TNF-α in total anterior pituitary cells, lactotropes and somatotropes from both female and male rats. Also, HN inhibited the apoptotic effect of TNF-α on pituitary tumor cells. In summary, our results demonstrate that HNr is present in the anterior pituitary gland, its expression showing sexual dimorphism, which suggests that gonadal steroids may be involved in the regulation of HNr expression in this gland. Antiapoptotic action of HN in anterior pituitary cells suggests that this peptide could be involved in the homeostasis of this gland. HNr is present and functional in GH3 cells, but it lacks regulation by estrogens, suggesting that HN could participate in the pathogenesis of pituitary tumors. PMID:25360890

MRI features of growth hormone deficiency in children with short stature caused by pituitary lesions.

PubMed

Xu, Chao; Zhang, Xinxian; Dong, Lina; Zhu, Bin; Xin, Tao

2017-06-01

We verified the advantages of using magnetic resonance imaging (MRI) for improving the diagnostic quality of growth hormone deficiency (GHD) in children with short stature caused by pituitary lesions. Clinical data obtained from 577 GHD patients with short stature caused by pituitary lesions were retrospectively analyzed. There were 354 cases (61.3%) with anterior pituitary dysplasia; 45 cases (7.8%) of pituitary stalk interruption syndrome (PSIS); 15 cases (2.6%) of pituitary hyperplasia due to primary hypothyroidism; 38 cases (6.6%) of Rathke cleft cyst; 68 cases (11.8%) of empty sella syndrome; 16 cases (2.8%) of pituitary invasion from Langerhans cell histiocytosis; 2 cases (0.3%) of sellar regional arachnoid cyst and 39 cases (6.8%) of craniopharyngioma. MRI results showed that the height of anterior pituitary in patients was less than normal. Location, size and signals of posterior pituitary and pituitary stalk were normal in anterior pituitary dysplasia. In all cases pituitary hyperplasia was caused by hypothyroidism. MRI results showed that anterior pituitary was enlarged, and we detected upward apophysis and obvious homogeneous enhancement. There were no pituitary stalk interruption and abnormal signal. We also observed that after hormone replacement therapy the size of pituitary gland was reduced. Anterior pituitary atrophy was observed in Rathke cleft cyst, empty sella syndrome, sellar regional arachnoid cyst and craniopharyngioma. The microstructure of hypophysis and sellar region was studied with MRI. We detected pituitary lesions, and the characteristics of various pituitary diseases of GHD in children with short stature. It was concluded that in children with GHD caused by pituitary lesions, MRI was an excellent method for early diagnosis. This method offers clinical practicability and we believe it can be used for differential diagnosis and to monitor the therapeutic effects.

Functional importance of blood flow dynamics and partial oxygen pressure in the anterior pituitary.

PubMed

Schaeffer, Marie; Hodson, David J; Lafont, Chrystel; Mollard, Patrice

2010-12-01

The pulsatile release of hormone is obligatory for the control of a range of important body homeostatic functions. To generate these pulses, endocrine organs have developed finely regulated mechanisms to modulate blood flow both to meet the metabolic demand associated with intense endocrine cell activity and to ensure the temporally precise uptake of secreted hormone into the bloodstream. With a particular focus on the pituitary gland as a model system, we review here the importance of the interplay between blood flow regulation and oxygen tensions in the functioning of endocrine systems, and the known regulatory signals involved in the modification of flow patterns under both normal physiological and pathological conditions. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Hypothalamic-pituitary dysfunction following traumatic brain injury affects functional improvement during acute inpatient rehabilitation.

PubMed

Rosario, Emily R; Aqeel, Rubina; Brown, Meghan A; Sanchez, Gabriel; Moore, Colleen; Patterson, David

2013-01-01

To evaluate the occurrence of hypothalamic-pituitary dysfunction following a traumatic brain injury (TBI) and to determine its effect on functional improvement in acute inpatient rehabilitation. A retrospective chart review identified male patients with a primary diagnosis of TBI with or without a skull fracture, an onset date within 6 months prior to admission, and were 16 years of age or older. The percentage of individuals in this population with abnormal hormone levels was determined on the basis of the established normal reference range for each hormone assay. The functional independence measure, which assesses functional outcomes in acute inpatient rehabilitation, was used to examine the relationship between hormone levels and functional improvement. Hypothalamic-pituitary dysfunction was identified in nearly 70% of men following TBI. Hypogonadism, or low testosterone levels, was observed in 66% of the patients, followed by low levels of free T4 in 46% and low levels of insulin growth factor-1 in 26% of patients. Hypopituitarism associated with impaired functional recovery. Specifically, the functional independence measure change per day was significantly lower in patients with low levels of testosterone and insulin growth factor-1. These findings suggest the importance of testosterone and insulin growth factor-1 activity in the early stages of physical and cognitive rehabilitation.

EEG sleep in Cushing's disease and Cushing's syndrome: comparison with patients with major depressive disorder.

PubMed

Shipley, J E; Schteingart, D E; Tandon, R; Pande, A C; Grunhaus, L; Haskett, R F; Starkman, M N

1992-07-15

Because patients with Cushing' syndrome (CS) and Major depressive disorder (MDD) share features of hypercortisolism and the depressive syndrome, we compared electro-encephalographic (EEG) sleep in patients with pituitary-ACTH-dependent Cushing's syndrome (Cushing's disease, CD), patients with ACTH-independent Cushing's syndrome (AICS), patients with major depressive disorder (MDD), and normal subjects. There were substantial similarities in the abnormal polysomnography profiles of patients with CD, AICS, and MDD. All three patient groups demonstrated poorer sleep continuity, shortened rapid eye movement (REM) latency, and increased first REM period density compared with normal subjects. In addition, AICS patients and MDD patients had elevated REM activity and density. These findings are discussed in terms of models of pathophysiology that relate abnormalities in sleep, mood, and hypothalamic-pituitary-adrenal function.

Combined pituitary hormone deficiency in german shepherd dogs with dwarfism.

PubMed

Kooistra, H S; Voorhout, G; Mol, J A; Rijnberk, A

2000-10-01

In German shepherd dogs pituitary dwarfism is known as an autosomal recessive inherited abnormality. To investigate whether the function of cells other than the somatotropes may also be impaired in this disease, the secretory capacity of the pituitary anterior lobe (AL) cells was studied by a combined pituitary AL stimulation test with four releasing hormones (4RH test) in four male and four female German shepherd dwarfs. In addition, the morphology of the pituitary was investigated by computed tomography. The physical features of the eight German shepherd dwarfs were primarily characterized by growth retardation and stagnant development of the hair coat. The results of the 4RH test confirmed the presence of hyposomatotropism. The basal plasma TSH and prolactin concentrations were also low and did not change upon stimulation. Basal plasma concentrations of LH were relatively low and responded only slightly to suprapituitary stimulation. With respect to the plasma FSH levels there was a clear gender difference. In the males plasma FSH concentrations remained below the detection limit throughout the 4RH test, whereas in the females the basal plasma FSH levels were slightly lower and there was only a small increase following suprapituitary stimulation, compared with the values in age-matched controls. In contrast, basal and stimulated plasma ACTH concentrations did not differ between the dwarfs and the controls. Computed tomography of the pituitary fossa revealed a normal sized pituitary with cysts in five dogs, an enlarged pituitary with cysts in two dogs, and a small pituitary gland without cysts in the remaining dog. The results of this study demonstrate that German shepherd dwarfs have a combined deficiency of GH, TSH, and prolactin together with impaired release of gonadotropins, whereas ACTH secretion is preserved. The combined pituitary hormone deficiency is associated with cyst formation and pituitary hypoplasia.

A descriptive study to find possible correlation between MRI findings of pituitary gland and serum prolactin level.

PubMed

Azeemuddin, Muhammad; Naqi, Rohana; Wasay, Mohammad

2013-06-01

To explore equation, if any, between findings of magnetic resonance imaging of pituitary gland and serum prolactin level. The retrospective, descriptive study was conducted at the Department of Radiology, Aga Khan University Hospital, Karachi, and related to patients' records from April 19, 2006 to April 23, 2009. Seventy patients underwent magnetic resonance imaging of brain for pituitary gland. Inclusion criteria were all patients referred with relevant clinical symptoms or deranged serum prolactin level. Patients who were claustrophobic or had a pacemaker, aneurysm clip, metallic foreign body in the orbit or with no laboratory investigation were excluded from the study. SPSS 19 was used for statistical analysis. Of the 70 patients, normal imaging was noted in 29 (41.4%) patients. Out of these, 18 (62.06%) patients had normal and 11 (37.93%) had raised serum prolactin levels. Microadenoma was found in 23 (32.8%) patients. Out of these, 10 (42.47%) had normal and 13 (56.52%) had raised prolactin levels. Macroadenoma was found in 16 (22.8 %). Out of these, 8 (50%) had normal and 8 (50%) had raised prolactin levels. Pituitary cyst was located in 2 (2.8 %) patients. Out of these, 1 (50%) had normal and 1 (50%) had raised serum prolactin levels. Magnetic resonance imaging of pituitary gland was not associated with serum prolactin levels in patients with clinical suspicion of pituitary abnormality. Therefore, regular monitoring of serum prolactin is suggested.

Chronic glue sniffing with transient central hypothyroidism and hypergonadotropism.

PubMed

Chen, Hua-Fen; Chen, Shwe-Winn; Chen, Peter; Su, Mei-Chin; See, Ting-Ting; Lee, Hsin-Yu

2003-12-01

Neuropsychiatric, gastrointestinal and muscular disorders associated with glue sniffing have been widely reported, but endocrinologic abnormalities of glue exposure are rarely mentioned in the literature. We report a 26-year old male patient, a chronic glue sniffer, who presented with weakness of both lower limbs. On physical examination, he had reduced muscle strength of his 4 limbs, especially in his lower limbs. Laboratory examination revealed hypokalemia with hyperchloremic metabolic acidosis. His thyroid function showed low TSH, T4, T3, free T4 and reverse T3 level. Other pituitary functions were normal apart from high FSH and LH level. TSH response to TRH stimulation was normal, but there was impaired T3 response to TRH. MRI of pituitary showed no significant changes. He continued glue sniffing after discharge. He repeatedly came to our hospital for recurrent hypokalemic paralysis. His serum T4 and free T4 level were low when he had certain amount of glue sniffing and it returned to normal after he stopped sniffing or sniffed less amount of glue. His serum T3 concentrations were normal most of the times thereafter. His FSH and LH level were persistently elevated, even after he did not sniff glue for 2 weeks. Low free T4, TSH and reverse T3 level associated with glue sniffing in our patient were compatible with central hypothyroidism. Toluene, a neurotoxic organic solvent, is present in glues. Being highly lipophilic, it can easily enter and is retained within the lipid-rich nervous system after being inhaled. Like other organic solvents, toluene has been shown to affect dopaminergic and adrenergic turnover within various parts of the brain. The effects on these neurotransmitters could lead to abnormal secretion of pituitary hormones resulting in transient central hypothyroidism and abnormal gonadotropin levels. Long-term harmful effect of central hypothyroidism and chronic influence of abnormal gonadotropins to reproduction function needs further observation.

Tissue-specific expression of squirrel monkey chorionic gonadotropin

PubMed Central

Vasauskas, Audrey A.; Hubler, Tina R.; Boston, Lori; Scammell, Jonathan G.

2010-01-01

Pituitary gonadotropins LH and FSH play central roles in reproductive function. In Old World primates, LH stimulates ovulation in females and testosterone production in males. Recent studies have found that squirrel monkeys and other New World primates lack expression of LH in the pituitary. Instead, chorionic gonadotropin (CG), which is normally only expressed in the placenta of Old World primates, is the active luteotropic pituitary hormone in these animals. The goal of this study was to investigate the tissue-specific regulation of squirrel monkey CG. We isolated the squirrel monkey CGβ gene and promoter from genomic DNA from squirrel monkey B-lymphoblasts and compared the promoter sequence to that of the common marmoset, another New World primate, and human CGβ and LHβ. Using reporter gene assays, we found that a squirrel monkey CGβ promoter fragment (−1898/+9) is active in both mouse pituitary LβT2 and human placenta JEG3 cells, but not in rat adrenal PC12 cells. Furthermore, within this construct separate cis-elements are responsible for pituitary- and placenta-specific expression. Pituitary-specific expression is governed by Egr-1 binding sites in the proximal 250 bp of the promoter, whereas placenta-specific expression is controlled by AP-2 sites further upstream. Thus, selective expression of the squirrel monkey CGβ promoter in pituitary and placental cells is governed by distinct cis-elements that exhibit homology with human LHβ and marmoset CGβ promoters, respectively. PMID:21130091

Intravoxel Incoherent Motion in Normal Pituitary Gland: Initial Study with Turbo Spin-Echo Diffusion-Weighted Imaging.

PubMed

Kamimura, K; Nakajo, M; Fukukura, Y; Iwanaga, T; Saito, T; Sasaki, M; Fujisaki, T; Takemura, A; Okuaki, T; Yoshiura, T

2016-12-01

DWI with conventional single-shot EPI of the pituitary gland is hampered by strong susceptibility artifacts. Our purpose was to evaluate the feasibility of intravoxel incoherent motion assessment by using DWI based on TSE of the normal anterior pituitary lobe. The intravoxel incoherent motion parameters, including the true diffusion coefficient (D), the perfusion fraction (f), and the pseudo-diffusion coefficient (D*), were obtained with TSE-DWI in 5 brain regions (the pons, the WM and GM of the vermis, and the genu and splenium of the corpus callosum) in 8 healthy volunteers, and their agreement with those obtained with EPI-DWI was evaluated by using the intraclass correlation coefficient. The 3 intravoxel incoherent motion parameters in the anterior pituitary lobe were compared with those in the brain regions by using the Dunnett test. The agreement between TSE-DWI and EPI-DWI was moderate (intraclass correlation coefficient = 0.571) for D, substantial (0.699) for f', but fair (0.405) for D*. D in the anterior pituitary lobe was significantly higher than in the 5 brain regions (P < .001). The f in the anterior pituitary lobe was significantly higher than in the 5 brain regions (P < .001), except for the vermian GM. The pituitary D* was not significantly different from that in the 5 brain regions. Our results demonstrated the feasibility of intravoxel incoherent motion assessment of the normal anterior pituitary lobe by using TSE-DWI. High D and f values in the anterior pituitary lobe were thought to reflect its microstructural and perfusion characteristics. © 2016 by American Journal of Neuroradiology.

The Ames dwarf gene, df, is required early in pituitary ontogeny for the extinction of Rpx transcription and initiation of lineage-specific cell proliferation.

PubMed

Gage, P J; Brinkmeier, M L; Scarlett, L M; Knapp, L T; Camper, S A; Mahon, K A

1996-12-01

Two nonallelic dwarfing mutations in mice define genes important for pituitary development and function. Mice homozygous for either the Ames (df) or Snell (Pit 1dw) dwarf mutations exhibit severe proportional dwarfism, hypothyroidism, and infertility due to the cytodifferentiation failure of three anterior pituitary cell types: thyrotropes, somatotropes, and lactotropes. Analysis of double heterozygotes and double mutants has provided evidence that the df and dw genes act sequentially in the same genetic pathway. Double heterozygotes had no reduction in growth rate or final adult size. Double homozygotes had essentially the same phenotype as the single mutants and were recovered at the predicted frequency, indicating that there are no previously unrecognized, redundant functions of the two genes. Several lines of evidence demonstrate that df acts earlier in the differentiation pathway than Pit1. The df mutants fail to extinguish expression of the homeobox gene Rpx on embryonic day 13.5 (e13.5), and the size of their nascent pituitary glands is reduced by e14.5. In contrast, Pit1dw mutants down-regulate Rpx appropriately and exhibit normal cell proliferation up to e14.5. The failure to extinguish Rpx and the concomitant hypocellularity of df pituitaries suggest the importance of Rpx repression in lineage-specific cell proliferation before the appearance of lineage-specific markers. Later, Pit-1 and hypothalamic neuropeptides act sequentially to regulate marker gene transcription and cell proliferation. These results establish the time of df action in a cascade of genes that regulate pituitary ontogeny.

Perturbation of Gene Expression and Steroidogenesis with In vitro Exposure of Fathead Minnow Ovaries to Ketoconazole

EPA Science Inventory

Various chemicals in the environment can disrupt normal endocrine function, including steroid hormone synthesis, causing deleterious effects. Because these compounds can act at different levels of the hypothalamus-pituitary-gonadal (HPG) axis, their effects can lead to a mixture...

From Consternation to Revelation: Discovery of a Role for IGSF1 in Pituitary Control of Thyroid Function.

PubMed

Bernard, Daniel J; Brûlé, Emilie; Smith, Courtney L; Joustra, Sjoerd D; Wit, Jan M

2018-03-01

Immunoglobulin superfamily, member 1 (IGSF1) is a transmembrane glycoprotein highly expressed in the mammalian pituitary gland. Shortly after its discovery in 1998, the protein was proposed to function as a coreceptor for inhibins (and was even temporarily renamed inhibin binding protein). However, subsequent investigations, both in vitro and in vivo , failed to support a role for IGSF1 in inhibin action. Research on IGSF1 nearly ground to a halt until 2011, when next-generation sequencing identified mutations in the X-linked IGSF1 gene in boys and men with congenital central hypothyroidism. IGSF1 was localized to thyrotrope cells, implicating the protein in pituitary control of the thyroid. Investigations in two Igsf1 knockout mouse models converged to show that IGSF1 deficiency leads to reduced expression of the receptor for thyrotropin-releasing hormone (TRH) and impaired TRH stimulation of thyrotropin secretion, providing a candidate mechanism for the central hypothyroidism observed in patients. Nevertheless, the normal functions of IGSF1 in thyrotropes and other cells remain unresolved. Moreover, IGSF1 mutations are also commonly associated with other clinical phenotypes, including prolactin and growth hormone dysregulation, and macroorchidism. How the loss of IGSF1 produces these characteristics is unknown. Although early studies of IGSF1 ran into roadblocks and blind alleys, armed with the results of detailed clinical investigations, powerful mouse models, and new reagents, the field is now poised to discover IGSF1's function in endocrine tissues, including the pituitary and testes.

Transient dwarfism and hypogonadism in mice lacking Otx1 reveal prepubescent stage-specific control of pituitary levels of GH, FSH and LH.

PubMed

Acampora, D; Mazan, S; Tuorto, F; Avantaggiato, V; Tremblay, J J; Lazzaro, D; di Carlo, A; Mariano, A; Macchia, P E; Corte, G; Macchia, V; Drouin, J; Brûlet, P; Simeone, A

1998-04-01

Genetic and molecular approaches have enabled the identification of regulatory genes critically involved in determining cell types in the pituitary gland and/or in the hypothalamus. Here we report that Otx1, a homeobox-containing gene of the Otx gene family, is postnatally transcribed and translated in the pituitary gland. Cell culture experiments indicate that Otx1 may activate transcription of the growth hormone (GH), follicle-stimulating hormone (betaFSH), luteinizing hormone (betaLH) and alpha-glycoprotein subunit (alphaGSU) genes. Analysis of Otx1 null mice indicates that, at the prepubescent stage, they exhibit transient dwarfism and hypogonadism due to low levels of pituitary GH, FSH and LH hormones which, in turn, dramatically affect downstream molecular and organ targets. Nevertheless, Otx1-/- mice gradually recover from most of these abnormalities, showing normal levels of pituitary hormones with restored growth and gonadal function at 4 months of age. Expression patterns of related hypothalamic and pituitary cell type restricted genes, growth hormone releasing hormone (GRH), gonadotropin releasing hormone (GnRH) and their pituitary receptors (GRHR and GnRHR) suggest that, in Otx1-/- mice, hypothalamic and pituitary cells of the somatotropic and gonadotropic lineages appear unaltered and that the ability to synthesize GH, FSH and LH, rather than the number of cells producing these hormones, is affected. Our data indicate that Otx1 is a new pituitary transcription factor involved at the prepubescent stage in the control of GH, FSH and LH hormone levels and suggest that a complex regulatory mechanism might exist to control the physiological need for pituitary hormones at specific postnatal stages.

Hypopituitarism Presenting as Adrenal Insufficiency and Hypothyroidism in a Patient with Wilson's Disease: a Case Report

PubMed Central

2016-01-01

Wilson's disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson's disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson's disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson's disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory. PMID:27478349

Hypopituitarism Presenting as Adrenal Insufficiency and Hypothyroidism in a Patient with Wilson's Disease: a Case Report.

PubMed

Lee, Hae Won; Kang, Jin Du; Yeo, Chang Woo; Yoon, Sung Woon; Lee, Kwang Jae; Choi, Mun Ki

2016-08-01

Wilson's disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson's disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson's disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson's disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory.

Comparison of mechanisms of action of luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix and LHRH agonist triptorelin on the gene expression of pituitary LHRH receptors in rats

PubMed Central

Kovacs, Magdolna; Schally, Andrew V.

2001-01-01

The mechanisms through which luteinizing hormone (LH)-releasing hormone (LHRH) antagonists suppress pituitary gonadotroph functions and LHRH-receptor (LHRH-R) expression are incompletely understood. Consequently, we investigated the direct effect of LHRH antagonist cetrorelix in vitro on the expression of the pituitary LHRH-R gene and its ability to counteract the exogenous LHRH and the agonist triptorelin in the regulation of this gene. We also compared the effects of chronic administration of cetrorelix and triptorelin on the LHRH-R mRNA level and gonadotropin secretion in ovariectomized (OVX) and normal female rats. The exposure of pituitary cells in vitro to 3-min pulses of 1 nM LHRH or 0.1 nM triptorelin for 5 h increased the LHRH-R mRNA level by 77–88%. Continuous perfusion of the cells with 50 nM cetrorelix did not cause any significant changes, but prevented the stimulatory effect of LHRH pulses on the receptor mRNA expression. In OVX rats, 10 days after administration of a depot formulation of cetrorelix, releasing 100 μg of peptide daily, the elevated LHRH-R mRNA level was decreased by 73%, whereas daily injection of 100 μg of triptorelin caused a 41% suppression. In normal female rats, cetrorelix treatment suppressed the LHRH-R mRNA level by 33%, but triptorelin increased it by 150%. The highly elevated serum LH levels in OVX rats and the normal LH concentration of cycling rats were rapidly and completely suppressed by cetrorelix. Triptorelin decreased the serum LH in OVX rats to the precastration level, but had no effect on basal LH in normal rats. Our results confirm that LHRH antagonists, such as cetrorelix, inhibit the gene expression of pituitary LHRH-R indirectly, by counteracting the stimulatory effect of LHRH. A rapid suppression of serum LH by LHRH antagonists would be advantageous in the treatment of sex hormone-dependent tumors and other conditions. PMID:11593037

p21, an important mediator of quiescence during pituitary tumor formation, is dispensable for normal pituitary development during embryogenesis.

PubMed Central

Monahan, Pamela; Himes, Ashley D.; Parfieniuk, Agata; Raetzman, Lori T.

2011-01-01

A delicate balance between proliferation and differentiation must be maintained in the developing pituitary to ensure the formation of the appropriate number of hormone producing cells. In the adult, proliferation is actively restrained to prevent tumor formation. The cyclin dependent kinase inhibitors (CDKIs) of the CIP/KIP family, p21, p27 and p57, mediate cell cycle inhibition. Although p21 is induced in the pituitary upon loss of Notch signaling or initiation of tumor formation to halt cell cycle progression, its role in normal pituitary organogenesis has not been explored. In wildtype pituitaries, expression of p21 is limited to a subset of cells embryonically as well as during the postnatal proliferative phase. Mice lacking p21 do not have altered cell proliferation during early embryogenesis, but do show a slight delay in separation of proliferating progenitors from the oral ectoderm. By embryonic day 16.5, p21 mutants have an alteration in the spatial distribution of proliferating pituitary progenitors, however there is no overall change in proliferation. At postnatal day 21, there appears to be no change in proliferation, as assessed by cells expressing Ki67 protein. However, p21 mutant pituitaries have significantly less mRNA of Myc and the cyclins Ccnb1, Ccnd1, Ccnd2 and Ccne1 than wildtype pituitaries. Interestingly, unlike the redundant role in cell cycle inhibition uncovered in p27/p57 double mutants, the pituitary of p21/p27 double mutants has a similar proliferation profile to p27 single mutants at the time points examined. Taken together, these studies demonstrate that unlike p27 or p57, p21 does not play a major role in control of progenitor proliferation in the developing pituitary. However, p21 may be required to maintain normal levels of cell cycle components. PMID:22154697

Transient hypogonadotropic hypogonadism in an amateur kickboxer after head trauma.

PubMed

Tanriverdi, F; Unluhizarci, K; Selcuklu, A; Casanueva, F F; Kelestimur, F

2007-02-01

Traumatic brain injury (TBI) is a frequent health problem and increased prevalence of neurendocrine dysfunction in patients with TBI has been reported. Sports injuries and particularly boxing may result in pituitary dysfunction. However, transient hypogonadotropic hypogonadism after an acute head trauma due to boxing and/or kickboxing has not been defined yet. We describe the case of a 20-yr-old male amateur kickboxer who was admitted to hospital complaining of decreased libido and impotence 2 weeks after an intensive bout. Basal hormone levels were compatible with mild hyperprolactinemia and hypogonadotpopic hypogonadism. GH axis was evaluated by GHRH+GHRP-6 test and peak GH level was within normal reference range. Three months later his complaints improved and abnormalities in basal hormone levels normalized. He was also re-evaluated 9 months after the first evaluation; basal hormone levels were within normal ranges and he had no complaints. In conclusion acute head trauma due to kickboxing may cause transient gonadotropin deficiency. Therefore, screening the pituitary functions of sportsmen dealing with combative sports is crucial.

Neuropeptides linking the control of appetite with reproductive function in domestic animals

USDA-ARS?s Scientific Manuscript database

The occurrence of puberty and maintenance of normal reproductive cycles are regulated by secretion of gonadotropin hormones from the pituitary gland, which is dependent upon the pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. It is well established that secretion of...

VARIATIONS IN CLINICAL AND IMAGING FINDINGS BY TIME OF DIAGNOSIS IN FEMALES WITH HYPOPITUITARISM ATTRIBUTED TO LYMPHOCYTIC HYPOPHYSITIS.

PubMed

Tirosh, Amit; Hirsch, Dania; Robenshtok, Eyal; Masri-Iraqi, Hiba; Yoel, Uri; Toledano, Yoel; Twito, Orit; Tsvetov, Gloria; Shimon, Ilan

2016-04-01

To describe the various patterns of presentation, including assisting analyses, associated with the timing of diagnosis of females with hypopituitarism and suspected clinical diagnosis of lymphocytic hypophysitis. A retrospective study of 9 consecutive females with pituitary dysfunction developed during or after pregnancy. All subjects were treated in our clinics between 2008 and 2014. Data were collected on clinical characteristics, pituitary hormone levels, and imaging findings. The study group included 9 patients with a mean age 33.7 ± 7.8 years at delivery. The probable cause of disease was lymphocytic hypophysitis. Headache or specific symptoms/signs of hypopituitarism appeared within 1 year of delivery. Five patients had headache, and 8 had difficulty breastfeeding or amenorrhea. Laboratory findings included central hypocortisolism (8/9 patients), hypogonadotropic hypogonadism (8/9), and central hypothyroidism (6/7). Insulin-like growth factor-1 (IGF-1) levels were low in 8/8 patients. Prolactin levels were low in 3/9 patients, and 1 patient had diabetes insipidus. Seven patients were diagnosed less than 1 year from symptom onset; 4 (57%) complained of headaches, and 5 (71%) had panhypopituitarism. Two patients were diagnosed later. Both had difficulty breastfeeding and amenorrhea, and one also had headaches. Both had panhypopituitarism and reduced pituitary volume. None of the patients fully recovered pituitary function. Normalization of the thyrotroph axis occurred in 3 patients, gonadotroph function in 3, the corticotroph axis in 2, and IGF-1 normalized in 1 subject. Hypopituitarism attributed to lymphocytic hypophysitis may present during pregnancy or early postpartum period with a clear clinical picture, or later, with indolent and nonspecific symptoms and signs.

Outcome of Endoscopic Transsphenoidal Surgery for Acromegaly.

PubMed

Kim, Jung Hee; Hur, Kyu Yeon; Lee, Jung Hyun; Lee, Ji Hyun; Se, Young-Bem; Kim, Hey In; Lee, Seung Hoon; Nam, Do-Hyun; Kim, Seong Yeon; Kim, Kwang-Won; Kong, Doo-Sik; Kim, Yong Hwy

2017-08-01

Endoscopic transsphenoidal surgery has recently been introduced in pituitary surgery. We investigated outcomes and complications of endoscopic surgery in 2 referral centers in Korea. We enrolled 134 patients with acromegaly (microadenomas, n = 15; macroadenomas, n = 119) who underwent endoscopic transsphenoidal surgery at Seoul National University Hospital (n = 74) and Samsung Medical Center (n = 60) between January 2009 and March 2016. Remission was defined as having a normal insulin-like growth factor-1 and a suppressed growth hormone (GH) <1 ng/mL during an oral glucose tolerance test. Remission was achieved in 73.1% of patients, including 13 of 15 microadenoma patients (86.7%) and 86 of 119 macroadenoma patients (72.3%). A multivariate analysis to determine a predictor of biochemical remission demonstrated that absence of cavernous sinus invasion and immediate postoperative GH levels <2.5 ng/dL were significant predictors of remission (adjusted odds ratio [OR], 5.14; 95% confidence interval [CI], 1.52-17.3 and OR, 9.60; 95% CI, 3.41-26.9, respectively). After surgery, normal pituitary function was maintained in 34 patients (25.4%). Sixty-four patients (47.7%) presented complete (n = 59, 44.0%) or incomplete (n = 5, 3.7%) recovery of pituitary function. Hypopituitarism persisted in 20 patients (14.9%) and worsened in 16 patients (11.9%). Postoperatively, transient diabetes insipidus was reported in 52 patients (38.8%) but only persisted in 2 patients (1.5%). Other postoperative complications were epistaxis (n = 2), cerebral fluid leakage (n = 4), infection (n = 1), and intracerebral hemorrhage (n = 1). Endoscopic transsphenoidal surgery for acromegaly presented high remission rates and a low incidence of endocrine deficits and complications. Regardless of surgical techniques, invasive pituitary tumors were associated with poor outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Three-dimensional magnetic resonance volumetry of the pituitary gland is effective in detecting short stature in children

PubMed Central

HAN, XUE; XIU, JIANJUN; HUANG, ZHAOQIN; ZHANG, JIE; ZHANG, ZHONGHE; DONG, YIN; YUAN, XIANSHUN; LIU, QINGWEI

2014-01-01

The aim of the present study was to obtain standard reference values for the pituitary gland volumes of healthy children and to analyze the potential diagnostic values of pituitary gland volumetry for growth hormone deficiency (GHD) and idiopathic short stature (ISS). The volume of the pituitary gland was measured using a thin-section three-dimensional (3D) magnetic resonance imaging (MRI) sequence of magnetization-prepared rapid gradient echo imaging with a section thickness of 1 mm. A group of 75 healthy children aged between 1 and 19 years were recruited to obtain normal volumetry values of the pituitary gland. These individuals demonstrated no evidence of abnormalities to the central nervous or endocrine systems prior to the study. An additional group of 55 children with GHD (n=32) or ISS (n=23) aged between 0 and 14 years were included in the measurement of pituitary gland volume and height. The Student’s t-test was used to evaluate the repetition test, while Pearson’s correlation coefficient and regression analyses were performed to examine the correlations between the volume and height of the pituitary glands. Pituitary gland volume and height demonstrated an increasing trend with age in the healthy children. In addition, the pituitary gland volume exhibited a growth spurt in the early teenage years (10–14 years-old), which was more prominent in females. The growth spurt was not observed for pituitary gland height. When compared with the healthy children, 65.6% of the children with GHD and 34.8% of the children with ISS had smaller pituitary gland volumes. Similarly, 37.5% of the children with GHD and 26.1% of the children with ISS had a smaller pituitary gland height compared with the healthy children. The pituitary gland volume performed significantly better compared with height with regard to the detection rate. Therefore, the results indicated that 3D MRI volumetry was useful for understanding the developmental characteristics of the pituitary gland in healthy children, and that the reference data provided by 3D MRI were effective in the diagnosis of short stature following associations with neuroimaging and clinical functional abnormalities of the pituitary gland. PMID:25009618

Three-dimensional magnetic resonance volumetry of the pituitary gland is effective in detecting short stature in children.

PubMed

Han, Xue; Xiu, Jianjun; Huang, Zhaoqin; Zhang, Jie; Zhang, Zhonghe; Dong, Yin; Yuan, Xianshun; Liu, Qingwei

2014-08-01

The aim of the present study was to obtain standard reference values for the pituitary gland volumes of healthy children and to analyze the potential diagnostic values of pituitary gland volumetry for growth hormone deficiency (GHD) and idiopathic short stature (ISS). The volume of the pituitary gland was measured using a thin-section three-dimensional (3D) magnetic resonance imaging (MRI) sequence of magnetization-prepared rapid gradient echo imaging with a section thickness of 1 mm. A group of 75 healthy children aged between 1 and 19 years were recruited to obtain normal volumetry values of the pituitary gland. These individuals demonstrated no evidence of abnormalities to the central nervous or endocrine systems prior to the study. An additional group of 55 children with GHD (n=32) or ISS (n=23) aged between 0 and 14 years were included in the measurement of pituitary gland volume and height. The Student's t-test was used to evaluate the repetition test, while Pearson's correlation coefficient and regression analyses were performed to examine the correlations between the volume and height of the pituitary glands. Pituitary gland volume and height demonstrated an increasing trend with age in the healthy children. In addition, the pituitary gland volume exhibited a growth spurt in the early teenage years (10-14 years-old), which was more prominent in females. The growth spurt was not observed for pituitary gland height. When compared with the healthy children, 65.6% of the children with GHD and 34.8% of the children with ISS had smaller pituitary gland volumes. Similarly, 37.5% of the children with GHD and 26.1% of the children with ISS had a smaller pituitary gland height compared with the healthy children. The pituitary gland volume performed significantly better compared with height with regard to the detection rate. Therefore, the results indicated that 3D MRI volumetry was useful for understanding the developmental characteristics of the pituitary gland in healthy children, and that the reference data provided by 3D MRI were effective in the diagnosis of short stature following associations with neuroimaging and clinical functional abnormalities of the pituitary gland.

Thyrotropin-producing pituitary adenoma simultaneously existing with Graves' disease: a case report.

PubMed

Arai, Nobuhiko; Inaba, Makoto; Ichijyo, Takamasa; Kagami, Hiroshi; Mine, Yutaka

2017-01-06

Thyrotropin-producing pituitary tumor is relatively rare. In particular, concurrent cases associated with Graves' disease are extremely rare and only nine cases have been reported so far. We describe a case of a thyrotropin-producing pituitary adenoma concomitant with Graves' disease, which was successfully treated. A 40-year-old Japanese woman presented with mild signs of hyperthyroidism. She had positive anti-thyroid-stimulating hormone receptor antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody. Her levels of serum thyroid-stimulating hormone, which ranged from low to normal in the presence of high levels of serum free thyroid hormones, were considered to be close to a state of syndrome of inappropriate secretion of thyroid-stimulating hormone. Magnetic resonance imaging showed a macropituitary tumor. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease was suspected. Initial therapy included anti-thyroid medication, which was immediately discontinued due to worsening symptoms. Subsequently, surgical therapy for the pituitary tumor was conducted, and her levels of free thyroid hormones, including the thyroid-stimulating hormone, became normal. On postoperative examination, her anti-thyroid-stimulating hormone receptor antibody levels decreased, and the anti-thyroglobulin antibody became negative. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease is rarely reported. The diagnosis of this condition is complicated, and the appropriate treatment strategy has not been clearly established. This case suggests that physicians should consider the coexistence of thyrotropin-producing pituitary adenoma with Graves' disease in cases in which thyroid-stimulating hormone values range from low to normal in the presence of thyrotoxicosis, and the surgical treatment of thyrotropin-producing pituitary adenoma could be the first-line therapy in patients with both thyrotropin-producing pituitary adenoma and Graves' disease.

Partial hypopituitarism and Langerhans cell histiocytosis

PubMed Central

Balaguruswamy, S; Chattington, P D

2011-01-01

A case of multisystem Langerhans cell histiocytosis with pituitary involvement nearly 20 years after initial presentation. A 48-year-old man had histiocytosis X 22 years ago initially involving the groin; subsequently his external auditory meatus, scalp, gum, mandibular bone, perineum and axilla were involved and treated. The pituitary gland was involved 4 years ago. A thyrotropin-releasing hormone test showed delayed response suggestive of hypothalamic disease. Prolactin levels were normal. A gonadotropin-releasing hormone test showed impaired testosterone and gonadotrophin response in keeping with pituitary disease. A glucagon stimulation test showed an impaired growth hormone response but a normal cortisol increase. MRI pituitary showed an empty sella. There was no evidence of diabetes insipidus. Bone mineral densitometry was normal. He has partial hypopituitarism needing thyroxine and testosterone replacement. He also developed type 2 diabetes mellitus 9 years ago. He is closely monitored for any development of diabetes insipidus and the need for growth hormone supplementation. PMID:22715201

Transcription factor 7-like 1 is involved in hypothalamo–pituitary axis development in mice and humans

PubMed Central

Gaston-Massuet, Carles; McCabe, Mark J.; Scagliotti, Valeria; Young, Rodrigo M.; Carreno, Gabriela; Gregory, Louise C.; Jayakody, Sujatha A.; Pozzi, Sara; Gualtieri, Angelica; Basu, Basudha; Koniordou, Markela; Wu, Chun-I; Bancalari, Rodrigo E.; Rahikkala, Elisa; Veijola, Riitta; Lopponen, Tuija; Graziola, Federica; Turton, James; Signore, Massimo; Mousavy Gharavy, Seyedeh Neda; Charolidi, Nicoletta; Sokol, Sergei Y.; Merrill, Bradley J.; Dattani, Mehul T.; Martinez-Barbera, Juan Pedro

2016-01-01

Aberrant embryonic development of the hypothalamus and/or pituitary gland in humans results in congenital hypopituitarism (CH). Transcription factor 7-like 1 (TCF7L1), an important regulator of the WNT/β-catenin signaling pathway, is expressed in the developing forebrain and pituitary gland, but its role during hypothalamo–pituitary (HP) axis formation or involvement in human CH remains elusive. Using a conditional genetic approach in the mouse, we first demonstrate that TCF7L1 is required in the prospective hypothalamus to maintain normal expression of the hypothalamic signals involved in the induction and subsequent expansion of Rathke’s pouch progenitors. Next, we reveal that the function of TCF7L1 during HP axis development depends exclusively on the repressing activity of TCF7L1 and does not require its interaction with β-catenin. Finally, we report the identification of two independent missense variants in human TCF7L1, p.R92P and p.R400Q, in a cohort of patients with forebrain and/or pituitary defects. We demonstrate that these variants exhibit reduced repressing activity in vitro and in vivo relative to wild-type TCF7L1. Together, our data provide support for a conserved molecular function of TCF7L1 as a transcriptional repressor during HP axis development in mammals and identify variants in this transcription factor that are likely to contribute to the etiology of CH. PMID:26764381

Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro.

PubMed

Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gahete, Manuel D; Jiménez-Reina, Luis; Venegas-Moreno, Eva; de la Riva, Andrés; Arráez, Miguel Ángel; González-Molero, Inmaculada; Schmid, Herbert A; Maraver-Selfa, Silvia; Gavilán-Villarejo, Inmaculada; García-Arnés, Juan Antonio; Japón, Miguel A; Soto-Moreno, Alfonso; Gálvez, María A; Luque, Raúl M; Castaño, Justo P

2016-11-01

Somatostatin analogs (SSA) are the mainstay of pharmacological treatment for pituitary adenomas. However, some patients escape from therapy with octreotide, a somatostatin receptor 2 (sst2)-preferring SSA, and pasireotide, a novel multi-sst-preferring SSA, may help to overcome this problem. It has been proposed that correspondence between sst1-sst5 expression pattern and SSA-binding profile could predict patient's response. To explore the cellular/molecular features associated with octreotide/pasireotide response, we performed a parallel comparison of their in vitro effects, evaluating sst1-sst5 expression, intracellular Ca 2+ signaling ([Ca 2+ ] i ), hormone secretion and cell viability, in a series of 85 pituitary samples. Somatotropinomas expressed sst5>sst2, yet octreotide reduced [Ca 2+ ] i more efficiently than pasireotide, while both SSA similarly decreased growth hormone release/expression and viability. Corticotropinomas predominantly expressed sst5, but displayed limited response to pasireotide, while octreotide reduced functional endpoints. Non-functioning adenomas preferentially expressed sst3 but, surprisingly, both SSA increased cell viability. Prolactinomas mainly expressed sst1 but were virtually unresponsive to SSA. Finally, both SSA decreased [Ca 2+ ] i in normal pituitaries. In conclusion, both SSA act in vitro on pituitary adenomas exerting both similar and distinct effects; however, no evident correspondence was found with the sst1-sst5 profile. Thus, it seems plausible that additional factors, besides the simple abundance of a given sst, critically influence the SSA response. © 2016 Society for Endocrinology.

Adjuvant or radical fractionated stereotactic radiotherapy for patients with pituitary functional and nonfunctional macroadenoma

PubMed Central

2011-01-01

Purpose To evaluate the efficacy and toxicity of stereotactic fractionated radiotherapy (SFRT) for patients with pituitary macroadenoma (PMA). Methods and Materials Between March 2000 and March 2009, 27 patients (male to female ratio, 1.25) with PMA underwent SFRT (median dose, 50.4 Gy). Mean age of the patients was 56.5 years (range, 20.3 - 77.4). In all but one patient, SFRT was administered for salvage treatment after surgical resection (transphenoidal resection in 23, transphenoidal resection followed by craniotomy in 2 and multiple transphenoidal resections in another patient). In 10 (37%) patients, the PMAs were functional (3 ACTH-secreting, 3 prolactinomas, 2 growth hormone-secreting and 2 multiple hormone-secretion). Three (11.1%) and 9 (33.3%) patients had PMA abutting and compressing the optic chiasm, respectively. Mean tumor volume was 2.9 ± 4.6 cm3. Eighteen (66.7%) patients had hypopituitarism prior to SFRT. The mean follow-up period after SFRT was 72.4 ± 37.2 months. Results Tumor size decreased for 6 (22.2%) patients and remained unchanged for 19 (70.4%) other patients. Two (7.4%) patients had tumor growth inside the prescribed treatment volume. The estimated 5-year tumor growth control was 95.5% after SFRT. Biochemical remission occurred in 3 (30%) patients with functional PMA. Two patients with normal anterior pituitary function before SFRT developed new deficits 25 and 65 months after treatment. The 5-year survival without new anterior pituitary deficit was thus 95.8%. Five patients with visual field defect had improved visual function and 1 patient with no visual defect prior to SFRT, but an optic chiasm abutting tumor, had a decline in visual function. The estimated 5-year vision and pituitary function preservation rates were 93.2% and 95.8%, respectively. Conclusions SFRT is a safe and effective treatment for patients with PMA, although longer follow-up is needed to evaluate long-term outcomes. In this study, approximately 1 patient with visual field defect out of two had an improved visual function. PMID:22152397

Tissue-specific expression of squirrel monkey chorionic gonadotropin.

PubMed

Vasauskas, Audrey A; Hubler, Tina R; Boston, Lori; Scammell, Jonathan G

2011-02-01

Pituitary gonadotropins LH and FSH play central roles in reproductive function. In Old World primates, LH stimulates ovulation in females and testosterone production in males. Recent studies have found that squirrel monkeys and other New World primates lack expression of LH in the pituitary. Instead, chorionic gonadotropin (CG), which is normally only expressed in the placenta of Old World primates, is the active luteotropic pituitary hormone in these animals. The goal of this study was to investigate the tissue-specific regulation of squirrel monkey CG. We isolated the squirrel monkey CGβ gene and promoter from genomic DNA from squirrel monkey B-lymphoblasts and compared the promoter sequence to that of the common marmoset, another New World primate, and human and rhesus macaque CGβ and LHβ. Using reporter gene assays, we found that a squirrel monkey CGβ promoter fragment (-1898/+9) is active in both mouse pituitary LβT2 and human placenta JEG3 cells, but not in rat adrenal PC12 cells. Furthermore, within this construct separate cis-elements are responsible for pituitary- and placenta-specific expression. Pituitary-specific expression is governed by Egr-1 binding sites in the proximal 250 bp of the promoter, whereas placenta-specific expression is controlled by AP-2 sites further upstream. Thus, selective expression of the squirrel monkey CGβ promoter in pituitary and placental cells is governed by distinct cis-elements that exhibit homology with human LHβ and marmoset CGβ promoters, respectively. Copyright © 2010 Elsevier Inc. All rights reserved.

Long-Term Outcomes of Fractionated Stereotactic Radiation Therapy for Pituitary Adenomas at the BC Cancer Agency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Julian O.; Ma, Roy; Division of Radiation Oncology and Developmental Radiotherapeutics, University of British Columbia, Vancouver

2013-11-01

Purpose: To assess the long-term disease control and toxicity outcomes of fractionated stereotactic radiation therapy (FSRT) in patients with pituitary adenomas treated at the BC Cancer Agency. Methods and Materials: To ensure a minimum of 5 years of clinical follow-up, this study identified a cohort of 76 patients treated consecutively with FSRT between 1998 and 2007 for pituitary adenomas: 71% (54/76) had nonfunctioning and 29% (22/76) had functioning adenomas (15 adrenocorticotrophic hormone-secreting, 5 growth hormone-secreting, and 2 prolactin-secreting). Surgery was used before FSRT in 96% (73/76) of patients. A median isocenter dose of 50.4 Gy was delivered in 28 fractions,more » with 100% of the planning target volume covered by the 90% isodose. Patients were followed up clinically by endocrinologists, ophthalmologists, and radiation oncologists. Serial magnetic resonance imaging was used to assess tumor response. Results: With a median follow-up time of 6.8 years (range, 0.6 - 13.1 years), the 7-year progression-free survival was 97.1% and disease-specific survival was 100%. Of the 2 patients with tumor progression, both had disease control after salvage surgery. Of the 22 patients with functioning adenomas, 50% (11/22) had complete and 9% (2/22) had partial responses after FSRT. Of the patients with normal pituitary function at baseline, 48% (14/29) experienced 1 or more hormone deficiencies after FSRT. Although 79% (60/76) of optic chiasms were at least partially within the planning target volumes, no patient experienced radiation-induced optic neuropathy. No patient experienced radionecrosis. No secondary malignancy occurred during follow-up. Conclusion: In this study of long-term follow-up of patients treated for pituitary adenomas, FSRT was safe and effective.« less

Functional and morphological changes in the adenohypophysis of dogs with induced primary hypothyroidism: loss of TSH hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with transdifferentiation.

PubMed

Diaz-Espiñeira, M M; Mol, J A; van den Ingh, T S G A M; van der Vlugt-Meijer, R H; Rijnberk, A; Kooistra, H S

2008-07-01

From case studies in humans it is known that primary hypothyroidism (PH) may be associated with morphological and functional changes of the pituitary. There is no insight into the time scale of these changes. In this study, seven beagle dogs were followed up for 3 years after the induction of primary hypothyroidism. Three of these dogs were followed up for another 1.5 years while receiving l-thyroxine. Adenohypophyseal function was investigated at 2-month intervals with the combined intravenous injection of CRH, GHRH, GnRH, and TRH, and measurement of the plasma concentrations of ACTH, GH, LH, PRL, and TSH. In addition, after 2 years of hypothyroidism a single TRH-stimulation test and a somatostatin test were performed, with measurements of the same pituitary hormones. Every 6 months the pituitary gland was visualized by computed tomography (CT). Induction of PH led to high plasma TSH concentrations for a few months, where after concentrations gradually declined to values no longer significantly different from pre-PH values. A blunted response to stimulation of TSH release preceded this decline. Basal plasma GH concentrations increased during PH and there was a paradoxical hyperresponsiveness to TRH stimulation. Basal GH concentrations remained elevated and returned only to low values during l-thyroxine treatment. Basal PRL concentrations decreased significantly during PH and normalized after several months of l-thyroxine treatment. The pituitary gland became enlarged in all dogs. Histomorphology and immunohistochemical studies in 4 dogs, after 3 years of PH, revealed thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and decreased numbers of mammotrophs. Several cells stained for both GH and TSH. In conclusion, with time PH led to a loss of the TSH response to low T4 concentrations, hypersecretion of GH, and hyposecretion of PRL. The enlarged pituitaries were characterized by thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and double-staining cells, which are indicative of transdifferentiation.

Plurihormonal cells of normal anterior pituitary: Facts and conclusions

PubMed Central

Mitrofanova, Lubov B.; Konovalov, Petr V.; Krylova, Julia S.; Polyakova, Victoria O.; Kvetnoy, Igor M.

2017-01-01

Introduction plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. Objective To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of adult humans in autopsy material. Materials and methods We studied 10 pituitary glands of 4 women and 6 men with cardiovascular and oncological diseases. Double staining immunohistochemistry using 11 hormone combinations was performed in all the cases. These combinations were: prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH), prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH, TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin, TSH/prolactin, ACTH/GH, and FSH/GH. Results We found that the same cells of the normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co-expression coefficients of prolactin, GH and TSH with other hormones showed that the TSH co-expression coefficient was significantly the least (9,5±6,9%; 9,6±7,8%; 1,0±1,3% correspondingly). Conclusion Plurihormonality of normal adenohypophysis is an actually existing phenomenon. Identification of different hormones in pituitary adenomas enables to find new ways to improve both diagnostic process and targeted treatment. PMID:28418929

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome

PubMed Central

Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu

2017-01-01

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD. PMID:28443260

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome.

PubMed

Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Won Kyoung; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu

2017-03-01

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

The long-term effects of megavoltage radiotherapy as sole or combined therapy for large prolactinomas: studies with high definition computerized tomography.

PubMed

Johnston, D G; Hall, K; Kendall-Taylor, P; Ross, W M; Crombie, A L; Cook, D B; Watson, M J

1986-06-01

The long-term sequelae of external pituitary irradiation alone or in combination with surgery and/or bromocriptine therapy have been studied in 14 patients with large prolactinomas over an observation period of 6-22 years (mean 13 years). Galactorrhoea was abolished in four of the five females with this symptom, but menstrual disturbance persisted in five of six patients. Sexual function was normal without sex hormone replacement in only one of the eight males after treatment. Neurological deficits were abolished or improved by treatment in all 9 patients with this presentation. Serum prolactin levels declined after treatment (P less than 0.001) and fell to within the normal range off bromocriptine therapy in six of the 14 patients at a mean of 9 years (range 5-17 years) after radiotherapy. All patients had anterior pituitary deficiency of some degree at reassessment, and 13 required replacement treatment. Serial skull radiographs revealed remineralization of the fossa floor in five patients and a decrease in fossa size in three. All five patients who did not also have surgery had evidence of tumour shrinkage without bromocriptine treatment (on CT scan or metrizamide cisternography). Fourth generation CT scans on completion of the study revealed a decrease in tumour mass in all patients, with varying degrees of empty sella in 13 and a cystic intrasellar tumour in the remaining one. Residual tumour was demonstrated in 10 patients, three of whom had normal serum prolactin levels, while one patient without visible tumour had persistent hyperprolactinaemia. Radiotherapy, alone or in combination with surgery and bromocriptine, effectively decreases prolactin secretion and tumour size in patients with large prolactinomas at the expense of other anterior pituitary function. Circulating prolactin levels are a poor marker of residual tumour volume.

Constitution and behavior of follicular structures in the human anterior pituitary gland.

PubMed Central

Ciocca, D. R.; Puy, L. A.; Stati, A. O.

1984-01-01

The follicular structures present in the human pituitary gland were studied, at the light-microscopic level, using histochemical and immunocytochemical techniques. The antisera applied in the peroxidase-antiperoxidase procedure were anti-hFSH beta, anti-hLH beta, anti-hPRL, anti-hGH, anti-hTSH beta, anti-hLPH beta, anti-pACTH, and anti-hACTH. In the 10 normal pituitaries examined, follicles were always found in the three areas of the adenohypophysis. The wall of the pars distalis follicles showed the seven immunoreactive cell types studied, while follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells were the only ones present in the wall of the pars tuberalis follicles. Most of the cell types studied were also present in the wall of the intermediate area follicles, but these follicles had characteristics not found in the other two areas. They were very large, with frequent interconnections forming a three-dimensional network of anastomotic cavities, and the colloid had different histochemical affinity. None of the hormones studied could be detected by immunocytochemistry within the follicular colloid. Three of the ten pituitary adenomas examined showed numerous follicular structures. Some of the follicles in the adenomatous pituitaries were similar to those found in the normal adenohypophysis, but there were also follicles filled with only traces of colloid and numerous blood cells in the cavity, and follicles filled with neoformed connective tissue. In one of these cases, FSH/LH immunoreactive adenoma cells were seen in the wall of the follicles. The results obtained suggest that the finding of pituitary adenomas with follicular structures is not uncommon and that the follicles originate from the tumor cells. In addition, the follicles seem to have several functional stages, explaining the finding of different types of follicular formation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 PMID:6326578

Psychiatric Symptoms due to Thyroid Disease in a Female Adolescent

PubMed Central

Capetillo-Ventura, Nelly; Baeza, Inmaculada

2014-01-01

The hypothalamic-pituitary-thyroid axis is involved in the production of thyroid hormone which is needed to maintain the normal functioning of various organs and systems, including the central nervous system. This study reports a case of hypothyroidism in a fifteen-year-old female adolescent who was attended for psychiatric symptoms. This case reveals the importance of evaluating thyroid function in children and adolescents with neuropsychiatric symptoms. PMID:25436160

Eight-year follow-up of a child with a GH/prolactin-secreting adenoma: efficacy of pegvisomant therapy.

PubMed

Bergamaschi, S; Ronchi, C L; Giavoli, C; Ferrante, E; Verrua, E; Ferrari, D I; Lania, A; Rusconi, R; Spada, A; Beck-Peccoz, P

2010-01-01

A 3.4-year-old girl was admitted to the Pediatric Department because of tall stature (116.0 cm, +5.1 SDS) and increased height velocity (16.3 cm/year, +6.1 SDS). Basal hormonal evaluation revealed elevated insulin-like growth factor I (IGF-I) levels (938 ng/ml, nv 40-190), prolactin (PRL) (98.0 ng/ml, nv 1.7-24.0) and mean growth hormone (GH) nocturnal concentration (147 ng/ml). Basal adrenal, gonadal and thyroid functions were normal. Hand-wrist bone age was 3.6 years. Magnetic resonance imaging revealed a macroadenoma with moderate suprasellar invasion. The adenoma was surgically removed and histological characterization confirmed the diagnosis of GH/PRL-secreting adenoma. The patient was admitted to our Endocrine Unit when 7.9 years old, because of the persistence of elevated GH, IGF-I and PRL levels, although there was a slight height velocity reduction and absence of tumor recurrence. Treatment with cabergoline was initiated, but only PRL levels normalized. Afterwards, octreotide long-acting release (LAR) was added without reaching the normalization of GH and IGF-I levels. Thus, treatment with octreotide LAR was discontinued and pegvisomant was added to cabergoline, leading to the normalization of IGF-I levels and height velocity without side effects. Other anterior pituitary functions were always normal. To conclude, treatment of pituitary gigantism with pegvisomant was effective and well tolerated in a young giant unresponsive to combined cabergoline and octreotide treatment.

Long term outcome following repeat transsphenoidal surgery for recurrent endocrine-inactive pituitary adenomas

PubMed Central

Chang, Edward F.; Zada, Gabriel; Wilson, Charles B.; Blevins, Lewis S.; Kunwar, Sandeep

2010-01-01

It is widely accepted that the standard first-line treatment for most endocrine inactive pituitary macroadenomas (EIA) is surgery, usually via a transsphenoidal approach. What is less clear is what approach to take when these tumors recur, especially when this recurrence involves areas which are difficult to surgically remove tumor from, such as the suprasellar region or cavernous sinuses. We present long term follow-up for a series of 81 patients who underwent repeat surgery for recurrent non-secreting pituitary adenomas. We analyzed data collected from all adult patients undergoing their second microsurgical transsphenoidal resection of a histologically proven endocrine-inactive pituitary adenoma at the University of California at San Francisco between January 1970 and March 2001. Data for these patients were collected by review of medical records, mail, and/or telephone interviews. Visual function, anterior pituitary function, and tumor control rates were analyzed for the series. Records were available for a total of 81 recurrent EIA patients. The median time between their initial and repeat operations was 4.1 years. The mean tumor size was 2.2 ± 0.2 cm. A total of 35/81 patients had greater than 5 years of follow-up. A total of 24/81 patients had greater than 10 years of follow-up. Over one half of these patients presented with visual disturbance, and we found that 39% of these patients experienced improved vision with a second surgery. More importantly, no one with normal vision suffered any appreciable decline in vision. Approximately, 35% of patients with pre-operative anterior pituitary dysfunction recovered function after surgery in our series; and no patient’s function worsened. A total of 4/52 (8%) patients with greater than 2 years of post-op follow-up experienced a clinically meaningful tumor recurrence requiring additional treatment. Our data suggest that when performed by experienced transsphenoidal surgeons, durable tumor control can be obtained in these frequently locally aggressive tumors with acceptable rates of post-operative morbidity. PMID:20217484

Pituitary gigantism: a case report.

PubMed

Bhattacharjee, Rana; Roy, Ajitesh; Goswami, Soumik; Selvan, Chitra; Chakraborty, Partha P; Ghosh, Sujoy; Biswas, Dibakar; Dasgupta, Ranen; Mukhopadhyay, Satinath; Chowdhury, Subhankar

2012-12-01

To present a rare case of gigantism. A 25-year-old lady presented with increased statural growth and enlarged body parts noticed since the age of 14 years, primary amenorrhea, and frontal headache for the last 2 years. She has also been suffering from non-inflammatory low back pain with progressive kyphosis and pain in the knees, ankles, and elbows for the last 5 years. There was no history of visual disturbance, vomiting, galactorrhoea, cold intolerance. She had no siblings. Family history was non-contributory. Blood pressure was normal. Height 221 cm, weight 138 kg, body mass index (BMI)28. There was coarsening of facial features along with frontal bossing and prognathism, large hands and feet, and small goitre. Patient had severe kyphosis and osteoarthritis of knees. Confrontation perimetry suggested bitemporal hemianopia. Breast and pubic hair were of Tanner stage 1. Serum insulin like growth factor-1 (IGF1) was 703 ng/ml with all glucose suppressedgrowth hormone (GH)values of >40 ng/ml. Prolactin was 174 ng/ml. Basal serum Lutenising Hormone (LH), follicle stimulating Hormone (FSH) was low. Oral glucose tolerance test (OGTT), liver and renal function tests, basal cortisol and thyroid profile, Calcium, phosphorus and Intact Parathyroid hormone (iPTH) were normal. Computed tomographyscan of brain showed large pituitary macroadenoma. Automated perimetry confirmed bitemporal hemianopia. A diagnosis of gigantism due to GH secreting pituitary macroadenoma with hypogonadotrophichypogonadism was made. Debulking pituitary surgery followed by somatostatin analogue therapy with gonadal steroid replacement had been planned, but the patient refused further treatment.

Pituitary Gigantism: A Case Report

PubMed Central

Bhattacharjee, Rana; Roy, Ajitesh; Goswami, Soumik; Selvan, Chitra; Chakraborty, Partha P.; Ghosh, Sujoy; Biswas, Dibakar; Dasgupta, Ranen; Mukhopadhyay, Satinath; Chowdhury, Subhankar

2012-01-01

Objective: To present a rare case of gigantism. Case Report: A 25-year-old lady presented with increased statural growth and enlarged body parts noticed since the age of 14 years, primary amenorrhea, and frontal headache for the last 2 years. She has also been suffering from non-inflammatory low back pain with progressive kyphosis and pain in the knees, ankles, and elbows for the last 5 years. There was no history of visual disturbance, vomiting, galactorrhoea, cold intolerance. She had no siblings. Family history was non-contributory. Blood pressure was normal. Height 221 cm, weight 138 kg, body mass index (BMI)28. There was coarsening of facial features along with frontal bossing and prognathism, large hands and feet, and small goitre. Patient had severe kyphosis and osteoarthritis of knees. Confrontation perimetry suggested bitemporal hemianopia. Breast and pubic hair were of Tanner stage 1. Serum insulin like growth factor-1 (IGF1) was 703 ng/ml with all glucose suppressedgrowth hormone (GH)values of >40 ng/ml. Prolactin was 174 ng/ml. Basal serum Lutenising Hormone (LH), follicle stimulating Hormone (FSH) was low. Oral glucose tolerance test (OGTT), liver and renal function tests, basal cortisol and thyroid profile, Calcium, phosphorus and Intact Parathyroid hormone (iPTH) were normal. Computed tomographyscan of brain showed large pituitary macroadenoma. Automated perimetry confirmed bitemporal hemianopia. A diagnosis of gigantism due to GH secreting pituitary macroadenoma with hypogonadotrophichypogonadism was made. Debulking pituitary surgery followed by somatostatin analogue therapy with gonadal steroid replacement had been planned, but the patient refused further treatment. PMID:23565401

Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS.

PubMed

Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R; Changelian, Armen; Laws, Edward R; Santagata, Sandro; Agar, Nathalie Y R; Van Berkel, Gary J

2015-08-01

Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections, using a fully automated droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS system for spatially resolved sampling, HPLC separation, and mass spectrometric detection. Excellent correlation was found between the protein distribution data obtained with this method and data obtained with matrix-assisted laser desorption/ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland. AVP was most abundant in the posterior pituitary gland region (neurohypophysis), and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH-secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH-secreting adenomas and in normal anterior adenohypophysis compared with non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis, as expected. This work reveals that a fully automated droplet-based liquid-microjunction surface-sampling system coupled to HPLC-ESI-MS-MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, including AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity, and specificity of this method support the potential of this basic technology, with further advancement, for assisting surgical decision-making. Graphical Abstract Mass spectrometry based profiling of hormones in human pituitary gland and tumor thin tissue sections.

Long-acting peptidomimergic control of gigantism caused by pituitary acidophilic stem cell adenoma.

PubMed

Maheshwari, H G; Prezant, T R; Herman-Bonert, V; Shahinian, H; Kovacs, K; Melmed, S

2000-09-01

Gigantism is caused by GH hypersecretion occurring before epiphyseal long bone closure and usually is associated with pituitary adenoma. A 15-yr-old female patient presented with accelerated growth due to a large pituitary tumor that was surgically resected to relieve pressure effects. Second surgery to remove residual tumor tissue was followed by administration of octreotide LAR, a long-acting depot somatostatin analog, together with long-acting cabergoline. Height was over the 95th percentile, with evidence of a recent growth spurt. Serum GH levels were more than 60 ng/mL (normal, <10 ng/mL) with no suppression to 75 g oral glucose, and serum PRL (>8,000 ng/mL; normal, <23 ng/mL) and insulin-like growth factor I levels (845 ng/mL; age-matched normal, 242-660 ng/mL) were elevated. Histology, immunostaining, and electron microscopy demonstrated a pituitary acidophil stem cell adenoma. Tumor tissue expressed both somatostatin receptor type 2 and dopamine receptor type 2. The Gs alpha subunit, GHRH receptor, and MEN1 genes were intact, and tumor tissue abundantly expressed pituitary tumor transforming gene (PTTG). Serum GH and PRL levels were controlled after two surgeries, and with continued cabergoline and octreotide LAR GH, PRL, and insulin-like growth factor I levels were normalized. In conclusion, administration of long-acting somatostatin analog every 4 weeks in combination with a long-acting dopamine agonist biweekly controlled biochemical parameters and accelerated growth in a patient with gigantism caused by a rare pituitary acidophil stem cell adenoma.

Pituitary size in patients with Laron syndrome (primary GH insensitivity).

PubMed

Kornreich, Liora; Horev, Gadi; Schwarz, Michael; Karmazyn, Boaz; Laron, Zvi

2003-03-01

The purpose of the present study was to investigate whether lifelong secretion of high levels of GH, characteristic of Laron syndrome, leads to an increase in the size of the pituitary gland. Eleven patients (six females, five males) with Laron syndrome underwent magnetic resonance imaging of the pituitary region with a system operating at 0.5 T. There were nine adults aged 36-68 Years and two children, a 4-Year-old boy and a 9-Year-old girl. The latter patient had been treated with IGF-I (150-180 mg/kg per day) since the age of 3 Years; all the other patients were untreated. The height of the adenohypophysis was measured on the sagittal images and compared with reference values for age and sex. The height of the adenohypophysis was within the normal range for age and gender in all patients, except for one male, who had a small gland. No congenital anomalies of the pituitary-hypothalamic region were detected. Despite the lifelong high levels of GH, no pituitary hypertrophy was detected. The anatomy of the pituitary-hypothalamic region in Laron syndrome is normal.

The Kenny-Caffey syndrome: growth retardation and hypocalcemia in a young boy.

PubMed

Lee, W K; Vargas, A; Barnes, J; Root, A W

1983-04-01

A 2-year-old black boy with the Kenny-Caffey syndrome was first evaluated because of growth retardation and hypocalcemia. Hypothalamic-pituitary function was normal. Basal serum somatomedin C levels were normal for age, but did not increase during short-term administration of human growth hormone. Serum immunoreactive parathyroid hormone levels remained inappropriately low during spontaneous and induced hypocalcemia, indicating that hypocalcemia was the consequence of hypoparathyroidism. The manifestations of 15 patients with this syndrome are tabulated.

Permanent hypopituitarism is rare after structural traumatic brain injury in early childhood.

PubMed

Heather, Natasha L; Jefferies, Craig; Hofman, Paul L; Derraik, José G B; Brennan, Christine; Kelly, Patrick; Hamill, James K M; Jones, Rhys G; Rowe, Deborah L; Cutfield, Wayne S

2012-02-01

We sought to determine the incidence of permanent hypopituitarism in a potentially high-risk group: young children after structural traumatic brain injury (TBI). We conducted a cross-sectional study with longitudinal follow-up. Dynamic tests of pituitary function (GH and ACTH) were performed in all subjects and potential abnormalities critically evaluated. Puberty was clinically staged; baseline thyroid function, prolactin, IGF-I, serum sodium, and osmolality were compared with age-matched data. Diagnosis of GH deficiency was based on an integrated assessment of stimulated GH peak (<5 μg/liter suggestive of deficiency), IGF-I, and growth pattern. ACTH deficiency was diagnosed based on a subnormal response to two serial Synacthen tests (peak cortisol <500 nmol/liter) and a metyrapone test. We studied 198 survivors of structural TBI sustained in early childhood (112 male, age at injury 1.7 ± 1.5 yr) 6.5 ± 3.2 yr after injury. Sixty-four of the injuries (33%) were inflicted and 134 (68%) accidental. Two participants had developed precocious puberty, which is within the expected background population rate. Peak stimulated GH was subnormal in 16 participants (8%), in the context of normal IGF-I and normal growth. Stimulated peak cortisol was low in 17 (8%), but all had normal ACTH function on follow-up. One participant had a transient low serum T(4). Therefore, no cases of hypopituitarism were recorded. Permanent hypopituitarism is rare after both inflicted and accidental structural TBI in early childhood. Precocious puberty was the only pituitary hormone abnormality found, but the prevalence did not exceed that of the normal population.

Gigantism in sibling unrelated to multiple endocrine neoplasia: case report.

PubMed

Matsuno, A; Teramoto, A; Yamada, S; Kitanaka, S; Tanaka, T; Sanno, N; Osamura, R Y; Kirino, T

1994-11-01

The cases of gigantism sisters with somatotroph adenomas unrelated to multiple endocrine neoplasia (MEN) Type 1 are reported. The sisters grew rapidly since they were 5 or 6 years old and were diagnosed to have gigantism with pituitary adenoma by computed tomographic scan and magnetic resonance imaging. A serum endocrinological examination showed the elevated growth hormone values. After thyroxine-releasing hormone stimulation, growth hormone values exhibited a paradoxical rise. They were supposed to be unrelated to MEN Type 1, because analysis of the 11th chromosomes and the other endocrine functions were normal. They were operated on by the transphenoidal method. Immunohistochemical staining of both tumor specimens confirmed somatotroph adenomas. Pituitary adenoma associated with MEN Type 1 is a well-recognized entity. However, the sporadic occurrence of pituitary adenoma unrelated to MEN Type 1, especially in siblings, is extremely rare. Fifteen cases of pituitary adenomas in siblings were described in the literature. As for gigantism, only two brothers were reported. Our case of gigantism sisters is the second sporadic case. In our review of the isolated cases of pituitary adenoma in siblings described in the literature, 12 (70%) of 17 cases including ours are acromegaly or gigantism. This incidence is much higher than that of MEN Type 1 patients with pituitary adenomas. The cause of the familial occurrence of pituitary adenomas is still unclear, although autosomal recessive inheritance has been suggested. It has been stated that point mutations in codon 201 or 227 of the Gs alpha gene located in chromosome 20 were found in about 35 to 40% of somatotroph adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothalamic-Pituitary-Adrenal Axis Function in Children with Attention-Deficit Hyperactivity Disorder.

ERIC Educational Resources Information Center

Kaneko, Motohisa; And Others

1993-01-01

This study with 30 children showing attention deficit hyperactivity disorder (ADHD) found a normal diurnal saliva cortisol rhythm in only 43.3 percent of the subjects and a dexamethasone suppression in 46.7 percent, with both these abnormalities more frequent in the severely than the mildly hyperactive group. Results suggest abnormalities in…

Infrasellar pituitary gangliocytoma causing Cushing's syndrome.

PubMed

Domingue, Marie-Eve; Marbaix, Etienne; Do Rego, Jean-Luc; Col, Vincent; Raftopoulos, Christian; Duprez, Thierry; Vaudry, Hubert; Maiter, Dominique

2015-10-01

Pituitary gangliocytomas are uncommon neuronal tumours that may present with endocrine disorders, the most frequent being acromegaly caused by growth hormone hypersecretion. Cushing's syndrome is very rarely seen with gangliocytomas. We report the unique case of a 62 year-old woman whose clinical picture and endocrine testing clearly demonstrated adrenocorticotropin (ACTH)-dependent Cushing's syndrome. Pituitary magnetic resonance imaging showed a 12-mm homogeneous, infra- and retrosellar mass first diagnosed as pituitary macroadenoma. Transsphenoidal surgery was performed and allowed complete resection of the tumour with sparing of normal anterior pituitary. Very low postoperative serum cortisol and ACTH levels were observed in the early postoperative period and the patient is still in remission 18 months after surgery, thus demonstrating that the resected lesion was entirely responsible for the clinical picture. Histological and immunocytochemical analyses demonstrated a benign tumour composed of mature neuronal cells suggestive of a gangliocytoma, expressing both ACTH and corticotropin-releasing hormone (CRH). The tumour was surrounded by a rim of pituitary tissue containing ACTH-producing endocrine cells. Careful analysis of the resected lesion did not reveal any pituitary microadenoma. We search literature for similar cases and retraced only nine cases of gangliocytomas associated with Cushing's syndrome. In most of them, the tumour was combined with either pituitary corticotroph adenoma or hyperplasia. Our case represents a unique case of an infrasellar pituitary gangliocytoma which was able to cause Cushing's syndrome by both direct ACTH production and CRH-induced stimulation of neighbour normal corticotroph cells.

Response of Indian growth hormone deficient children to growth hormone therapy: association with pituitary size.

PubMed

Khadilkar, Vaman V; Prasad, Hemchand Krishna; Ekbote, Veena H; Rustagi, Vaishakhi T; Singh, Joshita; Chiplonkar, Shashi A; Khadilkar, Anuradha V

2015-05-01

To ascertain the impact of pituitary size as judged by Magnetic Resonance Imaging (MRI), on response to Growth Hormone (GH) therapy in GH deficient children. Thirty nine children (9.1 ± 2.7 y, 22 boys) with non-acquired GH deficiency (21 Isolated GH deficiency and 18 Combined pituitary hormone deficiency) were consecutively recruited and followed up for one year. Clinical, radiological (bone age and MRI) and biochemical parameters were studied. Children with hypoplastic pituitary (pituitary height < 3 mm) had more severe height deficit (height for age Z-score -6.0 vs. -5.0) and retardation of skeletal maturation (bone age chronological age ratio of 0.59 vs. 0.48) at baseline as compared to children with normal pituitary heights (p < 0.05 for both). After one year of GH therapy, height for age Z scores and percentage change in height for age Z scores were significantly higher in children with hypoplastic pituitaries (13.8 ± 3.6 and 28.7 % vs. 11.2 ± 4.1 and 21.4 %). Significant co-relation was observed between pituitary height and height for age Z-scores at baseline (r = 0.39, p < 0.05). The predicted adult height using Tanner Whitehouse-2 equations improved from 140.8 to 152.3 cm in children with hypoplastic pituitary when compared to an increase from 145.8 to 153.5 cm observed in children with normal pituitary height (p < 0.05). Indian growth hormone deficient children with hypoplastic pituitary respond better to therapy with GH in short term.

Functional hypothalamic amenorrhea due to increased CRH tone in melanocortin receptor 2-deficient mice.

PubMed

Matsuwaki, Takashi; Nishihara, Masugi; Sato, Tsuyoshi; Yoda, Tetsuya; Iwakura, Yoichiro; Chida, Dai

2010-11-01

Exposure to chronic stressors results in dysregulation of the hypothalamic-pituitary-adrenal axis and a disruption in reproduction. CRH, the principal regulator of the hypothalamic-pituitary-adrenal axis induces the secretion of ACTH from the pituitary, which stimulates adrenal steroidogenesis via the specific cell-surface melanocortin 2 receptor (MC2R). Previously, we demonstrated that MC2R(-/-) mice had undetectable levels of corticosterone despite high ACTH levels. Here, we evaluated the reproductive functions of female MC2R(-/-) mice and analyzed the mechanism of the disrupted cyclicity of these mice. The expression of CRH in the paraventricular nucleus was significantly increased in MC2R(-/-) mice under nonstressed conditions. Although MC2R(-/-) females were fertile, they showed a prolonged estrous cycle. After hormonal stimulation, MC2R(-/-) females produced nearly-normal numbers of eggs, but slightly less than MC2R(+/-) females, and showed near-normal ovarian histology. During diestrus, the number of GnRH-positive cells in the medial preoptic area was significantly reduced in MC2R(-/-) females. CRH type 1 receptor antagonist restored estrous cyclicity in MC2R(-/-) females. Kisspeptin-positive areas in the arcuate nucleus were comparable, whereas kisspeptin-positive areas in the anteroventral periventricular nucleus in MC2R(-/-) females were significantly reduced compared with MC2R(+/-) females, suggesting that arcuate nucleus kisspeptin is not involved, but anteroventral periventricular nucleus kisspeptin may be involved, in the maintenance of estrous cyclicity. Our findings show that high levels of hypothalamic CRH disturb estrous cyclicity in the female animals and that the MC2R(-/-) female is a unique animal model of functional hypothalamic amenorrhea.

Nutrient restriction induces failure of reproductive function and molecular changes in hypothalamus-pituitary-gonadal axis in postpubertal gilts.

PubMed

Zhou, Dongsheng; Zhuo, Yong; Che, Lianqiang; Lin, Yan; Fang, Zhengfeng; Wu, De

2014-07-01

People on a diet to lose weight may be at risk of reproductive failure. To investigate the effects of nutrient restriction on reproductive function and the underlying mechanism, changes of reproductive traits, hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis were examined in postpubertal gilts at anestrus induced by nutrient restriction. Gilts having experienced two estrus cycles were fed a normal (CON, 2.86 kg/d) or nutrient restricted (NR, 1 kg/d) food regimens to expect anestrus. NR gilts experienced another three estrus cycles, but did not express estrus symptoms at the anticipated fourth estrus. Blood samples were collected at 5 days' interval for consecutive three times for measurement of hormone concentrations at the 23th day of the fourth estrus cycle. Individual progesterone concentrations of NR gilts from three consecutive blood samples were below 1.0 ng/mL versus 2.0 ng/mL in CON gilts, which was considered anestrus. NR gilts had impaired development of reproductive tract characterized by absence of large follicles (diameter ≥ 6 mm), decreased number of corepus lutea and atrophy of uterus and ovary tissues. Circulating concentrations of IGF-I, kisspeptin, estradiol, progesterone and leptin were significantly lower in NR gilts than that in CON gilts. Nutrient restriction down-regulated gene expressions of kiss-1, G-protein coupled protein 54, gonadotropin-releasing hormone, estrogen receptor α, progesterone receptor, leptin receptor, follicle-stimulating hormone and luteinizing hormone and insulin-like growth factor I in hypothalamus-pituitary-gonadal axis of gilts. Collectively, nutrient restriction resulted in impairment of reproductive function and changes of hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis, which shed light on the underlying mechanism by which nutrient restriction influenced reproductive function.

Time Course of Resolution of Hyperprolactinemia After Transsphenoidal Surgery Among Patients Presenting with Pituitary Stalk Compression.

PubMed

Zaidi, Hasan A; Cote, David J; Castlen, Joseph P; Burke, William T; Liu, Yong-Hui; Smith, Timothy R; Laws, Edward R

2017-01-01

Primary lactotroph disinhibition, or stalk effect, occurs when mechanical compression of the pituitary stalk disrupts the tonic inhibition by dopamine released by the hypothalamus. The resolution of pituitary stalk effect-related hyperprolactinemia postoperatively has not been studied in a large cohort of patients. We performed a retrospective review to investigate the time course of recovery of lactotroph disinhibition after transsphenoidal surgery. Medical records were retrospectively reviewed for all patients undergoing transsphenoidal surgery with the senior author from April 2008 to November 2014. Of 556 pituitary adenomas, 289 (52.0%) were eliminated: 77 (13.9%) had an immunohistochemically confirmed prolactinoma, 119 (21.4%) patients had previous surgery, 93 (16.7%) had incomplete medical records, leaving 267 patients (48.0%) for final analysis. Of these patients, 72 (27.0%) had increased serum prolactin levels (≥23.3 ng/mL), suggestive of pituitary stalk effect (maximum prolactin level = 148.0 ng/mL). Patients with stalk effect were more likely than those with normal serum prolactin levels to present with menstrual dysfunction (29.7% vs. 19.4%; P < 0.01) and galactorrhea (11.1% vs. 2.1%; P < 0.01). Patients with lactotroph disinhibition were more likely to harbor macroadenomas than were patients who did not show lactotroph disinhibition (81.9% vs. 70.2%; P = 0.06). Among patients with increased preoperative prolactin, 77.8% experienced normalization of serum prolactin postoperatively, galactorrhea improved in 100%, sexual dysfunction resolved in 66.6%, and menstrual dysfunction among premenopausal females normalized in 73.3% at last follow-up (mean, 5.35 years; range, 0.1-10 years). Transsphenoidal surgery can provide durable normalization of serum prolactin levels and related symptoms caused by pituitary stalk compression-related lactotroph disinhibition. Copyright © 2016 Elsevier Inc. All rights reserved.

hpttg is over-expressed in pituitary adenomas and other primary epithelial neoplasias.

PubMed

Sáez, C; Japón, M A; Ramos-Morales, F; Romero, F; Segura, D I; Tortolero, M; Pintor-Toro, J A

1999-09-23

The role of oncogenes in pituitary tumorigenesis remains elusive since few genetic changes have been identified so far in pituitary tumors. Pituitary tumor-transforming gene (pttg) has been recently cloned from rat GH4 pituitary tumor cells. We have previously isolated and characterized hpttg from human thymus. In the present study, we analyse the expression of hpttg mRNA in a series of human pituitary adenomas. We show that hpttg is highly expressed in the majority of pituitary adenomas while only very low levels of mRNA can be detected in normal pituitary gland by Northern blot analysis. hPTTG protein was immunolocalized mainly in the cytoplasm of adenoma cells. Other common extra-cranial malignant tumors were also analysed by immunohistochemistry. Interestingly, strong hPTTG immunoreactivity was detected in most adenocarcinomas of mammary and pulmonary origins.

Expression of Eag1 K+ channel and ErbBs in human pituitary adenomas: cytoskeleton arrangement patterns in cultured cells.

PubMed

del Pliego, Margarita González; Aguirre-Benítez, Elsa; Paisano-Cerón, Karina; Valdovinos-Ramírez, Irene; Rangel-Morales, Carlos; Rodríguez-Mata, Verónica; Solano-Agama, Carmen; Martín-Tapia, Dolores; de la Vega, María Teresa; Saldoval-Balanzario, Miguel; Camacho, Javier; Mendoza-Garrido, María Eugenia

2013-01-01

Pituitary adenomas can invade surrounded tissue, but the mechanism remains elusive. Ether à go-go-1 (Eag1) potassium channel and epidermal growth factor receptors (ErbB1 and ErbB2) have been associated to invasive phenotypes or poor prognosis in cancer patients. However, cells arrange their cytoskeleton in order to acquire a successful migration pattern. We have studied ErbBs and Eag1 expression, and cytoskeleton arrangements in 11 human pituitary adenomas. Eag1, ErbB1 and ErbB2 expression were studied by immunochemistry in tissue and cultured cells. The cytoskeleton arrangement was analyzed in cultured cells by immunofluorescence. Normal pituitary tissue showed ErbB2 expression and Eag1 only in few cells. However, Eag1 and ErbB2 were expressed in all the tumors analyzed. ErbB1 expression was observed variable and did not show specificity for a tumor characteristic. Cultured cells from micro- and macro-adenomas clinically functional organize their cytoskeleton suggesting a mesenchymal pattern, and a round leucocyte/amoeboid pattern from invasive clinically silent adenoma. Pituitary tumors over-express EGF receptors and the ErbB2 repeated expression suggests is a characteristic of adenomas. Eag 1 was express, in different extent, and could be a therapeutic target. The cytoskeleton arrangements observed suggest that pituitary tumor cells acquire different patterns: mesenchymal, and leucocyte/amoeboid, the last observed in the invasive adenomas. Amoeboid migration pattern has been associated with high invasion capacity.

Pituitary adenylate cyclase-activating polypeptide: a novel peptide with protean implications.

PubMed

Pisegna, Joseph R; Oh, David S

2007-02-01

The purpose of this review is to highlight the importance of pituitary adenylate cyclase-activating polypeptide in physiological processes and to describe how this peptide is becoming increasingly recognized as having a major role in the body. Since its discovery in 1989, investigators have sought to determine the site of biological activity and the function of pituitary adenylate cyclase-activating polypeptide in maintaining homeostasis. Since its discovery, pituitary adenylate cyclase-activating polypeptide appears to play an important role in the regulation of processes within the central nervous system and gastrointestinal tract, as well in reproductive biology. Pituitary adenylate cyclase-activating polypeptide has been shown to regulate tumor cell growth and to regulate immune function through its effects on T lympocytes. These discoveries suggest the importance of pituitary adenylate cyclase-activating polypeptide in neuronal development, neuronal function, gastrointestinal tract function and reproduction. Future studies will examine more closely the role of pituitary adenylate cyclase-activating polypeptide in regulation of malignantly transformed cells, as well as in regulation of immune function.

An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism

PubMed Central

Vargas, Guadalupe; Balcazar-Hernandez, Lourdes-Josefina; Melgar, Virgilio; Magriña-Mercado, Roser-Montserrat; Gonzalez, Baldomero; Baquera, Javier

2017-01-01

A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH. Learning points: Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty. Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH. Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function. PMID:28721217

An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism.

PubMed

Vargas, Guadalupe; Balcazar-Hernandez, Lourdes-Josefina; Melgar, Virgilio; Magriña-Mercado, Roser-Montserrat; Gonzalez, Baldomero; Baquera, Javier; Mercado, Moisés

2017-01-01

A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH. Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty.Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH.Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function.

PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes

PubMed Central

Cristina, Carolina; Díaz-Torga, Graciela S; Goya, Rodolfo G; Kakar, Sham S; Perez-Millán, María I; Passos, Vanessa Q; Giannella-Neto, Daniel; Bronstein, Marcello D; Becu-Villalobos, Damasia

2007-01-01

Background Pituitary tumor transforming gene (pttg) is a novel oncogene that is expressed at higher level in most of the tumors analyzed to date compared to normal tissues. Nevertheless, its expression in prolactinomas and its relation with the pituitary dopamine receptor 2 (D2R) are not well defined. We sought to determine the pituitary level of pttg in three different experimental models of prolactinomas with altered dopaminergic control of the pituitary: the dopaminergic D2R knockout female mouse, the estrogen-treated rat, and the senescent female rat. These three models shared the characteristics of increased pituitary weight, hyperprolactinemia, lactotrope hyperplasia and reduced or absent dopaminergic action at the pituitary level. We also studied samples from human macroprolactinomas, which were characterized as responsive or resistant to dopamine agonist therapy. Results When compared to female wild-type mice, pituitaries from female D2R knockout mice had decreased PTTG concentration, while no difference in pttg mRNA level was found. In senescent rats no difference in pituitary PTTG protein expression was found when compared to young rats. But, in young female rats treated with a synthetic estrogen (Diethylstylbestrol, 20 mg) PTTG protein expression was enhanced (P = 0.029). Therefore, in the three experimental models of prolactinomas, pituitary size was increased and there was hyperprolactinemia, but PTTG levels followed different patterns. Patients with macroprolactinomas were divided in those in which dopaminergic therapy normalized or failed to normalize prolactin levels (responsive and resistant, respectively). When pituitary pttg mRNA level was analyzed in these macroprolactinomas, no differences were found. We next analyzed estrogen action at the pituitary by measuring pituitary estrogen receptor α levels. The D2R knockout female mice have low estrogen levels and in accordance, pituitary estrogen receptors were increased (P = 0.047). On the other hand, in senescent rats estrogen levels were slightly though not significantly higher, and estrogen receptors were similar between groups. The estrogen-treated rats had high pharmacological levels of the synthetic estrogen, and estrogen receptors were markedly lower than in controls (P < 0.0001). Finally, in patients with dopamine resistant or responsive prolactinomas no significant differences in estrogen receptor α levels were found. Therefore, pituitary PTTG was increased only if estrogen action was increased, which correlated with a decrease in pituitary estrogen receptor level. Conclusion We conclude that PTTG does not correlate with prolactin levels or tumor size in animal models of prolactinoma, and its pituitary content is not related to a decrease in dopaminergic control of the lactotrope, but may be influenced by estrogen action at the pituitary level. Therefore it is increased only in prolactinomas generated by estrogen treatment, and not in prolactinomas arising from deficient dopamine control, or in dopamine resistant compared with dopamine responsive human prolactinomas. These results are important in the search for reliable prognostic indicators for patients with pituitary adenomas which will make tumor-specific therapy possible, and help to elucidate the poorly understood phenomenon of pituitary tumorigenesis. PMID:17222350

Thyroid hormone is essential for pituitary somatotropes and lactotropes.

PubMed

Stahl, J H; Kendall, S K; Brinkmeier, M L; Greco, T L; Watkins-Chow, D E; Campos-Barros, A; Lloyd, R V; Camper, S A

1999-04-01

Mice homozygous for a disruption in the alpha-subunit essential for TSH, LH, and FSH activity (alphaGsu-/-) exhibit hypothyroidism and hypogonadism similar to that observed in TSH receptor-deficient hypothyroid mice (hyt) and GnRH-deficient hypogonadal mutants (hpg). Although the five major hormone-producing cells of the anterior pituitary are present in alphaGsu-/- mice, the relative proportions of each cell type are altered dramatically. Thyrotropes exhibit hypertrophy and hyperplasia, and somatotropes and lactotropes are underrepresented. The size and number of gonadotropes in alphaGsu mutants are not remarkable in contrast to the hypertrophy characteristic of gonadectomized animals. The reduction in lactotropes is more severe in alphaGsu mutants (13-fold relative to wild-type) than in hyt or hpg mutants (4.5- and 1.5-fold, respectively). In addition, T4 replacement therapy of alphaGsu mutants restores lactotropes to near-normal levels, illustrating the importance of T4, but not alpha-subunit, for lactotrope proliferation and function. T4 replacement is permissive for gonadotrope hypertrophy in alphaGsu mutants, consistent with the role for T4 in the function of gonadotropes. This study reveals the importance of thyroid hormone in developing the appropriate proportions of anterior pituitary cell types.

Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl.

PubMed

Rix, M; Laurberg, P; Hoejberg, A S; Brock-Jacobsen, B

2005-08-01

The use of a growth hormone (GH) receptor antagonist, pegvisomant has shown great promise in adults with acromegaly, but experience in paediatric patients is lacking. We aimed to describe the results of pegvisomant therapy in a 12-year-old girl with an aggressive GH-secreting pituitary tumour. To evaluate the ability of pegvisomant therapy to control the effects of peripheral GH excess in a case of pituitary gigantism. Pegvisomant was introduced at 10 mg/day, given subcutaneously, and gradually increased to 20 mg/day until serum IGF-I was normal for age. A large pituitary adenoma with suprasellar extension was diagnosed in a 12-year-old girl with progressive tall stature (178 cm), GH hypersecretion without suppression during oral glucose loading (nadir serum GH, 90 mU/l), high serum IGF-I and serum prolactin levels. Surgical extirpation was not possible because tumour tissue was fibrous and adherent to the optical nerves. Histological examination showed a mixed GH- and prolactin-secreting adenoma with lymphocytic infiltration of B and T cells. Treatment with a dopamine agonist, cabergoline, normalized serum prolactin, but GH secretion was resistant to both somatostatin analogue, octreotide and cabergoline. Radiation followed by pegvisomant therapy titrated up in dose to 20 mg/day led to a marked reduction in GH secretion and normalization of IGF-I, and to growth arrest and improvement of well-being. We suggest that treatment in pituitary gigantism with pegvisomant is safe and may normalize IGF-I levels and effectively stop growing.

Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC–ESI-MS–MS

DOE PAGES

Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R.; ...

2015-06-18

Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections using a fully automated droplet-based liquid microjunction surface sampling-HPLC-ESI-MS/MS system for spatially resolved sampling, HPLC separation, and mass spectral detection. Excellent correlation was found between the protein distribution data obtained with this droplet-based liquid microjunction surface sampling-HPLC-ESI-MS/MS system and those data obtained with matrix assisted laser desorption ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland.more » AVP was most abundant in the posterior pituitary gland region (neurohypophysis) and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH secreting adenomas and in normal anterior adenohypophysis compared to non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis as anticipated. This work demonstrates that a fully automated droplet-based liquid microjunction surface sampling system coupled to HPLC-ESI-MS/MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, such as AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity and specificity of the current methodology support the potential of this basic technology with further advancement for assisting surgical decision-making.« less

Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC–ESI-MS–MS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R.

Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections using a fully automated droplet-based liquid microjunction surface sampling-HPLC-ESI-MS/MS system for spatially resolved sampling, HPLC separation, and mass spectral detection. Excellent correlation was found between the protein distribution data obtained with this droplet-based liquid microjunction surface sampling-HPLC-ESI-MS/MS system and those data obtained with matrix assisted laser desorption ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland.more » AVP was most abundant in the posterior pituitary gland region (neurohypophysis) and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH secreting adenomas and in normal anterior adenohypophysis compared to non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis as anticipated. This work demonstrates that a fully automated droplet-based liquid microjunction surface sampling system coupled to HPLC-ESI-MS/MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, such as AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity and specificity of the current methodology support the potential of this basic technology with further advancement for assisting surgical decision-making.« less

Different degrees of somatotroph ablation compromise pituitary growth hormone cell network structure and other pituitary endocrine cell types.

PubMed

Waite, Eleanor; Lafont, Chrystel; Carmignac, Danielle; Chauvet, Norbert; Coutry, Nathalie; Christian, Helen; Robinson, Iain; Mollard, Patrice; Le Tissier, Paul

2010-01-01

We have generated transgenic mice with somatotroph-specific expression of a modified influenza virus ion channel, (H37A)M2, leading to ablation of GH cells with three levels of severity, dependent on transgene copy number. GH-M2(low) mice grow normally and have normal-size pituitaries but 40-50% reduction in pituitary GH content in adult animals. GH-M2(med) mice have male-specific transient growth retardation and a reduction in pituitary GH content by 75% at 42 d and 97% by 100 d. GH-M2(high) mice are severely dwarfed with undetectable pituitary GH. The GH secretory response of GH-M2(low) and GH-M2(med) mice to GH-releasing peptide-6 and GHRH was markedly attenuated. The content of other pituitary hormones was affected depending on transgene copy number: no effect in GH-M2(low) mice, prolactin and TSH reduced in GH-M2(med) mice, and all hormones reduced in GH-M2(high) mice. The effect on non-GH hormone content was associated with increased macrophage invasion of the pituitary. Somatotroph ablation affected GH cell network organization with limited disruption in GH-M2(low) mice but more severe disruption in GH-M2(med) mice. The remaining somatotrophs formed tight clusters after puberty, which contrasts with GHRH-M2 mice with a secondary reduction in somatotrophs that do not form clusters. A reduction in pituitary beta-catenin staining was correlated with GH-M2 transgene copy number, suggesting M2 expression has an effect on cell-cell communication in somatotrophs and other pituitary cell types. GH-M2 transgenic mice demonstrate that differing degrees of somatotroph ablation lead to correlated secondary effects on cell populations and cellular network organization.

Chronic suppression of testicular function by constant infusion of gonadotropin-releasing hormone agonist and testosterone supplementation in the bonnet monkey (Macaca radiata).

PubMed

Ravindranath, N; Ramesh, V; Krishnamurthy, H N; Rao, A J; Moudgal, R N

1992-03-01

To study the efficacy of long-term buserelin acetate infusion to desensitize pituitary and block testicular function in adult male monkeys (Macaca radiata). Proven fertile male monkeys exhibiting normal testicular function. Each of the control (n = 5) and experimental monkeys (n = 10) received a fresh miniosmotic pump every 21 days, whereas pumps in controls delivered vehicle of experimentals released 50 micrograms buserelin acetate every 24 hours. On day 170 (renewed every 60 days) a silastic capsule containing crystalline testosterone (T) was implanted in the experimental monkeys. At the end of 3 years, treatment was stopped, and recovery of testicular function and fertility monitored. (1) Treatment resulted in marked reduction of nocturnal but not basal serum T; (2) the pituitary remained desensitized to buserelin acetate throughout the 3-year period; (3) animals were largely azoospermic with occasional oligospermia exhibited by two monkeys; and (4) withdrawal of treatment restored testicular function, with 70% of animals regaining fertility. Long-term infertility (but restorable) can be induced in male monkeys by constant infusion of buserelin acetate and T.

Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder

PubMed Central

Bonert, Vivien; Moser, Franklin; Mirocha, James; Melmed, Shlomo

2017-01-01

Objectives: Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Design: Prospective controlled study in an outpatient clinic. Methods: Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Results: Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm3 [standard deviation (SD), 227.3 mm3] in PTSD subjects vs 835.2 mm3 (SD, 302.8 mm3) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects (P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. Conclusions: The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches. PMID:29264511

Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas.

PubMed

Ntali, Georgia; Wass, John A

2018-04-01

Non-functioning pituitary adenomas (NFPAs) are benign pituitary neoplasms that do not cause a hormonal hypersecretory syndrome. An improved understanding of their epidemiology, clinical presentation and diagnosis is needed. A literature review was performed using Pubmed to identify research reports and clinical case series on NFPAs. They account for 14-54% of pituitary adenomas and have a prevalence of 7-41.3/100,000 population. Their standardized incidence rate is 0.65-2.34/100,000 and the peak occurence is from the fourth to the eighth decade. The clinical spectrum of NFPAs varies from being completely asymptomatic to causing significant hypothalamic/pituitary dysfunction and visual field compromise due to their large size. Most patients present with symptoms of mass effect, such as headaches, visual field defects, ophthalmoplegias, and hypopituitarism but also hyperprolactinaemia due to pituitary stalk deviation and less frequently pituitary apoplexy. Non-functioning pituitary incidentalomas are found on brain imaging performed for an unrelated reason. Diagnostic approach includes magnetic resonance imaging of the sellar region, laboratory evaluations, screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm. This article reviews the epidemiology, clinical behaviour and diagnostic approach of non-functioning pituitary adenomas.

Diabetes insipidus secondary to sarcoidosis presenting with caseating granuloma

PubMed Central

Alam, Taimour; Thomas, Steven

2011-01-01

Diabetes insipidus is a rare complication of sarcoid infiltration of the hypothalamic-pituitary region. Non-caseating granuloma formation is typical of sarcoidosis. Anterior and posterior pituitary function may be affected. MRI coupled with endocrinology assessment is the usual method of investigation. A 25-year-old Caucasian male with no significant medical history presented with polyuria and polydipsia. Water deprivation test confirmed diabetes insipidus. CT scanning of the chest confirmed lymphadenopathy. Lymph node biopsy revealed caseating granuloma. Extensive investigation for tuberculosis was negative. The patient was started on intranasal desmopressin and steroids with marked improvement in symptoms. This is the first reported case of neurosarcoidosis with diabetes insipidus and caseation on histology that we are aware of. Differentiating between caseation due to sarcoidosis and tuberculosis on histology is possible by the use of special stains. Return of normal endocrine function is unusual and the patient is likely to require desmopressin therapy for life. PMID:22707619

Long-term negative impact on quality of life in patients with successfully treated Cushing's disease.

PubMed

Heald, Adrian H; Ghosh, Sandip; Bray, Stephanie; Gibson, Christine; Anderson, Simon G; Buckler, Helen; Fowler, Helen L

2004-10-01

A cohort of pituitary tumour patients, who had undergone definitive treatment within a 15-year period at a single neuroscience centre, were investigated as to whether there were differences in psychological well-being and psychosocial functioning, dependent on endocrine pathology and treatment variables. A detailed assessment of 114 patients with benign pituitary tumours in relation to primary diagnosis and mode of treatment was carried out. Psychological rating scales used were: the Hospital Anxiety and Depression Scale--UK version (HADS-UK), the World Health Organization Quality of Life Scale--abbreviated version (WHOQOL-BREF), General Health Questionnaire 28 (GHQ-28), the Functional Assessment of Cancer Therapy (FACT) and the Social Adjustment Scale--modified (SAS1 and SAS2; the former completed by the patient and the latter by another person who knows the patient well). All Cushing's patients were biochemically cured as defined by a normal 24-h urine free cortisol excretion within the previous 6 months. Patients with treated Cushing's disease had significantly impaired psychological well-being and psychosocial functioning across all tested domains compared with all other pituitary tumours, where scores were similar. When participants with Cushing's disease were excluded, patients who had undergone transfrontal surgery scored significantly higher on GHQ and HADS ratings than transsphenoidally treated patients. Cushing's disease even when biochemically stable has long-term adverse effects on mood and social functioning. We hypothesize that this may be related to irreversible changes in central neural function. Further studies are necessary to define the precise pathways involved.

Developmental disorders of the hypothalamus and pituitary gland associated with congenital hypopituitarism.

PubMed

Mehta, Ameeta; Dattani, Mehul T

2008-02-01

The pituitary gland is a complex organ secreting six hormones from five different cell types. It is the end product of a carefully orchestrated pattern of expression of signalling molecules and transcription factors. Naturally occurring and transgenic murine models have demonstrated a role for many of these molecules in the aetiology of congenital hypopituitarism. These include the transcription factors HESX1, PROP1, POU1F1, LHX3, LHX4, PITX1, PITX2, SOX2 and SOX3. The expression pattern of these transcription factors dictates the phenotype that results when the gene encoding the relevant transcription factor is mutated. The highly variable phenotype may consist of isolated hypopituitarism or more complex disorders such as septo-optic dysplasia and holoprosencephaly. However, the overall incidence of mutations in known transcription factors in patients with hypopituitarism is low, indicating that many genes remain to be identified; characterization of these will further elucidate the pathogenesis of this complex condition and also shed light on normal pituitary development and function.

Endoscopic endonasal surgery for giant pituitary adenomas: advantages and limitations.

PubMed

Koutourousiou, Maria; Gardner, Paul A; Fernandez-Miranda, Juan C; Paluzzi, Alessandro; Wang, Eric W; Snyderman, Carl H

2013-03-01

Giant pituitary adenomas (> 4 cm in maximum diameter) represent a significant surgical challenge. Endoscopic endonasal surgery (EES) has recently been introduced as a treatment option for these tumors. The authors present the results of EES for giant adenomas and analyze the advantages and limitations of this technique. The authors retrospectively reviewed the medical files and imaging studies of 54 patients with giant pituitary adenomas who underwent EES and studied the factors affecting surgical outcome. Preoperative visual impairment was present in 45 patients (83%) and partial or complete pituitary deficiency in 28 cases (52%), and 7 patients (13%) presented with apoplexy. Near-total resection (> 90%) was achieved in 36 patients (66.7%). Vision was improved or normalized in 36 cases (80%) and worsened in 2 cases due to apoplexy of residual tumor. Significant factors that limited the degree of resection were a multilobular configuration of the adenoma (p = 0.002) and extension to the middle fossa (p = 0.045). Cavernous sinus invasion, tumor size, and intraventricular or posterior fossa extension did not influence the surgical outcome. Complications included apoplexy of residual adenoma (3.7%), permanent diabetes insipidus (9.6%), new pituitary insufficiency (16.7%), and CSF leak (16.7%, which was reduced to 7.4% in recent years). Fourteen patients underwent radiation therapy after EES for residual mass or, in a later stage, for recurrence, and 10 with functional pituitary adenomas received medical treatment. During a mean follow-up of 37.9 months (range 1-114 months), 7 patients were reoperated on for tumor recurrence. Three patients were lost to follow-up. Endoscopic endonasal surgery provides effective initial management of giant pituitary adenomas with favorable results compared with traditional microscopic transsphenoidal and transcranial approaches.

Imaging of pediatric pituitary endocrinopathies

PubMed Central

Chaudhary, Vikas; Bano, Shahina

2012-01-01

Accurate investigation of the hypothalamic-pituitary area is required in pediatric patients for diagnosis of endocrine-related disorders. These disorders include hypopituitarism, growth failure, diencephalic syndrome, delayed puberty, precocious puberty, diabetes insipidus, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and hyperpituitarism. Magnetic resonance imaging (MRI) is the modality of choice to visualize hypothalamic-pituitary axis and associated endocrinopathies. Neuroimaging can be normal or disclose abnormalities related to pituitary-hypothalamic axis like (i) congenital and developmental malformations; (ii) tumors; (iii) cystic lesions; and (iv) infectious and inflammatory conditions. Classical midline anomalies like septo-optic dysplasias or corpus callosum agenesis are commonly associated with pituitary endocrinopathies and also need careful evaluation. In this radiological review, we will discuss neuroendocrine disorders related to hypothalamic pituitary-axis. PMID:23087850

Loss of Gq/11 Family G Proteins in the Nervous System Causes Pituitary Somatotroph Hypoplasia and Dwarfism in Mice

PubMed Central

Wettschureck, N.; Moers, A.; Wallenwein, B.; Parlow, A. F.; Maser-Gluth, C.; Offermanns, S.

2005-01-01

Heterotrimeric G proteins of the Gq/11 family transduce signals from a variety of neurotransmitter and hormone receptors and have therefore been implicated in various functions of the nervous system. Using the Cre/loxP system, we generated mice which lack the genes coding for the α subunits of the two main members of the Gq/11 family, gnaq and gna11, selectively in neuronal and glial precursor cells. Mice with defective gnaq and gna11 genes were morphologically normal, but they died shortly after birth. Mice carrying a single gna11 allele survived the early postnatal period but died within 3 to 6 weeks as anorectic dwarfs. In these mice, postnatal proliferation of pituitary somatotroph cells was strongly impaired, and plasma growth hormone (GH) levels were reduced to 15%. Hypothalamic levels of GH-releasing hormone (GHRH), an important stimulator of somatotroph proliferation, were strongly decreased, and exogenous administration of GHRH restored normal proliferation. The hypothalamic effects of ghrelin, a regulator of GHRH production and food intake, were reduced in these mice, suggesting that an impairment of ghrelin receptor signaling might contribute to GHRH deficiency and abnormal eating behavior. Taken together, our findings show that Gq/11 signaling is required for normal hypothalamic function and that impairment of this signaling pathway causes somatotroph hypoplasia, dwarfism, and anorexia. PMID:15713647

[A case of GH and TSH secreting pituitary macroadenoma].

PubMed

Gołkowski, Filip; Buziak-Bereza, Monika; Stefańska, Agnieszka; Trofimiuk, Małgorzata; Pantofliński, Jacek; Huszno, Bohdan; Czepko, Ryszard; Adamek, Dariusz

2006-01-01

A case of GH and TSH secreting pituitary macroadenoma is reported. A 45-year-old female presented clinical features of acromegaly (the abnormal growth of the hands and feet, with lower jaw protrusion), diabetes mellitus, hypertension, nodular goiter and hyperthyroidism of unclear origin. NMR pituitary imaging revealed intra and extrasellar tumor. The laboratory examinations showed very high plasma levels of GH and IGF-1 and normal level of TSH coexisting with high plasma levels of free thyroid hormones. Pharmacological pretreatment with somatostatin analogues caused the substantial reduction of GH and TSH plasma levels. Histological and immunohistochemical examination of the tissue obtained at transsphenoidal surgery showed GH and TSH secreting adenoma. The laboratory examinations after surgery showed normal GH and IGF-1 plasma levels and reduced insulin requirement, what indicates radical operation. The very low plasma levels of TSH and free thyroid hormones after surgery and immunohistochemical examination suggest central hyperthyroidism due to TSH secreting pituitary tumor (thyrotropinoma).

Reliability of magnetic resonance imaging for the detection of hypopituitarism in children with optic nerve hypoplasia.

PubMed

Ramakrishnaiah, Raghu H; Shelton, Julie B; Glasier, Charles M; Phillips, Paul H

2014-01-01

It is essential to identify hypopituitarism in children with optic nerve hypoplasia (ONH) because they are at risk for developmental delay, seizures, or death. The purpose of this study is to determine the reliability of neurohypophyseal abnormalities on magnetic resonance imaging (MRI) for the detection of hypopituitarism in children with ONH. Cross-sectional study. One hundred one children with clinical ONH who underwent MRI of the brain and orbits and a detailed pediatric endocrinologic evaluation. Magnetic resonance imaging studies were performed on 1.5-Tesla scanners. The imaging protocol included sagittal T1-weighted images, axial fast fluid-attenuated inversion-recovery/T2-weighted images, and diffusion-weighted images of the brain. Orbital imaging included fat-saturated axial and coronal images and high-resolution axial T2-weighted images. The MRI studies were reviewed by 2 pediatric neuroradiologists for optic nerve hypoplasia, absent or ectopic posterior pituitary, absent pituitary infundibulum, absent septum pellucidum, migration anomalies, and hemispheric injury. Medical records were reviewed for clinical examination findings and endocrinologic status. All patients underwent a clinical evaluation by a pediatric endocrinologist and a standardized panel of serologic testing that included serum insulin-like growth factor-1, insulin-like growth factor binding protein-3, prolactin, cortisol, adrenocorticotropic hormone, thyroid-stimulating hormone, and free thyroxine levels. Radiologists were masked to patients' endocrinologic status and funduscopic findings. Sensitivity and specificity of MRI findings for the detection of hypopituitarism. Neurohypophyseal abnormalities, including absent pituitary infundibulum, ectopic posterior pituitary bright spot, and absent posterior pituitary bright spot, occurred in 33 children. Magnetic resonance imaging disclosed neurohypophyseal abnormalities in 27 of the 28 children with hypopituitarism (sensitivity, 96%). A normal neurohypophysis occurred in 67 of 73 children with normal endocrinologic function (specificity, 92%). Neurohypophyseal abnormalities on MRI are sensitive and specific indicators of hypopituitarism in children with ONH. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Effects of neonatal hypo- and hyperthyroidism on pituitary growth hormone content in the rat.

PubMed

Coulombe, P; Ruel, J; Dussault, J H

1980-12-01

Thyroid hormones play an important role in growth and development. Therefore, we investigated the effects of neonatal hypo- and hyperthyroidism on pituitary GH content in the rat. In control rats, pituitary GH content increased from 4.16 +/- 0.34 at 2 days to 43.7 +/- 4.2 microgram/gland (mean +/- SE) at 15 days of age, with a t 1/2 of increment of 3.48 +/- 0.40 days. Between 18-60 days of age, pituitary GH content increased from 56.9 +/- 4.0 to 300 +/- 28 microgram/gland, with a t 1/2 of 18.2 +/- 1.5 days. The administration of T3 had no significant effect on the pituitary GH content of these animals. In neonatal hypothyroid rats, pituitary GH content was significantly lower than that of controls at 2 days of age (P < 0.01) and decreased from 8 days on, with a t 1/2 of 3.71 +/- 0.25 days. However, 24 h after the administration of T3 (100 microgram/100 g BW), pituitary GH content was significantly increased in these animals. Similarly, the administration of T3 (0.4 microgram/100 g BW) to 14-day-old hypothyroid rats restored the pituitary GH content to 70-80% of normal after 5 days of therapy. Conversely, hyperthyroidism induced in 14-day-old normal or hypothyroid rats resulted in a significant decrease in their pituitary GH contents after 5 days of treatment. Therefore, the present results indicate that during the neonatal period, thyroid hormones play a primary role in the control of GH accumulation in the pituitary. Furthermore, the lack of increase in pituitary GH content after the administration of T3 during development might suggest that the rate of formation of GH is already maximum during this period of life in the rat, or, alternatively, that the pituitary nuclear T3 receptors are near full saturation during development. Finally, a generally similar effect of T3 on pituitary GH response was observed in the neonatal rat as well as in the adult animal.

Pituitary apoplexy: pathophysiology, diagnosis and management.

PubMed

Glezer, Andrea; Bronstein, Marcello D

2015-06-01

Pituitary apoplexy is characterized by sudden increase in pituitary gland volume secondary to ischemia and/or necrosis, usually in a pituitary adenoma. Most cases occur during the 5th decade of life, predominantly in males and in previously unknown clinically non-functioning pituitary adenomas. There are some predisposing factors as arterial hypertension, anticoagulant therapy and major surgery. Clinical picture comprises headache, visual impairment, cranial nerve palsies and hypopituitarism. Most cases improve with both surgical and expectant management and the best approach in the acute phase is still controversial. Surgery, usually by transsphenoidal route, is indicated if consciousness and/or vision are impaired, despite glucocorticoid replacement and electrolyte support. Pituitary function is impaired in most patients before apoplexy and ACTH deficiency is common, which makes glucocorticoid replacement needed in most cases. Pituitary deficiencies, once established, usually do not recover, regardless the treatment. Sellar imaging and endocrinological function must be periodic reevaluated.

G protein-coupled estrogen receptor regulates embryonic heart rate in zebrafish

PubMed Central

Romano, Shannon N.; Edwards, Hailey E.; Ryan, Kevin J.

2017-01-01

Estrogens act by binding to estrogen receptors alpha and beta (ERα, ERβ), ligand-dependent transcription factors that play crucial roles in sex differentiation, tumor growth and cardiovascular physiology. Estrogens also activate the G protein-coupled estrogen receptor (GPER), however the function of GPER in vivo is less well understood. Here we find that GPER is required for normal heart rate in zebrafish embryos. Acute exposure to estrogens increased heart rate in wildtype and in ERα and ERβ mutant embryos but not in GPER mutants. GPER mutant embryos exhibited reduced basal heart rate, while heart rate was normal in ERα and ERβ mutants. We detected gper transcript in discrete regions of the brain and pituitary but not in the heart, suggesting that GPER acts centrally to regulate heart rate. In the pituitary, we observed gper expression in cells that regulate levels of thyroid hormone triiodothyronine (T3), a hormone known to increase heart rate. Compared to wild type, GPER mutants had reduced levels of T3 and estrogens, suggesting pituitary abnormalities. Exposure to exogenous T3, but not estradiol, rescued the reduced heart rate phenotype in gper mutant embryos, demonstrating that T3 acts downstream of GPER to regulate heart rate. Using genetic and mass spectrometry approaches, we find that GPER regulates maternal estrogen levels, which are required for normal embryonic heart rate. Our results demonstrate that estradiol plays a previously unappreciated role in the acute modulation of heart rate during zebrafish embryonic development and suggest that GPER regulates embryonic heart rate by altering maternal estrogen levels and embryonic T3 levels. PMID:29065151

G protein-coupled estrogen receptor regulates embryonic heart rate in zebrafish.

PubMed

Romano, Shannon N; Edwards, Hailey E; Souder, Jaclyn Paige; Ryan, Kevin J; Cui, Xiangqin; Gorelick, Daniel A

2017-10-01

Estrogens act by binding to estrogen receptors alpha and beta (ERα, ERβ), ligand-dependent transcription factors that play crucial roles in sex differentiation, tumor growth and cardiovascular physiology. Estrogens also activate the G protein-coupled estrogen receptor (GPER), however the function of GPER in vivo is less well understood. Here we find that GPER is required for normal heart rate in zebrafish embryos. Acute exposure to estrogens increased heart rate in wildtype and in ERα and ERβ mutant embryos but not in GPER mutants. GPER mutant embryos exhibited reduced basal heart rate, while heart rate was normal in ERα and ERβ mutants. We detected gper transcript in discrete regions of the brain and pituitary but not in the heart, suggesting that GPER acts centrally to regulate heart rate. In the pituitary, we observed gper expression in cells that regulate levels of thyroid hormone triiodothyronine (T3), a hormone known to increase heart rate. Compared to wild type, GPER mutants had reduced levels of T3 and estrogens, suggesting pituitary abnormalities. Exposure to exogenous T3, but not estradiol, rescued the reduced heart rate phenotype in gper mutant embryos, demonstrating that T3 acts downstream of GPER to regulate heart rate. Using genetic and mass spectrometry approaches, we find that GPER regulates maternal estrogen levels, which are required for normal embryonic heart rate. Our results demonstrate that estradiol plays a previously unappreciated role in the acute modulation of heart rate during zebrafish embryonic development and suggest that GPER regulates embryonic heart rate by altering maternal estrogen levels and embryonic T3 levels.

Pituitary function within the first year after traumatic brain injury or subarachnoid haemorrhage.

PubMed

Tölli, A; Borg, J; Bellander, B-M; Johansson, F; Höybye, C

2017-02-01

Reports on long-term variations in pituitary function after traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH) diverge. The aim of the current study was to evaluate the prevalence and changes in pituitary function during the first year after moderate and severe TBI and SAH and to explore the relation between pituitary function and injury variables. Adults with moderate and severe TBI or SAH were evaluated at 10 days, 3, 6 and 12 months post-injury/illness. Demographic, clinical, radiological, laboratory, including hormonal data were collected. A total of 91 adults, 56 (15 women/41 men) with TBI and 35 (27 women/8 men) with SAH were included. Perturbations in pituitary function were frequent early after the event but declined during the first year of follow-up. The most frequent deficiency was hypogonadotrope hypogonadism which was seen in approximately 25 % of the patients. Most of the variations were transient and without clinical significance. At 12 months, two patients were on replacement with hydrocortisone, four men on testosterone and one man on replacement with growth hormone. No relations were seen between hormonal levels and injury variables. Perturbations in pituitary function continue to occur during the first year after TBI and SAH, but only a few patients need replacement therapy. Our study could not identify a marker of increased risk of pituitary dysfunction that could guide routine screening. However, data demonstrate the need for systematic follow-up of pituitary function after moderate or severe TBI or SAH.

Reversal of Physiological Deficits Caused by Diminished Levels of Peptidylglycine α-Amidating Monooxygenase by Dietary Copper

PubMed Central

Bousquet-Moore, D.; Ma, X. M.; Nillni, E. A.; Czyzyk, T. A.; Pintar, J. E.; Eipper, B. A.; Mains, R. E.

2009-01-01

Amidated peptides are critically involved in many physiological functions. Genetic deletion of peptidylglycine α-amidating monooxygenase (PAM), the only enzyme that can synthesize these peptides, is embryonically lethal. The goal of the present study was the identification of physiological functions impaired by haploinsufficiency of PAM. Regulation of the hypothalamic-pituitary-thyroid axis and body temperature, functions requiring contributions from multiple amidated peptides, were selected for evaluation. Based on serum T4 and pituitary TSH-β mRNA levels, mice heterozygous for PAM (PAM+/−) were euthyroid at baseline. Feedback within the hypothalamic-pituitary-thyroid axis was impaired in PAM+/− mice made hypothyroid using a low iodine/propylthiouracil diet. Despite their normal endocrine response to cold, PAM+/− mice were unable to maintain body temperature as well as wild-type littermates when kept in a 4 C environment. When provided with additional dietary copper, PAM+/− mice maintained body temperature as well as wild-type mice. Pharmacological activation of vasoconstriction or shivering also allowed PAM+/− mice to maintain body temperature. Cold-induced vasoconstriction was deficient in PAM+/− mice. This deficit was eliminated in PAM+/− mice receiving a diet with supplemental copper. These results suggest that dietary deficiency of copper, coupled with genetic deficits in PAM, could result in physiological deficits in humans. PMID:19022883

A case of functional growth hormone deficiency and early growth retardation in a child with IFT172 mutations.

PubMed

Lucas-Herald, Angela K; Kinning, Esther; Iida, Aritoshi; Wang, Zheng; Miyake, Noriko; Ikegawa, Shiro; McNeilly, Jane; Ahmed, S Faisal

2015-04-01

Ciliopathies are a group of rare conditions that present through a wide range of manifestations. Given the relative common occurrence of defects of the GH/IGF-I axis in children with short stature and growth retardation, the association between ciliopathies and these defects needs further attention. Our patient is a boy who was born at term and noted to have early growth retardation and weight gain within the first 18 months of life. Biochemical tests demonstrated low IGF-I but a normal peak GH on stimulation and an adequate increase in IGF-I on administration of recombinant human growth hormone (rhGH). A magnetic resonance imaging scan revealed pituitary hypoplasia and an ectopic posterior pituitary. His growth responded well to rhGH therapy. Subsequently he also developed a retinopathy of his rods and cones, metaphyseal dysplasia, and hypertension with renal failure requiring renal replacement therapy. Whole-exome sequencing demonstrated compound heterozygous mutations of IFT172, thus consistent with a ciliopathy. This is the first reported case of a child with a mutation in IFT172 who presented with growth retardation in early childhood and was initially managed as a case of functional GH deficiency that responded to rhGH therapy. This case highlights the importance of ciliary function in pituitary development and the link between early onset growth failure and ciliopathies.

A patient with thyrotropinoma cosecreting growth hormone and follicle-stimulating hormone with low alpha-glycoprotein: a new subentity?

PubMed

Elhadd, Tarik A; Ghosh, Sujoy; Teoh, Wei Leng; Trevethick, Katy Ann; Hanzely, Zoltan; Dunn, Laurence T; Malik, Iqbal A; Collier, Andrew

2009-08-01

Thyrotropinomas are rare pituitary tumors. In 25 percent of cases there is autonomous secretion of a second pituitary hormone, adding to the clinical complexity. We report a patient with thyrotropin (TSH)-dependant hyperthyroidism along with growth hormone (GH) and follicle-stimulating hormone (FSH) hypersecretion but low alpha-glycoprotein (alpha-subunit) concentrations, a hitherto unique constellation of findings. A 67-year-old Scottish lady presented with longstanding ankle edema, paroxysmal atrial fibrillation, uncontrolled hypertension, fine tremors, warm peripheries, and agitation. Initial findings were a small goiter, elevated serum TSH of 7.37 mU/L (normal range, 0.30-6.0 mU/L), a free-thyroxine concentration of 34.9 pmol/L (normal range, 9.0-24.0 pmol/L), a flat TSH response to TSH-releasing hormone, and serum alpha-subunit of 3.1 IU/L (normal, <3.0 IU/L). There was no evidence of an abnormal thyroid hormone beta receptor by genotyping. Serum FSH was 56.8 U/L, but the luteinizing hormone (LH) was 23.6 U/L (postmenopausal FSH and LH reference ranges both >30 U/L) Basal insulin-like growth factor I was elevated to 487 microg/L with the concomitant serum GH being 14.1 mU/L, and subsequent serum GH values 30 minutes after 75 g oral glucose being 19.1 mU/L and 150 minutes later being 13.7 mU/L. An magnetic resonance imaging pituitary revealed a macroadenoma. Pituitary adenomectomy was performed with the histology confirming a pituitary adenoma, and the immunohistochemistry staining showed positive reactivity for FSH with scattered cells staining for GH and TSH. Staining for other anterior pituitary hormones was negative. After pituitary surgery she became clinically and biochemically euthyroid, the serum IFG-1 became normal, but the pattern of serum FSH and LH did not change. This case of plurihormonal thyrotropinoma is unique in having hypersecretion of TSH, GH, and FSH with low alpha-subunit. Such a combination may represent a new subentity of TSHomas.

Pituitary cell differentiation from stem cells and other cells: toward restorative therapy for hypopituitarism?

PubMed

Willems, Christophe; Vankelecom, Hugo

2014-01-01

The pituitary gland, key regulator of our endocrine system, produces multiple hormones that steer essential physiological processes. Hence, deficient pituitary function (hypopituitarism) leads to severe disorders. Hypopituitarism can be caused by defective embryonic development, or by damage through tumor growth/resection and traumatic brain injury. Lifelong hormone replacement is needed but associated with significant side effects. It would be more desirable to restore pituitary tissue and function. Recently, we showed that the adult (mouse) pituitary holds regenerative capacity in which local stem cells are involved. Repair of deficient pituitary may therefore be achieved by activating these resident stem cells. Alternatively, pituitary dysfunction may be mended by cell (replacement) therapy. The hormonal cells to be transplanted could be obtained by (trans-)differentiating various kinds of stem cells or other cells. Here, we summarize the studies on pituitary cell regeneration and on (trans-)differentiation toward hormonal cells, and speculate on restorative therapies for pituitary deficiency.

Isoliquiritigenin exhibits anti-proliferative properties in the pituitary independent of estrogen receptor function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weis, Karen E.; Raetzman, Lori T., E-mail: raetzma

The plant flavonoid isoliquiritigenin (ISL) is a botanical estrogen widely taken as an herbal supplement to ease the symptoms of menopause. ISL has been also shown to have anti-tumor properties in a number of cancer cell backgrounds. However, the effects of ISL on normal cells are less well known and virtually unstudied in the context of the pituitary gland. We have established a pituitary explant culture model to screen chemical agents for gene expression changes within the pituitary gland during a period of active proliferation and differentiation. Using this whole-organ culture system we found ISL to be weakly estrogenic basedmore » on its ability to induce Cckar mRNA expression, an estrogen receptor (ER) mediated gene. Using a range of ISL from 200 nM to 200 μM, we discovered that ISL promoted cell proliferation at a low concentration, yet potently inhibited proliferation at the highest concentration. ICI 182,780 failed to antagonize ISL's repression of pituitary cell proliferation, indicating the effect is independent of ER signaling. Coincident with a decrease in proliferating cells, we observed down-regulation of transcript for cyclin D2 and E2 and a strong induction of mRNA and protein for the cyclin dependent kinase inhibitor Cdkn1a (p21). Importantly, high dose ISL did not alter the balance of progenitor vs. differentiated cell types within the pituitary explants and they seemed otherwise healthy; however, TUNEL staining revealed an increase in apoptotic cell death in ISL treated cultures. Our results merit further examination of ISL as an anti-tumor agent in the pituitary gland. - Highlights: • Isoliquiritigenin possesses weak estrogenic activity based on induction of Cckar. • ISL can be anti-proliferative in pituitary explants without altering cell lineages. • Anti-proliferative behavior of ISL is not estrogen receptor mediated. • ISL induces p21 expression leading to cell cycle arrest and apoptosis.« less

Pituitary Tumors in Childhood: an update in their diagnosis, treatment and molecular genetics

PubMed Central

Keil, Margaret F.; Stratakis, Constantine A.

2009-01-01

Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to 1 per million children. Only 2 - 6% of surgically treated pituitary tumors occur in children. Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity. Tumors within the pituitary fossa are of two types mainly, craniopharyngiomas and adenomas; craniopharyngiomas cause symptoms by compressing normal pituitary, causing hormonal deficiencies and producing mass effects on surrounding tissues and the brain; adenomas produce a variety of hormonal conditions such as hyperprolactinemia, Cushing disease and acromegaly or gigantism. Little is known about the genetic causes of sporadic lesions, which comprise the majority of pituitary tumors, but in children, more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as multiple endocrine neoplasia type 1 (MEN 1), Carney complex, familial isolated pituitary adenoma (FIPA), and McCune-Albright syndrome. The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments. PMID:18416659

3D volumetry comparison using 3T magnetic resonance imaging between normal and adenoma-containing pituitary glands.

PubMed

Roldan-Valadez, Ernesto; Garcia-Ulloa, Ana Cristina; Gonzalez-Gutierrez, Omar; Martinez-Lopez, Manuel

2011-01-01

Computed-assisted three-dimensional data (3D) allows for an accurate evaluation of volumes compared with traditional measurements. An in vitro method comparison between geometric volume and 3D volumetry to obtain reference data for pituitary volumes in normal pituitary glands (PGs) and PGs containing adenomas. Prospective, transverse, analytical study. Forty-eight subjects underwent brain magnetic resonance imaging (MRI) with 3D sequencing for computer-aided volumetry. PG phantom volumes by both methods were compared. Using the best volumetric method, volumes of normal PGs and PGs with adenoma were compared. Statistical analysis used the Bland-Altman method, t-statistics, effect size and linear regression analysis. Method comparison between 3D volumetry and geometric volume revealed a lower bias and precision for 3D volumetry. A total of 27 patients exhibited normal PGs (mean age, 42.07 ± 16.17 years), although length, height, width, geometric volume and 3D volumetry were greater in women than in men. A total of 21 patients exhibited adenomas (mean age 39.62 ± 10.79 years), and length, height, width, geometric volume and 3D volumetry were greater in men than in women, with significant volumetric differences. Age did not influence pituitary volumes on linear regression analysis. Results from the present study showed that 3D volumetry was more accurate than the geometric method. In addition, the upper normal limits of PGs overlapped with lower volume limits during early stage microadenomas.

Comparison of two immunoradiometric assays for serum thyrotropin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scheinin, B.; Drew, H.; La France, N.

1985-05-01

An ultra-sensitive TSH assay capable of detecting subnormal TSH levels would be useful in confirming suppressed pituitary function as seen in hyperthyroidism. Two sensitive immunoradiometric TSH assays (IRMA's) were studied to determine how well they distinguished thyrotoxic patients from normal subjects. Serono Diagnostics' method employs three monoclonal antibodies specific for different regions of the TSH molecule with a minimum detectable dose (MDD) limit of 0.1 ..mu..IU/ml. Precision studies using a low TSH control in the 1.8 ..mu..IU/ml range gave CV's of 15.0%. Boots-Celltech Diagnostics method is a two site IRMA using two monoclonal antibodies. The MDD limit is 0.05 ..mu..IU/mlmore » with precision CV's of 29.3% at a TSH control range of 0.62 ..mu..IU/ml. In 24 chemically thyrotoxic patients, the mean serum TSH concentration was significantly lower than in the normal control subjects: for Serono, 0.19 ..mu..IU/ml vs. 2.34 ..mu..IU/ml and for Boots Celltech, 0.18 IU/ml vs 2.06 ..mu..IU/ml. The range of TSH was 0 to 0.5 ..mu..IU/ml in thyrotoxic patients using Serono with the exception of one patient having a TSH value of 0.8 ..mu..IU/ml. The normal range was 0.6 to 6.0 ..mu..IU/ml. For Boots Celltech the thyrotoxic range was 0 to 0.2 ..mu..IU/ml with that same thyrotoxic patient giving a TSH value of 0.7 ..mu..IU/ml with a normal range of 0.6 to 5.0 IU/ml. Serum TSH measurements using both procedures are highly sensitive for distinguishing thyrotoxic patients from normal subjects and are useful to confirm suppressed pituitary function.« less

Developmental abnormalities of the posterior pituitary gland.

PubMed

di Iorgi, Natascia; Secco, Andrea; Napoli, Flavia; Calandra, Erika; Rossi, Andrea; Maghnie, Mohamad

2009-01-01

While the molecular mechanisms of anterior pituitary development are now better understood than in the past, both in animals and in humans, little is known about the mechanisms regulating posterior pituitary development. The posterior pituitary gland is formed by the evagination of neural tissue from the floor of the third ventricle. It consists of the distal axons of the hypothalamic magnocellular neurones that shape the neurohypophysis. After its downward migration, it is encapsulated together with the ascending ectodermal cells of Rathke's pouch which form the anterior pituitary. By the end of the first trimester, this development is completed and vasopressin and oxytocin can be detected in neurohypophyseal tissue. Abnormal posterior pituitary migration such as the ectopic posterior pituitary lobe appearing at the level of median eminence or along the pituitary stalk have been reported in idiopathic GH deficiency or in subjects with HESX1, LHX4 and SOX3 gene mutations. Another intriguing feature of abnormal posterior pituitary development involves genetic forms of posterior pituitary neurodegeneration that have been reported in autosomal-dominant central diabetes insipidus and Wolfram disease. Defining the phenotype of the posterior pituitary gland can have significant clinical implications for management and counseling, as well as providing considerable insight into normal and abnormal mechanisms of posterior pituitary development in humans.

Neuropsychological and hypothalamic-pituitary-axis function in female patients with melancholic and non-melancholic depression.

PubMed

Michopoulos, Ioannis; Zervas, Iannis M; Pantelis, Chris; Tsaltas, Eleftheria; Papakosta, Vassiliki-Maria; Boufidou, Fotini; Nikolaou, Chrissoula; Papageorgiou, Charalambos; Soldatos, Costas R; Lykouras, Lefteris

2008-06-01

Executive function deficits in depression implicate involvement of frontal-striatal circuits. However, studies of hypothalamic-pituitary-axis (HPA) function suggest that stress-related brain changes of hippocampus may also implicate prefrontal-hippocampal circuits, which may explain the profile of both executive dysfunction and memory deficits. In this study we examined the performance of patients with major depressive disorder (MDD) on tasks of memory and executive function in relation to melancholic features and to cortisol levels. Our hypothesis was that raised cortisol levels in melancholic patients would correlate with these deficits. Forty female MDD patients, 20 having melancholic features (MEL vs. Non-MEL), and 20 sex-age- and education-matched normal controls were investigated using the Cambridge neuropsychological test automated battery (CANTAB), to assess memory (paired associative learning, PAL; short-term recognition memory, SRM) and executive (intradimensional/extradimensional set-shifting, ID/ED; Stockings of Cambridge, SOC) functions. Plasma and salivary cortisol levels were measured. The MDD patients performed worse than controls on PAL and both executive tasks. The MEL group differed from controls on all tests, and differed from the non-MEL only at the ED stage of the ID/ED task. Patient cortisol levels were within the normal range and did not correlate with neuropsychological performance for any group. MDD patients showed neuropsychological deficits on tasks of executive function and memory, supporting the model of frontal-temporal dysfunction. MEL vs. non-MEL performed worse overall and demonstrated a qualitative difference in set shifting, perhaps implicating more extensive prefrontal involvement. Cortisol levels did not correlate with depression severity or the observed deficits.

Pituitary Dysfunction from an Unruptured Ophthalmic Internal Carotid Artery Aneurysm with Improved 2-year Follow-up Results: A Case Report.

PubMed

Qi, Meng; Ye, Ming; Li, Meng; Zhang, Peng

2018-01-01

Internal carotid artery (ICA) supraclinoid segment aneurysms extending into the sellar region and leading to pituitary dysfunction are a rare occurrence. To date, long-term follow up of pituitary function 2 years post-treatment has never been reported. Herein, we present a case of pituitary dysfunction due to an unruptured ophthalmic segment internal carotid artery aneurysm and report improved 2-year follow-up results. A 76-year-old male presented with disturbed consciousness due to hyponatremia, which was caused by hypoadrenocorticism resulting from pituitary dysfunction complicated by hypogonadism and hypothyroidism. Computed tomography angiography revealed an intracranial aneurysm of the ophthalmic segment of the right ICA with an intrasellar extension. Thus, digital subtraction angiography and coil embolization were performed, followed by hormone replacement therapy. A 2-year follow-up revealed a partial improvement in the pituitary function, including complete restoration of thyroid-stimulating hormone level and other thyroid hormones levels, and partial restoration of testosterone levels, followed by discontinuation of thyroid hormone replacement therapy. However, the mechanisms of such pituitary dysfunction and the effects of various treatments, including clipping and coiling, on different hormones of pituitary function recovery remain unclear. A long-term follow-up of >2 years may elucidate the pituitary function recovery post-treatment and provide a medication adjustment for hormone replacement therapy.

High-Resolution DCE-MRI of the Pituitary Gland Using Radial k-Space Acquisition with Compressed Sensing Reconstruction.

PubMed

Rossi Espagnet, M C; Bangiyev, L; Haber, M; Block, K T; Babb, J; Ruggiero, V; Boada, F; Gonen, O; Fatterpekar, G M

2015-08-01

The pituitary gland is located outside of the blood-brain barrier. Dynamic T1 weighted contrast enhanced sequence is considered to be the gold standard to evaluate this region. However, it does not allow assessment of intrinsic permeability properties of the gland. Our aim was to demonstrate the utility of radial volumetric interpolated brain examination with the golden-angle radial sparse parallel technique to evaluate permeability characteristics of the individual components (anterior and posterior gland and the median eminence) of the pituitary gland and areas of differential enhancement and to optimize the study acquisition time. A retrospective study was performed in 52 patients (group 1, 25 patients with normal pituitary glands; and group 2, 27 patients with a known diagnosis of microadenoma). Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were evaluated with an ROI-based method to obtain signal-time curves and permeability measures of individual normal structures within the pituitary gland and areas of differential enhancement. Statistical analyses were performed to assess differences in the permeability parameters of these individual regions and optimize the study acquisition time. Signal-time curves from the posterior pituitary gland and median eminence demonstrated a faster wash-in and time of maximum enhancement with a lower peak of enhancement compared with the anterior pituitary gland (P < .005). Time-optimization analysis demonstrated that 120 seconds is ideal for dynamic pituitary gland evaluation. In the absence of a clinical history, differences in the signal-time curves allow easy distinction between a simple cyst and a microadenoma. This retrospective study confirms the ability of the golden-angle radial sparse parallel technique to evaluate the permeability characteristics of the pituitary gland and establishes 120 seconds as the ideal acquisition time for dynamic pituitary gland imaging. © 2015 by American Journal of Neuroradiology.

High-Resolution DCE-MRI of the Pituitary Gland Using Radial k-Space Acquisition with Compressed Sensing Reconstruction

PubMed Central

Rossi Espagnet, M.C.; Bangiyev, L.; Haber, M.; Block, K.T.; Babb, J.; Ruggiero, V.; Boada, F.; Gonen, O.; Fatterpekar, G.M.

2015-01-01

BACKGROUNDANDPURPOSE The pituitary gland is located outside of the blood-brain barrier. Dynamic T1 weighted contrast enhanced sequence is considered to be the gold standard to evaluate this region. However, it does not allow assessment of intrinsic permeability properties of the gland. Our aim was to demonstrate the utility of radial volumetric interpolated brain examination with the golden-angle radial sparse parallel technique to evaluate permeability characteristics of the individual components (anterior and posterior gland and the median eminence) of the pituitary gland and areas of differential enhancement and to optimize the study acquisition time. MATERIALS AND METHODS A retrospective study was performed in 52 patients (group 1, 25 patients with normal pituitary glands; and group 2, 27 patients with a known diagnosis of microadenoma). Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were evaluated with an ROI-based method to obtain signal-time curves and permeability measures of individual normal structures within the pituitary gland and areas of differential enhancement. Statistical analyses were performed to assess differences in the permeability parameters of these individual regions and optimize the study acquisition time. RESULTS Signal-time curves from the posterior pituitary gland and median eminence demonstrated a faster wash-in and time of maximum enhancement with a lower peak of enhancement compared with the anterior pituitary gland (P < .005). Time-optimization analysis demonstrated that 120 seconds is ideal for dynamic pituitary gland evaluation. In the absence of a clinical history, differences in the signal-time curves allow easy distinction between a simple cyst and a microadenoma. CONCLUSIONS This retrospective study confirms the ability of the golden-angle radial sparse parallel technique to evaluate the permeability characteristics of the pituitary gland and establishes 120 seconds as the ideal acquisition time for dynamic pituitary gland imaging. PMID:25953760

A DWARF MUTATION IN THE RABBIT

PubMed Central

Greene, Harry S. N.

1940-01-01

An hereditary type of dwarfism in the rabbit has been described. In contrast to the dwarfs described in other animals, this type is evident at birth and conforms to the classification, nannosomia primordialis, as used in human pathology. In homozygous form the variation is lethal and produces a miniature individual approximately one-third the size of its normal sibs. Heterozygous animals are approximately two-thirds the size of normal sibs at birth and never attain an equal stature. The expression of the variation is modified by genetic factors carried by a line of cretinoid animals and, rarely, dwarfs derived from crosses with this line survive for 1 to 2 months. The striking changes in such survivors are hypertrophy and hyperplasia of the acidophilic cells of the pituitary and atrophy of the gonads. Such changes are not present in ordinary dwarfs and it is concluded that the acidophilic hyperplasia represents the influence of the modifying factors of the cretinoid line and supplies the growth hormone responsible for survival. The gonadotropic hormone is not supplied by the secretory activity of these cells and as a result the gonads atrophy. The evidence at hand indicates that the primary effect of the dwarfing gene is an inhibition of the secretory functions of the pituitary. In homozygous individuals, the inhibition is complete and the variation is expressed as a lethal dwarf. In heterozygous animals, the function of the organ is altered, producing an undersized individual. The modifying factors of the cretinoid line act either to partially remove the inhibition or to alter the constitution of the animal so that life is possible for a short period without the full complement of pituitary hormones. PMID:19871001

Neonatal hydrocortisone therapy does not have a serious suppressive effect on the later function of the hypothalamus-pituitary-adrenal axis.

PubMed

Takayanagi, Toshimitsu; Matsuo, Koji; Egashira, Tomoko; Mizukami, Tomoko

2015-05-01

This study investigated whether providing extremely low birthweight (ELBW) infants with a large amount of hydrocortisone had a serious suppressive effect on the later function of the hypothalamus-pituitary-adrenal (HPA) axis. We evaluated the function of the HPA axis in 58 ELBW infants receiving 9.0 ± 7.2 mg/kg of intravenous and 68.1 ± 34.1 mg/kg of oral hydrocortisone using a human corticotropin-releasing hormone stimulation test. The mean age at investigation was 12.0 ± 5.2 months. The response was judged to be normal when the maximum to minimum ratio of the plasma adrenocorticotropic hormone (ACTH) concentration was >2, the peak value of the serum cortisol concentration was >552 nmol/L, or the increment was >193 nmol/L than baseline concentration. Of the 58 infants studied, 51 (88%) displayed a normal response to both the ACTH and cortisol secretion and seven infants (12%) who were judged to be poor responders exhibited a peak cortisol value of >386 nmol/L without any episode of adrenal insufficiency. Providing ELBW infants with a daily low dose of long-term hydrocortisone therapy should not lead to a serious suppressive effect on the later function of the HPA axis, regardless of the administration method. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

The association of sphenoidal encephalocele and right anophthalmia with septo-optic dysplasia: a case report.

PubMed

Erol, Fatih Serhat; Ucler, Necati; Kaplan, Metin; Yilmaz, Ilhan

2012-01-01

Septo-optic dysplasia (SOD) is an extremely rare congenital anomaly, characterized with optic nerve hypoplasia and absence of septum pellucidum and/or pituitary dysfunction. In addition to classical findings of SOD, we report for the first time an 11-year-old boy, with encephalocele extending to the right sphenoidal sinus, right anophthalmia and normal pituitary functions. Despite all the major anomalies, the patient's presenting symptoms were very few and during the 11-year period the SDO had caused no complaints in our case. These findings show that the SOD course may be fairly benign. No neurological problem was encountered in the patient's follow-up, except headache. We believe that SOD should be kept in mind because of its rarity and the severity of its combined pathologies.

Sudden headache, third nerve palsy and visual deficit: thinking outside the subarachnoid haemorrhage box.

PubMed

Ní Chróinín, Danielle; Lambert, John

2013-11-01

A 75-year-old lady presented with sudden severe headache and vomiting. Examination was normal, and CT and lumbar puncture not convincing for subarachnoid haemorrhage. Shortly thereafter, she developed painless diplopia. Examination confirmed right third cranial nerve palsy plus homonymous left inferior quadrantanopia. Urgent cerebral MRI with angiography was requested to assess for a possible posterior communicating artery aneurysm, but revealed an unsuspected pituitary mass. Pituitary adenoma with pituitary apoplexy was diagnosed. Pituitary apopolexy is a syndrome comprising sudden headache, meningism, visual and/or oculomotor deficits, with an intrasellar mass. It is commonly due to haemorrhage or infarction within a pituitary adenoma. Treatment includes prompt steroid administration, and potentially surgical decompression. While subarachnoid haemorrhage is an important, well-recognised cause of sudden severe headache, other aetiologies, including pituitary apoplexy, should be considered and sought.

Mutation analysis of inhibitory guanine nucleotide binding protein alpha (GNAI) loci in young and familial pituitary adenomas.

PubMed

Demir, Hande; Donner, Iikki; Kivipelto, Leena; Kuismin, Outi; Schalin-Jäntti, Camilla; De Menis, Ernesto; Karhu, Auli

2014-01-01

Pituitary adenomas are neoplasms of the anterior pituitary lobe and account for 15-20% of all intracranial tumors. Although most pituitary tumors are benign they can cause severe symptoms related to tumor size as well as hypopituitarism and/or hypersecretion of one or more pituitary hormones. Most pituitary adenomas are sporadic, but it has been estimated that 5% of patients have a familial background. Germline mutations of the tumor suppressor gene aryl hydrocarbon receptor-interacting protein (AIP) predispose to hereditary pituitary neoplasia. Recently, it has been demonstrated that AIP mutations predispose to pituitary tumorigenesis through defective inhibitory GTP binding protein (Gαi) signaling. This finding prompted us to examine whether germline loss-of-function mutations in inhibitory guanine nucleotide (GTP) binding protein alpha (GNAI) loci are involved in genetic predisposition of pituitary tumors. To our knowledge, this is the first time GNAI genes are sequenced in order to examine the occurrence of inactivating germline mutations. Thus far, only somatic gain-of-function hot-spot mutations have been studied in these loci. Here, we have analyzed the coding regions of GNAI1, GNAI2, and GNAI3 in a set of young sporadic somatotropinoma patients (n = 32; mean age of diagnosis 32 years) and familial index cases (n = 14), thus in patients with a disease phenotype similar to that observed in AIP mutation carriers. In addition, expression of Gαi proteins was studied in human growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH)-secreting and non-functional pituitary tumors. No pathogenic germline mutations affecting the Gαi proteins were detected. The result suggests that loss-of-function mutations of GNAI loci are rare or nonexistent in familial pituitary adenomas.

Mutation Analysis of Inhibitory Guanine Nucleotide Binding Protein Alpha (GNAI) Loci in Young and Familial Pituitary Adenomas

PubMed Central

Demir, Hande; Donner, Iikki; Kivipelto, Leena; Kuismin, Outi; Schalin-Jäntti, Camilla; De Menis, Ernesto; Karhu, Auli

2014-01-01

Pituitary adenomas are neoplasms of the anterior pituitary lobe and account for 15–20% of all intracranial tumors. Although most pituitary tumors are benign they can cause severe symptoms related to tumor size as well as hypopituitarism and/or hypersecretion of one or more pituitary hormones. Most pituitary adenomas are sporadic, but it has been estimated that 5% of patients have a familial background. Germline mutations of the tumor suppressor gene aryl hydrocarbon receptor-interacting protein (AIP) predispose to hereditary pituitary neoplasia. Recently, it has been demonstrated that AIP mutations predispose to pituitary tumorigenesis through defective inhibitory GTP binding protein (Gαi) signaling. This finding prompted us to examine whether germline loss-of-function mutations in inhibitory guanine nucleotide (GTP) binding protein alpha (GNAI) loci are involved in genetic predisposition of pituitary tumors. To our knowledge, this is the first time GNAI genes are sequenced in order to examine the occurrence of inactivating germline mutations. Thus far, only somatic gain-of-function hot-spot mutations have been studied in these loci. Here, we have analyzed the coding regions of GNAI1 , GNAI2, and GNAI3 in a set of young sporadic somatotropinoma patients (n = 32; mean age of diagnosis 32 years) and familial index cases (n = 14), thus in patients with a disease phenotype similar to that observed in AIP mutation carriers. In addition, expression of Gαi proteins was studied in human growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH)-secreting and non-functional pituitary tumors. No pathogenic germline mutations affecting the Gαi proteins were detected. The result suggests that loss-of-function mutations of GNAI loci are rare or nonexistent in familial pituitary adenomas. PMID:25291362

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy.

PubMed

Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

2017-01-01

Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T 4 ) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy

PubMed Central

Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

2017-01-01

Abstract. Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T4) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts. PMID:29026274

Occurrence of primary lymphocytic hypophysitis in two horses and presence of scattered T-lymphocytes in the normal equine pituitary gland.

PubMed

Grau-Roma, Llorenç; Peckham, Robert; Paton, Jacqui; Stahel, Anina; de Brot, Simone

2017-01-01

The postmortem examination of a 14-y-old Appaloosa gelding with clinically diagnosed pituitary pars intermedia dysfunction showed a unique finding of moderate multifocal lymphocytic hypophysitis (LH). The pituitary glands of 24 horses submitted for postmortem examination were examined grossly and examined histologically for the presence of lymphocytes. Of these 23 horses, 1 additional case suffered from moderate LH. The 2 cases with LH tested negative for Equid herpesvirus 1 and 4 by polymerase chain reaction and immunohistochemistry (IHC), and no viral particles were observed by electron microscopy in 1 case examined. The cause of LH remains unknown, but based on the T-lymphocytic nature of the inflammation and the human literature, an immune-mediated origin is hypothesized. In addition, the review of 24 cases revealed that 10 horses had few and small multifocal lymphocytic infiltrates within the pituitary gland; the remaining 12 horses showed no evident lymphocytes when examined by hematoxylin and eosin. IHC for CD3 showed the presence of a small number of individual T-lymphocytes scattered through the gland in all examined horses, which appears therefore to be a normal feature of the pituitary gland in horses.

Hyperthyroidism and acromegaly due to a thyrotropin- and growth hormone-secreting pituitary tumor. Lack of hormonal response to bromocriptine.

PubMed

Carlson, H E; Linfoot, J A; Braunstein, G D; Kovacs, K; Young, R T

1983-05-01

A 47-year-old woman with acromegaly and hyperthyroidism was found to have an inappropriately normal serum thyrotropin level (1.5 to 2.5 microU/ml) that responded poorly to thyrotropin-releasing hormone but showed partial responsiveness to changes in circulating thyroid hormones. Serum alpha-subunit levels were high-normal and showed a normal response to thyrotropin-releasing hormone. Growth hormone and thyrotropin hypersecretion persisted despite radiotherapy and bromocriptine treatment. Selective trans-sphenoidal removal of a pituitary adenoma led to normalization of both growth hormone and thyrotropin levels. Both thyrotropes and somatotropes were demonstrated in the adenoma by the immunoperoxidase technique and electron microscopy.

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2012-08-01

as they relate to functional outcome. At 6 months post injury, patients will be screened for anterior pituitary function 121 subjects have been...are indicative of anterior pituitary function, including somatomedin (IGF-1), thyroid stimulating hormone (TSH), thyroxine (Free T4), prolactin, and...incidence of single and multiple pituitary hormone deficiencies. The clinical characteristics, MRI imaging results, EEG and MEG results of the

Role of the new growth hormone-releasing secretagogues in the diagnosis of some hypothalamopituitary pathologies.

PubMed

Casanueva, F F; Micic, D; Pombo, M; Leal, A; Bokser, L; Zugaza, J L; Dieguez, C

1996-08-01

Growth hormone (GH)-releasing hormone (GHRH) and somatostatin have a dominant role in regulating GH secretion. However, results of studies using the new class of GH secretogogues, particularly GHRP-6, indicate that there may also be other, as yet undefined, hypothalamic mechanisms involved. Studies in adults with hypothalamopituitary disconnection (functional pituitary stalk transection), show GHRP-6-mediated GH release to be completely blocked, indicating a main action at the hypothalamic rather than the pituitary level. The synergistic effect of GHRH plus GHRP-6 administration on GH release seen in normal adults (and virtually unaffected by age, obesity, or sex) is also absent in these patients, providing further support for this conclusion. Studies of the effects of GHRP-6 in children with GH deficiency due to perinatal pituitary stalk transection have produced similar findings. It is suggested that the combined GHRH plus GHRH-6 test should be a promising tool for diagnosing GH deficiency states in both children and adults, and may identify a subgroup of patients with GH deficiency caused by interruption of the hypothalamopituitary connection.

A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.

PubMed

Porcu, Eleonora; Medici, Marco; Pistis, Giorgio; Volpato, Claudia B; Wilson, Scott G; Cappola, Anne R; Bos, Steffan D; Deelen, Joris; den Heijer, Martin; Freathy, Rachel M; Lahti, Jari; Liu, Chunyu; Lopez, Lorna M; Nolte, Ilja M; O'Connell, Jeffrey R; Tanaka, Toshiko; Trompet, Stella; Arnold, Alice; Bandinelli, Stefania; Beekman, Marian; Böhringer, Stefan; Brown, Suzanne J; Buckley, Brendan M; Camaschella, Clara; de Craen, Anton J M; Davies, Gail; de Visser, Marieke C H; Ford, Ian; Forsen, Tom; Frayling, Timothy M; Fugazzola, Laura; Gögele, Martin; Hattersley, Andrew T; Hermus, Ad R; Hofman, Albert; Houwing-Duistermaat, Jeanine J; Jensen, Richard A; Kajantie, Eero; Kloppenburg, Margreet; Lim, Ee M; Masciullo, Corrado; Mariotti, Stefano; Minelli, Cosetta; Mitchell, Braxton D; Nagaraja, Ramaiah; Netea-Maier, Romana T; Palotie, Aarno; Persani, Luca; Piras, Maria G; Psaty, Bruce M; Räikkönen, Katri; Richards, J Brent; Rivadeneira, Fernando; Sala, Cinzia; Sabra, Mona M; Sattar, Naveed; Shields, Beverley M; Soranzo, Nicole; Starr, John M; Stott, David J; Sweep, Fred C G J; Usala, Gianluca; van der Klauw, Melanie M; van Heemst, Diana; van Mullem, Alies; Vermeulen, Sita H; Visser, W Edward; Walsh, John P; Westendorp, Rudi G J; Widen, Elisabeth; Zhai, Guangju; Cucca, Francesco; Deary, Ian J; Eriksson, Johan G; Ferrucci, Luigi; Fox, Caroline S; Jukema, J Wouter; Kiemeney, Lambertus A; Pramstaller, Peter P; Schlessinger, David; Shuldiner, Alan R; Slagboom, Eline P; Uitterlinden, André G; Vaidya, Bijay; Visser, Theo J; Wolffenbuttel, Bruce H R; Meulenbelt, Ingrid; Rotter, Jerome I; Spector, Tim D; Hicks, Andrew A; Toniolo, Daniela; Sanna, Serena; Peeters, Robin P; Naitza, Silvia

2013-01-01

Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.

Zebrafish pit1 mutants lack three pituitary cell types and develop severe dwarfism.

PubMed

Nica, Gabriela; Herzog, Wiebke; Sonntag, Carmen; Hammerschmidt, Matthias

2004-05-01

The Pou domain transcription factor Pit-1 is required for lineage determination and cellular commitment processes during mammalian adenohypophysis development. Here we report the cloning and mutational analysis of a pit1 homolog from zebrafish. Compared with mouse, zebrafish pit1 starts to be expressed at a much earlier stage of adenohypophysis development. However, as in the mouse, expression is restricted to a subset of pituitary cell types, excluding proopiomelanocortin (pomc)-expressing cells (corticotropes, melanotropes) and possibly gonadotropes. We could identify two N-ethyl-N-nitrosourea-induced zebrafish pit1 null mutants. Most mutants die during larval stages, whereas survivors develop severe dwarfism. Mutant larvae lack lactotropes, somatotropes, and thyrotropes, although the adenohypophysis is of normal size, without any sign of increased apoptosis rates. Instead, mutant embryos initiate ectopic expression of pomc in pit1-positive cells, leading to an expansion of the Pomc lineage. Similarly, the number of gonadotropes seems increased, as indicated by the expression of gsualpha, a marker for thyrotropes and gonadotropes. In pit1 mutants, the total number of gsualpha-positive cells is normal despite the loss of gsualpha and tshbeta coexpressing cells. Together, these data suggest a transfating of the Pit1 lineage to the Pomc and possibly the gonadotroph lineages in the mutant, and a pomc- and gonadotropin-repressive role of Pit1 during normal zebrafish development. This is different from mouse, for which a repressive role of Pit-1 has only been reported for the gonadotropin Lhbeta, but not for Pomc. In sum, our data point to both conserved and class-specific aspects of Pit1 function during pituitary development in different vertebrate species.

Functional central hypothyroidism in the elderly.

PubMed

Sell, Maren A; Schott, Matthias; Tharandt, Lutz; Cissewski, Klaus; Scherbaum, Werner A; Willenberg, Holger S

2008-06-01

Previous studies have shown that blood concentrations of free thyroxin and basal thyroid-stimulating hormone (TSH) decrease during adult life. Suggested mechanisms include reduced thyroid activity resulting from decreased serum TSH concentrations, impairment of peripheral 5'-deiodinase, and an increase in reverse 3,5,3'-triiodothyronine due to non-thyroidal illness. However, testing of pituitary reserves leads to contradictory results and has infrequently been evaluated in studies. We investigated whether the response of TSH to thyrotropin-releasing hormone (TRH) is preserved during aging. This was tested in a cohort of 387 subjects aged 13 to 100 years in whom thyroid disease was excluded by normal thyroid ultrasound, normal values for free thyroxin, free triiodothyronin, TSH, and negative thyroid peroxidase antibodies. Serum concentrations of free thyroxin remained almost unchanged, whereas free triiodothyronin and TSH levels were lower in older subjects. In addition, the TSH response to TRH was blunted in older subjects, especially in male individuals. There is evidence that the decreased thyroid hormone levels observed in aging are due to lower TSH concentrations, and that lower TSH concentrations may be linked to an impaired pituitary activity.

Case of pituitary stalk transection syndrome ascertained after breech delivery.

PubMed

Fukuta, Kaori; Hidaka, Takao; Ono, Yosuke; Kochi, Keiko; Yasoshima, Kuniaki; Arai, Takashi

2016-02-01

Pituitary stalk transection syndrome (PSTS) is a rare complication that can accompany breech delivery. Early diagnosis of this syndrome is difficult, and it may cause a serious delay in the diagnosis. We present a case of PSTS ascertained after breech delivery. A 20-year-old woman presented with primary amenorrhea. The patient was born by breech delivery and had a history of treatment for pituitary dwarfism. Her laboratory findings showed pituitary hypothyroidism, and hormone replacement therapy was initiated. At 28 years old, she became pregnant and had a normal delivery at 38 weeks' gestation. One year after delivery, her thyroid hormone level changed. Laboratory test showed adrenocortical insufficiency, and magnetic resonance imaging of the pituitary gland showed transection of the pituitary stalk and development of an ectopic posterior lobe. These findings were compatible with PSTS. When a patient who has been born by breech delivery presents with symptoms of pituitary deficiency, PSTS should be considered in the differential diagnosis. © 2015 Japan Society of Obstetrics and Gynecology.

Identification of a novel splicing mutation in the growth hormone (GH)-releasing hormone receptor gene in a Chinese family with pituitary dwarfism.

PubMed

Wang, Qi; Diao, Ying; Xu, Zhenping; Li, Xiaohui; Luo, Xiao Ping; Xu, Haibo; Ouyang, Ping; Liu, Mugen; Hu, Zhongli; Wang, Qing K; Liu, Jing Yu

2009-12-10

A Chinese family with autosomal recessive pituitary dwarfism was identified and the proband was evaluated by MRI and hormonal analysis, which revealed pituitary dwarfism with a complete growth hormone deficiency. MRI showed a pituitary gland with a small anterior pituitary of 2.2mm and evidence of hypoplastic pituitary. Linkage analysis with markers spanning 17 known genes for dwarfism revealed linkage of the family to the growth hormone-releasing hormone receptor (GHRHR) gene. Mutational analysis of all exons and exon-intron boundaries of GHRHR was carried out using direct DNA sequence analysis. A novel homozygosis mutation, a G to A transition located in the splice donor site at the beginning of intron 8 (IVS8+1G>A), was identified in the proband. The two other patients in the family are homozygous, whereas the living mother of the proband is heterozygous for the IVS8+1G>A mutation. The mutation was not found in 100 normal chromosomes from healthy Chinese individuals of Han nationality. An in vitro splicing assay using HeLa cells transfected with expression vectors containing the normal or the mutant GHRHR minigenes consisting of genomic fragments spanning exons 7-9 showed that the IVS8+1G>A mutation caused abnormal splicing, which is predicted to give rise to truncation or frameshift, leading to severely truncated GHRHR proteins. These results provide strong evidence that the splicing mutation IVS8+1G>A of GHRHR is a cause of pituitary dwarfism in the Chinese family.

Administration of L-thyroxine does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate in functional hypothalamic amenorrhea.

PubMed

De Leo, V; la Marca, A; Lanzetta, D; Morgante, G

2000-05-01

To investigate the hypothalamo-pituitary-ovarian axis in women with functional hypothalamic amenorrhea to determine whether the combination of L-thyroxine and clomiphene citrate produces a qualitative and quantitative increase in induced ovulatory cycles. Gynecological Endocrinology Research Center, University of Siena (Italy). 16 young women with functional hypothalamic amenorrhea and 15 women with normal cycles in early follicular phase. Administration of 50 microgram GnRH and 200 microgram TRH. The women with functional hypothalamic amenorrhea were divided into groups A (n=8) and B (n=8). Both groups were given 100 mg/day clomiphene for 5 days/month for 3 months. Women in group A were also given 75 mcg/day thyroid hormone (L-thyroxine) for 3 months. Comparison of basal and stimulated levels of gonadotropins, TSH and Prl, in groups A and B. Qualitative and quantitative comparison of ovulatory cycles induced in the groups. Administration of clomiphene and clomiphene plus L-thyroxine was evaluated in the second and third months of treatment and was followed by a total of 11 ovulatory cycles, six in group A and five in group B. No significant difference was found between groups. Mean progesterone concentrations measured 16 days after the last clomiphene tablet were 5.5+/-1.2 ng/ml in group A and 5.1+/-1.3 ngl/ml in group B. Administration of L-thyroxine with clomiphene does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate or the number of ovulatory cycles and does not reduce luteal phase defects.

Functional expression of the thyrotropin receptor in C cells: new insights into their involvement in the hypothalamic-pituitary-thyroid axis

PubMed Central

Morillo-Bernal, Jesús; Fernández-Santos, José M; Utrilla, José C; de Miguel, Manuel; García-Marín, Rocío; Martín-Lacave, Inés

2009-01-01

Thyroid C cells, or parafollicular cells, are mainly known for producing calcitonin, a hormone involved in calcium homeostasis with hypocalcemic and hypophosphatemic effects. Classically, the main endocrine activity of this cell population has been believed to be restricted to its roles in serum calcium and bone metabolism. Nonetheless, in the last few years evidence has been accumulating in the literature with regard to local regulatory peptides secreted by C cells, such as somatostatin, ghrelin, thyrotropin releasing hormone or the recently described cocaine- and amphetamine-related transcript, which could modify thyroid function. As thyrotropin is the main hormone controlling the hypothalamic-pituitary-thyroid axis and, accordingly, thyroid function, we have examined the functional expression of the thyrotropin receptor in C-cell lines and in thyroid tissues. We have found that rat and human C-cell lines express the thyrotropin receptor at both mRNA and protein levels. Furthermore, incubation of C cells with thyrotropin resulted in a 10-fold inhibition of thyrotropin-receptor expression, and a concomitant decrease of the steady-state mRNA levels for calcitonin and calcitonin gene-related peptide determined by quantitative real-time PCR was found. Finally, thyrotropin receptor expression by C cells was confirmed at protein level in both normal and pathological thyroid tissues by immunohistochemistry and immunofluorescence. These results confirm that C cells, under regulation by thyrotropin, are involved in the hypothalamic-pituitary-thyroid axis and suggest a putative role in local fine-tuning of follicular cell activity. PMID:19493188

Preoperative preparation of patients with pituitary gland disorders.

PubMed

Malenković, Vesna; Gvozdenović, Ljiljana; Milaković, Branko; Sabljak, Vera; Ladjević, Nebojsa; Zivaljević, Vladan

2011-01-01

This paper presents the most common disorders of pituitary function: acromegaly, hypopituitarism, diabetes insipidus and syndrome similar to diabetes insipidus, in terms of their importance in preoperative preparation of patients. Pituitary function manages almost the entire endocrine system using the negative feedback mechanism that is impaired by these diseases. The cause of acromegaly is a pituitary adenoma, which produces growth hormone in adults. Primary therapy of acromegaly is surgical, with or without associated radiotherapy. If a patient with acromegaly as comorbidity prepares for non-elective neurosurgical operation, then it requires consultation with brain surgeons for possible delays of that operation and primary surgical treatment of pituitary gland. If operative treatment of pituitary gland is carried out, the preoperative preparation (for other surgical interventions) should consider the need for perioperative glucocorticoid supplementation. Panhypopituitarism consequences are different in children and adults and the first step in diagnosis is to assess the function of target organs. Change of electrolytes and water occurs in the case of pituitary lesions in the form of central or nephrogenic diabetes insipidus as a syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Preoperative preparation of patients with pituitary dysfunction should be multidisciplinary, whether it is a neurosurgical or some other surgical intervention. The aim is to evaluate the result of insufficient production of pituitary hormones (hypopituitarism), excessive production of adenohypophysis hormones (acromegaly, Cushing's disease and hyperprolactinemia) and the influence of pituitary tumours in surrounding structures (compression syndrome) and to determine the level of perioperative risk. Pharmacological suppressive therapy of the hyperfunctional pituitary disorders can have significant interactions with drugs used in the perioperative period.

Sensitivity of T-Lymphocytes to Hormones of the Anterior Pituitary Gland.

PubMed

Tishevskaya, N V; Gevorkyan, N M; Kozlova, N I

2017-01-01

The review provides information about the features of the sensitivity of thymocytes, lymphoid organs' cells and T-lymphocytes of peripheral blood to the hormones secreted by anterior pituitary gland's cells: growth hormone, thyrotropin, adrenocorticotropic hormone, prolactin and β-endorphin. Some aspects of the T-lymphocytes's response to humoral signals from the hypophysis are shown in the article. Also the pituitary hormones' role in the regulation of proliferation, differentiation, and cytokine production of T-lymphocytes in normal and pathological conditions of the organism being discussed.

Familial acromegaly with pituitary adenoma. Report of three affected siblings.

PubMed

Abbassioun, K; Fatourehchi, V; Amirjamshidi, A; Meibodi, N A

1986-03-01

The authors report the cases of three brothers with pituitary adenomas who had classical findings of acromegaly and gigantism. Two had irreducibly elevated growth hormone (GH) values and underwent transsphenoidal microsurgical extirpation of their tumors. The third acromegalic brother had a normal GH value and evidence of panhypopituitarism; he had a small intrasellar tumor and a partially empty sella. The pattern of inheritance was probably autosomal recessive. A review of literature indicated that familial incidence of isolated acromegaly with pituitary adenomas is rare.

[The use of acupuncture in combined balneotherapy of erectile dysfunction in patients with lumbosacral osteochondrosis].

PubMed

Zhuravlev, I E; Tereshin, A T

2010-01-01

The objective of the present study was to elucidate effects of therapeutic and preventive measures on restoration of compromised erectile function in patients with osteochondrosis of the lumbosacral spine segment (LSSS). The patients were treated using corporal and auricular acupuncture, Narzan mineral water baths, manual therapy, remedial gymnastics, and psychotherapeutic correction of sexual dysadaptation. This combined treatment resulted in the elimination of algic syndrome in 77.5% of the patients, restoration of sexual function in 62.5%, and normalization of hemodynamics in cavernous bodies in 65.2%. The functional activity of the hypothalamo-pituitary-testicular axis was normalized in 65% of the LSSS patients of strong and moderate sexual constitution. Introduction of acupuncture in the combined medicamentous therapy increased its efficiency by 15%. In 57.5% of the patients with strong and moderate sexual constitution, the restored sexual function persisted for at least 12 months.

Outcome of prolactinoma after pregnancy and lactation: a study on 73 patients.

PubMed

Domingue, Marie-Eve; Devuyst, France; Alexopoulou, Orsalia; Corvilain, Bernard; Maiter, Dominique

2014-05-01

Prolactinoma is the most frequent pituitary tumour among women of child-bearing age. Only a few studies have addressed the outcome of prolactinoma after pregnancy. To study remission, defined as prolactin normalization without medical treatment, after pregnancy and lactation in women with prolactinoma. A retrospective study conducted in 2 Belgian academic centres including 73 patients (54 microprolactinomas and 19 macroprolactinomas) with 104 pregnancies continuing beyond first trimester. Dopamine agonists were stopped in early pregnancy in all treated cases. Prolactin level and adenoma size at pituitary magnetic resonance imaging (MRI) were recorded before pregnancy and throughout follow-up. Thirty of 73 women (41%) were in remission after a median follow-up of 22 months after delivery or cessation of lactation. Adenoma size at diagnosis was smaller in women in remission (5 vs 8 mm). There was a nonsignificant higher rate of remission for microprolactinomas than for macroprolactinoma (46% vs 26%). The first pituitary MRI after pregnancy and lactation showed no tumour and a decreased adenoma size in 23% and 39% of women, respectively. MRI normalization was associated with remission. The number of pregnancies per woman as well as breastfeeding and its duration did not influence remission rate. More than 40% of women with previous diagnosis of prolactinoma have normal PRL level without medical treatment for a median follow-up of 22 months after pregnancy and lactation. The likelihood of remission is associated with a smaller initial adenoma size and normalization of pituitary MRI after pregnancy. © 2013 John Wiley & Sons Ltd.

Agenesis of internal carotid artery associated with isolated growth hormone deficiency: a case report and literature review.

PubMed

Stagi, Stefano; Traficante, Giovanna; Lapi, Elisabetta; Pantaleo, Marilena; Becciani, Sabrina; Mortilla, Marzia; Seminara, Salvatore; de Martino, Maurizio

2015-10-19

Agenesis of the internal carotid artery (ICA) is a rare congenital abnormality, sporadically reported to be associated with a combined congenital hypopituitarism. Nevertheless, only a few cases have been extensively described, and none of these have been characterized by an isolated growth hormone (GH) deficiency. Here, we describe a 17-year old boy referred to our hospital for fatigue, decreased muscle strength and severe headache reported after the cessation of rhGH treatment for a GH deficiency diagnosed at the age of 2 years and 3 months. Magnetic resonance imaging (MRI) showed an adenohypophyseal hypoplasia with a lack of posterior pituitary hyperintensity, whereas MRI angiography indicated the absence of a normal flow void in the left ICA. Endocrinological tests confirmed the GH deficiency (GH peak after growth-hormone-releasing hormone (GHRH) + arginine: 2.42 ng/mL) with a very low IGF-I value (31 ng/mL) and normal function of other pituitary axes. To the best of our knowledge this is the first confirmed case of an isolated GH deficiency in a patient with ICA agenesis. The presence of an isolated pituitary deficit is unlike to be considered only as an effect of hemodynamic mechanism, suggesting a role for genetic factor(s) as a common cause of these two rare birth defects. Further studies could clarify this issue and the underlying mechanisms to better understand the etiopathogenetic characteristics of this disorder.

Diabetes insipidus in pediatric germinomas of the suprasellar region: characteristic features and significance of the pituitary bright spot.

PubMed

Kilday, John-Paul; Laughlin, Suzanne; Urbach, Stacey; Bouffet, Eric; Bartels, Ute

2015-01-01

The pituitary bright spot is acknowledged to indicate functional integrity of the posterior pituitary gland, whilst its absence supports a diagnosis of central diabetes insipidus (DI). This feature was evaluated, together with the incidence and clinical characteristics of DI in children with suprasellar/neurohypophyseal germinomas. We performed a review of all suprasellar (SS) or bifocal (BF) germinoma pediatric patients treated in Toronto since 2000. Demographics, symptomatology, treatment outcome and imaging were evaluated. Nineteen patients fulfilled inclusion criteria (10 SS, 9 BF; median age 12.5 years (6.2-16.8 years)). All remained alive at 6.4 years median follow-up (1.2-13.7 years) after receiving chemotherapy and radiotherapy (13 focal/ventricular, four whole brain, two neuraxis), with only one progression. All had symptoms of DI at presentation with a symptom interval above one year in eight cases (42 %). Desmopressin was commenced and maintained in 16 patients (84 %). The pituitary bright spot was lost in most diagnostic interpretable cases, but was appreciated in three patients (18 %) who had normal serum sodium values compared to 'absent' cases (p = 0.013). For two such cases, spots remained visible until last follow-up (range 0.4-3.3 years), with one still receiving desmopressin. No case of bright spot recovery was observed following therapy. Protracted symptom intervals for germinoma-induced central DI may reflect poor clinical awareness. Explanations for persistence of the pituitary bright spot in symptomatic patients remain elusive. Desmopressin seldom reverses the clinical features of germinoma-induced DI to allow discontinuation, nor does treatment cause bright spot recovery.

Genetic regulation of pituitary gland development in human and mouse.

PubMed

Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C A F; Dattani, Mehul T

2009-12-01

Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke's pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans.

Genetic Regulation of Pituitary Gland Development in Human and Mouse

PubMed Central

Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C. A. F.; Dattani, Mehul T.

2009-01-01

Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans. PMID:19837867

Pituitary origin of persistently elevated human chorionic gonadotropin in a patient with gonadal failure.

PubMed

Merhi, Zaher; Pollack, Staci E

2013-01-01

To report a case of persistently elevated low levels of hCG to increase awareness of pituitary origin of persistently elevated hCG in patients with gonadal failure. Case report and literature review. Large university-affiliated infertility practice. A 16-year-old patient with primary amenorrhea, normal secondary sex characteristics, ovarian failure, and a 46,XY karyotype. Her past medical history was significant for focal segmental glomerulosclerosis, leading to a diagnosis of Frasier syndrome. At age 31 years, she desired pregnancy by oocyte donation and was found to have persistently elevated low levels of hCG (>35 mIU/mL). Pituitary hCG. Both serum free β-hCG and hyperglycosylated hCG were undetectable. Total serum hCG diluted appropriately was not blocked by blocking agent and was detected in the urine. Subsequent treatment with exogenous E(2), in preparation of a donor oocyte cycle, suppressed her hCG levels (down to 8 mIU/mL). These results indicated a pituitary source of the serum hCG. This report reinforces the need to consider pituitary hCG as the origin of persistently elevated hCG levels in patients with gonadal failure. Although levels of hCG <14 mIU/mL have been considered normal in postmenopausal women, our case suggests that patients with gonadal failure at younger ages might have a higher pituitary output of hCG. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization.

PubMed Central

Lloyd, R. V.; Cano, M.; Chandler, W. F.; Barkan, A. L.; Horvath, E.; Kovacs, K.

1989-01-01

Acidophilic pituitary adenomas commonly produce growth hormone (GH) or prolactin (PRL), according to studies employing immunohistochemical and ultrastructural methods. To examine this question, in situ hybridization with oligonucleotide probes was done on routinely processed tissues received in the pathology laboratory to analyze for the presence of GH and PRL messenger RNA (mRNA) in 4 normal pituitaries, 10 prolactinomas, and 16 GH-secreting adenomas. Most acidophilic cells in normal pituitaries expressed either GH or PRL hormone and the respective mRNAs, but GH mRNA and PRL hormone were also detected in some of the same cells. Patients with a clinical diagnosis of prolactinoma had cells with only PRL mRNA in their tumors, while most (14 of 16) patients with a clinical diagnosis of acromegaly or gigantism had both GH and PRL mRNAs in their tumors. The GH adenomas varied in these studies. In situ hybridization was helpful in characterizing the adenoma from a patient with acromegaly who had immunoreactive PRL, but no immunoreactive GH in the resected tumor; in situ hybridization analysis revealed mRNAs for both GH and PRL in the same tumor cells. Our findings indicate that pituitary adenomas from patients with acromegaly commonly express PRL mRNA. It is concluded that in situ hybridization provides new information about the clinical biology and the histopathologic classification of pituitary adenomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:2466405

Submicroscopic deletion involving the fibroblast growth factor receptor 1 gene in a patient with combined pituitary hormone deficiency.

PubMed

Fukami, Maki; Iso, Manami; Sato, Naoko; Igarashi, Maki; Seo, Misuzu; Kazukawa, Itsuro; Kinoshita, Eiichi; Dateki, Sumito; Ogata, Tsutomu

2013-01-01

Combined pituitary hormone deficiency (CPHD), isolated hypogonadotropic hypogonadism (IHH), Kallmann syndrome (KS), and septo-optic dysplasia (SOD) are genetically related conditions caused by abnormal development of the anterior midline in the forebrain. Although mutations in the fibroblast growth factor receptor 1 (FGFR1) gene have been implicated in the development of IHH, KS, and SOD, the relevance of FGFR1 abnormalities to CPHD remains to be elucidated. Here, we report a Japanese female patient with CPHD and FGFR1 haploinsufficiency. The patient was identified through copy-number analyses and direct sequencing of FGFR1 performed for 69 patients with CPHD. The patient presented with a combined deficiency of GH, LH and FSH, and multiple neurological abnormalities. In addition, normal TSH values along with a low free T4 level indicated the presence of central hypothyroidism. Molecular analyses identified a heterozygous ~ 8.5 Mb deletion involving 56 genes and pseudogenes. None of these genes except FGFR1 have been associated with brain development. No FGFR1 abnormalities were identified in the remaining 68 patients, although two patients carried nucleotide substitutions (p.V102I and p.S107L) that were assessed as benign polymorphism by in vitro functional assays. These results indicate a possible role of FGFR1 in anterior pituitary function and the rarity of FGFR1 abnormalities in patients with CPHD.

The nuclear receptor corepressor (NCoR) controls thyroid hormone sensitivity and the set point of the hypothalamic-pituitary-thyroid axis.

PubMed

Astapova, Inna; Vella, Kristen R; Ramadoss, Preeti; Holtz, Kaila A; Rodwin, Benjamin A; Liao, Xiao-Hui; Weiss, Roy E; Rosenberg, Michael A; Rosenzweig, Anthony; Hollenberg, Anthony N

2011-02-01

The role of nuclear receptor corepressor (NCoR) in thyroid hormone (TH) action has been difficult to discern because global deletion of NCoR is embryonic lethal. To circumvent this, we developed mice that globally express a modified NCoR protein (NCoRΔID) that cannot be recruited to the thyroid hormone receptor (TR). These mice present with low serum T(4) and T(3) concentrations accompanied by normal TSH levels, suggesting central hypothyroidism. However, they grow normally and have increased energy expenditure and normal or elevated TR-target gene expression across multiple tissues, which is not consistent with hypothyroidism. Although these findings imply an increased peripheral sensitivity to TH, the hypothalamic-pituitary-thyroid axis is not more sensitive to acute changes in TH concentrations but appears to be reset to recognize the reduced TH levels as normal. Furthermore, the thyroid gland itself, although normal in size, has reduced levels of nonthyroglobulin-bound T(4) and T(3) and demonstrates decreased responsiveness to TSH. Thus, the TR-NCoR interaction controls systemic TH sensitivity as well as the set point at all levels of the hypothalamic-pituitary-thyroid axis. These findings suggest that NCoR levels could alter cell-specific TH action that would not be reflected by the serum TSH.

Development of pituitary adenoma in women with hyperprolactinaemia: clinical, endocrine, and radiological characteristics.

PubMed Central

Pontiroli, A E; Falsetti, L

1984-01-01

Sixty eight women referred for treatment of hyperprolactinaemia entered a three year follow up study to determine the clinical and endocrine course of the disease and its association with microadenoma of the pituitary. Details recorded before treatment included medical history, gonadotrophin and ovarian hormonal concentrations, and release of prolactin in response to protirelin (thyrotrophin releasing hormone), benserazide, cimetidine, and nomifensine. Sellar tomography was then performed yearly for three years in all women, 54 of them also undergoing computed coronal and sagittal tomography. At baseline evaluation 27 women showed radiological evidence of pituitary adenoma; at the end of the follow up period the number had increased to 41. Amenorrhoea, steady and raised serum prolactin concentrations, a low ratio of luteinising hormone to follicle stimulating hormone, a longer duration of disease, and low serum progesterone concentrations were more common in women with a final diagnosis of pituitary adenoma than in those whose sella remained normal. Tests for release of prolactin had yielded abnormal results from the outset in all 41 women with radiological evidence of pituitary adenoma and in about half of those whose sella had remained radiologically normal. Response to medical treatment (metergoline in 20 patients, bromocriptine in 21) was similar and showed no difference between patients with tumorous and non-tumorous hyperprolactinaemia. These findings suggest that a large proportion of women with hyperprolactinaemia may harbour a prolactin secreting pituitary adenoma which becomes apparent over a relatively short period. Amenorrhoea and steady and raised serum prolactin concentrations are more common in these women. Tests for release of prolactin are of predictive value in identifying women who will develop a pituitary adenoma. PMID:6421360

Notch Signaling in Postnatal Pituitary Expansion: Proliferation, Progenitors, and Cell Specification

PubMed Central

Nantie, Leah B.; Himes, Ashley D.; Getz, Dan R.

2014-01-01

Mutations in PROP1 account for up to half of the cases of combined pituitary hormone deficiency that result from known causes. Despite this, few signaling molecules and pathways that influence PROP1 expression have been identified. Notch signaling has been linked to Prop1 expression, but the developmental periods during which Notch signaling influences Prop1 and overall pituitary development remain unclear. To test the requirement for Notch signaling in establishing the normal pituitary hormone milieu, we generated mice with early embryonic conditional loss of Notch2 (conditional knockout) and examined the consequences of chemical Notch inhibition during early postnatal pituitary maturation. We show that loss of Notch2 has little influence on early embryonic pituitary proliferation but is crucial for postnatal progenitor maintenance and proliferation. In addition, we show that Notch signaling is necessary embryonically and postnatally for Prop1 expression and robust Pit1 lineage hormone cell expansion, as well as repression of the corticotrope lineage. Taken together, our studies identify temporal and cell type–specific roles for Notch signaling and highlight the importance of this pathway throughout pituitary development. PMID:24673559

Early endocrine alterations reflect prolonged stress and relate to 1-year functional outcome in patients with severe brain injury.

PubMed

Marina, Djordje; Klose, Marianne; Nordenbo, Annette; Liebach, Annette; Feldt-Rasmussen, Ulla

2015-06-01

Severe brain injury may increase the risk of developing acute and chronic hypopituitarism. Pituitary hormone alterations developed in the early recovery phase after brain injury may have implications for long-term functional recovery. The objective of the present study was to assess the pattern and prevalence of pituitary hormone alterations 3 months after a severe brain injury with relation to functional outcome at a 1-year follow-up. Prospective study at a tertiary university referral centre. A total of 163 patients admitted to neurorehabilitation after severe traumatic brain injury (TBI, n=111) or non-TBI (n=52) were included. The main outcome measures were endocrine alterations 3.3 months (median) after the brain injury and their relationship to the functioning and ability of the patients at a 1-year follow-up, as measured by the Functional Independence Measure and the Glasgow Outcome Scale-Extended. Three months after the injury, elevated stress hormones (i.e. 30 min stimulated cortisol, prolactin and/or IGF1) and/or suppressed gonadal or thyroid hormones were recorded in 68 and 32% of the patients respectively. At 1 year after the injury, lower functioning level (Functional Independence Measure) and lower capability of performing normal life activities (Glasgow Outcome Scale-Extended) were related to both the elevated stress hormones (P≤0.01) and the reduced gonadal and/or thyroid hormones (P≤0.01) measured at 3 months. The present study suggests that brain injury-related endocrine alterations that mimic secondary hypogonadism and hypothyroidism and that occur with elevated stress hormones most probably reflect a prolonged stress response 2-5 months after severe brain injury, rather than pituitary insufficiency per se. These endocrine alterations thus seem to reflect a more severe disease state and relate to 1-year functional outcome. © 2015 European Society of Endocrinology.

Pituitary gland imaging and outcome.

PubMed

Di Iorgi, Natascia; Morana, Giovanni; Gallizia, Anna Lisa; Maghnie, Mohamad

2012-01-01

Magnetic resonance imaging (MRI) allows a detailed and precise anatomical study of the pituitary gland by differentiating between the anterior and posterior pituitary lobes. The identification of posterior pituitary hyperintensity, now considered a marker of neurohypophyseal functional integrity, has been the most striking advance for the diagnosis and understanding of anterior and posterior pituitary diseases. The advent of MRI has in fact led to a significant improvement in the understanding of the pathogenesis of disorders that affect the hypothalamo-pituitary area. Today, there is convincing evidence to support the hypothesis that marked MRI differences in pituitary morphology indicate a diverse range of disorders which affect the organogenesis and function of the anterior pituitary gland with different prognoses. Furthermore, the association of extrapituitary malformations accurately defined by MRI has supported a better definition of several conditions linked to pituitary hormone deficiencies and midline defects. MRI is a very informative procedure that should be used to support a diagnosis of hypopituitarism. It is useful in clinical management, because it helps endocrinologists determine which patients to target for further molecular studies and genetic counselling, which ones to screen for additional hormone deficits, and which ones may need growth hormone replacement into adult life. Copyright © 2012 S. Karger AG, Basel.

A journey through the pituitary gland: Development, structure and function, with emphasis on embryo-foetal and later development.

PubMed

Musumeci, Giuseppe; Castorina, Sergio; Castrogiovanni, Paola; Loreto, Carla; Leonardi, Rosi; Aiello, Flavia Concetta; Magro, Gaetano; Imbesi, Rosa

2015-01-01

The pituitary gland and the hypothalamus are morphologically and functionally associated in the endocrine and neuroendocrine control of other endocrine glands. They therefore play a key role in a number of regulatory feedback processes that co-ordinate the whole endocrine system. Here we review the neuroendocrine system, from the discoveries that led to its identification to some recently clarified embryological, functional, and morphological aspects. In particular we review the pituitary gland and the main notions related to its development, organization, cell differentiation, and vascularization. Given the crucial importance of the factors controlling neuroendocrine system development to understand parvocellular neuron function and the aetiology of the congenital disorders related to hypothalamic-pituitary axis dysfunction, we also provide an overview of the molecular and genetic studies that have advanced our knowledge in the field. Through the action of the hypothalamus, the pituitary gland is involved in the control of a broad range of key aspects of our lives: the review focuses on the hypothalamic-pituitary-gonadal axis, particularly GnRH, whose abnormal secretion is associated with clinical conditions involving delayed or absent puberty and reproductive dysfunction. Copyright © 2015 Elsevier GmbH. All rights reserved.

Ets-1 is a target of MAPK signaling in the embryonic anterior pituitary gland during glucocorticoid initiation of pituitary growth hormone expression

USDA-ARS?s Scientific Manuscript database

Glucocorticoids play a critical role in functional differentiation of somatotrophs, the growth hormone (GH)-producing cells within the anterior pituitary gland. In chicken embryonic day 11 (e11) pituitary cells, premature induction of growth hormone (GH) resulting from corticosterone (CORT) treatmen...

Diagnostic Usefulness of Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor Binding Protein 3 in Children with Suspected Pituitary Dwarfism.

PubMed

Zelazowska-Rutkowska, Beata; Trusiak, Marta; Bossowski, Artur; Cylwik, Bogdan

2018-05-01

Pituitary dwarfism (also known as short stature) is a medical condition in which the pituitary gland does not produce enough growth hormone (GH). To confirm the diagnosis of growth hormone deficiency the overnight profile of GH secretion and GH provocative tests are usually performed; however, due to wide GH fluctuations throughout the day and night and the invasiveness of stimulation tests, their clinical utility is limited. Therefore, screening for IGF-1 (insulin-like growth factor 1) and IGFBP-3 (insulin-like growth factor binding protein type 3) is proposed, suggesting that these tests provide a more accurate reflection of the mean plasma GH level, although the results of these tests are still problematic. In this context, the aim of this study was to assess the diagnostic usefulness of IGF-1 and IGFBP-3 in children with suspected pituitary dwarfism. Studies were carried out in 127 children with abnormal growth and low spontaneous 24-hour plasma GH profiles and abnormal results of GH stimulation tests. Fasting serum IGF-1 and IGFBP-3 were determined by chemiluminescent quantitative measurement using the IMMULITE 1000 IGF-1 and IGFBP-3 kits (Siemens Healthcare Diagnostics, United Kingdom) on the IMMULITE 1000 analyzer (Siemens Healthcare Diagnostics, USA). Results were compared to the normal range by children's age. Mean serum IGF-1 concentrations were within the lower normal range (41.7% cases), and 58.3% results were below the normal reference range in the study group. The average serum IGFBP-3 levels were within the lower normal range. We conclude that IGF-1 test can be a useful tool in the diagnosis of pituitary dwarfism in children suspected of this condition, but due to relatively poor sensitivity the testing cannot be performed alone, but in combination with other tests. The IGFBP-3 test is not useful for the diagnosis of this disease.

Responsiveness to a Physiological Regimen of GnRH Therapy and Relation to Genotype in Women With Isolated Hypogonadotropic Hypogonadism

PubMed Central

Abel, Brent S.; Shaw, Natalie D.; Brown, Jenifer M.; Adams, Judith M.; Alati, Teresa; Martin, Kathryn A.; Pitteloud, Nelly; Seminara, Stephanie B.; Plummer, Lacey; Pignatelli, Duarte; Crowley, William F.; Welt, Corrine K.

2013-01-01

Context: Isolated hypogonadotropic hypogonadism (IHH) is caused by defective GnRH secretion or action resulting in absent or incomplete pubertal development and infertility. Most women with IHH ovulate with physiological GnRH replacement, implicating GnRH deficiency as the etiology. However, a subset does not respond normally, suggesting the presence of defects at the pituitary or ovary. Objectives: The objective of the study was to unmask pituitary or ovarian defects in IHH women using a physiological regimen of GnRH replacement, relating these responses to genes known to cause IHH. Design, Setting, and Subjects: This study is a retrospective analysis of 37 IHH women treated with iv pulsatile GnRH (75 ng/kg per bolus). Main Outcome Measures: Serum gonadotropin and sex steroid levels were measured, and 14 genes implicated in IHH were sequenced. Results: During their first cycle of GnRH replacement, normal cycles were recreated in 60% (22 of 37) of IHH women. Thirty percent of women (12 of 37) demonstrated an attenuated gonadotropin response, indicating pituitary resistance, and 10% (3 of 37) exhibited an exaggerated FSH response, consistent with ovarian resistance. Mutations in CHD7, FGFR1, KAL1, TAC3, and TACR3 were documented in IHH women with normal cycles, whereas mutations were identified in GNRHR, PROKR2, and FGFR1 in those with pituitary resistance. Women with ovarian resistance were mutation negative. Conclusions: Although physiological replacement with GnRH recreates normal menstrual cycle dynamics in most IHH women, hypogonadotropic responses in the first week of treatment identify a subset of women with pituitary dysfunction, only some of whom have mutations in GNRHR. IHH women with hypergonadotropic responses to GnRH replacement, consistent with an additional ovarian defect, did not have mutations in genes known to cause IHH, similar to our findings in a subset of IHH men with evidence of an additional testicular defect. PMID:23341491

ZBTB20 is required for anterior pituitary development and lactotrope specification.

PubMed

Cao, Dongmei; Ma, Xianhua; Cai, Jiao; Luan, Jing; Liu, An-Jun; Yang, Rui; Cao, Yi; Zhu, Xiaotong; Zhang, Hai; Chen, Yu-Xia; Shi, Yuguang; Shi, Guang-Xia; Zou, Dajin; Cao, Xuetao; Grusby, Michael J; Xie, Zhifang; Zhang, Weiping J

2016-04-15

The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20-null mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification.

ZBTB20 is required for anterior pituitary development and lactotrope specification

PubMed Central

Cao, Dongmei; Ma, Xianhua; Cai, Jiao; Luan, Jing; Liu, An-Jun; Yang, Rui; Cao, Yi; Zhu, Xiaotong; Zhang, Hai; Chen, Yu-Xia; Shi, Yuguang; Shi, Guang-Xia; Zou, Dajin; Cao, Xuetao; Grusby, Michael J.; Xie, Zhifang; Zhang, Weiping J.

2016-01-01

The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20-null mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification. PMID:27079169

Function of the hypothalamic-pituitary-gonadal axis in long-term survivors of hematopoietic stem cell transplantation for hematological diseases.

PubMed

Somali, Maria; Mpatakoias, Vassilios; Avramides, Avraam; Sakellari, Ioanna; Kaloyannidis, Panayotis; Smias, Christos; Anagnostopoulos, Achilleas; Kourtis, Anargyros; Rousso, David; Panidis, Dimitrios; Vagenakis, Apostolos

2005-07-01

Gonadal dysfunction in adult long-term survivors of hematopoietic stem cell transplantation (HSCT) is an adverse effect of conditioning regimens consisting of chemotherapy and total body irradiation (TBI). The impact of conditioning regimens consisting of chemotherapy alone on the function of the hypothalamic-pituitary-gonadal (HPG) axis was evaluated in a series of 41 female and 31 male patients who had undergone either autologous or allogeneic bone marrow/peripheral blood stem cell transplantation; mean age at transplantation was 32.6 years and mean time interval from transplantation was 1.5 years (range 0.2-9.8 years). Provocative testing of the HPG axis by administration of luteinizing hormone-releasing hormone was included in the first endocrinological evaluation. The follow-up period extended to three consecutive years. Gonadal dysfunction was not reported by any of the patients prior to their underlying illness. Hypergonadotrophic hypogonadism was observed in 97% of female and 19% of male patients. Leydig cell strain (normal testosterone, high luteinizing hormone levels) was evident in 32% and spermatogenesis damage (high follicle-stimulating hormone levels) in 68% of the male population. At the conclusion of the study four women (10%) had regained spontaneous menses and all hypogonadal men had resumed normal testosterone levels. Our results indicate a high incidence of gonadal dysfunction due to target organ failure in HSCT recipients not treated by TBI.

GH in the dwarf dopaminergic D2 receptor knockout mouse: somatotrope population, GH release, and responsiveness to GH-releasing factors and somatostatin.

PubMed

García-Tornadú, Isabel; Rubinstein, Marcelo; Gaylinn, Bruce D; Hill, David; Arany, Edith; Low, Malcolm J; Díaz-Torga, Graciela; Becu-Villalobos, Damasia

2006-09-01

Recently, the importance of the dopaminergic D2 receptor (D2R) subtype in normal body growth and neonatal GH secretion has been highlighted. Disruption of D2R alters the GHRH-GH-IGF-I axis and impairs body growth in adult male mice. The D2R knockout (KO) dwarf mouse has not been well characterized; we therefore sought to determine somatotrope function in the adult pituitary. Using immunohistochemistry and confocal microscopy, we found a significant decrease in the somatotrope population in pituitaries from KO mice (P=0.043), which was paralleled by a decreased GH output from pituitary cells cultured in vitro. In cells from adult mice the response amplitude to GHRH differed between genotypes (lower in KO), but this difference was less dramatic after taking into account the lower basal release and hormone content in the KO cells. Furthermore, there were no significant differences in cAMP generation in response to GHRH between genotypes. By Western blot, GHRH-receptor in pituitary membranes from KO mice was reduced to 46% of the level found in wildtype (WT) mice (P=0.016). Somatostatin induced a concentration-dependent decrease in GH and prolactin (PRL) secretion in both genotypes, and 1x10(-7) M ghrelin released GH in cells from both genotypes (P=0.017) in a proportionate manner to basal levels. These results suggest that KO somatotropes maintain a regulated secretory function. Finally, we tested the direct effect of dopamine on GH and PRL secretion in cells from both genotypes at 20 days and 6 months of life. As expected, we found that dopamine could reduce PRL levels at both ages in WT mice but not in KO mice, but there was no consistent effect of the neurotransmitter on GH release in either genotype at the ages studied. The present study demonstrates that in the adult male D2R KO mouse, there is a reduction in pituitary GH content and secretory activity. Our results point to an involvement of D2R signaling at the hypothalamic level as dopamine did not release GH acting at the pituitary level either in 1-month-old or adult mice. The similarity of the pituitary defect in the D2R KO mouse to that of GHRH-deficient models suggests a probable mechanism. A loss of dopamine signaling via hypothalamic D2Rs at a critical age causes the reduced release of GHRH from hypophyseotropic neurons leading to inadequate clonal expansion of the somatotrope population. Our data also reveal that somatotrope cell number is much more sensitive to changes in neonatal GHRH input than their capacity to develop properly regulated GH-secretory function.

Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes

PubMed Central

Cheung, Leonard Y. M.; Okano, Hideyuki

2016-01-01

The hypothalamic-pituitary axes are the coordinating centers for multiple endocrine gland functions and physiological processes. Defects in the hypothalamus or pituitary gland can cause reduced growth and severe short stature, affecting approximately 1 in 4000 children, and a large percentage of cases of pituitary hormone deficiencies do not have an identified genetic cause. SOX21 is a protein that regulates hair, neural, and trophoblast stem cell differentiation. Mice lacking Sox21 have reduced growth, but the etiology of this growth defect has not been described. We studied the expression of Sox21 in hypothalamic-pituitary development and examined multiple endocrine axes in these mice. We find no evidence of reduced intrauterine growth, food intake, or physical activity, but there is evidence for increased energy expenditure in mutants. In addition, despite changes in pituitary hormone expression, hypothalamic-pituitary axes appear to be functional. Therefore, SOX21 variants may be a cause of non-endocrine short stature in humans. PMID:27616671

Morphological changes in the pituitary-adrenocortical axis in natives of La Paz

NASA Astrophysics Data System (ADS)

Gosney, John; Heath, Donald; Williams, David; Rios-Dalenz, Jaime

1991-03-01

Increased activity of the hypothalamic-pituitary-adrenocortical axis is part of the response to the stress of initial exposure to hypoxia, but there is evidence to suggest that it persists after homeostatic stability has been regained and acclimatization achieved. The adrenal glands of five lifelong residents of La Paz, Bolivia, who had lived at altitudes in the range 3600 3800 m, were significantly larger than those in age-matched controls from sea level (15.3g vs 10.4g; P<0.001) and appeared hyperplastic. The pituitary glands of the highlanders were not significantly different in size from those of the controls (0.67 g vs 0.51 g), but contained larger populations of corticotrophs expressed in terms of the total cell population of their anterior lobes (25.6% vs 19.4%; P<0.001). In conjunction with other studies of this endocrine axis in man and animals exposed to a hypoxic environment, these data suggest that greater amounts of adrenocorticotrophic hormone (ACTH) are required to maintain normal adrenocortical function under such circumstances, probably as a result of hypoxic inhibition of adrenocortical sensitivity to stimulation. Physiological hyperplasia of the adrenal cortex may be common in people living at high altitude.

The role of the sonic hedgehog signalling pathway in patients with midline defects and congenital hypopituitarism.

PubMed

Gregory, L C; Gaston-Massuet, C; Andoniadou, C L; Carreno, G; Webb, E A; Kelberman, D; McCabe, M J; Panagiotakopoulos, L; Saldanha, J W; Spoudeas, H A; Torpiano, J; Rossi, M; Raine, J; Canham, N; Martinez-Barbera, J P; Dattani, M T

2015-05-01

The Gli family of zinc finger (GLI) transcription factors mediates the sonic hedgehog signalling pathway (HH) essential for CNS, early pituitary and ventral forebrain development in mice. Human mutations in this pathway have been described in patients with holoprosencephaly (HPE), isolated congenital hypopituitarism (CH) and cranial/midline facial abnormalities. Mutations in Sonic hedgehog (SHH) have been associated with HPE but not CH, despite murine studies indicating involvement in pituitary development. We aimed to establish the role of the HH pathway in the aetiology of hypothalamo-pituitary disorders by screening our cohort of patients with midline defects and/or CH for mutations in SHH, GLI2, Shh brain enhancer 2 (SBE2) and growth-arrest specific 1 (GAS1). Two variants and a deletion of GLI2 were identified in three patients. A novel variant at a highly conserved residue in the zinc finger DNA-binding domain, c.1552G > A [pE518K], was identified in a patient with growth hormone deficiency and low normal free T4. A nonsynonymous variant, c.2159G > A [p.R720H], was identified in a patient with a short neck, cleft palate and hypogonadotrophic hypogonadism. A 26·6 Mb deletion, 2q12·3-q21·3, encompassing GLI2 and 77 other genes, was identified in a patient with short stature and impaired growth. Human embryonic expression studies and molecular characterisation of the GLI2 mutant p.E518K support the potential pathogenicity of GLI2 mutations. No mutations were identified in GAS1 or SBE2. A novel SHH variant, c.1295T>A [p.I432N], was identified in two siblings with variable midline defects but normal pituitary function. Our data suggest that mutations in SHH, GAS1 and SBE2 are not associated with hypopituitarism, although GLI2 is an important candidate for CH. © 2014 John Wiley & Sons Ltd.

Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study.

PubMed

Tahara, Shigeyuki; Murakami, Mami; Kaneko, Tomomi; Shimatsu, Akira

2017-07-28

A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levels<2.5μg/L and normalized insulin-like growth factor-1 [IGF-1]) at month 3. Thirty-three patients (acromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg. The median age was 52 years (range, 31-79) and 20 patients were males. At month 3, 18.2% of patients (6/33; 90% confidence interval: 8.2%, 32.8%) had biochemical control (21.2% [7/33] when including a patient with mean GH<2.5μg/L and IGF-1< lower limit of normal). Reductions in the median GH and IGF-1 levels observed at month 3 were maintained up to month 12; the median percent change from baseline to month 12 in GH and IGF-1 levels were -74.71% and -59.33%, respectively. Twenty-nine patients completed the 12-month core phase, 1 withdrew consent, and 3 discontinued treatment due to adverse events (AEs; diabetes mellitus, hyperglycemia, liver function abnormality, n=1 each). Almost all patients (97%; 32/33) experienced AEs; the most common AEs were nasopharyngitis (48.5%), hyperglycemia (42.4%), diabetes mellitus (24.2%), constipation (18.2%), and hypoglycemia (15.2%). Serious AEs were reported in 7 patients with the most common being hyperglycemia (n=2). Long-acting pasireotide demonstrated clinically relevant efficacy and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

[Effects on structure and secretion of pituitary gland in rats after electromagnetic pulse exposure].

PubMed

Fang, Heng-hu; Zeng, Gui-ying; Nie, Qing; Kang, Jing-bo; Ren, Dong-qing; Zhou, Jia-xing; Li, Yun-ming

2010-12-07

To investigate the exposure effect of electromagnetic pulse (EMP) on the structure and secretion of pituitary gland in rats. Forty-eight male SD rats were randomly divided into eight groups. Four groups were subject to the EMP exposure of 200 kV/m and the others received a sham exposure. At different time points (12, 24, 48 & 96 h) post-exposure, the pathological changes of pituitary gland were observed by light and transmission electron microscope. And the serum levels of prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH) and luteinizing hormone (LH) were measured dynamically by radioimmunoassay. At 12 h post-exposure, swollen mitochondria with cristae loss, dilatation of Golgi complex and diffusive lysosomes were found in endocrine cells of pituitary gland. The above changes became gradually worse. Mitochondrial vacuolization, the formation of myelin figures, distinct dilatation of endoplasmic reticulum, the occurrence of numerous secondary lysosomes and the clustering of heterochromatin under the nuclear membranes could be observed at 48 h. These lesions were alleviated to some degree at 96 h. The serum levels of PRL and ACTH both increased significantly at 12 h (P < 0.01, P < 0.05) and returned to normal at 24 h. The level of GH decreased significantly at 12 h and then returned gradually to normal at 48 h. The level of TSH decreased at 12 h and reached the lowest point at 24 h, then returned to normal at 96 h. LH increased significantly from 24 h to 96 h. The EMP exposure of 200 kV/m may induce the changes of the structure and secretion of pituitary gland in rats.

Central hypothyroidism - a neglected thyroid disorder.

PubMed

Beck-Peccoz, Paolo; Rodari, Giulia; Giavoli, Claudia; Lania, Andrea

2017-10-01

Central hypothyroidism is a rare and heterogeneous disorder that is characterized by a defect in thyroid hormone secretion in an otherwise normal thyroid gland due to insufficient stimulation by TSH. The disease results from the abnormal function of the pituitary gland, the hypothalamus, or both. Moreover, central hypothyroidism can be isolated or combined with other pituitary hormone deficiencies, which are mostly acquired and are rarely congenital. The clinical manifestations of central hypothyroidism are usually milder than those observed in primary hypothyroidism. Obtaining a positive diagnosis for central hypothyroidism can be difficult from both a clinical and a biochemical perspective. The diagnosis of central hypothyroidism is based on low circulating levels of free T 4 in the presence of low to normal TSH concentrations. The correct diagnosis of both acquired (also termed sporadic) and congenital (also termed genetic) central hypothyroidism can be hindered by methodological interference in free T 4 or TSH measurements; routine utilization of total T 4 or T 3 measurements; concurrent systemic illness that is characterized by low levels of free T 4 and normal TSH concentrations; the use of the sole TSH-reflex strategy, which is the measurement of the sole level of TSH, without free T 4 , if levels of TSH are in the normal range; and the diagnosis of congenital hypothyroidism based on TSH analysis without the concomitant measurement of serum levels of T 4 . In this Review, we discuss current knowledge of the causes of central hypothyroidism, emphasizing possible pitfalls in the diagnosis and treatment of this disorder.

Pituitary Magnetic Resonance Imaging for Sellar and Parasellar Masses: Ten-Year Experience in 2598 Patients

PubMed Central

Famini, Pouyan; Maya, Marcel M.

2011-01-01

Context: Sellar and parasellar masses present with overlapping clinical and radiological features ranging from asymptomatic incidental presentations and hormonal effects to compressive local mass effects. Pituitary masses are diagnosed with increased frequency with magnetic resonance imaging (MRI) advancements and availability, but indications and diagnostic outcomes of MRI screening for sellar lesions are not defined. Although pituitary adenomas are the most frequently encountered sellar mass lesions, other etiologies should be considered in the differential diagnosis of a sellar mass. Setting: The study was conducted at a tertiary pituitary center. Patients: This study was a retrospective review of 2598 subjects undergoing at least one pituitary MRI scan from 1999 to 2009. Main Outcome Measure: Prevalence and diagnosis of specific sellar and parasellar masses as screened by pituitary MRI. Results: The most common indications for pituitary imaging, excluding known mass follow-up, were for evaluation of hyperprolactinemia or hypogonadism. A normal pituitary gland was reported in 47% of subjects undergoing pituitary MRI. The most common pituitary adenomas initially identified by MRI included prolactinoma (40%), nonfunctioning adenoma (37%), and GH adenoma (13%). Nonadenomatous sellar masses accounted for 18% of visible lesions, of which the most common were Rathke's cleft cyst (19%), craniopharyngioma (15%), and meningioma (15%). Metastases accounted for 5% of nonpituitary lesions and breast cancer was the most common primary source. Conclusions: Half of all pituitary MRI scans performed in a large patient population yielded no visible lesion. Nonadenomatous pituitary lesions should be considered in the diagnosis of sellar masses observed on MRI, and a high clinical suspicion is required to exclude the presence of a nonfunctioning pituitary adenoma. PMID:21470998

Using kisspeptin to assess GnRH function in an unusual case of primary amenorrhoea.

PubMed

Vimalesvaran, S; Narayanaswamy, S; Yang, L; Prague, J K; Buckley, A; Miras, A D; Franks, S; Meeran, K; Dhillo, W S

2017-01-01

Primary amenorrhoea is defined as the failure to commence menstruation by the age of 15 years, in the presence of normal secondary sexual development. The potential causes of primary amenorrhoea extend from structural to chromosomal abnormalities. Polycystic ovarian syndrome (PCOS) is a common cause of secondary amenorrhoea but an uncommon cause of primary amenorrhoea. An early and prompt diagnosis of PCOS is important, as up to 30% of these women are predisposed to glucose intolerance and obesity, with the subgroup of women presenting with primary amenorrhoea and PCOS displaying a higher incidence of metabolic dysfunction. We describe a case of an 18-year-old female presenting with primary amenorrhoea of unknown aetiology. Although initial investigations did not demonstrate clinical or biochemical hyperandrogenism or any radiological evidence of polycystic ovaries, a raised luteinising hormone (LH) suggested a diagnosis of PCOS. If PCOS was the correct diagnosis, then one would expect intact hypothalamic GnRH and pituitary gonadotropin release. We used the novel hormone kisspeptin to confirm intact hypothalamic GnRH release and a GnRH stimulation test to confirm intact pituitary gonadotroph function. This case highlights that kisspeptin is a potential unique tool to test GnRH function in patients presenting with reproductive disorders. Polycystic ovarian syndrome (PCOS) can present with primary amenorrhoea, and therefore, should be considered in the differential diagnosis.PCOS is a heterogeneous condition that may present in lean women with few or absent signs of hyperandrogenism.GnRH stimulation tests are useful in evaluating pituitary function; however, to date, we do not have a viable test of GnRH function. Kisspeptin has the potential to form a novel diagnostic tool for assessing hypothalamic GnRH function by monitoring gonadotropin response as a surrogate marker of GnRH release.Confirmation of intact GnRH function helps consolidate a diagnosis in primary amenorrhoea and gives an indication of future fertility.

Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome.

PubMed

McCormack, Shana E; Li, Dong; Kim, Yeon Joo; Lee, Ji Young; Kim, Soo-Hyun; Rapaport, Robert; Levine, Michael A

2017-07-01

Pituitary stalk interruption syndrome (PSIS, ORPHA95496) is a congenital defect of the pituitary gland characterized by the triad of a very thin/interrupted pituitary stalk, an ectopic (or absent) posterior pituitary gland, and hypoplasia or aplasia of the anterior pituitary gland. Complex genetic patterns of inheritance of this disorder are increasingly recognized. The objective of this study was to identify a genetic cause of PSIS in an affected child. Whole exome sequencing (WES) was performed by using standard techniques, with prioritized genetic variants confirmed via Sanger sequencing. To investigate the effects of one candidate variant on mutant WDR11 function, Western blotting and coimmunofluorescence were used to assess binding capacity, and leptomycin B exposure along with immunofluorescence was used to assess nuclear localization. We describe a child who presented in infancy with combined pituitary hormone deficiencies and whose brain imaging demonstrated a small anterior pituitary, ectopic posterior pituitary, and a thin, interrupted stalk. WES demonstrated heterozygous missense mutations in two genes required for pituitary development, a known loss-of-function mutation in PROKR2 (c.253C>T;p.R85C) inherited from an unaffected mother, and a WDR11 (c.1306A>G;p.I436V) mutation inherited from an unaffected father. Mutant WDR11 loses its capacity to bind to its functional partner, EMX1, and to localize to the nucleus. WES in a child with PSIS and his unaffected family implicates a digenic mechanism of inheritance. In cases of hypopituitarism in which there is incomplete segregation of a monogenic genotype with the phenotype, the possibility that a second genetic locus is involved should be considered. Copyright © 2017 Endocrine Society

Magnocellular Neurons and Posterior Pituitary Function.

PubMed

Brown, Colin H

2016-09-15

The posterior pituitary gland secretes oxytocin and vasopressin (the antidiuretic hormone) into the blood system. Oxytocin is required for normal delivery of the young and for delivery of milk to the young during lactation. Vasopressin increases water reabsorption in the kidney to maintain body fluid balance and causes vasoconstriction to increase blood pressure. Oxytocin and vasopressin secretion occurs from the axon terminals of magnocellular neurons whose cell bodies are principally found in the hypothalamic supraoptic nucleus and paraventricular nucleus. The physiological functions of oxytocin and vasopressin depend on their secretion, which is principally determined by the pattern of action potentials initiated at the cell bodies. Appropriate secretion of oxytocin and vasopressin to meet the challenges of changing physiological conditions relies mainly on integration of afferent information on reproductive, osmotic, and cardiovascular status with local regulation of magnocellular neurons by glia as well as intrinsic regulation by the magnocellular neurons themselves. This review focuses on the control of magnocellular neuron activity with a particular emphasis on their regulation by reproductive function, body fluid balance, and cardiovascular status. © 2016 American Physiological Society. Compr Physiol 6:1701-1741, 2016. Copyright © 2016 John Wiley & Sons, Inc.

A case of transient central diabetes insipidus after aorto-coronary bypass operation.

PubMed

Yu, Chung-Hoon; Cho, Jang-Hee; Jung, Hee-Yeon; Lim, Jeong-Hoon; Jin, Mi-Kyung; Kwon, Owen; Hong, Kyung-Deuk; Choi, Ji-Young; Yoon, Se-Hee; Kim, Chan-Duck; Kim, Yong-Lim; Kim, Gun-Jik; Park, Sun-Hee

2012-09-01

Diabetes insipidus (DI) is characterized by excessive urination and thirst. This disease results from inadequate output of antidiuretic hormone (ADH) from the pituitary gland or the absence of the normal response to ADH in the kidney. We present a case of transient central DI in a patient who underwent a cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CABG). A 44-yr-old male underwent a CABG operation. An hour after the operation, the patient developed polyuria and was diagnosed with central DI. The patient responded to desmopressin and completely recovered five days after surgery. It is probable that transient cerebral ischemia resulted in the dysfunction of osmotic receptors in the hypothalamus or hypothalamus-pituitary axis during CPB. It is also possible that cardiac standstill altered the left atrial non-osmotic receptor function and suppressed ADH release. Therefore, we suggest that central DI is a possible cause of polyuria after CPB.

A Case of Transient Central Diabetes Insipidus after Aorto-Coronary Bypass Operation

PubMed Central

Yu, Chung-Hoon; Cho, Jang-Hee; Jung, Hee-Yeon; Lim, Jeong-Hoon; Jin, Mi-Kyung; Kwon, Owen; Hong, Kyung-Deuk; Choi, Ji-Young; Yoon, Se-Hee; Kim, Chan-Duck; Kim, Yong-Lim; Kim, Gun-Jik

2012-01-01

Diabetes insipidus (DI) is characterized by excessive urination and thirst. This disease results from inadequate output of antidiuretic hormone (ADH) from the pituitary gland or the absence of the normal response to ADH in the kidney. We present a case of transient central DI in a patient who underwent a cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CABG). A 44-yr-old male underwent a CABG operation. An hour after the operation, the patient developed polyuria and was diagnosed with central DI. The patient responded to desmopressin and completely recovered five days after surgery. It is probable that transient cerebral ischemia resulted in the dysfunction of osmotic receptors in the hypothalamus or hypothalamus-pituitary axis during CPB. It is also possible that cardiac standstill altered the left atrial non-osmotic receptor function and suppressed ADH release. Therefore, we suggest that central DI is a possible cause of polyuria after CPB. PMID:22969261

Cystic Mammary Adenocarcinoma Associated with a Prolactin-secreting Pituitary Adenoma in a New Zealand White Rabbit (Oryctolagus cuniculus)

PubMed Central

Sikoski, Paul; Trybus, James; Cline, J Mark; Muhammad, F Salih; Eckhoff, Andrew; Tan, Josh; Lockard, Mandy; Jolley, Tammy; Britt, Susan; Kock, Nancy D

2008-01-01

A 44-mo-old, female, nulliparous New Zealand White Rabbit (Oryctolagus cuniculus) presented with bilaterally diffusely enlarged mammary glands with enlarged, discolored teats that exuded brown, mucoid discharge. The complete blood count and serum chemistry panels were within normal limits, bacteria were not isolated from a culture of the discharge, and the clinical signs did not resolve with antibiotic treatment. Computed tomography and serum prolactin levels supported the diagnosis of mammary gland dysplasia, possibly due to a prolactin-secreting pituitary adenoma. Histologic evaluation confirmed the presence of a pituitary adenoma, mammary hyperplasia, dysplasia, and cystic mammary adenocarcinoma. Immunohistochemical staining confirmed the presence of abundant prolactin secreting cells in the pituitary adenoma. This is the second report of hyperprolactinemia with mammary dysplasia in rabbits, and the first report of cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a rabbit. PMID:18589874

Genetics of Isolated Growth Hormone Deficiency

PubMed Central

2010-01-01

When a child is not following the normal, predicted growth curve, an evaluation for underlying illnesses and central nervous system abnormalities is required, and appropriate consideration should be given to genetic defects causing growth hormone (GH) deficiency (GHD). Because Insulin−like Growth Factor−I (IGF−I) plays a pivotal role, GHD could also be considered as a form of IGF−I deficiency (IGFD). Although IGFD can develop at any level of the GH−releasing hormone (GHRH)−GH−IGF axis, a differentiation should be made between GHD (absent to low GH in circulation) and IGFD (normal to high GH in circulation). The main focus of this review is on the GH gene, the various gene alterations and their possible impact on the pituitary gland. However, although transcription factors regulating the pituitary gland development may cause multiple pituitary hormone deficiency, they may present initially as GHD. Conflict of interest:None declared. PMID:21274339

Pituitary response to thyrotropin releasing hormone in children with overweight and obesity.

PubMed

Rijks, Jesse; Penders, Bas; Dorenbos, Elke; Straetemans, Saartje; Gerver, Willem-Jan; Vreugdenhil, Anita

2016-08-03

Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9-5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r(2) = 0.484, p < 0.001) and the TSH incremental area under the curve during the TRH stimulation test (r(2) = 0.307, p < 0.001). These results suggest that pituitary TSH release in response to TRH stimulation might be an important factor contributing to high normal serum TSH concentrations, which is a regular finding in children with overweight and obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies.

Pituitary response to thyrotropin releasing hormone in children with overweight and obesity

PubMed Central

Rijks, Jesse; Penders, Bas; Dorenbos, Elke; Straetemans, Saartje; Gerver, Willem-Jan; Vreugdenhil, Anita

2016-01-01

Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9–5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r2 = 0.484, p < 0.001) and the TSH incremental area under the curve during the TRH stimulation test (r2 = 0.307, p < 0.001). These results suggest that pituitary TSH release in response to TRH stimulation might be an important factor contributing to high normal serum TSH concentrations, which is a regular finding in children with overweight and obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies. PMID:27485208

Pituitary gland and pregnancy.

PubMed

Foyouzi, Nastaran; Frisbaek, Yr; Norwitz, Errol R

2004-12-01

The hypothalamic-pituitary-adrenal axis is central to mammalian reproductive function, including conception, pregnancy maintenance, parturition, and breastfeeding. Pregnancy is associated with substantial physiologic changes within this endocrine axis to meet the demands of pregnancy, which include support of the fetus (volume support, nutritional and oxygen supply, clearance of fetal waste), protection of the fetus (from starvation, drugs, toxins), preparation of the uterus for labor, and protection of the mother from potential cardiovascular injury at delivery. This article reviews the anatomy, embryology, and physiology of the pituitary. The effect of pregnancy on pituitary structure and function, in health and disease, also is discussed.

A novel mutation in SOX3 polyalanine tract: a case of Kabuki syndrome with combined pituitary hormone deficiency harboring double mutations in MLL2 and SOX3.

PubMed

Takagi, Masaki; Ishii, Tomohiro; Torii, Chiharu; Kosaki, Kenjiro; Hasegawa, Tomonobu

2014-12-01

Both duplications encompassing SOX3 and loss-of function mutations in SOX3 have been reported in a minor portion of X-linked isolated growth hormone deficiency (GHD) or combined pituitary hormone deficiency (CPHD) patients with or without mental retardation. We report a Japanese male patient with molecularly confirmed Kabuki syndrome who was found to have CPHD. We analyzed all coding exons and flanking introns of currently known nine genes responsible for CPHD by PCR-based sequencing. In this CPHD patient, we identified a novel hemizygous 21-base pair deletion, resulting in the loss of 7 alanine residues from polyalanine (PA) tracts of SOX3. The clinically and endocrinologically normal mother of the patient carried the same deletion in a heterozygous manner. In vitro experiments showed that the del 7A SOX3 had increased transactivation of the HESX1 promoter. Our study provides additional evidence that deletion in PA tracts of SOX3 is associated with hypopituitarism. Female carriers of SOX3 PA tract deletions will show a broad phenotypic spectrum, ranging from clinically normal to CPHD.

[Late evaluation of the pituitary-gonadal axis in survivors of severe traumatic brain injury].

PubMed

Hohl, Alexandre; Daltrozo, Jordana Bernardi; Pereira, Camila Girardi; Weber, Thaís Rossoni; Pinto, Heyde Francine; Gullo, Jackson da Silva; Bernardini, Juçara Deitos; Coral, Marisa Helena César; Walz, Roger

2009-11-01

The purpose of this study is to evaluate pituitary function impairment in order to verify the prevalence of sex hormone deficiency and to analyze the profile of TBI population. Thirty patients were studied, 22 were male and 8 were female. All patients had their gonadal function assessed and they were evaluated at a median of 4 years post-trauma. The average age of the men was 38 years at the time of the evaluation, while the mean age of women was 42 years. The majority of TBI was related to traffic accidents (63.3%). Three patients (10%) had low FSH and only 1 patient (3.3%) had low LH. There was no biochemical evidence of hypogonadism in women. Two male patients presented low testosterone (9.1%) and were diagnosed with hypogonadism. Prolactin levels were normal in all patients. Two cases of hypogonadism (9.1%) were diagnosed among men in this study. It is therefore necessary that medical professionals involved in the management of TBI patients are aware of hypogonadism as a complication of TBI, in order to diagnose it early.

The glucagon test in the diagnosis of growth hormone deficiency in children with short stature younger than 6 years.

PubMed

Secco, Andrea; di Iorgi, Natascia; Napoli, Flavia; Calandra, Erika; Ghezzi, Michele; Frassinetti, Costanza; Parodi, Stefano; Casini, Maria Rosaria; Lorini, Renata; Loche, Sandro; Maghnie, Mohamad

2009-11-01

Few studies have addressed the diagnostic role of the glucagon test in children with suspected GH deficiency (GHD). The objective of the study was to investigate the diagnostic value of the glucagon test as an alternative test to insulin tolerance test (ITT) and arginine in GHD children younger than 6 yr. This study was conducted in two pediatric endocrinology centers. Forty-eight children (median age 4.2 yr, median height -3.0 sd score) with GHD confirmed by a peak GH to ITT and arginine less than 10 microg/liter (median 4.7 and 3.4 microg/liter, respectively) underwent a glucagon stimulation test. Magnetic resonance imaging showed normal hypothalamic-pituitary anatomy in 24 children, isolated anterior pituitary hypoplasia in seven, and structural hypothalamic-pituitary abnormalities in 17. Median GH peak response to glucagon (13.5 microg/liter) was significantly higher than that observed after ITT and arginine (P < 0.0001). GH peak after glucagon was less than 10 microg/liter in 20 subjects (group 1) and greater than 10 microg/liter in 28 subjects (group 2) without significant clinical or biochemical differences between the two groups. Median GH peak after glucagon was similar between patients with multiple pituitary hormone deficiency and those with isolated GHD and between subjects with and without structural hypothalamic-pituitary abnormalities. The magnitude of the GH peak after glucagon was negatively correlated to age at diagnosis (rho = -0.636, P < 0.0001). This study shows that glucagon has an effective GH-releasing activity and can be used to evaluate somatotroph function in young children with short stature. Normative data for this test in young children need to be established before its use in clinical practice.

[Acromegaly and pregnancy: report of six new cases].

PubMed

Persechini, M-L; Gennero, I; Grunenwald, S; Vezzosi, D; Bennet, A; Caron, P

2014-11-01

Pregnancies in acromegalic women are rare. Data from the literature indicate absence of congenital malformation in newborns, an increase of pituitary adenoma volume rarely clinically symptomatic, an increased risk of gestational diabetes and gravid hypertension in women with non-controlled GH/IGF-1 hypersecretion before gestation. The changes of somatotroph function are rarely described. Report of six new pregnancies in five women with acromegaly. Before pregnancy three women had incomplete surgical resection of GH-secreting pituitary adenoma, all were treated with somatostatin analogues, and the medical treatment was withdrawal at the diagnosis of gestation. We studied clinical (blood pressure, headaches, visual field), biological (blood glucose concentration) signs, GH and IGF-1 levels were measured during each trimester of pregnancy as well as in post-partum and were compared with pregestational values, MRI of the pituitary performed during the second trimester and in the post-partum were compared with MRI examen before pregnancy. All those pregnancies were normal without gestational diabetes, gravid hypertension and pituitary tumor syndrome. Clinical signs of acromegaly improved in 50 % of the patients, and IGF-1 decreased (22 %) in comparison of pregestational value without significant change in GH levels. No newborn had congenital malformation. Pregnancies in those women with acromegaly are uneventful without obstetrical or foetal complication, but a maternal follow-up is necessary in order to diagnose gravid hypertension and gestational diabetes. On the other hand, a clinical monitoring of pituitary tumor syndrome is necessary in women with non-operated GH-secreting macroadenoma before pregnancy. During the first trimester of gestation, an improvement of acromegalic signs can be due to a decrease of IGF-1 levels related to hepatic GH-resistance state secondary to physiological secretion of estrogens during gestation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Effects of growth hormone treatment on the pituitary expression of GHRH receptor mRNA in uremic rats.

PubMed

Ferrando, Susana; Rodríguez, Julián; Santos, Fernando; Weruaga, Ana; Fernández, Marta; Carbajo, Eduardo; García, Enrique

2002-09-01

A decreased ability of pituitary cells to secrete growth hormone (GH) in response to growth hormone releasing hormone (GHRH) stimulation has been shown in young uremic rats. The aim of the current study was to examine the effect of uremia and GH treatment on pituitary GHRH receptor expression. Pituitary GHRH receptor mRNA levels were analyzed by RNase protection assay in young female rats made uremic by subtotal nephrectomy, either untreated (UREM) or treated with 10 IU/kg/day of GH (UREM-GH), and normal renal function animals fed ad libitum (SAL) or pair-fed with the UREM group (SPF). Rats were sacrificed 14 days after the second stage nephrectomy. Renal failure was confirmed by concentrations (X +/- SEM) of serum urea nitrogen (mmol/L) and creatinine (micromol/L) in UREM (20 +/- 1 and 89.4 +/- 4.5) and UREM-GH (16 +/- 1 and 91.4 +/- 6.9) that were much higher (P < 0.001) than those of sham animals (SAL, 3 +/- 0 and 26.5 +/- 2.2; SPF, 4 +/- 0 and 26.5 +/- 2.1). UREM rats became growth retarded as shown by a daily longitudinal tibia growth rate below (P < 0.05) that observed in SAL animals (156 +/- 3 vs. 220 +/- 5 microm/day). GH treatment resulted in significant growth rate acceleration (213 +/- 6 microm/day). GHRH receptor mRNA levels were no different among the SAL (0.43 +/- 0.03), SPF (0.43 +/- 0.08) and UREM (0.44 +/- 0.04) groups, whereas UREM-GH rats had significantly higher values (0.72 +/- 0.07). The status of pituitary GHRH receptor is not modified by nutritional deficit or by severe uremia causing growth retardation. By contrast, the growth promoting effect of GH administration is associated with stimulated GHRH receptor gene expression.

A cellular and molecular basis for the selective desmopressin-induced ACTH release in Cushing disease patients: key role of AVPR1b receptor and potential therapeutic implications.

PubMed

Luque, R M; Ibáñez-Costa, A; López-Sánchez, L M; Jiménez-Reina, L; Venegas-Moreno, E; Gálvez, M A; Villa-Osaba, A; Madrazo-Atutxa, A M; Japón, M A; de la Riva, A; Cano, D A; Benito-López, P; Soto-Moreno, A; Gahete, M D; Leal-Cerro, A; Castaño, J P

2013-10-01

Desmopressin is a synthetic agonist of vasopressin receptors (AVPRs). The desmopressin stimulation test is used in the diagnosis and postsurgery prognosis of Cushing disease (CD). However, the cellular and molecular mechanisms underlying the desmopressin-induced ACTH increase in patients with CD are poorly understood. The objectives of this study were to determine, for the first time, whether desmopressin acts directly and exclusively on pituitary corticotropinoma cells to stimulate ACTH expression/release and to elucidate the cellular and molecular mechanisms involved in desmopressin-induced ACTH increase in CD. A total of 8 normal pituitaries (NPs), 23 corticotropinomas, 14 nonfunctioning pituitary adenomas, 17 somatotropinomas, and 3 prolactinomas were analyzed for AVPR expression by quantitative real-time RT-PCR. Primary cultures derived from corticotropinomas, nonfunctioning pituitary adenomas, somatotropinomas, prolactinomas, and NPs were treated with desmopressin, and ACTH secretion/expression, [Ca(2+)]i kinetics, and AVPR expression and/or proliferative response were evaluated. The relationship between AVPR expression and plasma adrenocorticotropin/cortisol levels obtained from desmopressin tests was assessed. Desmopressin affects all functional parameters evaluated in corticotropinoma cells but not in NPs or other pituitary adenomas cells. These effects might be due to the dramatic elevation of AVPR1b expression levels found in corticotropinomas. In line with this notion, the use of an AVPR1b antagonist completely blocked desmopressin stimulatory effects. Remarkably, only AVPR1b expression was positively correlated with elevated plasma adrenocorticotropin levels in corticotropinomas. The present results provide a cellular and molecular basis to support the desmopressin stimulation test as a reliable, specific test for the diagnosis and postsurgery prognosis of CD. Furthermore, our data indicate that AVPR1b is responsible for the direct/exclusive desmopressin stimulatory pituitary effects observed in CD, thus opening the possibility of exploring AVPR1b antagonists as potential therapeutic tools for CD treatment.

Sex differences in the effect of acute peripheral IL-1β administration on the brain and serum BDNF and VEGF expression in rats.

PubMed

Obuchowicz, Ewa; Nowacka, Marta; Paul-Samojedny, Monika; Bielecka-Wajdman, Anna M; Małecki, Andrzej

2017-02-01

The present study was designed to evaluate, for the first time, the potential sex differences in BDNF and VEGF systems under normal conditions and in response to IL-1β given ip. Peripheral overproduction of this cytokine mediates the pathophysiology of various acute neuroinflammatory states. Until now, the effect of IL-1β on VEGF expression in rat brain structures and its serum level has not been examined. In male and female rats, the BDNF and VEGF mRNA expression, and BDNF level were evaluated in the amygdala, hippocampus, hypothalamus and pituitary gland. The VEGF levels were determined in the pituitary. Serum BDNF and VEGF levels were also measured. The pituitary BDNF mRNA, and BDNF and VEGF levels were higher in females than in male rats whereas in males, the BDNF levels were higher in the other brain structures. The serum BDNF concentration was similar in both groups but VEGF levels were enhanced in females. Following IL-1β (50μg/kg ip.) administration, a higher serum IL-1β level was detected in females than in males. In male rats, IL-1β decreased BDNF mRNA in all the brain structures, except for the pituitary, and VEGF mRNA in the amygdala. In opposite, IL-1β challenge in females increased the pituitary VEGF mRNA and serum BDNF and VEGF levels. These results suggest that in females BDNF and VEGF may play a more important role in the pituitary function. In males, amygdala trophic system seems to be especially sensitive to the enhanced peripheral IL-1β production. Our findings point to the need to consider sex-related differences to be able to draw reliable conclusions about changes in BDNF and VEGF levels during inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pituitary iron and volume imaging in healthy controls.

PubMed

Noetzli, L J; Panigrahy, A; Hyderi, A; Dongelyan, A; Coates, T D; Wood, J C

2012-02-01

Patients with transfusional iron overload develop iron deposits in the pituitary gland, which are associated with volume loss and HH. The purpose of this study was to characterize R2 and volumetric data in a healthy population for diagnostic use in patients with transfusional iron overload. One hundred healthy controls without iron overload between the ages of 2 and 48 were recruited to have MR imaging of the brain to assess their pituitary R2 and volume. Pituitary R2 was assessed with a 8-echo spin-echo sequence, and pituitary volumes, by a 3D spoiled gradient-echo sequence with 1-mm(3) resolution. A 2-component continuous piecewise linear approximation was used for creating volumetric and R2 nomograms. Equations were generated from regression relationships for convenient z-score calculation. Pituitary R2 rose weakly with age (r(2) = 0.19, P < .0001). Anterior and total pituitary volumes increased steadily up to 18 years of age, after which volume slightly decreased. Females had larger pituitary glands, most likely representing their larger lactotroph population. From these data, a clinician can calculate the z scores for R2 and pituitary volume in patients with iron overload. Normal ranges are well-differentiated from values previously associated with endocrine disease in transfusional siderosis; this finding suggests that preclinical iron overload can be recognized and appropriately treated.

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2014-08-01

outcome. At 6 months post injury, patients will be screened for anterior pituitary function f the 61 mTBI subjects with IGF-1 results at the 6 month... anterior pituitary function, including somatomedin (IGF-1), thyroid stimulating hormone (TSH), thyroxine (Free T4), prolactin, and total cortisol in...resolution of PCS at six months after mTBI. We will also examine the incidence of single and multiple pituitary hormone deficiencies. The clinical

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2013-08-01

injury, patients will be screened for anterior pituitary function of the 56 mTBI subjects with IGF-1 results, of the 63 who completed the 6 month... anterior pituitary function, including somatomedin (IGF -1 ), thyroid stimulating hormone (TSH), thyroxine (Free T4), prolactin, and total cortisol in all...resolution of PCS at six months after mTBI. We will also examine the incidence of single and multiple pituitary hormone deficiencies. The clinical

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2011-08-01

patients will be screened for anterior pituitary function. 67 subjects have been recruited as of July 31, 2011; 26 have reached the 6 month point...and resolution of PCS at six months after MTBI. At 6 months post-injury, patients will be screened for anterior pituitary function by measuring...IGF1, total testosterone in males, 17 beta estradiols in females, prolactin, TSH, and morning cortisols. The incidence of single and multiple pituitary

Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes.

PubMed

Mehta, M K; Garde, S V; Sheth, A R

1995-01-01

To compare the distribution of peptide hormones in presumably normal human testicular tissues and specimens exhibiting any of five pathologies. Biopsies from patients having testicular malfunctions were prepared as sections and specifically immunohistochemically stained for inhibin, FSH, serotonin, AUP, and oxytocin. Immunocytochemical studies revealed the presence of various hypophysial-pituitary-intestinal hormones, viz., FSH, inhibin, arginine vasopressin (AVP), calcitonin, serotonin, oxytocin, adrenocorticotropin (ACTH), gastrin, secretin, and somatostatin in human testicular biopsies exhibiting normal spermatogenesis, Sertoli-cell-only syndrome, spermatogenic arrest, Leydig cell hyperplasia, Leydig cell tumor, and seminoma. Intensity of immunostaining for all peptides except FSH was stronger in cases of subfertile as compared to normal testis. Intensity of immunostaining with inhibin was maximum in Leydig cell tumor. These regulatory peptides may be involved in the pathophysiology of the testes.

The role of polyhalogenated aromatic hydrocarbons on thyroid hormone disruption and cognitive function: a review.

PubMed

Builee, T L; Hatherill, J R

2004-11-01

Thyroid hormones (TH) are essential to normal brain development, influencing behavior and cognitive function in both adult and children. It is suggested that conditions found in TH abnormalities such as hypothyroidism, hyperthyroidism and generalized resistance to thyroid hormone (GRTH) share symptomatic behavioral impulses found in cases of attention deficit hyperactivity disorder (ADHD) and other cognitive disorders. Disrupters of TH are various and prevalent in the environment. This paper reviews the mechanisms of TH disruption caused by the general class of polyhalogenated aromatic hydrocarbons (PHAH)'s acting as thyroid disrupters (TD). PHAHs influence the hypothalamus-pituitary-thyroid (HPT) axis, as mimicry agents affecting synthesis and secretion of TH. Exposure to PHAH induces liver microsomal enzymes UDP-glucuronosyltransferase (UGT) resulting in accelerated clearance of TH. PHAHs can compromise function of transport and receptor binding proteins such as transthyretin and aryl hydrocarbon receptors (Ahr). Glucose metabolism and catecholamine synthesis are disrupted in the brain by the presence of PHAH. Further, PHAH can alter brain growth and development by perturbing cytoskeletal formation, thereby affecting neuronal migration, elongation and branching. The complex relationships between PHAH and cognitive function are examined in regard to the disruption of T4 regulation in the hypothalamus-pituitary-thyroid axis, blood, brain, neurons, liver and pre and postnatal development.

Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas: Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region.

PubMed

Casar-Borota, Olivera; Botling, Johan; Granberg, Dan; Stigare, Jerker; Wikström, Johan; Boldt, Henning Bünsow; Kristensen, Bjarne Winther; Pontén, Fredrik; Trouillas, Jacqueline

2017-09-01

Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.

Somatotroph Hyperplasia

PubMed Central

Thorner, M. O.; Perryman, R. L.; Cronin, M. J.; Rogol, A. D.; Draznin, M.; Johanson, A.; Vale, W.; Horvath, E.; Kovacs, K.

1982-01-01

A 21-yr-old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growth hormone (GH) (95±9.4 ng/ml; mean±SEM) and somatomedin C (11 U/ml) levels were elevated, and an increase in GH levels after glucose instead of normal suppression, increase after thyrotropin-releasing hormone (TRH) administration instead of no change, and decrease after dopamine administration instead of stimulation were observed. The pituitary fossa volume was greater than normal (1,440 mm3) and the presence of a pituitary tumor was assumed. After tissue removal at transsphenoidal surgery, histological study revealed somatotroph hyperplasia rather than a discrete adenoma. Postoperatively, she remained clinically acromegalic and continued to show increased GH and somatomedin levels. A search was made for ectopic source of a growth hormone-releasing factor (GRF). Computer tomographic scan revealed a 5-cm Diam tumor in the tail of the pancreas. Following removal of this tumor, serum GH fell from 70 to 3 ng/ml over 2 h, and remained low for the subsequent 5 mo. Serum somatomedin C levels fell from 7.2 to normal by 6 wk postoperatively. There were no longer paradoxical GH responses to glucose, TRH, and dopamine. Both the medium that held the tumor cells at surgery and extracts of the tumor contained a peptide with GRF activity. The GRF contained in the tumor extract coeluted on Sephadex G-50 chromatography with rat hypothalamic GH-releasing activity. Stimulation of GH from rat somatotrophs in vitro was achieved at the nanomolar range, using the tumor extract. The patient's course demonstrates the importance of careful interpretation of pituitary histology. Elevated serum GH and somatomedin C levels in a patient with an enlarged sella turcica and the characteristic responses seen in acromegaly to TRH, dopamine, and glucose do not occur exclusively in patients with discrete pituitary tumors and acromegaly. This condition can also occur with somatotroph hyperplasia and then revert to normal after removal of the GRF source. Thus, in patients with acromegaly a consideration of ectopic GRF secretion should be made, and therefore, careful pituitary histology is mandatory. Consideration for chest and abdominal computer tomographic scans before pituitary surgery, in spite of their low yield, may be justified. Images PMID:6290540

Leptin inhibits testosterone secretion from adult rat testis in vitro.

PubMed

Tena-Sempere, M; Pinilla, L; González, L C; Diéguez, C; Casanueva, F F; Aguilar, E

1999-05-01

Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed adult rats. In addition, 10(-9) M leptin inhibited LH and FSH secretion by incubated hemi-pituitaries from fasted adult males, whereas, at all doses tested, it was ineffective in modulating PRL release. Our results show that leptin, depending on the state of sexual maturation, is able to inhibit testosterone secretion acting at the testicular level. Furthermore, the present data suggest that the actions of leptin on the reproductive system are complex and are probably carried out at different levels of the hypothalamic-pituitary-gonadal axis.

TSH-induced hyperthyroidism caused by a pituitary tumor.

PubMed

Beck-Peccoz, Paolo; Persani, Luca

2006-09-01

A 45-year-old man presented with frontal headache and visual disturbances to our clinic. For the previous 5 years, he had been receiving treatment for long-lasting mild hyperthyroidism with antithyroid therapy, but therapy had not been carefully followed. During the last 2 years he had also complained of erectile dysfunction and loss of libido. On physical examination, he had a small goiter, normal skin, no Graves' ophthalmopathy, normal BMI, and reduced testis volume and pubic hair. Serum levels of free T3 and T4, serum prolactin, testosterone, serum gonadotropins, insulin-like growth factor 1, adrenocorticotropic hormone, and cortisol were measured. MRI scan, TSH-releasing hormone test, and T3 suppression test were carried out. Levels of pituitary glycoprotein hormone alpha-subunit and sex-hormone-binding protein were also measured. Hyperthyroidism caused by a mixed pituitary adenoma that secretes prolactin and TSH. Trans-sphenoidal resection of the pituitary tumor. After surgery, T3 suppression test failed to completely suppress TSH secretion, which suggested a persistence of residual adenomatous cells. Hyperthyroidism and hypogonadism recurred after 5 years, therefore, treatment with lanreotide was initiated, and resulted in complete resolution of signs and symptoms of the disease.

Decreased expression of SFRP2 promotes development of the pituitary corticotroph adenoma by upregulating Wnt signaling

PubMed Central

Sun, Yuhao; Pan, Sijian; Gu, Changwei; Chen, Xiao; Wang, Weiqing; Ning, Guang; Bian, Liuguan; Sun, Qingfang

2018-01-01

Cushing's disease is primarily caused by pituitary adrenocorticotropin-secreting adenoma. However, its pathogenesis has remained obscure. In the present study, whole transcriptome analysis was performed by RNA sequencing (RNA-Seq) and expression of secreted frizzled-related protein 2 (SFRP2) was decreased in corticotroph tumors compared with normal pituitary glands. Furthermore, the RNA-Seq results were validated and the expression of SFRP2 in tumor tissues was analyzed by comparing another cohort of 23 patients with Cushing's disease and 3 normal human pituitary samples using reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemistry staining. Clinically, there was an association between lower SFRP2 expression and aggressive adenoma characteristics, including larger size and invasiveness. Conversely, SFRP2 overexpression reduced the ability of AtT20 cells to proliferate and migrate, and reduced production of the adrenocorticotrophic hormone in vitro. Mechanistically, overexpressed SFRP2 reduced the level of β-catenin in the cytoplasm and nucleus, and decreased Wnt signaling activity in AtT20 cells. Therefore, SFRP2 appears to act as a tumor suppressor in Cushing's disease by regulating the activity of the Wnt signaling pathway. PMID:29620167

Genetic disorders of the anterior pituitary gland.

PubMed

Teller, W M

1985-01-01

This survey deals with disorders caused by genetically disturbed function of the anterior pituitary gland. Genetic Dwarfism may be caused by isolated growth hormone deficiency (IGHD) or panpituitary diseases, such as congenital absence of the pituitary or familial panhypopituitarism. Genetic disturbances of isolated pituitary hormone secretion without dwarfism may occur as isolated gonadotropin deficiency (IGD), isolated luteinizing hormone deficiency ("fertile eunuch"), Kallmann syndrome (olfactogenital dysplasia), isolated thyrotropin deficiency (ITD) and isolated corticotropin deficiency (ICD). Pituitary dysfunction may also be associated with other genetic disease entities.

Analysis of mouse models carrying the I26T and R160C substitutions in the transcriptional repressor HESX1 as models for septo-optic dysplasia and hypopituitarism

PubMed Central

Sajedi, Ezat; Gaston-Massuet, Carles; Signore, Massimo; Andoniadou, Cynthia L.; Kelberman, Daniel; Castro, Sandra; Etchevers, Heather C.; Gerrelli, Dianne; Dattani, Mehul T.; Martinez-Barbera, Juan Pedro

2008-01-01

SUMMARY A homozygous substitution of the highly conserved isoleucine at position 26 by threonine (I26T) in the transcriptional repressor HESX1 has been associated with anterior pituitary hypoplasia in a human patient, with no forebrain or eye defects. Two individuals carrying a homozygous substitution of the conserved arginine at position 160 by cysteine (R160C) manifest septo-optic dysplasia (SOD), a condition characterised by pituitary abnormalities associated with midline telencephalic structure defects and optic nerve hypoplasia. We have generated two knock-in mouse models containing either the I26T or R160C substitution in the genomic locus. Hesx1I26T/I26T embryos show pituitary defects comparable with Hesx1−/− mouse mutants, with frequent occurrence of ocular abnormalities, although the telencephalon develops normally. Hesx1R160C/R160C mutants display forebrain and pituitary defects that are identical to those observed in Hesx1−/− null mice. We also show that the expression pattern of HESX1 during early human development is very similar to that described in the mouse, suggesting that the function of HESX1 is conserved between the two species. Together, these results suggest that the I26T mutation yields a hypomorphic allele, whereas R160C produces a null allele and, consequently, a more severe phenotype in both mice and humans. PMID:19093031

Extracellular signal-regulated kinase 1 and 2 are not required for GnRH neuron development and normal female reproductive axis function in mice.

PubMed

Wierman, Margaret E; Xu, Mei; Pierce, A; Bliesner, B; Bliss, S P; Roberson, M S

2012-01-01

Selective deletion of extracellular signal-regulated kinase (ERK) 1 and ERK2 in the pituitary gonadotrope and ovarian granulosa cells disrupts female reproductive axis function. Thus, we asked if ERK1 and ERK2 are critical for GnRH neuron ontogeny or the central control of female reproductive function. GnRH-Cre-recombinase (Cre+) expressing mice were crossed with mice with a global deletion of ERK1 and a floxed ERK2 allele (Erk1-/Erk2fl/fl) to selectively delete ERK2 in GnRH neurons. Cre-recombinase mRNA was selectively expressed in the brain of Cre+ mice. GnRH neuron number and location were determined during embryogenesis and in the adult. GnRH neuron counts at E15 did not differ between experimental and control groups (1,198 ± 65 and 1,160 ± 80 respectively, p = NS). In adults, numbers of GnRH neurons in the GnRHCre+Erk1-/Erk2- mice (741 ± 157) were similar to those in controls (756 ± 7), without alteration in their distribution across the forebrain. ERK1 and 2 deficiency did not alter the timing of vaginal opening, age at first estrus, or estrous cyclicity. Although ERK1 and 2 are components of a dominant signaling pathway in GnRH neuronal cells that modulates survival and control of GnRH gene expression, other signaling pathways compensate for their deletion in vivo to allow GnRH neuron survival and targeting and normal onset of female sexual maturation and reproductive function. In contrast to effects at the pituitary and the ovary, ERK1 and ERK2 are dispensable at the level of the GnRH neuron. Copyright © 2011 S. Karger AG, Basel.

Serotonin involvement in pituitary-adrenal function

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.; Kellar, K. J.; Kent, D.; Gonzales, C.; Berger, P. A.; Barchas, J. D.

1977-01-01

Experiments clarifying the effects of serotonin (5-HT) in the regulation of the hypothalamic-pituitary-adrenocortical system are surveyed. Lesion experiments which seek to determine functional maps of serotonergic input to areas involved in regulation are reported. Investigations of the effects of 5-HT levels on the plasma ACTH response to stress and the diurnal variation in basal plasma corticosterone are summarized, and the question of whether serotonergic transmission is involved in the regulation of all aspects of pituitary-adrenal function is considered with attention to the stimulatory and inhibitory action of 5-HT.

Absence of opioid stress-induced analgesia in mice lacking beta-endorphin by site-directed mutagenesis.

PubMed

Rubinstein, M; Mogil, J S; Japón, M; Chan, E C; Allen, R G; Low, M J

1996-04-30

A physiological role for beta-endorphin in endogenous pain inhibition was investigated by targeted mutagenesis of the proopiomelanocortin gene in mouse embryonic stem cells. The tyrosine codon at position 179 of the proopiomelanocortin gene was converted to a premature translational stop codon. The resulting transgenic mice display no overt developmental or behavioral alterations and have a normally functioning hypothalamic-pituitary-adrenal axis. Homozygous transgenic mice with a selective deficiency of beta-endorphin exhibit normal analgesia in response to morphine, indicating the presence of functional mu-opiate receptors. However, these mice lack the opioid (naloxone reversible) analgesia induced by mild swim stress. Mutant mice also display significantly greater nonopioid analgesia in response to cold water swim stress compared with controls and display paradoxical naloxone-induced analgesia. These changes may reflect compensatory upregulation of alternative pain inhibitory mechanisms.

Hormones and the bone marrow: panhypopituitarism and pancytopenia in a man with a pituitary adenoma.

PubMed

Lang, Dianna; Mead, Jennifer S; Sykes, David B

2015-05-01

In rare cases, pancytopenia results from hormonal deficiencies that arise in the setting of panhypopituitarism. Here we describe the unusual case of a 60-year-old man who presented with progressive fatigue and polyuria, and whose laboratory workup revealed a deficiency of the five hormones associated with the action of the anterior pituitary (thyroid hormone, testosterone, cortisol, prolactin, and insulin-like growth factor-1). Imaging of the pituitary demonstrated a cystic mass consistent with a pituitary adenoma replacing much of the normal pituitary tissue. His symptoms and hematologic abnormalities rapidly resolved with prednisone and levothyroxine supplementation. While the majority of reported cases of panhypopituitarism with bone marrow suppression are the result of peripartum sepsis or hemorrhage leading to pituitary gland necrosis (Sheehan's syndrome), it is also important to consider the diagnosis of hypopituitarism in patients with hypothyroidism, low cortisol levels, and pancytopenia. The causal relationship between pancytopenia and panhypopituitarism is not well understood, though it does reinforce the important influence of these endocrine hormones on the health of the bone marrow.

Thyrotropin-secreting pituitary adenomas: biological and molecular features, diagnosis and therapy.

PubMed

Losa, M; Fortunato, M; Molteni, L; Peretti, E; Mortini, P

2008-12-01

Central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism, representing 0.5-1.0% of all pituitary adenomas. The etiopathogenesis of TSH-secreting-adenomas is unknown and no definite role for various oncogenes has been proven. Patients with TSH-secreting adenoma usually present with signs and symptoms of hyperthyroidism milder than those in patients with hyperthyroidism of thyroid origin, in addition to symptoms secondary to mass effects of the pituitary tumour. Mixed pituitary tumours co-secrete growth hormone and prolactin. The characteristic biochemical abnormalities are normal or high serum TSH concentrations in the presence of elevated total and/or free thyroid hormones concentrations. Measurement of markers of peripheral thyroid hormone action and dynamic tests may aid in the differential diagnosis with the syndrome of resistance to thyroid hormone. Neuroimaging is fundamental to visualize the pituitary tumor. Therapy of TSH-secreting adenomas can be accomplished by surgery, radiation therapies, and medical treatment with somatostatin analogs or dopamine agonists. Nowadays, and in contrast with the first reports on this rare disease, most patients are well controlled by current therapies.

Adrenocorticotropin-producing pituitary carcinoma with liver metastasis.

PubMed

Lormeau, B; Miossec, P; Sibony, M; Valensi, P; Attali, J R

1997-04-01

We report here the extremely rare case of a twenty-eight year-old woman with a metastatic ACTH-secreting pituitary carcinoma. This is the thirteenth case to be described in the literature. Ten years ago Cushing's disease was diagnosed. After pituitary surgery, then bilateral adrenalectomy, a Nelson's syndrome appeared. The particularly extensive pituitary secondary development led to several pituitary surgical procedures, radiotherapy, and octreotide treatment. Eight years after Cushing's disease was diagnosed, liver tumors were discovered. Pathological examination and ACTH immunostaining demonstrated the secretory nature of these metastases. The lack of ectopic tumor, the LPH/ACTH equimolar ratio and a study of the plasma proopiomelanocortin derivatives by HPLC showed that the ACTH secretion originated in pituitary tissues (in situ and liver metastases). The processing of POMC seems thus to be normal in this kind of tumor and metastases. Intact POMC levels were very high, indicating an aggressive tumor, and ACTH/LPH production was paradoxically stimulated by octreotide. This case is also exceptional because of the slow development of the disease, which may be due to the complementary hepatic chemoembolization treatment.

Treatment of pituitary gigantism with the growth hormone receptor antagonist pegvisomant.

PubMed

Goldenberg, Naila; Racine, Michael S; Thomas, Pamela; Degnan, Bernard; Chandler, William; Barkan, Ariel

2008-08-01

Treatment of pituitary gigantism is complex and the results are usually unsatisfactory. The objective of the study was to describe the results of therapy of three children with pituitary gigantism by a GH receptor antagonist, pegvisomant. This was a descriptive case series of up to 3.5 yr duration. The study was conducted at a university hospital. Patients included three children (one female, two males) with pituitary gigantism whose GH hypersecretion was incompletely controlled by surgery, somatostatin analog, and dopamine agonist. The intervention was administration of pegvisomant. Plasma IGF-I and growth velocity were measured. In all three children, pegvisomant rapidly decreased plasma IGF-I concentrations. Growth velocity declined to subnormal or normal values. Statural growth fell into lower growth percentiles and acromegalic features resolved. Pituitary tumor size did not change in two children but increased in one boy despite concomitant therapy with a somatostatin analog. Pegvisomant may be an effective modality for the therapy of pituitary gigantism in children. Titration of the dose is necessary for optimal efficacy, and regular surveillance of tumor size is mandatory.

Phenotypical and Pharmacological Characterization of Stem-Like Cells in Human Pituitary Adenomas.

PubMed

Würth, Roberto; Barbieri, Federica; Pattarozzi, Alessandra; Gaudenzi, Germano; Gatto, Federico; Fiaschi, Pietro; Ravetti, Jean-Louis; Zona, Gianluigi; Daga, Antonio; Persani, Luca; Ferone, Diego; Vitale, Giovanni; Florio, Tullio

2017-09-01

The presence and functional role of tumor stem cells in benign tumors, and in human pituitary adenomas in particular, is a debated issue that still lacks a definitive formal demonstration. Fifty-six surgical specimens of human pituitary adenomas were processed to establish tumor stem-like cultures by selection and expansion in stem cell-permissive medium or isolating CD133-expressing cells. Phenotypic and functional characterization of these cells was performed (1) ex vivo, by immunohistochemistry analysis on paraffin-embedded tissues; (2) in vitro, attesting marker expression, proliferation, self-renewal, differentiation, and drug sensitivity; and (3) in vivo, using a zebrafish model. Within pituitary adenomas, we identified rare cell populations expressing stem cell markers but not pituitary hormones; we isolated and expanded in vitro these cells, obtaining fibroblast-free, stem-like cultures from 38 pituitary adenoma samples. These cells grow as spheroids, express stem cell markers (Oct4, Sox2, CD133, and nestin), show sustained in vitro proliferation as compared to primary cultures of differentiated pituitary adenoma cells, and are able to differentiate in hormone-expressing pituitary cells. Besides, pituisphere cells, apparently not tumorigenic in mice, engrafted in zebrafish embryos, inducing pro-angiogenic and invasive responses. Finally, pituitary adenoma stem-like cells express regulatory pituitary receptors (D2R, SSTR2, and SSTR5), whose activation by a dopamine/somatostatin chimeric agonist exerts antiproliferative effects. In conclusion, we provide evidence that human pituitary adenomas contain a subpopulation fulfilling biological and phenotypical signatures of tumor stem cells that may represent novel therapeutic targets for therapy-resistant tumors.

[Pituitary function of dysgenesic femal rats. Studies with grafting method].

PubMed

Vanhems, E; Busquet, J

1975-01-01

Misulban administered to pregnant rats on the 15th day of gestation provoked gonadal dysgenesia in the offspring. Study of the pituitary function of dysgenesic female rats, realized by grafting method, showed gonadotrophic hypersecretion.

A five year prospective investigation of anterior pituitary function after traumatic brain injury: is hypopituitarism long-term after head trauma associated with autoimmunity?

PubMed

Tanriverdi, Fatih; De Bellis, Annamaria; Ulutabanca, Halil; Bizzarro, Antonio; Sinisi, Antonio A; Bellastella, Giuseppe; Amoresano Paglionico, Vanda; Dalla Mora, Liliana; Selcuklu, Ahmed; Unluhizarci, Kursad; Casanueva, Felipe F; Kelestimur, Fahrettin

2013-08-15

Traumatic brain injury (TBI) has been recently recognized as a common cause of pituitary dysfunction. However, there are not sufficient numbers of prospective studies to understand the natural history of TBI induced hypopituitarism. The aim was to report the results of five years' prospective follow-up of anterior pituitary function in patients with mild, moderate and severe TBI. Moreover, we have prospectively investigated the associations between TBI induced hypopituitarism and presence of anti-hypothalamus antibodies (AHA) and anti-pituitary antibodies (APA). Twenty five patients (20 men, five women) were included who were prospectively evaluated 12 months and five years after TBI, and 17 of them also had a third-year evaluation. Growth hormone (GH) deficiency is the most common pituitary hormone deficit at one, three, and five years after TBI. Although most of the pituitary hormone deficiencies improve over time, there were substantial percentages of pituitary hormone deficiencies at the fifth year (28% GH, 4% adrenocorticotropic hormone [ACTH], and 4% gonadotropin deficiencies). Pituitary dysfunction was significantly higher in strongly AHA- and APA-positive (titers ≥1/16) patients at the fifth year. In patients with mild and moderate TBI, ACTH and GH deficiencies may improve over time in a considerable number of patients but, although rarely, may also worsen over the five-year period. However in severe TBI, ACTH and GH status of the patients at the first year evaluation persisted at the fifth year. Therefore, screening pituitary function after TBI for five years is important, especially in patients with mild TBI. Moreover, close strong associations between the presence of high titers of APA and/or AHA and hypopituitarism at the fifth year were shown for the first time.

A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and Gender-Specific Differences in the Regulation of Thyroid Function

PubMed Central

Volpato, Claudia B.; Wilson, Scott G.; Cappola, Anne R.; Bos, Steffan D.; Deelen, Joris; den Heijer, Martin; Freathy, Rachel M.; Lahti, Jari; Liu, Chunyu; Lopez, Lorna M.; Nolte, Ilja M.; O'Connell, Jeffrey R.; Tanaka, Toshiko; Trompet, Stella; Arnold, Alice; Bandinelli, Stefania; Beekman, Marian; Böhringer, Stefan; Brown, Suzanne J.; Buckley, Brendan M.; Camaschella, Clara; de Craen, Anton J. M.; Davies, Gail; de Visser, Marieke C. H.; Ford, Ian; Forsen, Tom; Frayling, Timothy M.; Fugazzola, Laura; Gögele, Martin; Hattersley, Andrew T.; Hermus, Ad R.; Hofman, Albert; Houwing-Duistermaat, Jeanine J.; Jensen, Richard A.; Kajantie, Eero; Kloppenburg, Margreet; Lim, Ee M.; Masciullo, Corrado; Mariotti, Stefano; Minelli, Cosetta; Mitchell, Braxton D.; Nagaraja, Ramaiah; Netea-Maier, Romana T.; Palotie, Aarno; Persani, Luca; Piras, Maria G.; Psaty, Bruce M.; Räikkönen, Katri; Richards, J. Brent; Rivadeneira, Fernando; Sala, Cinzia; Sabra, Mona M.; Sattar, Naveed; Shields, Beverley M.; Soranzo, Nicole; Starr, John M.; Stott, David J.; Sweep, Fred C. G. J.; Usala, Gianluca; van der Klauw, Melanie M.; van Heemst, Diana; van Mullem, Alies; H.Vermeulen, Sita; Visser, W. Edward; Walsh, John P.; Westendorp, Rudi G. J.; Widen, Elisabeth; Zhai, Guangju; Cucca, Francesco; Deary, Ian J.; Eriksson, Johan G.; Ferrucci, Luigi; Fox, Caroline S.; Jukema, J. Wouter; Kiemeney, Lambertus A.; Pramstaller, Peter P.; Schlessinger, David; Shuldiner, Alan R.; Slagboom, Eline P.; Uitterlinden, André G.; Vaidya, Bijay; Visser, Theo J.; Wolffenbuttel, Bruce H. R.; Meulenbelt, Ingrid; Rotter, Jerome I.; Spector, Tim D.; Hicks, Andrew A.; Toniolo, Daniela; Sanna, Serena; Peeters, Robin P.; Naitza, Silvia

2013-01-01

Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism. PMID:23408906

Expression of a Rho guanine nucleotide exchange factor, Ect2, in the developing mouse pituitary.

PubMed

Islam, M S; Tsuji, T; Higashida, C; Takahashi, M; Higashida, H; Koizumi, K

2010-05-01

The pituitary gland is a highly mitotically active tissue after birth. Various cell types are known to undergo proliferation in the anterior pituitary. However, little is known about the mechanisms regulating mitotic activity in this tissue. When searching for genes specifically expressed in the pituitary gland among those that we previously screened in Drosophila, we found epithelial cell-transforming gene 2 (Ect2). Ect2 is a guanine nucleotide exchange factor for Rho GTPases, which is known to play an essential role in cytokinesis. Although there have been many cellular studies regarding the function of Ect2, the temporal and spatial expression patterns of Ect2 in vivo have not been determined. In the present study, we examined the postnatal developmental expression of Ect2 in the mouse pituitary. Enhanced Ect2 expression was detected in the mouse pituitary gland during the first 3 weeks after birth, which coincided well with the period of rapid pituitary expansion associated with increased growth rate. Immunostaining analysis showed that Ect2-expressing cells were distributed in the anterior and intermediate lobes, but not the posterior lobe, of the pituitary. These Ect2-expressing cells frequently incorporated the thymidine analogue, EdU (5-ethynyl-2'-deoxyuridine), indicating that these cells were mitotically active. Taken together, the results demonstrate the functional role of Ect2 in postnatal proliferating cells in the two lobes of the pituitary, thereby suggesting roles in developmental growth of the mammalian pituitary.

Epithelial cell integrin β1 is required for developmental angiogenesis in the pituitary gland

PubMed Central

Scully, Kathleen M.; Skowronska-Krawczyk, Dorota; Krawczyk, Michal; Merkurjev, Daria; Taylor, Havilah; Livolsi, Antonia; Tollkuhn, Jessica; Stan, Radu V.; Rosenfeld, Michael G.

2016-01-01

As a key component of the vertebrate neuroendocrine system, the pituitary gland relies on the progressive and coordinated development of distinct hormone-producing cell types and an invading vascular network. The molecular mechanisms that drive formation of the pituitary vasculature, which is necessary for regulated synthesis and secretion of hormones that maintain homeostasis, metabolism, and endocrine function, remain poorly understood. Here, we report that expression of integrin β1 in embryonic pituitary epithelial cells is required for angiogenesis in the developing mouse pituitary gland. Deletion of pituitary epithelial integrin β1 before the onset of angiogenesis resulted in failure of invading endothelial cells to recruit pericytes efficiently, whereas deletion later in embryogenesis led to decreased vascular density and lumen formation. In both cases, lack of epithelial integrin β1 was associated with a complete absence of vasculature in the pituitary gland at birth. Within pituitary epithelial cells, integrin β1 directs a large transcriptional program that includes components of the extracellular matrix and associated signaling factors that are linked to the observed non–cell-autonomous effects on angiogenesis. We conclude that epithelial integrin β1 functions as a critical and canonical regulator of developmental angiogenesis in the pituitary gland, thus providing insight into the long-standing systems biology conundrum of how vascular invasion is coordinated with tissue development. PMID:27810956

Lineage-Specific Restraint of Pituitary Gonadotroph Cell Adenoma Growth

PubMed Central

Chesnokova, Vera; Zonis, Svetlana; Zhou, Cuiqi; Ben-Shlomo, Anat; Wawrowsky, Kolja; Toledano, Yoel; Tong, Yunguang; Kovacs, Kalman; Scheithauer, Bernd; Melmed, Shlomo

2011-01-01

Although pituitary adenomas are usually benign, unique trophic mechanisms restraining cell proliferation are unclear. As GH-secreting adenomas are associated with p53/p21-dependent senescence, we tested mechanisms constraining non-functioning pituitary adenoma growth. Thirty six gonadotroph-derived non-functioning pituitary adenomas all exhibited DNA damage, but undetectable p21 expression. However, these adenomas all expressed p16, and >90% abundantly expressed cytoplasmic clusterin associated with induction of the Cdk inhibitor p15 in 70% of gonadotroph and in 26% of somatotroph lineage adenomas (p = 0.006). Murine LβT2 and αT3 gonadotroph pituitary cells, and αGSU.PTTG transgenic mice with targeted gonadotroph cell adenomas also abundantly expressed clusterin and exhibited features of oncogene-induced senescence as evidenced by C/EBPβ and C/EBPδ induction. In turn, C/EBPs activated the clusterin promoter ∼5 fold, and elevated clusterin subsequently elicited p15 and p16 expression, acting to arrest murine gonadotroph cell proliferation. In contrast, specific clusterin suppression by RNAis enhanced gonadotroph proliferation. FOXL2, a tissue-specific gonadotroph lineage factor, also induced the clusterin promoter ∼3 fold in αT3 pituitary cells. As nine of 12 pituitary carcinomas were devoid of clusterin expression, this protein may limit proliferation of benign adenomatous pituitary cells. These results point to lineage-specific pathways restricting uncontrolled murine and human pituitary gonadotroph adenoma cell growth. PMID:21464964

The pituitary gland in patients with Langerhans cell histiocytosis: a clinical and radiological evaluation.

PubMed

Kurtulmus, Neslihan; Mert, Meral; Tanakol, Refik; Yarman, Sema

2015-04-01

Langerhans cell histiocytosis (LCH) is a rare disease in which the most common endocrine manifestation is diabetes insipidus (DI). Data on anterior pituitary function in patients with LCH are limited. Thus, the present study investigated anterior pituitary function in LCH patients with DI via the evaluation of clinical and radiological findings at disease onset and during follow-up. The present study retrospectively evaluated nine patients with LCH (five males and four females). All diagnoses of LCH were made following histological and/or immunophenotypic analyses of tissue biopsies, bronchoalveolar lavage, or cerebrospinal fluid (CSF). Basal and, if necessary, dynamic pituitary function tests were used to assess anterior pituitary function, and magnetic resonance imaging (MRI) scans were used to image the pituitary. The LCH treatment modality was based on organ involvement. The mean age at onset of DI was 27.6 years (range 15-60 years). One patient (11%) exhibited single organ involvement, while eight patients (89%) displayed multisystem organ involvement. On admittance, one patient had hypogonadotropic hypogonadism, one patient exhibited panhypopituitarism [hypogonadotropic hypogonadism, central hypothyroidism, hypocortisolism, and growth hormone (GH) deficiency], and four patients (44%) displayed hyperprolactinemia. The MRI data revealed infundibular enlargement in seven patients (78%), a thalamic mass in one patient (11%), and the absence of the bright spot in all patients. A single patient (11%) showed a mass in the pons that had a partially empty sella. The patients were treated with radiation therapy (RT), chemotherapy (CT), or a combination of both (RT+CT) and were followed up for a median of 91.8 months (range 2-318 months). Seven patients were assessed during the follow-up period, of whom four patients (57.1%) developed anterior pituitary hormone deficiency, three (43%) were diagnosed with GH deficiency, and one (14%) exhibited gonadotropin deficiency. The gonadotropin deficiency in the patient, which was diagnosed on admittance, was resolved during the follow-up period. DI persisted in all patients, and the conditions of the seven patients who have remained on follow-up are stable. In the present study, patients with LCH exhibited altered function in the anterior pituitary as well as the posterior pituitary, which may be due to the natural course of the disease or the effects of treatment. The present findings indicate that anterior pituitary function should be assessed in LCH patients on admittance and during follow-up, especially in LCH patients with multisystem organ involvement.

Notch-Dependent Pituitary SOX2+ Stem Cells Exhibit a Timed Functional Extinction in Regulation of the Postnatal Gland

PubMed Central

Zhu, Xiaoyan; Tollkuhn, Jessica; Taylor, Havilah; Rosenfeld, Michael G.

2015-01-01

Summary Although SOX2+ stem cells are present in the postnatal pituitary gland, how they are regulated molecularly and whether they are required for pituitary functions remain unresolved questions. Using a conditional knockout animal model, here we demonstrate that ablation of the canonical Notch signaling in the embryonic pituitary gland leads to progressive depletion of the SOX2+ stem cells and hypoplastic gland. Furthermore, we show that the SOX2+ stem cells initially play a significant role in contributing to postnatal pituitary gland expansion by self-renewal and differentiating into distinct lineages in the immediate postnatal period. However, we found that within several weeks postpartum, the SOX2+ stem cells switch to an essentially dormant state and are no longer required for homeostasis/tissue adaptation. Our results present a dynamic tissue homeostatic model in which stem cells provide an initial contribution to the growth of the neonatal pituitary gland, whereas the mature gland can be maintained in a stem cell-independent fashion. PMID:26651607

Clinical characteristics of patients with thyrotropin-secreting pituitary adenoma.

PubMed

Wu, Yung-Yen; Chang, Hung-Yu; Lin, Jen-Der; Chen, Kwang-Wen; Huang, Yu-Yao; Jung, Shih-Ming

2003-03-01

Thyroid-stimulating hormone (thyrotropin, TSH)-secreting pituitary adenoma is a very rare cause of hyperthyroidism. Diagnosis of this condition is often delayed due to lack of availability of TSH radioimmunoassay (RIA), the failure to recognize the utility of RIA and the incorrect attribution of the condition to other causes of thyrotoxicosis. This retrospective study analyzed the clinical characteristics of patients with this disorder treated from 1991 to 2002. Seven patients (6 females, 1 male; mean age, 48 years; range, 33 to 72 years) with a diagnosis of TSHsecreting pituitary adenoma based on detectable TSH levels with high serum free thyroid hormone or triiodothyronine concentrations and pituitary lesions found on neuroimaging were included in this study. Patient records including clinical features, endocrine studies, immunohistochemistry studies, and response to treatment were reviewed. All 7 patients had hyperthyroidism, elevated free thyroxine or triiodothyronine levels, and unsuppressed levels of TSH. Imaging studies demonstrated a pituitary mass or lesion in all patients. Six patients had macroadenomas and 1 patient had a microadenoma. One of the patients had coexisting acromegalic features and hypersecretion of growth hormone was diagnosed. All of the patients had been treated with thionamides or thyroidectomy for presumed primary hyperthyroidism. Serum alpha-subunit level was uncharacteristically normal in 2 patients and elevated in 1 patient. Alpha-subunit/TSH molar ratios were elevated in 3 patients. Five patients underwent transsphenoidal adenomectomy but only one of them remained well-controlled at follow-up. Three patients received administration of somatostatin analogs and they achieved normalization of serum TSH and free thyroid hormones during the period of therapy. TSH immunoassay has an important role in the evaluation of hyperthyroid patients to determine the presence of inappropriate secretion. TSH-secreting pituitary adenoma exhibits heterogeneity in clinical presentation, hormonal expression and therapeutic response.

A cross-sectional study to investigate long-term cognitive function in people with treated pituitary Cushing's disease.

PubMed

Heald, A; Parr, C; Gibson, C; O'driscoll, K; Fowler, H

2006-10-01

It has been proposed that exposure to high levels of endogenous steroids in untreated pituitary Cushing's disease damages hippocampal structures leading to impairment in learning and memory processes. We hypothesised that patients with treated pituitary Cushing's disease would perform significantly worse on tests of cognitive ability than those with nonfunctioning pituitary adenomas. Sixteen adults with pituitary Cushing's disease (PCD) and 16 adults with non-functioning pituitary adenomas (NFA) undertook the following comprehensive neuropsychological assessments: National Adult Reading Test (NART: premorbid abilities), California Verbal Learning Test (CVLT 2 UK: learning and recall), Stroop (executive functioning), Trail-Making Test (TMT: executive functioning and attention), Adult Memory and Information Processing Battery (AMIPB: Information Processing Speed and Story Recall subtests). There was no significant difference in premorbid IQ scores (NFA mean=101 SD=13; PCD mean=102, SD=13), in verbal learning nor any significant difference in the percentage of verbal material retained in story recall (AMIPB). Performance on higher executive tasks Stroop and TMT and on measures of information processing was similar. However, there were significant decrements between some mean scores for both groups and published normative data with a clear association between higher HADS depression scores and impaired objective memory and attention which was not specific to PCD. We found no difference in cognitive function between patients with PCD and NFA. The results suggest a discrepancy between patients' subjective perception of functional cognitive impairments and objective findings on psychometric testing and point to the influence of affective symptoms on cognitive performance, particularly in Cushing's disease.

Pituitary stalk interruption syndrome presenting as short stature: a case report.

PubMed

Ram, Nanik; Ali, Syed Ahsan; Hussain, Syed Zubair

2014-12-19

Pituitary stalk interruption syndrome is a rare congenital abnormality of the pituitary that is responsible for anterior pituitary deficiency. It is characterized by a classic triad of interrupted pituitary stalk, absent or ectopic posterior pituitary, and anterior pituitary hypoplasia or aplasia. Clinical presentation varies according to age. In adults it presents as short stature and anterior pituitary deficiency. Without early diagnosis and treatment, mortality and morbidity in these patients is high. Early diagnosis and treatment of this rare disease can prevent permanent short statue of the patient. We report the first case of pituitary stalk interruption syndrome from Pakistan. A 17-year-old Pakistani young man presented with short stature and underdeveloped secondary sexual characters. His siblings and parents were healthy, with normal height. An examination showed his blood pressure was 90/60 mmHg, and his height, weight, and body mass index were 142 cm, 34.5 kg, and 17.10 kg/m2, respectively. He had no hair growth on his face, axilla, or pubis. His testes were between 1 and 2 mL in size, with a 4 cm-at-stretch micropenis. His lab investigations showed that his thyroid stimulating hormone (TSH) was 8.58 uIU/mL (0.4 to 4.2), his free thyroid hormone level FT4 was 0.46 ng/dL (0.89 to 1.76), his prolactin was 21.1 ng/mL (3.0 to 14.7), and his baseline cortisol was 0.30 ug/dL (4.3 to 22.4). His cortisol level after 60 minutes of cosyntropin injection was 3.5 ug/dL (4.3 to 22.4), his insulin like growth factor IGF-1 was 31.56 ng/mL (247.3 to 481.7), his testosterone level was under 2.5 ng/dL (2 to 800), his follicle stimulating hormone FSH was 0.41 uIU/mL (0.0 to 10.0), and his leutinizing hormone LH was under 0.1 uIU/mL (1.2 to 7.8). His bone age was 10 years according to the Greulich and Pyle method, as shown by X-rays. The results from his pituitary magnetic resonance imaging scan were consistent with pituitary stalk interruption syndrome. We describe a young man who presented with short stature and was found to have pituitary stalk interruption syndrome. Despite the fact that this is a rare disorder, it should always be kept in the differential diagnosis of a patient presenting with short stature. Patients with this disease have an excellent opportunity to reach normal height if they present before the joining of epiphyses.

Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers.

PubMed

Gradiser, Marina; Matovinovic Osvatic, Martina; Dilber, Dario; Bilic-Curcic, Ines

2016-03-17

The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c-d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors.

Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers

PubMed Central

Gradiser, Marina; Matovinovic Osvatic, Martina; Dilber, Dario; Bilic-Curcic, Ines

2016-01-01

The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c–d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors. PMID:26999178

Chapter 11.18 - Neuroendocrine Control of Female Reproduction.

EPA Science Inventory

The hypothalamus and pituitary are known to play roles in reproductive function. A growing body of evidence indicates that environmental toxicants can alter female reproductive function by disrupting hypothalamic control of the pituitary and subsequently the endocrine control of ...

Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice.

PubMed

Lecoq, Anne-Lise; Zizzari, Philippe; Hage, Mirella; Decourtye, Lyvianne; Adam, Clovis; Viengchareun, Say; Veldhuis, Johannes D; Geoffroy, Valérie; Lombès, Marc; Tolle, Virginie; Guillou, Anne; Karhu, Auli; Kappeler, Laurent; Chanson, Philippe; Kamenický, Peter

2016-10-01

Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas, particularly of the somatotroph lineage. Mice with global heterozygous inactivation of Aip (Aip(+/-)) also develop pituitary adenomas but differ from AIP-mutated patients by the high penetrance of pituitary disease. The endocrine phenotype of these mice is unknown. The aim of this study was to determine the endocrine phenotype of Aip(+/-) mice by assessing the somatic growth, ultradian pattern of GH secretion and IGF1 concentrations of longitudinally followed male mice at 3 and 12 months of age. As the early stages of pituitary tumorigenesis are controversial, we also studied the pituitary histology and somatotroph cell proliferation in these mice. Aip(+/-) mice did not develop gigantism but exhibited a leaner phenotype than wild-type mice. Analysis of GH pulsatility by deconvolution in 12-month-old Aip(+/-) mice showed a mild increase in total GH secretion, a conserved GH pulsatility pattern, but a normal IGF1 concentration. No pituitary adenomas were detected up to 12 months of age. An increased ex vivo response to GHRH of pituitary explants from 3-month-old Aip(+/-) mice, together with areas of enlarged acini identified on reticulin staining in the pituitary of some Aip(+/-) mice, was suggestive of somatotroph hyperplasia. Global heterozygous Aip deficiency in mice is accompanied by subtle increase in GH secretion, which does not result in gigantism. The absence of pituitary adenomas in 12-month-old Aip(+/-) mice in our experimental conditions demonstrates the important phenotypic variability of this congenic mouse model. © 2016 Society for Endocrinology.

Pituitary disorders in pregnancy.

PubMed

Chrisoulidou, Alexandra; Boudina, Maria; Karavitaki, Niki; Bili, Eleni; Wass, John

2015-01-01

The pituitary gland is significantly affected during gestation in terms of both size and function. Due to this physiologic adaptation, endocrine evaluation and interpretation of imaging is far more complex than in the non-pregnant state. Pituitary disorders are rare in pregnancy, as they are usually associated with gonadal dysfunction, thereby posing difficulties with fertility. This review will focus on pituitary adenomas (prolactinomas, GH-secreting and ACTH-secreting), their diagnostic handicaps and the recommendations for treatment. We will also discuss the two pituitary disorders encountered in pregnancy, Sheehan's syndrome and lymphocytic hypophysitis.

[Clinical study on the postburn change in the hypothalamus-pituitary-adrenal hormones in severely burned patients].

PubMed

Li, Hong-mian; Liang, Zi-qian; Luo, Zuo-jie

2003-06-01

To investigate the postburn dynamic changes in the hypothalamus-pituitary-adrenal hormones in severely burned patients. Fifty burn patients were enrolled in the study. The plasma contents of total GC (cortisol), ACTH and aldosterone (ALDO) and urinary contents of 17-OHO and 17-KS were determined with radio-immunological assay (RIA) method after burn injury to compare with the normal values which were well established clinically. The postburn plasma and urinary contents of the above indices were increased evidently with two peak values in shock and infectious stages, whilst the majority of he indices were lower than the normal values after 6 postburn weeks (PBWs). The values of these hormones were the lowest in dying patients. On the other hand, the values approached normal levels in those patients whose burn wounds were healing. Increases of the plasma and urinary levels of hypothalamus-pituitary -adrenal hormones in severely burned patients were constantly seen. Burn shock and infection seemed to be the two major factors in inducing postburn stress reaction in burn victims. Abrupt decrease of the hormone levels in plasma and or urine indicated adrenal failure predicting a poor prognosis of the burn patients.

Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis.

PubMed

Lupi, Isabella; Cosottini, Mirco; Caturegli, Patrizio; Manetti, Luca; Urbani, Claudio; Cappellani, Daniele; Scattina, Ilaria; Martino, Enio; Marcocci, Claudio; Bogazzi, Fausto

2017-08-01

Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable. To identify clinical and radiological findings associated with response to glucocorticoids. 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months). MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis ( n  = 4, PH), and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis ( n  = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P  = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P  = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients ( P  = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced ( P  = 0.008) but diabetes insipidus persisted in all. Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids. © 2017 European Society of Endocrinology.

Pituitary Volume Prospectively Predicts Internalizing Symptoms in Adolescence

ERIC Educational Resources Information Center

Zipursky, Amy R.; Whittle, Sarah; Yucel, Murat; Lorenzetti, Valentina; Wood, Stephen J.; Lubman, Dan I.; Simmons, Julian G.; Allen, Nicholas B.

2011-01-01

Background: Early adolescence is a critical time for the development of both internalizing and externalizing disorders. We aimed to investigate whether pituitary volume, an index of hypothalamic-pituitary-adrenal (HPA) axis function, represents a vulnerability factor for the emergence of internalizing and externalizing symptoms during adolescence…

Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

PubMed Central

Michailidou, Z.; Carter, R. N.; Marshall, E.; Sutherland, H. G.; Brownstein, D. G.; Owen, E.; Cockett, K.; Kelly, V.; Ramage, L.; Al-Dujaili, E. A. S.; Ross, M.; Maraki, I.; Newton, K.; Holmes, M. C.; Seckl, J. R.; Morton, N. M.; Kenyon, C. J.; Chapman, K. E.

2008-01-01

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GRβgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin-aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet.—Michailidou, Z., Carter, R. N., Marshall, E., Sutherland, H. G., Brownstein, D. G., Owen, E., Cockett, K., Kelly, V., Ramage, L., Al-Dujaili, E. A. S., Ross, M., Maraki, I., Newton, K., Holmes, M. C., Seckl, J. R., Morton, N. M., Kenyon, C. J., Chapman, K. E. Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet. PMID:18697839

The Influence of the Size, Age and Sex on the Computed Tomographic Measured Size of the Pituitary Gland in Normal Horses.

PubMed

Crijns, C P; Van Bree, H J; Broeckx, B J G; Schauvliege, S; Van Loon, G; Martens, A; Vanderperren, K; Dingemanse, W B; Gielen, I M

2017-06-01

The objective of this study was to examine the influence of the size, age and sex of the horse on the size of the pituitary gland and determine the possibility of using the pituitary gland height-to-brain area ratio (P:B ratio) to allow comparison of different sized and aged horses. Thirty-two horses without pituitary pars inter-media dysfunction that underwent a contrast-enhanced computed tomographic (CT) examination were included in a cross-sectional study. On the CT images, the pituitary gland height was measured and the P:B ratio was calculated. These measurements were correlated to the size, age and sex of the horses. The pituitary gland height was significantly associated with the size (P < 0.001) and the age (P < 0.001), but not with the sex (P = 0.40), of the horses. No significant association was found between the P:B ratio and the size (P = 0.25), the age (P = 0.06) or the sex (P = 0.25) of the horses. In conclusion, the pituitary gland size varies between different sized and aged horses. The use of the P:B ratio is a valuable metric for making comparisons between the pituitary glands of these horses. © 2017 Blackwell Verlag GmbH.

Stimulation of growth in the little mouse.

PubMed

Beamer, W H; Eicher, E M

1976-10-01

The new mouse mutation little (lit) in the homozygous state causes a pituitary deficiency involving at least growth hormone (GH) and prolactin. The resultant growth failure of lit/lit mice was shown to be reversed by experimental conditions that enhanced levels of GH or GH and prolactin in the circulation. Two measures of growth, actual weight gain and bone dimension, were significantly improved by the physiological processes of pregnancy and pseudopregnancy, by extra-sellar graft of a normal mouse pituitary, and by treatment with GH but not prolactin. These data confirmed pituitary dysfunction as the basic defect caused by the mutation lit and showed that the GH deficiency is responsible for growth failure. However, the biological site of gene action, the pituitary or hypothalamus, has not been established. Little mice exhibit a number of characteristics similar to those of human genetic ateleotic dwarfism Type 1, namely genetic inheritance, time of onset of growth retardation, proportionate skeletal size reduction, and pituitary GH deficiency.

Pituitary gigantism presenting with depressive mood disorder and diabetic ketoacidosis in an Asian adolescent.

PubMed

Kuo, Sheng-Fong; Chuang, Wen-Yu; Ng, Sohching; Chen, Chih-Hung; Chang, Chen-Nen; Chou, Chi-Hsiang; Weng, Wei-Chieh; Yeh, Chih-Hua; Lin, Jen-Der

2013-01-01

Hyperglycemia is seldom described in young patients with pituitary gigantism. Here, we describe the case of a 17-year-old Taiwanese boy who developed depressive mood disorder and diabetic ketoacidosis (DKA) at the presentation of pituitary gigantism. The boy complained of lethargy and dysphoric mood in June 2008. He presented at the emergency department with epigastralgia and dyspnea in January 2009. Results of laboratory tests suggested type 1 diabetes mellitus with DKA. However, serum C-peptide level was normal on follow-up. Although he had no obvious features of acral enlargement, a high level of insulin-like growth factor 1 was detected, and a 75 g oral glucose suppression test showed no suppression of serum growth hormone levels. A pituitary macroadenoma was found on subsequent magnetic resonance imaging. The pituitary adenoma was surgically removed, followed by gamma-knife radiosurgery, and Sandostatin long-acting release treatment. He was then administered metformin, 500 mg twice daily, and to date, his serum glycohemoglobin has been <7%.

Height, BMI, and pituitary volume in individuals with and without isolated cleft lip and/or palate

PubMed Central

van der Plas, Ellen; Caspell, Chelsea J.; Aerts, Andrea M.; Tsalikian, Eva; Richman, Lynn C.; Dawson, Jeffrey D.; Nopoulos, Peg

2013-01-01

INTRODUCTION Individuals with isolated cleft lip and/or palate (ICLP) are often reported to be of shorter stature relative to peers, and the objective of this study was to explore the role of the pituitary in relationship to growth. METHODS Fifty-five males and 32 females with ICLP were compared to 121 healthy males and 158 healthy females with respect to height and BMI. Magnetic resonance imaging (MRI) scans were obtained from all ICLP participants and 47% of healthy group participants. RESULTS Males with ICLP were shorter than healthy males and had lower BMI. However, the trajectories for height and BMI did not differ between groups. Analyses in a separate sample of adult males suggested that height normalizes in males with ICLP in their early 30s. There were no differences in mean pituitary volume and pituitary trajectories between male groups. Females with ICLP were shorter than healthy females and also had slower growth rates. They did not differ in mean BMI or BMI trajectories. Furthermore, there were no differences in mean pituitary volume, or in pituitary trajectories. DISCUSSION Our findings suggest that there are no gross morphological differences in pituitary volume in individuals with ICLP, although more subtle differences may exist. PMID:22322386

Polycystic ovary syndrome and prolactinoma association.

PubMed

Yavasoglu, Irfan; Kucuk, Mert; Coskun, Adil; Guney, Engin; Kadikoylu, Gurhan; Bolaman, Zahit

2009-01-01

Hyperprolactinemia is the most common pituitary hormone hypersecretion syndrome in both men and women. Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting 5%-10% of reproductive age women. Here, we present a patient with irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia who was diagnosed as PCOS and prolactinoma and admitted to our clinic. Prolactinoma and PCOS association is a rare condition. This 33-year-old woman was admitted to the internal medicine outpatient clinic for irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia. Her laboratory results were as follows: prolactin was 74 ng/mL (normal range:1.8-20.3 ng/mL). Pelvic ultrasonography was correlated with polycystic ovary syndrome. Pituitary MRI showed 6x8 mm microadenoma at left half. Bromocriptine was started with 1.25 mg/day and increased to 5 mg/day. After six months of bromocriptine treatment her prolactin level was normal and no adenoma was detected in pituitary MRI. PCOS and prolactinoma association should be taken into account in PCOS cases with mild hyperprolactinoma.

Hypersomatotropism induced secondary polycythaemia leading to spontaneous pituitary apoplexy resulting in cure of acromegaly and remission of polycythaemia: 'The virtuous circle'.

PubMed

Patra, Shinjan; Biswas, Sugata Narayan; Datta, Joydip; Chakraborty, Partha Pratim

2017-12-07

A young man with subtle clinical features suggestive of hypersomatotropism presented with acute-onset severe headache. Relevant investigations confirmed polycythaemia and growth hormone (GH)-secreting pituitary macroadenoma with apoplexy. Secondary polycythaemia and myeloproliferative disorders were ruled out. At follow-up after 3 months, resolution of polycythaemia and acromegaly was observed, evident on normal haemoglobin levels, a normocellular marrow, and normal insulin-like growth factor-1 (IGF-1) with glucose-suppressed GH levels. Direct mitogenic properties of GH-IGF-1 axis on bone marrow progenitor cells may very rarely lead to erythroid hyperplasia and subsequent polycythaemia, reversible with successful therapy of acromegaly. In this case, polycythaemia secondary to hypersomatotropism likely resulted in pituitary apoplexy with subsequent remission of both acromegaly and resultant polycythaemia. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A child with pituitary gigantism and precocious adrenarche: does GH and/or PRL advance the onset of adrenarche?

PubMed

Iwatani, N; Kodama, M; Seto, H

1992-06-01

We describe a female child with pituitary gigantism and precocious adrenarche. From two years of age she showed unusual overgrowth, and at 5 years old she was 133.5 cm (+ 5.5 SD) tall and weighed 40.5 kg. Her precocious manifestations were public hair, acne vulgaris, hirsutism, and advanced bone age. Endocrinological examination revealed markedly increased serum growth hormone (GH) and prolactin (PRL), which responded paradoxically to a TRH test. In addition, the concentrations of serum dehydroepiandrosterone (DHA) and its sulfate (DHAS) were increased to adult levels, moving in accordance with changes in ACTH, which suggested that these androgens were secreted from the adrenal glands functionally. These androgens seemed to be responsible for her partial precocity. Prior reports have suggested that GH and/or PRL overproduction might have played a role in the induction of adrenarche. Also, in previous reports of 9 gigantism patients under 10 years old, the manifestation of precocious adrenarche was suggested in 8. Further investigation of the influence of GH and PRL on adrenal androgen production in children with pituitary gigantism is required. On the other hand, in short children with normal GH secretion, attention should be paid to whether or not the GH therapy in early childhood induces precocious adrenarche.

Central diabetes insipidus: a previously unreported side effect of temozolomide.

PubMed

Faje, Alexander T; Nachtigall, Lisa; Wexler, Deborah; Miller, Karen K; Klibanski, Anne; Makimura, Hideo

2013-10-01

Temozolomide (TMZ) is an alkylating agent primarily used to treat tumors of the central nervous system. We describe 2 patients with apparent TMZ-induced central diabetes insipidus. Using our institution's Research Patient Database Registry, we identified 3 additional potential cases of TMZ-induced diabetes insipidus among a group of 1545 patients treated with TMZ. A 53-year-old male with an oligoastrocytoma and a 38-year-old male with an oligodendroglioma each developed symptoms of polydipsia and polyuria approximately 2 months after the initiation of TMZ. Laboratory analyses demonstrated hypernatremia and urinary concentrating defects, consistent with the presence of diabetes insipidus, and the patients were successfully treated with desmopressin acetate. Desmopressin acetate was withdrawn after the discontinuation of TMZ, and diabetes insipidus did not recur. Magnetic resonance imaging of the pituitary and hypothalamus was unremarkable apart from the absence of a posterior pituitary bright spot in both of the cases. Anterior pituitary function tests were normal in both cases. Using the Research Patient Database Registry database, we identified the 2 index cases and 3 additional potential cases of diabetes insipidus for an estimated prevalence of 0.3% (5 cases of diabetes insipidus per 1545 patients prescribed TMZ). Central diabetes insipidus is a rare but reversible side effect of treatment with TMZ.

Central Diabetes Insipidus: A Previously Unreported Side Effect of Temozolomide

PubMed Central

Nachtigall, Lisa; Wexler, Deborah; Miller, Karen K.; Klibanski, Anne; Makimura, Hideo

2013-01-01

Context: Temozolomide (TMZ) is an alkylating agent primarily used to treat tumors of the central nervous system. We describe 2 patients with apparent TMZ-induced central diabetes insipidus. Using our institution's Research Patient Database Registry, we identified 3 additional potential cases of TMZ-induced diabetes insipidus among a group of 1545 patients treated with TMZ. Case Presentations: A 53-year-old male with an oligoastrocytoma and a 38-year-old male with an oligodendroglioma each developed symptoms of polydipsia and polyuria approximately 2 months after the initiation of TMZ. Laboratory analyses demonstrated hypernatremia and urinary concentrating defects, consistent with the presence of diabetes insipidus, and the patients were successfully treated with desmopressin acetate. Desmopressin acetate was withdrawn after the discontinuation of TMZ, and diabetes insipidus did not recur. Magnetic resonance imaging of the pituitary and hypothalamus was unremarkable apart from the absence of a posterior pituitary bright spot in both of the cases. Anterior pituitary function tests were normal in both cases. Using the Research Patient Database Registry database, we identified the 2 index cases and 3 additional potential cases of diabetes insipidus for an estimated prevalence of 0.3% (5 cases of diabetes insipidus per 1545 patients prescribed TMZ). Conclusions: Central diabetes insipidus is a rare but reversible side effect of treatment with TMZ. PMID:23928668

Pituitary gigantism in a 31 month old girl: endocrine studies and successful response to hypophysectomy.

PubMed

Espiner, E A; Carter, T A; Abbott, G D; Wrightson, P

1981-01-01

A case of pituitary gigantism occurring in a 31 month old female child is reported. Growth records indicate that the disorder began early in the second yr of life. Apart from her size and history of excessive sweating, there were no characteristic clinical features of endocrinopathy. Elevated and autonomous secretion of GH (60-109 microgram/l) and prolactin were corrected by the removal of an eosinophilic pituitary adenoma. In the subsequent 6 yr, despite the presence of immunoreactive GH (4.6-17.3 microgram/l), plasma somatomedin was subnormal and the patient showed growth failure which responded normally to exogenous GH therapy. This case, which appears to be the youngest example of verified pituitary gigantism on record, illustrates that a successful outcome can be achieved by surgical ablative therapy.

Effects of Environmental Toxicants on the Neuroendocrine Control of Female Reproduction

EPA Science Inventory

The hypothalamus and pituitary are known to play key roles in reproductive function. A growing body of evidence indicates that environmental toxicants can alter female reproductive function by disrupting hypothalamic control of the pituitary and subsequently, the endocrine contro...

Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement

PubMed Central

Sun, Yu; Bak, Beata; Schoenmakers, Nadia; van Trotsenburg, A.S. Paul; Oostdijk, Wilma; Voshol, Peter; Cambridge, Emma; White, Jacqueline K.; le Tissier, Paul; Gharavy, S. Neda Mousavy; Martinez-Barbera, Juan P.; Stokvis-Brantsma, Wilhelmina H.; Vulsma, Thomas; Kempers, Marlies J.; Persani, Luca; Campi, Irene; Bonomi, Marco; Beck-Peccoz, Paolo; Zhu, Hongdong; Davis, Timothy M.E.; Hokken-Koelega, Anita C.S.; Del Blanco, Daria Gorbenko; Rangasami, Jayanti J.; Ruivenkamp, Claudia A.L.; Laros, Jeroen F.J.; Kriek, Marjolein; Kant, Sarina G.; Bosch, Cathy A.J.; Biermasz, Nienke R.; Appelman-Dijkstra, Natasha M.; Corssmit, Eleonora P.; Hovens, Guido C.J.; Pereira, Alberto M.; den Dunnen, Johan T.; Wade, Michael G.; Breuning, Martijn H.; Hennekam, Raoul C.; Chatterjee, Krishna; Dattani, Mehul T.; Wit, Jan M.; Bernard, Daniel J.

2012-01-01

Congenital central hypothyroidism occurs either in isolation or in conjunction with other pituitary hormone deficits. Using exome and candidate gene sequencing, we identified eight distinct mutations and two deletions in IGSF1 in males from eleven unrelated families with central hypothyroidism, testicular enlargement, and variably low prolactin concentrations. IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary gland and the identified mutations impair its trafficking to the cell surface in heterologous cells. Igsf1-deficient male mice show diminished pituitary and serum thyroid-stimulating hormone (TSH) concentrations, reduced pituitary thyrotropin-releasing hormone (TRH) receptor expression, decreased triiodothyronine concentrations, and increased body mass. Collectively, our observations delineate a novel X-linked disorder in which loss-of-function mutations in IGSF1 cause central hypothyroidism, likely secondary to an associated impairment in pituitary TRH signaling. PMID:23143598

Testosterone replacement therapy: role of pituitary and thyroid in diagnosis and treatment

PubMed Central

Crawford, Megan

2016-01-01

Crosstalk among hormones characterizes endocrine function, and assessment of the hypogonadal man should take that into consideration. In men for whom testosterone deficiency is a concern, initial evaluation should include a thorough history and physical exam in which other endocrinopathies are being considered. Hypogonadism can be associated with both pituitary and thyroid dysfunction, for which appropriate biochemical evaluation should be undertaken in certain clinical scenarios. If low serum testosterone is confirmed measurement of luteinizing and follicle stimulating hormones (LH and FSH respectively) is essential to establish whether the hypogonadism is primary or secondary. In secondary hypogonadism measurement of prolactin is always necessary, and measurement of other pituitary hormones, along with pituitary imaging, may be indicated. Checking thyroid function may also be enlightening, and can raise additional therapeutic considerations. Correction of other pituitary axes may attenuate the need for testosterone replacement therapy in some cases. PMID:28078216

Hypopituitarism after acute brain injury.

PubMed

Urban, Randall J

2006-07-01

Acute brain injury has many causes, but the most common is trauma. There are 1.5-2.0 million traumatic brain injuries (TBI) in the United States yearly, with an associated cost exceeding 10 billion dollars. TBI is the most common cause of death and disability in young adults less than 35 years of age. The consequences of TBI can be severe, including disability in motor function, speech, cognition, and psychosocial and emotional skills. Recently, clinical studies have documented the occurrence of pituitary dysfunction after TBI and another cause of acute brain injury, subarachnoid hemorrhage (SAH). These studies have consistently demonstrated a 30-40% occurrence of pituitary dysfunction involving at least one anterior pituitary hormone following a moderate to severe TBI or SAH. Growth hormone (GH) deficiency is the most common pituitary hormone disorder, occurring in approximately 20% of patients when multiple tests of GH deficiency are used. Within 7-21 days of acute brain injury, adrenal insufficiency is the primary concern. Pituitary function can fluctuate over the first year after TBI, but it is well established by 1 year. Studies are ongoing to assess the effects of hormone replacement on motor function and cognition in TBI patients. Any subject with a moderate to severe acute brain injury should be screened for pituitary dysfunction.

IGF-I levels reflect hypopituitarism severity in adults with pituitary dysfunction.

PubMed

Tirosh, Amit; Toledano, Yoel; Masri-Iraqi, Hiba; Eizenberg, Yoav; Tzvetov, Gloria; Hirsch, Dania; Benbassat, Carlos; Robenshtok, Eyal; Shimon, Ilan

2016-08-01

To evaluate the utility of Insulin-like growth factor I (IGF-I) standard deviation score (SDS) as a surrogate marker of severity of hypopituitarism in adults with pituitary pathology. We performed a retrospective data analysis, including 269 consecutive patients with pituitary disease attending a tertiary endocrine clinic in 1990-2015. The medical files were reviewed for the complete pituitary hormone profile, including IGF-I, and clinical data. Age-adjusted assay reference ranges of IGF-I were used to calculate IGF-I SDS for each patient. The main outcome measures were positive and negative predictive values of low and high IGF-I SDS, respectively, for the various pituitary hormone deficiencies. IGF-I SDS correlated negatively with the number of altered pituitary axes (p < 0.001). Gonadotropin was affected in 76.6 % of cases, followed by thyrotropin (58.4 %), corticotropin (49.1 %), and prolactin (22.7 %). Positive and negative predictive values yielded a clear trend for the probability of low/high IGF-I SDS for all affected pituitary axes. Rates of diabetes insipidus correlated with IGF-I SDS values both for the full study population, and specifically for patients with non-functioning pituitary adenomas. IGF-I SDS can be used to evaluate the somatotroph function, as a valid substitute to absolute IGF-I levels. Moreover, IGF-I SDS predicted the extent of hypopituitarism in adults with pituitary disease, and thus can serve as a marker of hypopituitarism severity.

Childhood maltreatment and adult psychopathology: pathways to hypothalamic-pituitary-adrenal axis dysfunction

PubMed Central

Mello, Marcelo F.; Faria, Alvaro A.; Mello, Andrea F.; Carpenter, Linda L.; Tyrka, Audrey R.; Price, Lawrence H.

2015-01-01

Objective The aim of this paper was to examine the relationship between childhood maltreatment and adult psychopathology, as reflected in hypothalamic-pituitary-adrenal axis dysfunction. Method A selective review of the relevant literature was undertaken in order to identify key and illustrative research findings. Results There is now a substantial body of preclinical and clinical evidence derived from a variety of experimental paradigms showing how early-life stress is related to hypothalamic-pituitary-adrenal axis function and psychological state in adulthood, and how that relationship can be modulated by other factors. Discussion The risk for adult psychopathology and hypothalamic-pituitary-adrenal axis dysfunction is related to a complex interaction among multiple experiential factors, as well as to susceptibility genes that interact with those factors. Although acute hypothalamic-pituitary-adrenal axis responses to stress are generally adaptive, excessive responses can lead to deleterious effects. Early-life stress alters hypothalamic-pituitary-adrenal axis function and behavior, but the pattern of hypothalamic-pituitary-adrenal dysfunction and psychological outcome in adulthood reflect both the characteristics of the stressor and other modifying factors. Conclusion Research to date has identified multiple determinants of the hypothalamic-pituitary-adrenal axis dysfunction seen in adults with a history of childhood maltreatment or other early-life stress. Further work is needed to establish whether hypothalamic-pituitary-adrenal axis abnormalities in this context can be used to develop risk endophenotypes for psychiatric and physical illnesses. PMID:19967199

Pegvisomant: a growth hormone receptor antagonist used in the treatment of acromegaly.

PubMed

Tritos, Nicholas A; Biller, Beverly M K

2017-02-01

To review published data on pegvisomant and its therapeutic role in acromegaly. Electronic searches of the published literature were conducted using the keywords: acromegaly, growth hormone (GH) receptor (antagonist), pegvisomant, therapy. Relevant articles (n = 141) were retrieved and considered for inclusion in this manuscript. Pegvisomant is a genetically engineered, recombinant growth hormone receptor antagonist, which is effective in normalizing serum insulin-like growth factor 1 (IGF-1) levels in the majority of patients with acromegaly and ameliorating symptoms and signs associated with GH excess. Pegvisomant does not have direct antiproliferative effects on the underlying somatotroph pituitary adenoma, which is the etiology of GH excess in the vast majority of patients with acromegaly. Therefore, patients receiving pegvisomant monotherapy require regular pituitary imaging in order to monitor for possible increase in tumor size. Adverse events in patients on pegvisomant therapy include skin rashes, lipohypertrophy at injection sites, and idiosyncratic liver toxicity (generally asymptomatic transaminitis that is reversible upon drug discontinuation), thus necessitating regular patient monitoring. Pegvisomant is an effective therapeutic agent in patients with acromegaly who are not in remission after undergoing pituitary surgery. It mitigates excess GH action, as demonstrated by IGF-1 normalization, but has no direct effects on pituitary tumors causing acromegaly. Regular surveillance for possible tumor growth and adverse effects (hepatotoxicity, skin manifestations) is warranted.

Pituitary Medicine From Discovery to Patient-Focused Outcomes

PubMed Central

2016-01-01

Context: This perspective traces a pipeline of discovery in pituitary medicine over the past 75 years. Objective: To place in context past advances and predict future changes in understanding pituitary pathophysiology and clinical care. Design: Author's perspective on reports of pituitary advances in the published literature. Setting: Clinical and translational Endocrinology. Outcomes: Discovery of the hypothalamic-pituitary axis and mechanisms for pituitary control, have culminated in exquisite understanding of anterior pituitary cell function and dysfunction. Challenges facing the discipline include fundamental understanding of pituitary adenoma pathogenesis leading to more effective treatments of inexorably growing and debilitating hormone secreting pituitary tumors as well as medical management of non-secreting pituitary adenomas. Newly emerging pituitary syndromes include those associated with immune-targeted cancer therapies and head trauma. Conclusions: Novel diagnostic techniques including imaging genomic, proteomic, and biochemical analyses will yield further knowledge to enable diagnosis of heretofore cryptic syndromes, as well as sub classifications of pituitary syndromes for personalized treatment approaches. Cost effective personalized approaches to precision therapy must demonstrate value, and will be empowered by multidisciplinary approaches to integrating complex subcellular information to identify therapeutic targets for enabling maximal outcomes. These goals will be challenging to attain given the rarity of pituitary disorders and the difficulty in conducting appropriately powered prospective trials. PMID:26908107

Pituitary abscess: a case report and review of the literature

PubMed Central

Karagiannis, Apostolos K A; Dimitropoulou, Fotini; Papatheodorou, Athanasios; Lyra, Stavroula; Seretis, Andreas

2016-01-01

Summary Pituitary abscess is a rare life-threating entity that is usually misdiagnosed as a pituitary tumor with a definite diagnosis only made postoperatively. Over the last several decades, advances in healthcare have led to a significant decrease in morbidity and mortality due to pituitary abscess. We report a case of a 34-year-old woman who was admitted to our department for investigation of a pituitary mass and with symptoms of pituitary dysfunction, headaches and impaired vision. During her admission, she developed meningitis-like symptoms and was treated with antibiotics. She eventually underwent transsphenoidal surgery for excision of the pituitary mass. A significant amount of pus was evident intraoperatively; however, no pathogen was isolated. Six months later, the patient was well and had full recovery of the anterior pituitary function. Her menses returned, and she was only on treatment with desmopressin for diabetes insipidus that developed postoperatively. Learning points Pituitary abscess is a rare disease and the reported clinical features vary mimicking other pituitary lesions. The diagnosis of pituitary abscess is often very difficult to make and rarely included in the differential. The histological findings of acute inflammatory infiltration confirm the diagnosis of pituitary abscess. Medical and surgical treatment is usually recommended upon diagnosis of a pituitary abscess. PMID:27274845

Absence of opioid stress-induced analgesia in mice lacking beta-endorphin by site-directed mutagenesis.

PubMed Central

Rubinstein, M; Mogil, J S; Japón, M; Chan, E C; Allen, R G; Low, M J

1996-01-01

A physiological role for beta-endorphin in endogenous pain inhibition was investigated by targeted mutagenesis of the proopiomelanocortin gene in mouse embryonic stem cells. The tyrosine codon at position 179 of the proopiomelanocortin gene was converted to a premature translational stop codon. The resulting transgenic mice display no overt developmental or behavioral alterations and have a normally functioning hypothalamic-pituitary-adrenal axis. Homozygous transgenic mice with a selective deficiency of beta-endorphin exhibit normal analgesia in response to morphine, indicating the presence of functional mu-opiate receptors. However, these mice lack the opioid (naloxone reversible) analgesia induced by mild swim stress. Mutant mice also display significantly greater nonopioid analgesia in response to cold water swim stress compared with controls and display paradoxical naloxone-induced analgesia. These changes may reflect compensatory upregulation of alternative pain inhibitory mechanisms. Images Fig. 1 Fig. 2 PMID:8633004

A thyrotropin-secreting macroadenoma with positive growth hormone and prolactin immunostaining: A case report and literature review.

PubMed

Kuzu, F; Bayraktaroğlu, T; Zor, F; G N, B D; Salihoğlu, Y S; Kalaycı, M

2015-01-01

Thyrotropin (thyroid stimulating hormone [TSH]) secreting pituitary adenomas (TSHoma) are rare adenomas presenting with hyperthyroidism due to impaired negative feedback of thyroid hormone on the pituitary and inappropriate TSH secretion. This article presents a case of TSH-secreting macroadenoma without any clinical hyperthyroidism symptoms accompanying immunoreaction with growth hormone (GH) and prolactin. A 36-year-old female patient was admitted with complaints of irregular menses and blurred vision. On physical exam, she had bitemporal hemianopsia defect. Magnetic resonance imaging (MRI) evaluation showed suprasellar macroadenoma measuring 33 mm × 26 mm × 28 mm was detected on pituitary MRI. She had no hyperthyroidism symptoms clinically. Although free T4 and free T3 levels were elevated, TSH level was inappropriately within the upper limit of normal. Response to T3 suppression and thyrotropin releasing hormone-stimulation test was inadequate. Other pituitary hormones were normal. Transsphenoidal adenomectomy was performed due to parasellar compression findings. Immunohistochemically widespread reaction was observed with TSH, GH and prolactin in the adenoma. The patient underwent a second surgical procedure 2 months later due to macroscopic residual tumor, bitemporal hemianopsia and a suprasellar homogenous uptake with regular borders on indium-111 octreotide scintigraphy. After second surgery; due to ongoing symptoms and residual tumor, she was managed with octreotide and cabergoline treatment. On her follow-up with medical treatment, TSH and free T4 values were within normal limits. Although silent TSHomas are rare, they may arise with compression symptoms as in our case. The differential diagnosis of secondary hyperthyroidism should include TSHomas and thyroid hormone receptor resistance syndrome.

Gigantism: X-linked acrogigantism and GPR101 mutations.

PubMed

Iacovazzo, Donato; Korbonits, Márta

X-linked acrogigantism (XLAG) is a recently identified condition of early-onset GH excess resulting from the germline or somatic duplication of the GPR101 gene on chromosome Xq26.3. Thirty patients have been formally reported so far. The disease affects mostly females, occurs usually sporadically, and is characterised by early onset and marked overgrowth. Most patients present with concomitant hyperprolactinaemia. Histopathology shows pituitary hyperplasia or pituitary adenoma with or without associated hyperplasia. XLAG-related pituitary adenomas present peculiar histopathological features that should contribute to raise the suspicion of this rare condition. Treatment is frequently challenging and multi-modal. While females present with germline mutations, the sporadic male patients reported so far were somatic mosaics with variable levels of mosaicism, although no differences in the clinical phenotype were observed between patients with germline or somatic duplication. The GPR101 gene encodes an orphan G protein-coupled receptor normally expressed in the central nervous system, and at particularly high levels in the hypothalamus. While the physiological function and the endogenous ligand of GPR101 are unknown, the high expression of GPR101 in the arcuate nucleus and the occurrence of increased circulating GHRH levels in some patients with XLAG, suggest that increased hypothalamic GHRH secretion could play a role in the pathogenesis of this condition. In this review, we summarise the published evidence on XLAG and GPR101 and discuss the results of recent studies that have investigated the potential role of GPR101 variants in the pathogenesis of pituitary adenomas. Copyright © 2016 Elsevier Ltd. All rights reserved.

Treatment of Pituitary Gigantism with the Growth Hormone Receptor Antagonist Pegvisomant

PubMed Central

Goldenberg, Naila; Racine, Michael S.; Thomas, Pamela; Degnan, Bernard; Chandler, William; Barkan, Ariel

2008-01-01

Context: Treatment of pituitary gigantism is complex and the results are usually unsatisfactory. Objective: The objective of the study was to describe the results of therapy of three children with pituitary gigantism by a GH receptor antagonist, pegvisomant. Design: This was a descriptive case series of up to 3.5 yr duration. Setting: The study was conducted at a university hospital. Patients: Patients included three children (one female, two males) with pituitary gigantism whose GH hypersecretion was incompletely controlled by surgery, somatostatin analog, and dopamine agonist. Intervention: The intervention was administration of pegvisomant. Main Outcome Measures: Plasma IGF-I and growth velocity were measured. Results: In all three children, pegvisomant rapidly decreased plasma IGF-I concentrations. Growth velocity declined to subnormal or normal values. Statural growth fell into lower growth percentiles and acromegalic features resolved. Pituitary tumor size did not change in two children but increased in one boy despite concomitant therapy with a somatostatin analog. Conclusions: Pegvisomant may be an effective modality for the therapy of pituitary gigantism in children. Titration of the dose is necessary for optimal efficacy, and regular surveillance of tumor size is mandatory. PMID:18492755

The Enigma behind Pituitary and Sella Turcica

PubMed Central

Gopalakrishnan, Umarevathi; Mahendra, Lodd; Rangarajan, Sumanth; Madasamy, Ramasamy; Ibrahim, Mohammad

2015-01-01

The pituitary gland's role as a functional matrix for sella turcica has not been suggested in orthodontic literature. This paper is an attempt to correlate the role of pituitary gland in the development of sella turcica. A case report of dwarfism associated with hypopituitarism is presented to highlight the above hypothesis. PMID:26199763

ERK Signaling in the Pituitary Is Required for Female But Not Male Fertility

PubMed Central

Bliss, Stuart P.; Miller, Andrew; Navratil, Amy M.; Xie, JianJun; McDonough, Sean P.; Fisher, Patricia J.; Landreth, Gary E.; Roberson, Mark S.

2009-01-01

Males and females require different patterns of pituitary gonadotropin secretion for fertility. The mechanisms underlying these gender-specific profiles of pituitary hormone production are unknown; however, they are fundamental to understanding the sexually dimorphic control of reproductive function at the molecular level. Several studies suggest that ERK1 and -2 are essential modulators of hypothalamic GnRH-mediated regulation of pituitary gonadotropin production and fertility. To test this hypothesis, we generated mice with a pituitary-specific depletion of ERK1 and 2 and examined a range of physiological parameters including fertility. We find that ERK signaling is required in females for ovulation and fertility, whereas male reproductive function is unaffected by this signaling deficiency. The effects of ERK pathway ablation on LH biosynthesis underlie this gender-specific phenotype, and the molecular mechanism involves a requirement for ERK-dependent up-regulation of the transcription factor Egr1, which is necessary for LHβ expression. Together, these findings represent a significant advance in elucidating the molecular basis of gender-specific regulation of the hypothalamic-pituitary-gonadal axis and sexually dimorphic control of fertility. PMID:19372235

Etiology and treatment of hypogonadism in adolescents.

PubMed

Viswanathan, Vidhya; Eugster, Erica A

2009-12-01

Adequate functioning at all levels of the hypothalamic-pituitary-gonadal axis is necessary for normal gonadal development and subsequent sex steroid production. Deficiencies at any level of the axis can lead to a hypogonadal state. The causes of hypogonadism are heterogeneous and may involve any level of the reproductive system. This review discusses various causes of hypogonadism, describes the evaluation of hypogonadal states, and outlines treatment options for the induction of puberty in affected adolescents. Whereas some conditions are clearly delineated, the exact etiology and underlying pathogenesis of many disorders is unknown.

A non-invasive test for receptor binding applied to nephrogenic diabetes insipidus.

PubMed Central

Britton, K. E.; Tedder, R. S.; Khokhar, A. M.; Brown, N. J.; Davison, A.; Slater, J. D.

1977-01-01

Studies in animals have determined the importance of specific receptors to the action of many hormones and drugs. In man, a non-invasive external counting technique has been used and absence of receptor function has been demonstrated in a patient with nephrogenic diabetes insipidus using radioactively labelled arginine vasopressin. This is in contrast to the findings in a patient with pituitary diabetes insipidus and a normal control. These results suggest a model for the study of hormone and drug kinetics in man avoiding multiple samplings of biological fluids. PMID:196275

Diabetes insipidus with impaired osmotic regulation in septo-optic dysplasia and agenesis of the corpus callosum.

PubMed Central

Masera, N; Grant, D B; Stanhope, R; Preece, M A

1994-01-01

The clinical and endocrinological findings in 24 children with septo-optic dysplasia and/or agenesis of the corpus callosum are described with particular reference to posterior pituitary function. Nine had diabetes insipidus. The prevalence of diabetes insipidus was similar in children with complete and incomplete forms of septo-optic dysplasia. Maintenance of normal osmotic balance was very difficult in six of these children, even after the introduction of treatment with vasopressin, either as desmopressin, or lysine vasopressin spray in one of the early cases. PMID:8110009

Biological stress systems, adverse life events and the onset of chronic multisite musculoskeletal pain: a 6-year cohort study.

PubMed

Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Penninx, Brenda W J H; Dekker, Joost

2016-05-01

Dysregulated biological stress systems and adverse life events, independently and in interaction, have been hypothesised to initiate chronic pain. We examine whether (1) function of biological stress systems, (2) adverse life events, and (3) their combination predict the onset of chronic multisite musculoskeletal pain. Subjects (n=2039) of the Netherlands Study of Depression and Anxiety, free from chronic multisite musculoskeletal pain at baseline, were identified using the Chronic Pain Grade Questionnaire and followed up for the onset of chronic multisite musculoskeletal pain over 6 years. Baseline assessment of biological stress systems comprised function of the hypothalamic-pituitary-adrenal axis (1-h cortisol awakening response, evening levels, postdexamethasone levels), the immune system (basal and lipopolysaccharide-stimulated inflammation) and the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, respiratory sinus arrhythmia). The number of recent adverse life events was assessed at baseline using the List of Threatening Events Questionnaire. Hypothalamic-pituitary-adrenal axis, immune system and autonomic nervous system functioning was not associated with onset of chronic multisite musculoskeletal pain, either by itself or in interaction with adverse life events. Adverse life events did predict onset of chronic multisite musculoskeletal pain (HR per event=1.14, 95% CI 1.04 to 1.24, p=0.005). This longitudinal study could not confirm that dysregulated biological stress systems increase the risk of developing chronic multisite musculoskeletal pain. Adverse life events were a risk factor for the onset of chronic multisite musculoskeletal pain, suggesting that psychosocial factors play a role in triggering the development of this condition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The influence of sleep on human hypothalamic-pituitary-adrenal (HPA) axis reactivity: A systematic review.

PubMed

van Dalfsen, Jens H; Markus, C Rob

2018-06-01

Inadequate sleep is highly prevalent and known to decline both physical- and mental health. Literature suggests that altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis might underlie this association. This assumption is mainly based on changes in basal neuroendocrine activity and it is of equal importance to elucidate whether sleep may also influence HPA stress responsiveness. The present review provides a complete outline of recent human studies that have investigated how different aspects of sleep influence cortisol reactivity to laboratory stress. From the available data it can be concluded that both objective and subjective decrements in sleep quality potentiate the stress reactivity of the HPA axis. On the contrary, normal variations in sleep duration do not seem to influence cortisol stress responsiveness whereas excessive daytime sleepiness is associated with a blunting of the cortisol response. Given its well-established health consequences, sensitization of the HPA axis might well be a crucial component linking inadequate sleep to stress-related pathology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analysis of short- and long-term metabolic effects of growth hormone replacement therapy in adult patients with craniopharyngioma and non-functioning pituitary adenoma.

PubMed

Profka, E; Giavoli, C; Bergamaschi, S; Ferrante, E; Malchiodi, E; Sala, E; Verrua, E; Rodari, G; Filopanti, M; Beck-Peccoz, P; Spada, A

2015-04-01

Adult patients operated for craniopharyngioma develop more frequently GH deficiency (GHD) than patients operated for non-functioning pituitary adenoma (NFPA). The aim of the study was to compare both short- (1 year) and long-term (5 years) effects of rhGH in 38 GHD adult patients (19 operated for Craniopharyngioma (CP) and 19 for NFPA). IGF-I levels, body composition (BF%), BMI, lipid profile and glucose homeostasis were evaluated in all patients. Pituitary MRI was performed at baseline and during follow-up, as needed. At baseline no difference between the two groups was observed, apart from a higher prevalence of diabetes insipidus in CP patients (79 vs 21%). After 12 months, IGF-I SDS normalized and BF% significantly decreased only in the NFPA group. During long-term treatment, decrease in BF% and improvement in lipid profile shown by reduction in total- and LDL-cholesterol were present in NFPA group only, while increase in insulin levels and HbA1c and decrease of QUICKI were observed in CP patients only. Accordingly, after long-term therapy, the prevalence of metabolic syndrome (MS) was significantly higher in CP than in NFPA group (37% in CP and in 5% in NFPA group; p < 0.05). The present data suggest that CP patients are less sensitive to the positive rhGH effects on lipid profile and BF% and more prone to insulin sensitivity worsening than NFPA patients, resulting in increased prevalence of MS in CP only.

Recovery from diabetes insipidus and preservation of thyroid function after craniopharyngioma removal and pituitary stalk sectioning.

PubMed

Ogawa, Yoshikazu; Niizuma, Kuniyasu; Tominaga, Teiji

2017-11-01

Craniopharyngioma is a slow-growing tumor, but long-term tumor control with maintenance of quality of life is sometimes very difficult to achieve, and hypothalamic disturbance should be strictly avoided in the treatment. However, management of the pituitary gland and/or pituitary stalk varies among surgeons and institutions. This retrospective review identified 44 patients, 24 males and 20 females with craniopharyngiomas who were initially treated by surgery through the extended transsphenoidal approach with pituitary stalk sectioning at a single institute. If the tumor bed involved the posterior lobe of the pituitary gland, pituitary stalk, anterior and/or mid portion of the third ventricle floor, these structures were removed en-bloc together with the tumor. The closest attention was paid to preserve fine arteries running along the surface of optic chiasm and the lateral walls of the third ventricle. Surgical outcome and changes in postoperative endocrinological status were investigated. Gross total removal was achieved in 40 of 44 patients (91%), and all patients could discharge without autonomic and/or thermal disturbances. Tumor remnants were identified with tight adhesion to the perforating arteries in 2 cases, tight adhesion to mammillary bodies in 1, and optic chiasm in 1. Administration of anti-diuretic hormone could be discontinued in 23 of 44 patients (52.3%) with improved diabetes insipidus (DI), although no patient could discontinue glucocorticoid administration. Preservation of thyroid function was achieved in another 23 of 44 patients (52.3%), and recovery from DI was correlated with preservation of thyroid function (p=0.016). Pituitary dysfunction is partially reversible even with pituitary stalk sectioning. Regrowth of tumor in the anterior and/or mid portion of the third ventricle floor including pituitary stalk can possibly be prevented by aggressive tumor removal, and co-achievement of long-term tumor control with maintenance of quality of life could be possible to preserve the lateral wall of the third ventricle. Copyright © 2017 Elsevier B.V. All rights reserved.

Surgical Outcomes of Cavernous Sinus Syndrome in Pituitary Adenomas.

PubMed

Fu, Weilun; Duan, Lian; Geng, Sumin

2017-11-01

The type of pituitary adenoma with a manifestation that includes cavernous sinus syndrome is rare. Based on the clinical data of 70 patients, this study investigated the pathogenesis, imaging characteristics, and prognostic factors of pituitary adenoma with cavernous sinus syndrome. We conducted a retrospective analysis of the characteristics of patients with pituitary adenoma with cavernous sinus syndrome who received surgical treatment. The patients were classified into different prognosis groups according to the time required for them to recover from the cavernous sinus syndrome. Univariate analyses were conducted for the correlations between the prognosis and factors. Of the 3598 cases of pituitary adenomas, 70 (1.95%) presented cavernous sinus syndrome. Of the patients, 55.7% recovered within 2 weeks of surgery, 24.3% recovered from 2 weeks to 1 year after surgery, and 20% had not returned to normal after more than 1 year after surgery. Univariate analyses showed that shorter disease duration (P < 0.001), lower Knosp grade (P = 0.045), a transsphenoidal approach (P < 0.001), and associated pituitary apoplexy (P = 0.012) were predictive factors of early postoperative recovery. The prognosis of cavernous sinus syndrome differs depending on the mechanism of the syndrome. There was no significant difference in the prognosis between patients with total pituitary adenoma resection and subtotal resection. Timely surgery within 100 days of symptom occurrence, Knosp grade 0-2, and associated pituitary apoplexy are predictive factors of good prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Growth hormone (GH) secretion and pituitary size in children with short stature. Efficacy of GH therapy in GH-deficient children, depending on the pituitary size.

PubMed

Hilczer, Maciej; Szalecki, Mieczysław; Smyczynska, Joanna; Stawerska, Renata; Kaniewska, Danuta; Lewinski, Andrzej

2005-10-01

Certain relationships between pituitary size and growth hormone (GH) secretion have previously been observed, however they are still a matter of controversy. Organic abnormalities of the hypothalamic-hypophyseal region are important for predicting growth response to GH therapy. Evaluation of relations between GH secretion and the pituitary size in short children and estimation of the efficacy of GH therapy in children with GH deficiency (GHD). The analysis comprised 216 short children (159 boys). Two GH stimulation tests, as well as magnetic resonance image (MRI) examination, were performed in each patient. All the patients with GHD were treated with GH for, at least, one year. Significant correlations were found between pituitary height and GH secretion (p < 0.05). Patients were classified into three (3) groups: 1) pituitary hypoplasia (HP) for height age; 2) HP for the chronological age but not for the height age; 3) normal pituitary size. Significant differences in GH secretion were observed among the groups (6.1+/-5.3 vs. 8.1+/-4.4 vs. 12.3+/-9.1 ng/mL, respectively). There was a negative correlation between GH peak and height gain during GH therapy (r = -0.34). The highest growth improvement was noticed in patients with HP for the height age. Pituitary hypoplasia for the height age is related to more severe GH deficiency and the best response to GH therapy.

Stem cells in the canine pituitary gland and in pituitary adenomas.

PubMed

van Rijn, Sarah J; Tryfonidou, Marianna A; Hanson, Jeanette M; Penning, Louis C; Meij, Björn P

2013-12-01

Cushing's disease (CD) or pituitary-dependent hypercortisolism is a common endocrinopathy in dogs, with an estimated prevalence of 1 or 2 in 1000 dogs per year. It is caused by an adrenocorticotropic hormone secreting adenoma in the pars distalis or pars intermedia of the pituitary gland. The pituitary gland is a small endocrine gland located in the pituitary fossa. In the postnatal individual, the hypothalamus-pituitary axis plays a central role in maintaining homeostatic functions, like control of metabolism, reproduction, and growth. Stem cells are suggested to play a role in the homeostatic adaptations of the adult pituitary gland, such as the rapid specific cell-type expansion in response to pregnancy or lactation. Several cell populations have been suggested as pituitary stem cells, such as Side Population cells and cells expressing Sox2 or Nestin. These cell populations are discussed in this review. Also, stem and progenitor cells are thought to play a role in pituitary tumorigenesis, such as the development of pituitary adenomas in dogs. There are limited reports on the role of stem cells in pituitary adenomas, especially in dogs. Further studies are needed to identify and characterize this cell population and to develop specific cell targeting therapeutic strategies as a new way of treating canine CD.

V3 vasopressin receptor and corticotropic phenotype in pituitary and nonpituitary tumors.

PubMed

de Keyzer, Y; René, P; Lenne, F; Auzan, C; Clauser, E; Bertagna, X

1997-01-01

Pituitary corticotropic cells express a specific vasopressin receptor, called V1b or V3, through which vasopressin stimulates corticotropin secretion. We recently cloned a cDNA coding for this receptor and showed that it belongs to the G protein-coupled receptor family. V3 mRNA is readily detected by RT-PCR in normal human pituitaries and corticotropic pituitary adenomas but not in PRL or GH-secreting adenomas, thus demonstrating that, like POMC itself and the CRH receptor, V3 is a marker of the corticotropic phenotype. Nuclease protection experiments suggest that V3 is overexpressed in some corticotropic adenomas, and thus may play a role in tumor development by activating the phospholipase C-signalling pathway. In addition analysis of its expression in nonpituitary neuroendocrine tumors showed a striking association with carcinoids of the lung responsible for the ectopic ACTH syndrome.

Acromegaly diagnosed in a young woman presenting with headache and arthritis.

PubMed

Nachtigall, Lisa B

2006-10-01

A 38-year-old woman presented with severe headaches to her primary-care physician. The patient had been diagnosed with rheumatoid arthritis and had begun having headache 4 years previously. An MRI scan revealed an 11-12 mm pituitary tumor. Her physical examination was unremarkable for the classic acral or facial changes characteristic of acromegaly, and she was referred for neuroendocrine consultation for a presumed nonfunctioning adenoma. MRI of the pituitary, and laboratory investigations that included measurement of serum insulin-like growth factor 1 (IGF1) and prolactin levels. In view of the elevated level of IGF1 and presence of a pituitary adenoma, the patient was diagnosed with acromegaly caused by a pituitary adenoma that secretes growth hormone. The patient underwent trans-sphenoidal surgery, which resulted in resolution of joint pain and headache, eradication of the tumor mass, normal IGF1 levels, and appropriate suppression of growth hormone (confirmed by oral glucose tolerance test postoperatively).

Perinatal stress and early life programming of lung structure and function

PubMed Central

Wright, Rosalind J.

2010-01-01

Exposure to environmental toxins during critical periods of prenatal and/or postnatal development may alter the normal course of lung morphogenesis and maturation, potentially resulting in changes that affect both structure and function of the respiratory system. Moreover, these early effects may persist into adult life magnifying the potential public health impact. Aberrant or excessive pro-inflammatory immune responses, occurring both locally and systemically, that result in inflammatory damage to the airway are a central determinant of lung structure-function changes throughout life. Disruption of neuroendocrine function in early development, specifically the hypothalamic-pituitary-adrenal (HPA) axis, may alter functional status of the immune system. Autonomic nervous system (ANS) function (sympathovagal imbalance) is another integral component of airway function and immunity in childhood. This overview discusses the evidence linking psychological factors to alterations in these interrelated physiological processes that may, in turn, influence childhood lung function and identifies gaps in our understanding. PMID:20080145

A rare cause of hypophysitis: tuberculosis.

PubMed

Ates, Ihsan; Katipoglu, B; Copur, B; Yilmaz, N

2017-10-26

Hypophysitis is a heterogeneous inflammatory disease of pituitary gland. As it causes headache and visual defects, it mimics sellar tumors in clinical and radiological aspects. It may occur due to primary or secondary causes. Tuberculosis is one of the rare secondary causes of the hypophysitis. Subject and Results. A 30-year-old male patient presented with fatigue and headache. Panhypopituitarism was considered due to the results and the diagnostic magnetic resonance (MR) imaging revealed sagittal section diamater of pituitary gland higher than normal. Biopsy of the pituitary gland was concordant with the granulomatous hypophysitis. Other possible diagnosis was excluded. The tubercular hypophysitis, as a result of performed tests, is discussed hereby, in the case report.

MANAGEMENT OF ENDOCRINE DISEASE: Can we cure Cushing's disease? A personal view.

PubMed

Bertagna, X

2018-05-01

One of today's challenges in endocrinology is the treatment of Cushing's disease: Although pituitary surgery has the potential to 'cure' the patient and restore a completely normal pituitary adrenal axis, there are immediate failures and late recurrences that will ultimately require alternate therapeutic approaches. Their high number is in direct correlation with their serious limitations and they all appear to be 'default options'. This 'personal view' tries to shed some light on the inescapable difficulties of the current treatments of Cushing's disease and to provide some optimistic view for the future where the pituitary adenoma should be the 'reasonable obsession' of a successful therapeutist. © 2018 European Society of Endocrinology.

Pituitary disorders as a predictor of apathy and executive dysfunction in adult survivors of childhood brain tumors.

PubMed

Fox, Michelle E; King, Tricia Z

2016-11-01

The relationship between apathy and endocrine dysfunction, both frequent outcomes of neurological insult, has not yet been investigated in brain tumor survivors. The present study aimed to assess the relationship between pituitary disorders and apathy and other facets of executive function in long-term adult survivors of childhood brain tumors and to differentiate between apathy and depression in this population. Seventy-six adult survivors of childhood brain tumors at least 5 years past diagnosis participated. An informant completed the Frontal Systems Behavior Scale (FrSBe), and 75 of the 76 participants completed a Structured Clinical Interview for the DSM-IV-TR (SCID). Information on neuroendocrine dysfunction was obtained through medical chart review. Clinically significant levels of apathy on the FrSBe were identified in 41% of survivors. Pituitary dysfunction significantly explained 9% of the variance in apathy scores and affected whether an individual presented with clinical levels of apathy. Pituitary dysfunction predicted higher levels of executive dysfunction but did not impact whether a participant reached clinical levels of executive dysfunction. A past major depressive episode (MDE) significantly predicted current apathy but showed no relationship with pituitary disorders. Radiation treatment predicted pituitary dysfunction but not the differences in apathy or executive functions. Apathy and executive dysfunction in survivors of childhood brain tumors are strongly predicted by pituitary dysfunction, and individuals with pituitary dysfunction are more likely to present with clinical levels of apathy as adults. Clinical levels of apathy may present absent of current depression, and pituitary dysfunction impacts apathy uniquely. © 2016 Wiley Periodicals, Inc.

Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening.

PubMed

Mangupli, Ruth; Rostomyan, Liliya; Castermans, Emilie; Caberg, Jean-Hubert; Camperos, Paul; Krivoy, Jaime; Cuauro, Elvia; Bours, Vincent; Daly, Adrian F; Beckers, Albert

2016-10-01

Pituitary gigantism is a rare condition caused by growth hormone secreting hypersecretion, usually by a pituitary tumor. Acromegaly and gigantism cases that have a genetic cause are challenging to treat, due to large tumor size and poor responses to some medical therapies (e.g. AIP mutation affected cases and those with X-linked acrogigantism syndrome). We performed a retrospective study to identify gigantism cases among 160 somatotropinoma patients treated between 1985 and 2015 at the University Hospital of Caracas, Venezuela. We studied clinical details at diagnosis, hormonal responses to therapy and undertook targeted genetic testing. Among the 160 cases, eight patients (six males; 75 %) were diagnosed with pituitary gigantism and underwent genetic analysis that included array comparative genome hybridization for Xq26.3 duplications. All patients had GH secreting pituitary macroadenomas that were difficult to control with conventional treatment options, such as surgery or primary somatostatin receptor ligand (SRL) therapy. Combined therapy (long-acting SRL and pegvisomant) as primary treatment or after pituitary surgery and radiotherapy permitted the normalization of IGF-1 levels and clinical improvement. Novel AIP mutations were the found in three patients. None of the patients had Xq26.3 microduplications. Treatment of pituitary gigantism is frequently challenging; delayed control increases the harmful effects of GH excess, such as, excessive stature and symptom burden, so early diagnosis and effective treatment are particularly important in these cases.

The association of pituitary tumors and headache.

PubMed

Levy, Miles J

2011-04-01

Pituitary tumors may give rise to headache via numerous mechanisms. The traditional explanation for headache is dural stretch and cavernous sinus invasion, although this is not borne out by clinical studies. Certain functional pituitary tumors are associated with headache, notably growth hormone and prolactin-secreting tumors. The observation that somatostatin analogues can have a dramatic analgesic effect in acromegaly suggests that biochemical properties of the tumor may be important. The genetic predisposition of the patient to primary headache also determines whether headache occurs with pituitary tumors. This article attempts to outline the clinical features, management strategies, and key academic questions regarding the subject of pituitary tumors and headache.

Transsphenoidal Surgery for Pituitary Tumors and Other Sellar Masses.

PubMed

Owen, Tina J; Martin, Linda G; Chen, Annie V

2018-01-01

Transsphenoidal surgery is an option for dogs and cats with functional and nonfunctional pituitary masses or other sellar and parasellar masses. An adrenocorticotropic hormone-secreting tumor causing Cushing disease is the most common clinically relevant pituitary tumor in dogs, and the most common pituitary tumor seen in cats is a growth hormone-secreting tumor causing acromegaly. Transsphenoidal surgery can lead to rapid resolution of clinical signs and provide a cure for these patients. Because of the risks associated with this surgery, it should only be attempted by a cohesive pituitary surgery group with a sophisticated medical and surgical team. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term outcomes of children treated for Cushing's disease: a single center experience.

PubMed

Yordanova, Galina; Martin, Lee; Afshar, Farhad; Sabin, Ian; Alusi, Ghassan; Plowman, Nicholas P; Riddoch, Fiona; Evanson, Jane; Matson, Matthew; Grossman, Ashley B; Akker, Scott A; Monson, John P; Drake, William M; Savage, Martin O; Storr, Helen L

2016-12-01

Pediatric Cushing's disease (CD) is rare and there are limited data on the long-term outcomes. We assessed CD recurrence, body composition, pituitary function and psychiatric comorbidity in a cohort of pediatric CD patients. Retrospective review of 21 CD patients, mean age at diagnosis 12.1 years (5.7-17.8), managed in our center between 1986 and 2010. Mean follow-up from definitive treatment was 10.6 years (2.9-27.2). Fifteen patients were in remission following transsphenoidal surgery (TSS) and 5 were in remission following TSS + external pituitary radiotherapy (RT). One patient underwent bilateral adrenalectomy (BA). CD recurrence occurred in 3 (14.3 %) patients: 2 at 2 and 6 years after TSS and 1 7.6 years post-RT. The BA patient developed Nelson's syndrome requiring pituitary RT 0.6 years post-surgery. Short-term growth hormone deficiency (GHD) was present in 14 patients (81 % patients tested) (11 following TSS and 3 after RT) and 4 (44 % of tested) had long-term GHD. Gonadotropin deficiency caused impaired pubertal development in 9 patients (43 %), 4 requiring sex steroid replacement post-puberty. Four patients (19 %) had more than one pituitary hormone deficiency, 3 after TSS and 1 post-RT. Five patients (24 %) had long-term psychiatric co-morbidities (cognitive dysfunction or mood disturbance). There were significant long-term improvements in growth, weight and bone density but not complete reversal to normal in all patients. The long-term consequences of the diagnosis and treatment of CD in children is broadly similar to that seen in adults, with recurrence of CD after successful treatment uncommon but still seen. Pituitary hormone deficiencies occurred in the majority of patients after remission, and assessment and appropriate treatment of GHD is essential. However, while many parameters improve, some children may still have mild but persistent defects.

Assessment of normal perisellar anatomy in 1.5 T T2-weighted MRI and comparison with the anatomic criteria defining cavernous sinus invasion of pituitary adenomas.

PubMed

Knappe, U J; Jaursch-Hancke, C; Schönmayr, R; Lörcher, U

2009-08-01

The study aimed to evaluate the anatomical relations of sellar and perisellar structures with T2-weighted MRI and to apply criteria for cavernous sinus (CS) invasion by pituitary adenomas to normal sellar anatomy. Thin slice (3 mm) coronal T2-weighted MR-images (1.5 Tesla) were obtained in 117 individuals (234 CS) without pituitary disorders (58 females, 59 males; age 17 months to 87 years). In 99 cases data indicating the presence of arterial hypertension (AH) were available, 25 with AH, 74 without AH. The medial wall of the cavernous sinus was detectable in 33% of cases. The inferior rim of the horizontal part of the ICA was located at the level of the sellar floor in 33%, below in 47%, and above in 20%. The mean distance between the both ICAs was 17.8 mm (range, 7-38 mm). The mean distance between the pituitary and the ICA in AH was significantly shorter than in patients without AH (Chi-square, p=0.01). There was contact between the gland and the ICA in 41.5% of the cases. In 16.7% (39 sides) of all 234 SCs investigated, the area of contact between the ICA and the gland was at least 25% of the vessel's circumference. The medial intercarotid line (ICL) was crossed by the pituitary gland in 9% (21 of 234 CS), the central ICL was touched in another 5% (11 of 234 CS), lateral ICL was never reached. There was a weak correlation with age: a more extensive lateral extension of the gland was seen in individuals older than 40 years compared to younger individuals (Chi-square, p=0.03). There was a marked difference in the anatomical findings between both sides in 41.9% of cases. Inter- and intra-individual variations of the perisellar anatomy and its relation to the pituitary gland exist, which are partly related to age and AH. This must be remembered when the invasiveness of pituitary adenomas is assessed in MRI. Georg Thieme Verlag KG Stuttgart New York.

Changes in thrombospondin-1 levels in the endothelial cells of the anterior pituitary during estrogen-induced prolactin-secreting pituitary tumors

PubMed Central

Sarkar, Abby J; Chaturvedi, Kirti; Chen, Cui Ping; Sarkar, Dipak K

2010-01-01

Thrombospondin-1 (TSP-1), a multifunctional matrix glycoprotein, has been shown to control tumor growth by inhibiting angiogenesis in various tissues. However, the role of this glycoprotein in pituitary angiogenesis is not well studied. In this report, we determined the changes in the production and action of TSP-1 on endothelial cells in anterior pituitary following estradiol treatment, which is known to increase prolactin-secreting tumor growth and vascularization in this tissue. We showed that TSP-1 immunoreactive protein is distributed in the anterior pituitary, particularly in the endothelial cells. Estradiol treatment for 2 and 4 weeks decreased the total tissue immunoreactive level of TSP-1 as well as the endothelial cell-specific immunoreactive level of this protein in the anterior pituitary. The steroid treatment also decreased the protein levels of TSP-1 in anterior pituitary tissues and in purified pituitary endothelial cells in primary cultures. Determination of the effects of TSP-1 on proliferation and migration of pituitary-derived endothelial cells in primary cultures elucidated an inhibitory action of TSP-1 on these vascular cell functions. These results suggest that locally produced TSP-1 may regulate estrogen angiogenic action on the pituitary. PMID:17283240

Neurotrophins and their receptors in the rat pituitary gland: regulation of BDNF and trkB mRNA levels by adrenal hormones.

PubMed

Kononen, J; Soinila, S; Persson, H; Honkaniemi, J; Hökfelt, T; Pelto-Huikko, M

1994-12-01

We studied the expression of messenger ribonucleic acids (mRNAs) for neurotrophins and neurotrophin receptors in the rat pituitary gland and examined the influence of adrenal hormones on their mRNA levels, using in situ hybridization and Northern blot analysis. The only neurotrophin present at detectable levels in the pituitary was brain-derived neurotrophic factor (BDNF), which was observed in the anterior and intermediate lobes. Several transcripts of the putative receptor for BDNF, trkB, were present in the anterior and posterior lobes of the pituitary. A low amount of trkC mRNA was found in both the anterior and the intermediate lobe. Dexamethasone treatment decreased both BDNF and trkB mRNA levels in the anterior lobe of the pituitary. Adrenalectomy had no effect on trkB expression, but it decreased BDNF mRNA levels in comparison to the control animals. This effect could not be reversed by dexamethasone substitution, suggesting that BDNF, mRNA levels may be regulated not only by glucocorticoids but also by other adrenal hormones. These results demonstrate that BDNF, trkB and trkC are expressed in the pituitary gland and that glucocorticoids and possibly other adrenal hormones may modulate pituitary functions by regulating the expression of neurotrophic factors and their receptors. Whether BDNF acts as a secreted hormone, a trophic factor, or has autocrine/paracrine functions within the pituitary through its receptor, trkB, remains to be studied.

Transcriptome-Wide Identification of Preferentially Expressed Genes in the Hypothalamus and Pituitary Gland

PubMed Central

St-Amand, Jonny; Yoshioka, Mayumi; Tanaka, Keitaro; Nishida, Yuichiro

2012-01-01

To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the hypothalamus, pituitary gland, and parietal cortex in male mice (12–15 weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE tags for the hypothalamus, pituitary gland, and parietal cortex were 165824, 126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix, and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis, and turnover, cell differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland. PMID:22649398

Transcriptome-wide identification of preferentially expressed genes in the hypothalamus and pituitary gland.

PubMed

St-Amand, Jonny; Yoshioka, Mayumi; Tanaka, Keitaro; Nishida, Yuichiro

2011-01-01

To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the hypothalamus, pituitary gland, and parietal cortex in male mice (12-15 weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE tags for the hypothalamus, pituitary gland, and parietal cortex were 165824, 126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix, and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis, and turnover, cell differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland.

Radiotherapy-induced hypopituitarism in nasopharyngeal carcinoma: the tip of an iceberg.

PubMed

Ipekci, S H; Cakir, M; Kiyici, A; Koc, O; Artac, M

2015-07-01

Radiation-induced hypopituitarism is an important late complication of cranial radiotherapy in children and adults. The purpose of this cross-sectional study was to evaluate the effects of radiotherapy on pituitary function in adult nasopharyngeal carcinoma patients. Pituitary function was evaluated in 30 patients after cranial radiotherapy for nasopharyngeal carcinoma. Somatotroph and corticotroph axes were assessed by insulin tolerance test while gonadotroph and thyroid axes were evaluated by basal pituitary and end organ hormone levels at 10-133 months after radiotherapy. At least one hormonal disorder was observed in 28 (93%) patients after radiotherapy. 26 (87%) patients had one or more anterior pituitary hormone deficiencies. The rates of pituitary hormone deficiencies were 77% for growth hormone, followed by adrenocorticotropic hormone (73%), thyroid-stimulating hormone (27%) and gonadotropins (7%). Hyperprolactinemia was present in 13 (43%) patients. Radiation-induced hypopituitarism is more common than expected in patients with nasopharyngeal carcinoma. © Georg Thieme Verlag KG Stuttgart · New York.

Infrequent detectable somatic mutations of the RET and glial cell line-derived neurotrophic factor (GDNF) genes in human pituitary adenomas.

PubMed

Yoshimoto, K; Tanaka, C; Moritani, M; Shimizu, E; Yamaoka, T; Yamada, S; Sano, T; Itakura, M

1999-02-01

RET is a receptor tyrosine kinase expressed in neuroendocrine cells and tumors. RET is activated by a ligand complex comprising glial cell line-derived neurotrophic factor (GDNF) and GDNF receptor-alpha (GDNFR-alpha). Activating mutations of the RET proto-oncogene were found in multiple endocrine neoplasia (MEN) 2 and in sporadic medullary thyroid carcinoma and pheochromocytoma of neuroendocrine origin. Mutations of the RET proto-oncogene and the glial cell line-derived neurotrophic factor (GDNF) gene were examined in human pituitary tumors. No mutations of the RET proto-oncogene including the cysteine-rich region or codon 768 and 918 in the tyrosine kinase domain were detected in 172 human pituitary adenomas either by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) or by PCR-restriction fragment length polymorphism (RFLP). Further, somatic mutations of the GDNF gene in 33 human pituitary adenomas were not detected by PCR-SSCP. One polymorphism of the GDNF gene at codon 145 of TGC or TGT was observed in a prolactinoma. The RET proto-oncogene message was detected in a normal human pituitary gland or 4 of 4 human pituitary adenomas with reverse transcription (RT)-PCR, and in rodent pituitary tumor cell lines with Western blotting. The expression of GDNF gene was detected in 1 of 4 human somatotroph adenomas, 1 of 2 corticotroph adenomas, and 2 of 6 rodent pituitary tumor cell lines with RT-PCR. Based on these, it is concluded that somatic mutations of the RET proto-oncogene or the GDNF gene do not appear to play a major role in the pituitary tumorigenesis in examined tumors.

Somatic GNAS Mutation Causes Widespread and Diffuse Pituitary Disease in Acromegalic Patients with McCune-Albright Syndrome

PubMed Central

Vortmeyer, Alexander O.; Gläsker, Sven; Mehta, Gautam U.; Abu-Asab, Mones S.; Smith, Jonathan H.; Zhuang, Zhengping; Collins, Michael T.

2012-01-01

Context: McCune-Albright syndrome (MAS) is caused by sporadic mutations of the GNAS. Patients exhibit features of acromegaly. In most patients, GH-secreting pituitary adenomas have been held responsible for this presentation. However, surgical adenomectomy rarely eliminates excess GH production. Objective: The aim of this study was to elucidate pituitary pathology in patients with MAS and to explain the basis of failure of adenomectomy to eliminate GH hypersecretion. Design and Setting: We conducted a case series at the National Institutes of Health. Intervention(s): Interventions included medical therapy and transsphenoidal surgery. Patients and Main Outcome Measures: We studied clinical and imaging features and the histology and molecular features of the pituitary of four acromegalic MAS patients. Results: We identified widespread and diffuse pituitary gland disease. The primary pathological changes were characterized by hyperplastic and neoplastic change, associated with overrepresentation of somatotroph cells in structurally intact tissue areas. Genetic analysis of multiple microdissected samples of any type of histological area consistently revealed identical GNAS mutations in individual patients. The only patient with remission after surgery received complete hypophysectomy in addition to removal of multiple GH-secreting tumors. Conclusions: These findings indicate developmental effects of GNAS mutation on the entire anterior pituitary gland. The pituitary of individual cases contains a spectrum of changes with regions of normal appearing gland, hyperplasia, and areas of fully developed adenoma formation, as well as transitional stages between these entities. The primary change underlying acromegaly in MAS patients is somatotroph hyperplasia involving the entire pituitary gland, with or without development of somatotroph adenoma. Thus, successful clinical management, whether it is medical, surgical, or via irradiation, must target the entire pituitary, not just the adenomas evident on imaging. PMID:22564667

Clinical characteristics, etiologies and pathophysiology of patients with severe short stature with severe GH deficiency: questionnaire study on the data registered with the foundation for growth science, Japan.

PubMed

Hanew, Kunihiko; Tachibana, Katsuhiko; Yokoya, Susumu; Fujieda, Kenji; Tanaka, Toshiaki; Igarashi, Yutaka; Shimatsu, Akira; Tanaka, Hiroyuki; Tanizawa, Takakuni; Teramoto, Akira; Nishi, Yoshikazu; Hasegawa, Yukihiro; Hizuka, Naomi; Hirano, Takeki; Fujita, Keinosuke

2006-04-01

In this study, we sent questionnaires to doctors treating severe short stature with severe GH deficiency (GHD) (height SDS (HtSDS) below -4 and all peak GH to provocative stimuli below 2 micro/L) (abbreviated as Severe Case), and obtained effective replies of 51 cases. The clinical characteristics, etiologies, and pathophysiology of these patients were examined. Among the 51 Severe Cases no consanguinity was observed, 44 were IGHD (24 males and 20 females), 3 were GH-1 gene deletion, 2 were Pit-1 gene mutation, and 2 were achondroplasia. HtSDS in these Severe Cases was already remarkably low at 12 (-3.0) and 24 months old (-3.9), while their birth weight and birth length were within normal ranges. Among 44 patients with IGHD, 12 were isolated GHD, and the remaining 32 were combined pituitary hormone deficiency (CPHD). Pituitary MRI was undergone in 25 idiopathic GHD, and abnormal findings (pituitary atrophy, interruption of stalk, and ectopic posterior lobe) were observed in 21 patients with CPHD. More than half of these patients had the history of breech delivery. Three patients with GH-1 gene mutation showed normal pituitary MRI, whereas one of two patients with Pit-1 mutation showed pituitary atrophy and narrowing of pituitary stalk. In conclusion, Severe Cases tended to have CPHD, and the incidence of Severe Case was only 0.6% of total IGHD. Although GHD due to genetic disorders is considered to be extremely rare (0.06% of total IGHD), the incidence reaches high levels (9.8%) among Severe Cases. Growth disorders in these Severe Cases seem to occur soon after delivery. Much earlier diagnosis and hGH treatment are desirable to attain better final height in the Severe Cases. GH-1 and Pit-1 gene analyses are crucial, when genetic abnormalities other than achondroplasia are suspected.

Emerging pharmacotherapy for treatment of traumatic brain injury: targeting hypopituitarism and inflammation.

PubMed

Paterniti, Irene; Cordaro, Marika; Navarra, Michele; Esposito, Emanuela; Cuzzocrea, Salvatore

2015-01-01

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the developed world. In particular, TBI is an important cause of death and disability in young adults with consequences ranging from physical disabilities to long-term cognitive, behavioural, psychological and social defects. There is a large body of evidence that suggest that TBI conditions may adversely affect pituitary function in both the acute and chronic phases of recovery. Prevalence of hypopituitarism, from total to isolated pituitary deficiency, ranges from 5 to 90%. The time interval between TBI and pituitary function evaluation is one of the major factors responsible for variations in the prevalence of hypopituitarism reported. Diagnosis of hypopituitarism and accurate treatment of pituitary disorders offers the opportunity to improve mortality and outcome in TBI conditions. The aim of this paper is to review the history and pathophysiology of TBI and to summarize the best evidence of TBI as a cause of pituitary deficiency. Moreover, in this article we will describe the multiple changes which occur within the hypothalamic-pituitary-thyroid axis in critical illness, giving rise to 'sick euthyroid syndrome', focus our attention on thyroid hormones circulating levels from the initial insult to critical illness.

The dependence receptor Ret induces apoptosis in somatotrophs through a Pit-1/p53 pathway, preventing tumor growth

PubMed Central

Cañibano, Carmen; Rodriguez, Noela L; Saez, Carmen; Tovar, Sulay; Garcia-Lavandeira, Montse; Borrello, Maria Grazia; Vidal, Anxo; Costantini, Frank; Japon, Miguel; Dieguez, Carlos; Alvarez, Clara V

2007-01-01

Somatotrophs are the only pituitary cells that express Ret, GFRα1 and GDNF. This study investigated the effects of Ret in a somatotroph cell line, in primary pituitary cultures and in Ret KO mice. Ret regulates somatotroph numbers by inducing Pit-1 overexpression, leading to increased p53 expression and apoptosis, both of which can be prevented with Ret or Pit-1 siRNA. The Pit-1 overexpression is mediated by sustained activation of PKCδ, JNK, c/EBPα and CREB induced by a complex of Ret, caspase 3 and PKCδ. In the presence of GDNF, Akt is activated, and the Pit-1 overexpression and resulting apoptosis are blocked. The adenopituitary of Ret KO mice is larger than normal, showing Pit-1 and somatotroph hyperplasia. In normal animals, activation of the Ret/Pit-1/p53 pathway by retroviral introduction of Ret blocked tumor growth in vivo. Thus, somatotrophs have an intrinsic mechanism for controlling Pit-1/GH production through an apoptotic/survival pathway. Ret might be of value for treatment of pituitary adenomas. PMID:17380130

The dependence receptor Ret induces apoptosis in somatotrophs through a Pit-1/p53 pathway, preventing tumor growth.

PubMed

Cañibano, Carmen; Rodriguez, Noela L; Saez, Carmen; Tovar, Sulay; Garcia-Lavandeira, Montse; Borrello, Maria Grazia; Vidal, Anxo; Costantini, Frank; Japon, Miguel; Dieguez, Carlos; Alvarez, Clara V

2007-04-18

Somatotrophs are the only pituitary cells that express Ret, GFRalpha1 and GDNF. This study investigated the effects of Ret in a somatotroph cell line, in primary pituitary cultures and in Ret KO mice. Ret regulates somatotroph numbers by inducing Pit-1 overexpression, leading to increased p53 expression and apoptosis, both of which can be prevented with Ret or Pit-1 siRNA. The Pit-1 overexpression is mediated by sustained activation of PKCdelta, JNK, c/EBPalpha and CREB induced by a complex of Ret, caspase 3 and PKCdelta. In the presence of GDNF, Akt is activated, and the Pit-1 overexpression and resulting apoptosis are blocked. The adenopituitary of Ret KO mice is larger than normal, showing Pit-1 and somatotroph hyperplasia. In normal animals, activation of the Ret/Pit-1/p53 pathway by retroviral introduction of Ret blocked tumor growth in vivo. Thus, somatotrophs have an intrinsic mechanism for controlling Pit-1/GH production through an apoptotic/survival pathway. Ret might be of value for treatment of pituitary adenomas.

Diet-induced loss of cyclic ovarian function at normal body weight in a rodent model for bulimia nervosa.

PubMed

Leigh, A J; Stock, M J; Lacey, J H; Wilson, C A

1998-03-01

A bulimic rat model was used to test whether type and frequency of food intake mimicking that in human bulimia nervosa could disrupt oestrous cyclicity, induce an effect on glycoprotein (LH) structure, or affect both processes and if so, to determine whether any such effects were acute, or persisted after return to normal eating patterns. Voluntary hyperphagia was induced by offering female rats a varied and palatable choice of human food items--the 'cafeteria diet'. There were four groups: control (normal chow), obese (continuous cafeteria diet), post-obese (cafeteria diet, then fasted to reduce weight to that of controls) and binge (cafeteria alternated with normal diet every few days). Animals were maintained on these diets for 60 days (phase I). They were then given a GnRH challenge on day 2 of dioestrus of the cycle. Twenty-four hours later, half of the animals in each group were killed for assessment of effects on their reproductive organs. The remaining animals were returned to normal diets and kept for a further 40 days, when the GnRH challenge was repeated and the animals were killed 24 h later (phase II). All animals on the cafeteria diet in phase I exhibited significant disruption of oestrous cyclicity irrespective of body weight. LH released in response to the first GnRH challenge showed a prolonged half-life, and/or increased rate of secretion in the obese and post-obese groups but in the binge group the secretory/clearance properties resembled those of control animals. After the second GnRH challenge at the end of phase II, however, the LH of the binge group appeared to have different secretory or clearance characteristics, whereas that of the previously obese animals had returned to normal. These data show ovarian cyclicity was disrupted by hyperphagia and irregular eating, even at normal body weight. Relating ovarian function to pituitary output in terms of LH, the effects of the continuous cafeteria diet did not appear to persist in the animals that returned to normal diets, but in the binge group the effect, presumably of the diet manipulation, was manifested after return to a normal eating pattern. This finding suggests that irregular eating habits may exert a direct (and acute) effect on the ovary, but that effects on the pituitary (and LH glycoforms) take longer to be expressed, explaining many features of bulimia nervosa.

Hypopituitarism in the elderly: a narrative review on clinical management of hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes dysfunction.

PubMed

Curtò, L; Trimarchi, F

2016-10-01

Hypopituitarism is an uncommon and under-investigated endocrine disorder in old age since signs and symptoms are unspecific and, at least in part, can be attributed to the physiological effects of aging and related co-morbidities. Clinical presentation is often insidious being characterized by non-specific manifestations, such as weight gain, fatigue, low muscle strength, bradipsychism, hypotension or intolerance to cold. In these circumstances, hypopituitarism is a rarely life-threatening condition, but evolution may be more dramatic as a result of pituitary apoplexy, or when a serious condition of adrenal insufficiency suddenly occurs. Clinical presentation depends on the effects that each pituitary deficit can cause, and on their mutual relationship, but also, inevitably, it depends on the severity and duration of the deficit itself, as well as on the general condition of the patient. Indeed, indications and methods of hormone replacement therapy must include the need to normalize the endocrine profile without contributing to the worsening of intercurrent diseases, such as those of glucose and bone metabolism, and the cardiovascular system, or to the increasing cancer risk. Hormonal requirements of elderly patients are reduced compared to young adults, but a prompt diagnosis and appropriate treatment of pituitary deficiencies are strongly recommended, also in this age range.

The association between calcitonin gene-related peptide (CGRP), substance P and headache in pituitary tumours.

PubMed

Levy, M J; Classey, J D; Maneesri, S; Meeran, K; Powell, M; Goadsby, P J

2004-01-01

To determine if the differential expression of calcitonin gene-related peptide (CGRP) or substance P (SP) in a range of pituitary tumours was related to the presence or absence of headache. Using recognised immunohistochemical techniques we examined twenty-six consecutive pituitary adenoma specimens for the presence of CGRP and SP. We included one normal post mortem pituitary specimen for comparison. A separate observer divided the patients into two groups: headache and non-headache. The association between the presence of CGRP, SP and headache was observed. We observed CGRP in seven specimens (27%) and SP in six tumour specimens (23%), with cytoplasmic staining being the predominant morphological picture. CGRP and SP were co-expressed in the same tumour specimen in five cases. There was no significant association between the presence of CGRP and headache (chi(2) 0.86; P = 0.35). We did not observe CGRP or SP in the control specimen. There was no correlation between tumour subtype and the presence of CGRP or SP. The mechanism of pituitary tumour-associated headache remains undetermined. The significance of the presence of CGRP and SP in pituitary tumours is unknown but does not appear to be related to headache or endocrine activity of the tumour.

MR of the pituitary in patients with Prader-Willi syndrome: size determination and imaging findings.

PubMed

Miller, L; Angulo, M; Price, D; Taneja, S

1996-01-01

Prader-Willi syndrome (PWS) is an unusual genetic disorder characterized by short stature, obesity, hypogonadism, hypotonia, cognitive impairment, and dysmorphic facies. There is an interstitial deletion of the proximal long arm of chromosome 15 in about 70 % of patients. Some of these clinical features suggest a central hypothalamic/pituitary dysfunction, and recent investigations have demonstrated a marked impairment in spontaneous growth hormone (GH) secretion. We studied 15 GH-deficient PWS patients by magnetic resonance imaging (MRI) to determine whether there was a diminution in the gross morphological size of the anterior pituitary gland, the site of GH synthesis. We also set out to catalog the pertinent imaging findings in this patient population. Our results indicate that this is the first report documenting pituitary size by MRI in PWS patients. No statistically significant difference was found in the height of the anterior pituitary gland in PWS patients compared with either normal children or children with isolated GH deficiency. An interesting imaging finding is that three of 15 patients (20 %) demonstrated complete absence of the posterior pituitary bright spot (PPBS), and a fourth patient demonstrated a small PPBS. These observations reflect an objective physiologic disturbance in the hypothalamus. The clinical and radiologic implications of these findings are discussed.

The Infundibular Recess Passes through the Entire Pituitary Stalk.

PubMed

Tsutsumi, S; Hori, M; Ono, H; Tabuchi, T; Aoki, S; Yasumoto, Y

2016-12-01

The infundibular recess (IR), commonly illustrated as a V-shaped hollow in the sagittal view, is recognized as a small extension of the third ventricle into the pituitary stalk. The precise morphology of the human IR is unknown. The present study sought to delineate the morphology of the IR using magnetic resonance imaging. Subjects included 100 patients without acute cerebral infarcts, intracranial hemorrhage, intrasellar or suprasellar cysts, hydrocephalus, inflammatory disease, or brain tumors. Patients with symptoms of increased intracranial pressure, intracranial hypotension, or pituitary dysfunction were excluded. Thin-sliced, seamless T2-weighted sequences involving the optic chiasm, entire pituitary stalk, and pituitary gland were performed in axial and sagittal planes for each patient. The numbers of slices delineating the pituitary stalk and IR were recorded from the axial images and quantified as ratios. The pituitary stalk consistently appeared as a styloid- or cone-shaped structure with variable inclinations toward the third ventricle floor. The IR was delineated as a smoothly tapering, tubular extension of the third ventricle located in the central portion of the pituitary stalk. In 81 % of patients, the IR passed through the entire length of the pituitary stalk and reached the upper surface of the pituitary gland, which was identified in 40 % of the midsagittal images. The IR is a cerebrospinal fluid-filled canal passing through the center of the pituitary stalk and connects the third ventricle to the pituitary gland. It may function in conjunction with the pituitary gland.

Cellular and molecular specificity of pituitary gland physiology.

PubMed

Perez-Castro, Carolina; Renner, Ulrich; Haedo, Mariana R; Stalla, Gunter K; Arzt, Eduardo

2012-01-01

The anterior pituitary gland has the ability to respond to complex signals derived from central and peripheral systems. Perception of these signals and their integration are mediated by cell interactions and cross-talk of multiple signaling transduction pathways and transcriptional regulatory networks that cooperate for hormone secretion, cell plasticity, and ultimately specific pituitary responses that are essential for an appropriate physiological response. We discuss the physiopathological and molecular mechanisms related to this integrative regulatory system of the anterior pituitary gland and how it contributes to modulate the gland functions and impacts on body homeostasis.

Regulation of alternative splicing of Slo K+ channels in adrenal and pituitary during the stress-hyporesponsive period of rat development.

PubMed

Lai, Guey-Jen; McCobb, David P

2006-08-01

Stress triggers release of ACTH from the pituitary, glucocorticoids from the adrenal cortex, and epinephrine from the adrenal medulla. Although functions differ, these hormone systems interact in many ways. Previous evidence indicates that pituitary and steroid hormones regulate alternative splicing of the Slo gene at the stress axis-regulated exon (STREX), with functional implications for the calcium-activated K+ channels prominent in adrenal medullary and pituitary cells. Here we examine the role of corticosterone in Slo splicing regulation in pituitary and adrenal tissues during the stress-hyporesponsive period of early rat postnatal life. The sharp drop in plasma corticosterone (CORT) that defines this period offers a unique opportunity to test CORT's role in Slo splicing. We report that in both adrenal and pituitary tissues, the percentage of Slo transcripts having STREX declines and recovers in parallel with CORT. Moreover, addition of 500 nm CORT to cultures of anterior pituitary cells from 13-, 21-, and 30-d postnatal animals increased the percentage of Slo transcripts with STREX, whereas 20 microm CORT reduced STREX representation. Applied to adrenal chromaffin cells, 20 microm CORT decreased STREX inclusion, whereas neither 500 nm nor 2 microm had any effect. The mineralocorticoid receptor antagonist RU28318 abolished the effect of 500 nm CORT on splicing in pituitary cells, whereas the glucocorticoid receptor antagonist RU38486 blocked the effect of 20 microm CORT on adrenal chromaffin cells. These results support the hypothesis that the abrupt, transient drop in CORT during the stress-hyporesponsive period drives the transient decline in STREX splice variant representation in pituitary, but not adrenal.

Emerging Targets in Pituitary Adenomas: Role of the CXCL12/CXCR4-R7 System.

PubMed

Barbieri, Federica; Thellung, Stefano; Würth, Roberto; Gatto, Federico; Corsaro, Alessandro; Villa, Valentina; Nizzari, Mario; Albertelli, Manuela; Ferone, Diego; Florio, Tullio

2014-01-01

Chemokines are chemotactic regulators of immune surveillance in physiological and pathological conditions such as inflammation, infection, and cancer. Several chemokines and cognate receptors are constitutively expressed in the central nervous system, not only in glial and endothelial cells but also in neurons, controlling neurogenesis, neurite outgrowth, and axonal guidance during development. In particular, the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, form a functional network that controls plasticity in different brain areas, influencing neurotransmission, neuromodulation, and cell migration, and the dysregulation of this chemokinergic axis is involved in several neurodegenerative, neuroinflammatory, and malignant diseases. CXCR4 primarily mediates the transduction of proliferative signals, while CXCR7 seems to be mainly responsible for scavenging CXCL12. Importantly, the multiple intracellular signalling generated by CXCL12 interaction with its receptors influences hypothalamic modulation of neuroendocrine functions, although a direct modulation of pituitary functioning via autocrine/paracrine mechanisms was also reported. Both CXCL12 and CXCR4 are constitutively overexpressed in pituitary adenomas and their signalling induces cell survival and proliferation, as well as hormonal hypersecretion. In this review we focus on the physiological and pathological functions of immune-related cyto- and chemokines, mainly focusing on the CXCL12/CXCR4-7 axis, and their role in pituitary tumorigenesis. Accordingly, we discuss the potential targeting of CXCR4 as novel pharmacological approach for pituitary adenomas.

Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism.

PubMed

Shimatsu, Akira; Teramoto, Akira; Hizuka, Naomi; Kitai, Kazuo; Ramis, Joaquim; Chihara, Kazuo

2013-01-01

The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

Somatic GPR101 Duplication Causing X-Linked Acrogigantism (XLAG)-Diagnosis and Management.

PubMed

Rodd, Celia; Millette, Maude; Iacovazzo, Donato; Stiles, Craig E; Barry, Sayka; Evanson, Jane; Albrecht, Steffen; Caswell, Richard; Bunce, Benjamin; Jose, Sian; Trouillas, Jacqueline; Roncaroli, Federico; Sampson, Julian; Ellard, Sian; Korbonits, Márta

2016-05-01

Recent reports have proposed that sporadic or familial germline Xq26.3 microduplications involving the GPR101 gene are associated with early-onset X-linked acrogigantism (XLAG) with a female preponderance. A 4-year-old boy presented with rapid growth over the previous 2 years. He complained of sporadic headaches and had coarse facial features. His height Z-score was +4.89, and weight Z-score was +5.57. Laboratory testing revealed elevated serum prolactin (185 μg/L; normal, <18 μg/L), IGF-1 (745 μg/L; normal, 64-369 μg/L), and fasting GH > 35.0 μg/L. Magnetic resonance imaging demonstrated a homogenous bulky pituitary gland (18 × 15 × 13 mm) without obvious adenoma. A pituitary biopsy showed hyperplastic pituitary tissue with enlarged cords of GH and prolactin cells. Germline PRKAR1A, MEN1, AIP, DICER1, CDKN1B, and somatic GNAS mutations were negative. Medical management was challenging until institution of continuous sc infusion of short-acting octreotide combined with sc pegvisomant and oral cabergoline. The patient remains well controlled with minimal side effects 7 years after presentation. His phenotype suggested XLAG, but his peripheral leukocyte-, saliva-, and buccal cell-derived DNA tested negative for microduplication in Xq26.3 or GPR101. However, DNA isolated from the pituitary tissue and forearm skin showed duplicated dosage of GPR101, suggesting that he is mosaic for this genetic abnormality. Our patient is the first to be described with somatic microduplication leading to typical XLAG phenotype. This patient demonstrates that a negative test for Xq26.3 microduplication or GPR101 duplication on peripheral blood DNA does not exclude the diagnosis of XLAG because it can result from a mosaic mutation affecting the pituitary.

Sensorimotor cortex ablation induces time-dependent response of ACTH cells in adult rats: behavioral, immunohistomorphometric and hormonal study.

PubMed

Lavrnja, Irena; Trifunovic, Svetlana; Ajdzanovic, Vladimir; Pekovic, Sanja; Bjelobaba, Ivana; Stojiljkovic, Mirjana; Milosevic, Verica

2014-02-10

Traumatic brain injury (TBI) represents a serious event with far reaching complications, including pituitary dysfunction. Pars distalis corticotropes (ACTH cells), that represent the active module of hypothalamo-pituitary-adrenocortical axis, seem to be affected as well. Since pituitary failure after TBI has been associated with neurobehavioral impairments the aim of this study was to evaluate the effects of TBI on recovery of motor functions, morphology and secretory activity of ACTH cells in the pituitary of adult rats. Wistar male rats, initially exposed to sensorimotor cortex ablation (SCA), were sacrificed at the 2nd, 7th, 14th and 30th days post-surgery (dps). A beam walking test was used to evaluate the recovery of motor functions. Pituitary glands and blood were collected for morphological and hormonal analyses. During the first two weeks post-injury increased recovery of locomotor function was detected, reaching almost the control value at day 30. SCA induces significant increase of pituitary weights compared to their time-matched controls. The volume of ACTH-immunopositive cells was reduced at the 7th dps, while at the 14th dps their volume was enlarged, in comparison to corresponding sham controls. Volume density of ACTH cells was increased only at 14th dps, while at day 30 this increase was insignificant. The plasma level of ACTH transiently increased after the injury. The most pronounced changes were observed at the 7th and 14th dps, and were followed by decrease toward control levels at the 30th dps. Thus, temporal changes in the hypothalamic-pituitary-adrenal axis after traumatic brain injury appear to correlate with the recovery process. Copyright © 2013 Elsevier Inc. All rights reserved.

Pituitary Tumors

MedlinePlus

... or milk production), sex hormones (control the menstrual cycle and other sexual functions), thyroid gland hormones (control the thyroid gland), adrenal gland hormones, and vasopressin (a hormone involved in water and electrolyte balance). Symptoms of pituitary adenoma and ...

Fetal Alcohol Exposure Reduces Dopamine Receptor D2 and Increases Pituitary Weight and Prolactin Production via Epigenetic Mechanisms

PubMed Central

Gangisetty, Omkaram; Wynne, Olivia; Jabbar, Shaima; Nasello, Cara; Sarkar, Dipak K.

2015-01-01

Recent evidence indicated that alcohol exposure during the fetal period increases the susceptibility to tumor development in mammary and prostate tissues. Whether fetal alcohol exposure increases the susceptibility to prolactin-producing tumor (prolactinoma) development in the pituitary was studied by employing the animal model of estradiol-induced prolactinomas in Fischer 344 female rats. We employed an animal model of fetal alcohol exposure that simulates binge alcohol drinking during the first two trimesters of human pregnancy and involves feeding pregnant rats with a liquid diet containing 6.7% alcohol during gestational day 7 to day 21. Control rats were pair-fed with isocaloric liquid diet or fed ad libitum with rat chow diet. Adult alcohol exposed and control female offspring rats were used in this study on the day of estrus or after estrogen treatment. Results show that fetal alcohol-exposed rats had increased levels of pituitary weight, pituitary prolactin (PRL) protein and mRNA, and plasma PRL. However, these rats show decreased pituitary levels of dopamine D2 receptor (D2R) mRNA and protein and increased pituitary levels of D2R promoter methylation. Also, they show elevated pituitary mRNA levels of DNA methylating genes (DNMT1, DNMT3b, MeCP2) and histone modifying genes (HDAC2, HDAC4, G9a). When fetal alcohol exposed rats were treated neonatally with a DNA methylation inhibitor 5-Aza deoxycytidine and/or a HDAC inhibitor trichostatin-A their pituitary D2R mRNA, pituitary weights and plasma PRL levels were normalized. These data suggest that fetal alcohol exposure programs the pituitary to increase the susceptibility to the development of prolactinomas possibly by enhancing the methylation of the D2R gene promoter and repressing the synthesis and control of D2R on PRL-producing cells. PMID:26509893

[Panhypopituitarism and dwarfism in a man with a primary empty sella turcica (author's transl)].

PubMed

Turpin, G; Jambart, S; de Gennes, J L

1979-03-10

Endocrine features associated with the primary empty sella turcica syndrom are rare; they are usually related to a pituitary microadenoma and more rarely to an idiopathic panhypop ituitarism. A pituitary dwarfism with an idiopathic panhypopituitarism of hypothalamic origin, associated with an "empty" sella turcica containing functional and stimulable pituitary tissue, is reported in a 27 year old male Moraccan.

Olfactory function and quality of life following microscopic endonasal transsphenoidal pituitary surgery.

PubMed

Wang, Shousen; Chen, Yehuang; Li, Jianzhong; Wei, Liangfeng; Wang, Rumi

2015-01-01

Olfactory outcomes as well as oronasal postoperative complications of transsphenoidal pituitary surgery have not been well studied. The objective of this study was to investigate nasal symptoms including olfactory function as well as quality of life following transsphenoidal pituitary surgery. The study is designed as a prospective cohort study set in a single tertiary hospital. A total of 53 patients with pituitary adenomas were included. All patients underwent pituitary surgery with the right-sided endonasal transsphenoidal approach. Outcomes were assessed with the Chinese version of the Medical Outcomes Study Short Form-36 (SF-36) to survey patient health, the Chinese version of the 22-item Sinonasal Outcome Test (SNOT-22), and a Toyota and Takagi (T&T) olfactometer. Assessments were carried out before surgery and at 1 week, and 1 and 4 months after surgery. The overall SF-36 scores were significantly lower, but the SNOT-22 scores were higher at 1 week and 1 month postoperatively compared with baseline (all P < 0.001). The results of T&T olfactometer testing showed that there was a significant decline in the ability to detect odors postoperatively, even at 4 months. Multivariate linear regression analysis showed that lower education level, partial tumor removal, and longer duration of surgery were independent risk factors for a higher SNOT-22 score at 1 week after surgery. The findings show that microscopic endonasal transsphenoidal pituitary surgery impairs olfactory function in most patients for at least 4 months after surgery.

Olfactory Function and Quality of Life Following Microscopic Endonasal Transsphenoidal Pituitary Surgery

PubMed Central

Wang, Shousen; Chen, Yehuang; Li, Jianzhong; Wei, Liangfeng; Wang, Rumi

2015-01-01

Abstract Olfactory outcomes as well as oronasal postoperative complications of transsphenoidal pituitary surgery have not been well studied. The objective of this study was to investigate nasal symptoms including olfactory function as well as quality of life following transsphenoidal pituitary surgery. The study is designed as a prospective cohort study set in a single tertiary hospital. A total of 53 patients with pituitary adenomas were included. All patients underwent pituitary surgery with the right-sided endonasal transsphenoidal approach. Outcomes were assessed with the Chinese version of the Medical Outcomes Study Short Form-36 (SF-36) to survey patient health, the Chinese version of the 22-item Sinonasal Outcome Test (SNOT-22), and a Toyota and Takagi (T&T) olfactometer. Assessments were carried out before surgery and at 1 week, and 1 and 4 months after surgery. The overall SF-36 scores were significantly lower, but the SNOT-22 scores were higher at 1 week and 1 month postoperatively compared with baseline (all P < 0.001). The results of T&T olfactometer testing showed that there was a significant decline in the ability to detect odors postoperatively, even at 4 months. Multivariate linear regression analysis showed that lower education level, partial tumor removal, and longer duration of surgery were independent risk factors for a higher SNOT-22 score at 1 week after surgery. The findings show that microscopic endonasal transsphenoidal pituitary surgery impairs olfactory function in most patients for at least 4 months after surgery. PMID:25634190

Antidiuretic Hormone: Episodic Nocturnal Secretion in Adult Men,

DTIC Science & Technology

1975-07-01

distinguishes levels in normals, both dehydrated and with ad lib water, and in subjects with pituitary diabetes insipidus , nephrogenic diabetes ... insipidus , and inappropriate ADH secretion. Normal male and female volun- teers after an overnight (12 hour) dehydration averaged 7.2 pU/ml (range 4.2-11.5

Normal pituitary volumes in children and adolescents with bipolar disorder: a magnetic resonance imaging study.

PubMed

Chen, Hua Hsuan; Nicoletti, Mark; Sanches, Marsal; Hatch, John P; Sassi, Roberto B; Axelson, David; Brambilla, Paolo; Keshavan, Matcheri S; Ryan, Neal; Birmaher, Boris; Soares, Jair C

2004-01-01

The volume of the pituitary gland in adults with bipolar disorder has previously been reported to be smaller than that of healthy controls. Such abnormalities would be consistent with the HPA dysfunction reported in this illness. We conducted a study of children and adolescents with bipolar disorder to determine whether size abnormalities in the pituitary gland are already present early in illness course. Magnetic resonance imaging (MRI) morphometric analysis of the pituitary gland was carried out in 16 DSM-IV children and adolescents with bipolar disorder (mean age+/-sd=15.5+/-3.4 years) and 21 healthy controls (mean age+/-sd=16.9+/-3.8 years). Subjects underwent a 1.5 T MRI, with 3-D Spoiled Gradient Recalled (SPGR) acquisition. There was no statistically significant difference between pituitary gland volumes of bipolar patients compared to healthy controls (ANCOVA, age, gender, and ICV as covariates; F=1.77, df=1,32, P=.19). There was a statistically significant direct relationship between age and pituitary gland volume in both groups (r=.59, df=17, P=.007 for healthy controls; r=.61, df=12, P=.008 for bipolar patients). No evidence of size abnormalities in the pituitary gland was found in child and adolescent bipolar patients, contrary to reports involving adult bipolar patients. This suggests that anatomical abnormalities in this structure may develop later in illness course as a result of continued HPA dysfunction. (c) 2005 Wiley-Liss, Inc.

Cellular distribution and regulation of ghrelin messenger ribonucleic acid in the rat pituitary gland.

PubMed

Caminos, J E; Nogueiras, R; Blanco, M; Seoane, L M; Bravo, S; Alvarez, C V; García-Caballero, T; Casanueva, F F; Diéguez, C

2003-11-01

Ghrelin, a 28-amino-acid acylated peptide, strongly stimulates GH release and food intake. In the present study, we found that ghrelin is expressed in somatotrophs, lactotrophs, and thyrotrophs but not in corticotrophs or gonadotrophs of rat pituitary. Persistent expression of the ghrelin gene is found during postnatal development in male and female rats, although the levels significantly decrease in both cases from pituitaries of 20-d-old rats onward, but at 60 d old, the levels were higher in male than female rats. This sexually dimorphic pattern appears to be mediated by estrogens because ovariectomy, but not orchidectomy, increases pituitary ghrelin mRNA levels. Taking into account that somatotroph cell function is markedly influenced by thyroid hormones, glucocorticoids, GH, and metabolic status, we also assessed such influence. We found that ghrelin mRNA levels decrease in hypothyroid- and glucocorticoid-treated rats, increase in GH-deficient rats (dwarf rats), and remain unaffected by food deprivation. In conclusion, we have defined the specific cell types that express ghrelin in the rat anterior pituitary gland. These data provide direct morphological evidence that ghrelin may well be acting in a paracrine-like fashion in the regulation of anterior pituitary cell function. In addition, we clearly demonstrate that pituitary ghrelin mRNA levels are age and gender dependent. Finally, we show that pituitary ghrelin mRNA levels are influenced by alteration on thyroid hormone, glucocorticoids, and GH levels but not by fasting, which indicates that the regulation of ghrelin gene expression is tissue specific.

Aryl‐hydrocarbon receptor activity modulates prolactin expression in the pituitary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moran, Tyler B.; Brannick, Katherine E.; Raetzman, Lori T., E-mail: raetzman@life.illinois.edu

2012-11-15

Pituitary tumors account for 15% of intracranial neoplasms, however the extent to which environmental toxicants contribute to the proliferation and hormone expression of pituitary cells is unknown. Aryl-hydrocarbon receptor (AhR) interacting protein (AIP) loss of function mutations cause somatotrope and lactotrope adenomas in humans. AIP sequesters AhR and inhibits its transcriptional function. Because of the link between AIP and pituitary tumors, we hypothesize that exposure to dioxins, potent exogenous ligands for AhR that are persistent in the environment, may predispose to pituitary dysfunction through activation of AhR. In the present study, we examined the effect of AhR activation on proliferationmore » and endogenous pituitary hormone expression in the GH3 rat somatolactotrope tumor cell line and the effect of loss of AhR action in knockout mice. GH3 cells respond to nM doses of the reversible AhR agonist β-naphthoflavone with a robust induction of Cyp1a1. Although mRNA levels of the anti-proliferative signaling cytokine TGFbeta1 are suppressed upon β-naphthoflavone treatment, we did not observe an alteration in cell proliferation. AhR activation with β-naphthoflavone suppresses Ahr expression and impairs expression of prolactin (PRL), but not growth hormone (GH) mRNA in GH3 cells. In mice, loss of Ahr similarly leads to a reduction in Prl mRNA at P3, while Gh is unaffected. Additionally, there is a significant reduction in pituitary hormones Lhb and Fshb in the absence of Ahr. Overall, these results demonstrate that AhR is important for pituitary hormone expression and suggest that environmental dioxins can exert endocrine disrupting effects at the pituitary. -- Highlights: ► AhR signaling suppresses Prl mRNA expression. ► AhR signaling does not influence pituitary proliferation in culture. ► AhR is necessary for Prl, Lhb and Fshb expression at postnatal day 3.« less

Radiological remission and recovery of thirst appreciation after infliximab therapy in adipsic diabetes insipidus secondary to neurosarcoidosis.

PubMed

O'Reilly, M W; Sexton, D J; Dennedy, M C; Counihan, T J; Finucane, F M; O'Brien, T; O'Regan, A W

2015-08-01

Neurosarcoidosis is a rare and aggressive variant of systemic sarcoidosis which may result in hypothalamic-pituitary dysfunction. We report a case of hypothalamic hypopituitarism secondary to neurosarcoidosis complicated by adipsic diabetes insipidus (ADI). Initiation of anti-tumour necrosis factor-α (TNF-α) therapy resulted in both radiological disease remission and recovery of osmoregulated thirst appreciation after 3 months. A 22-year-old man was referred to the endocrinology service with profound weight gain, polyuria and lethargy. Biochemical testing confirmed anterior hypopituitarism while posterior pituitary failure was confirmed by hypotonic polyuria responding to desmopressin. Magnetic resonance imaging (MRI) demonstrated extensive hypothalamic infiltration; neurosarcoidosis was confirmed histologically after excisional cervical lymph node biopsy. Osmoregulated thirst appreciation was normal early in the disease course despite severe hypotonic polyuria. However, subsequent subjective loss of thirst appreciation and development of severe hypernatraemia in the setting of normal cognitive function indicated onset of ADI. Clinical management involved daily weighing, regular plasma sodium measurement, fixed daily fluid intake and oral desmopressin. We initiated immunosuppressive therapy with pulsed intravenous anti-TNF-α therapy (infliximab) after multidisciplinary team consultation. Infliximab therapy resulted in successful radiological disease remission and complete recovery of osmoregulated thirst appreciation. This was confirmed by subjective return of thirst response and maintenance of plasma sodium in the normal range in the absence of close biochemical monitoring. © The Author 2013. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assessment of Diverse Biological Indicators in Gulf War Illness: Are They Replicable Are They Related

DTIC Science & Technology

2016-04-01

compared to 50 healthy veteran controls in a protocol that includes physical and neuropsychological evaluations, neuroimaging (MRI, fMRI, DTI), adrenal...SUBJECT TERMS Gulf War illness, neuroimaging, neuropsychological testing, immune function, hypothalamic-pituitary-adrenal testing 16. SECURITY... neuropsychological evaluations, assessment of hypothalamic-pituitary-adrenal function, standard clinical diagnostic laboratory tests, and research

Non-functioning pituitary adenoma: immunohistochemical analysis of 85 cases.

PubMed

Mahta, Ali; Haghpanah, Vahid; Lashkari, Anahita; Heshmat, Ramin; Larijani, Bagher; Tavangar, Seyed Mohammad

2007-01-01

Pituitary adenomas without clinically active hypersecretion are summarized under the term non-functioning pituitary adenoma (NFPA). Since there are no specific serum markers, the differential diagnosis and treatment imply special difficulties. By using immunohistochemical methods we will have new insight into the nature and pathogenesis of these tumours. Ki-67 is a nuclear antigen detected by the monoclonal antibody MIB-1 and its labelling index (LI) is considered a marker of normal and abnormal cell proliferation. The aim of this study was to investigate the possible role of immunohistochemistry and MIB1-LI determination in NFPAs to predict tumoural behaviour and better management. In this clinicopathological study, 85 cases of NFPAs were analysed immunohistochemically. MIB1-LI was also determined in studied cases. Clinical presentation, treatment and follow-up data were also reviewed and the correlation between clinical and pathologic findings was established. Eighteen adenomas (21.2%) were immunoreactive to one or two adenohypophysial hormones of which 4 GH positive adenomas had aggressive behaviour (2 significant juxtasellar extensions and 2 recurrences). MIB-1 LI was more than 5% in only 5 cases including 2 invasive adenomas but with no evidence of recurrence. No significant statistical difference between clinical presentations in immunoreactive and non-immunoreactive NFPAs was observed except for unilateral temporal hemianopia which was more common in immunoreactive adenomas (P=0.022). NFPAs comprise several pathologically different types of tumours, some of which are potentially hormone producing, but some defects in hormone secretion or production of biologically inactive or insufficient amount of hormone may be the culprit in the lack of evidence of rising serum hormone levels. MIB-1 LI may be indicative of invasiveness but not a predictor of recurrence. Silent somatotropinomas may have more aggressive behaviour in comparison with other NFPAs.

Etiology and treatment of hypogonadism in adolescents.

PubMed

Viswanathan, Vidhya; Eugster, Erica A

2011-10-01

Adequate functioning at all levels of the hypothalamic-pituitary-gonadal axis is necessary for normal gonadal development and subsequent sex steroid production. Deficiencies at any level of the axis can lead to a hypogonadal state. The causes of hypogonadism are heterogeneous and may involve any level of the reproductive system. This review discusses various causes of hypogonadism, describes the evaluation of hypogonadal states, and outlines treatment options for the induction of puberty in affected adolescents. Whereas some conditions are clearly delineated, the exact etiology and underlying pathogenesis of many disorders is unknown. Copyright © 2011 Elsevier Inc. All rights reserved.

Dilated Cardiomyopathy Revealing Cushing Disease

PubMed Central

Marchand, Lucien; Segrestin, Bérénice; Lapoirie, Marion; Favrel, Véronique; Dementhon, Julie; Jouanneau, Emmanuel; Raverot, Gérald

2015-01-01

Abstract Cardiovascular impairments are frequent in Cushing's syndrome and the hypercortisolism can result in cardiac structural and functional changes that lead in rare cases to dilated cardiomyopathy (DCM). Such cardiac impairment may be reversible in response to a eucortisolaemic state. A 43-year-old man with a medical past of hypertension and history of smoking presented to the emergency department with global heart failure. Coronary angiography showed a significant stenosis of a marginal branch and cardiac MRI revealed a nonischemic DCM. The left ventricular ejection fraction (LVEF) was estimated as 28% to 30%. Clinicobiological features and pituitary imaging pointed toward Cushing's disease and administration of adrenolytic drugs (metyrapone and ketoconazole) was initiated. Despite the normalization of cortisol which had been achieved 2 months later, the patient presented an acute heart failure. A massive mitral regurgitation secondary to posterior papillary muscle rupture was diagnosed as a complication of the occlusion of the marginal branch. After 6 months of optimal pharmacological treatment for systolic heart failure, as well as treatment with inhibitors of steroidogenesis, there was no improvement of LVEF. The percutaneous mitral valve was therefore repaired and a defibrillator implanted. The severity of heart failure contraindicated pituitary surgery and the patient was instead treated by stereotaxic radiotherapy. This is the first case reporting a Cushing's syndrome DCM without improvement of LVEF despite normalization of serum cortisol levels. PMID:26579807

Hypogonadotropic Hypogonadism and Short Stature in Patients with Diabetes Due to Neurogenin 3 Deficiency.

PubMed

Rubio-Cabezas, Oscar; Gómez, José Luis; Gleisner, Andrea; Hattersley, Andrew T; Codner, Ethel

2016-10-01

Biallelic mutations in NEUROG3 are known to cause early-onset malabsorptive diarrhea due to congenital anendocrinosis and diabetes mellitus at a variable age. No other endocrine disorders have been described so far. We report four patients with homozygous NEUROG3 mutations who presented with short stature and failed to show any signs of pubertal development. Four patients (two males, two females) were diagnosed with homozygous mutations in NEUROG3 on the basis of congenital malabsorptive diarrhea and diabetes. All four had severe short stature and failed to develop secondary sexual characteristics at an appropriate age, despite some having normal body mass index. The absence of gonadal function persisted into the third decade in one patient. Upon testing, both basal and stimulated LH and FSH levels were low, with the remaining pituitary hormones within the normal range. Magnetic resonance imaging scans of the hypothalamic-pituitary axis did not reveal structural abnormalities. A diagnosis of hypogonadotropic hypogonadism was made, and replacement therapy with sex hormones was started. The high reproducibility of this novel phenotype suggests that central hypogonadism and short stature are common findings in patients with mutations in NEUROG3. Growth rate needs to be carefully monitored in these patients, who also should be routinely screened for hypogonadism when they reach the appropriate age. NEUROG3 mutations expand on the growing number of genetic causes of acquired hypogonadotropic hypogonadism.

The difficulties of pseudo-Cushing's syndrome (or "non-neoplastic hypercortisolism").

PubMed

Chabre, Olivier

2018-06-01

Pseudo-Cushing's syndrome covers different pathological conditions responsible for mild-to-moderate ACTH-dependent hypercortisolism, related not to an ACTH-secreting tumor but rather to CRH and/or AVP hypothalamic secretion through activation of various neural pathways, in patients generally displaying excess central adiposity. It is better termed "non-neoplastic hypercortisolism" (NNH). The main conditions implicated in NNH comprise: neuropsychiatric disorder, alcohol abuse, insulin-resistant obesity, polycystic ovary syndrome, and end-stage kidney disease. Glucocorticoid resistance is one differential diagnosis, as are some cases of primary adrenal disease with incompletely suppressed ACTH. Differentiating between NNH and mild-to-moderate Cushing's disease can be a real challenge. Clinical analysis, based on thorough history taking and screening for catabolic signs is essential; useful explorations include midnight serum or salivary cortisol and Dex/CRH and ddAVP stimulation response. Pituitary MRI suffers from limitations regarding both sensitivity and specificity, while bilateral inferior petrosal sinus sampling cannot distinguish between pituitary ACTH secretion by a tumor or by normal cells stimulated by endogenous CRH. Definitive diagnosis of functional etiology requires demonstrating that treatment of the underlying condition restores normal secretion of ACTH and cortisol, but this is not always possible. Lingering diagnostic uncertainty has to be accepted in certain patients, who will have to be followed up for some time before diagnosis can be considered more or less definitive. Copyright © 2018. Published by Elsevier Masson SAS.

[Hypopituitarism following traumatic brain injury: diagnostic and therapeutic issues].

PubMed

Lecoq, A-L; Chanson, P

2015-10-01

Traumatic Brain Injury (TBI) is a well-known public health problem worldwide and is a leading cause of death and disability, particularly in young adults. Besides neurological and psychiatric issues, pituitary dysfunction can also occur after TBI, in the acute or chronic phase. The exact prevalence of post-traumatic hypopituitarism is difficult to assess due to the wide heterogeneity of published studies and bias in interpretation of hormonal test results in this specific population. Predictive factors for hypopituitarism have been proposed and are helpful for the screening. The pathophysiology of pituitary dysfunction after TBI is not well understood but the vascular hypothesis is privileged. Activation of pituitary stem/progenitor cells is probably involved in the recovery of pituitary functions. Those cells also play a role in the induction of pituitary tumors, highlighting their crucial place in pituitary conditions. This review updates the current data related to anterior pituitary dysfunction after TBI and discusses the bias and difficulties encountered in its diagnosis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Effects of low-dose cranial radiation on growth hormone secretory dynamics and hypothalamic-pituitary function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Costin, G.

1988-08-01

Spontaneous growth hormone (GH) secretory dynamics and hypothalamic-pituitary function were studied in 16 long-term survivors of acute lymphoblastic leukemia who were aged 9 to 15 1/2 years and had been treated with prophylactic central nervous system radiation and combined chemotherapy. At the time of study, the mean height was -1.5 SD score below the mean, less than genetic potential, and significantly less than the mean pretreatment height of -0.25 SD score. Height velocity was subnormal for age and sexual stage in all patients. Two patients had compensated hypothyroidism, and four had evidence of gonadal failure. In 11 patients, the peakmore » GH level after two provocative tests was below 10 micrograms/L, which was consistent with GH deficiency. In ten of 13 patients tested, spontaneous GH secretion determined by a 24-hour GH concentration (GHC), GH pulse amplitude, frequency of GH pulses greater than or equal to 5 micrograms/L, and GH peak during wake and sleep hours was significantly less than in normal height controls. Although in three pubertal patients the 24-hour GHC was within normal limits, the GHC during sleep hours, GH pulse amplitude during 24 hours and sleep hours, and peak GH during wake hours were significantly less than in normal height controls. In all pubertal and in two of the prepubertal patients, the somatomedin C (SmC) level was significantly less than in controls. The 24-hour GHC correlated well with the GHC during sleep, peak-stimulated GH level, gonadal steroid level, and the SmC level, but not with height velocity, dose of radiation, or age at radiation. A significant increase in height velocity and the SmC level was noted in all patients treated with GH. These results indicate that GH deficiency occurs after 18 to 24 Gy of cranial radiation and that the puberty-associated growth spurt may mask the decline in height velocity owing to GH deficiency.« less

Diagnosis and Multimodality Management of Cushing's Disease: A Practical Review

PubMed Central

Zada, Gabriel

2013-01-01

Cushing's Disease is caused by oversecretion of ACTH from a pituitary adenoma and results in subsequent elevations of systemic cortisol, ultimately contributing to reduced patient survival. The diagnosis of Cushing's Disease frequently involves a stepwise approach including clinical, laboratory, neuroimaging, and sometimes interventional radiology techniques, often mandating multidisciplinary collaboration from numerous specialty practitioners. Pituitary microadenomas that do not appear on designated pituitary MRI or dynamic contrast protocols may pose a particularly challenging subset of this disease. The treatment of Cushing's Disease typically involves transsphenoidal surgical resection of the pituitary adenoma as a first-line option, yet may require the addition of adjunctive measures such as stereotactic radiosurgery or medical management to achieve normalization of serum cortisol levels. Vigilant long-term serial endocrine monitoring of patients is imperative in order to detect any recurrence that may occur, even years following initial remission. In this paper, a stepwise approach to the diagnosis, and various management strategies and associated outcomes in patients with Cushing's Disease are discussed. PMID:23401686

Pituitary tumor with gigantism, acromegaly and preclinical Cushing's disease diagnosed from the 10th row.

PubMed

Tourtelot, John B; Vesely, David L

2013-08-01

A 7'3" basketball player was noted to have 2 to 3 times thicker tissue in his hands than 6'10" players by an endocrinologist sitting 10 rows above the player in a basketball arena. This led to the diagnosis of pituitary gigantism where the history revealed that he was 7'3" at 15 years of age. At age 19 when the acryl enlargement was noted, a diagnostic workup revealed elevated growth hormones and insulin-like growth factor 1 (IGF-1) with a 2 × 1.3 cm pituitary tumor. His history suggested that his epiphyseal plates had closed at age 15, and because he continued to produce IGF-1, he now has acromegaly. His elevated adrenocorticotropic hormone (ACTH) before surgery suggests that he also had preclinical Cushing's disease. After pituitary transsphenoidal surgery, all acryl enlargement in hands and ligaments disappeared. His growth hormone, IGF-1 and ACTH returned to normal 2 weeks after surgery.

Effects of gonadoliberin analogue triptorelin on the pituitary-testicular complex in neonatal rats.

PubMed

Dygalo, N N; Shemenkova, T V; Kalinina, T S; Shishkina, G T

2014-02-01

Triptorelin, a synthetic analogue of neurohormone gonadoliberin (gonadotropin-releasing hormone, GnRH) administered daily to rats on postnatal days 5-7 suppressed the expression of GnRH receptor in the pituitary gland, but did not change functioning of the pituitary-testicular complex. Administration of triptorelin on postnatal days 12-14 (i.e. during the formation of pulsatile pattern of GnRH secretion and increasing levels of its mRNA receptor in the pituitary gland) had no effect on receptor expression, but increased the levels of luteinizing hormone mRNA in the pituitary gland and the weight of testes. At that time, blood levels of testosterone were lowered, which indicated disturbed pulsatile pattern of GnRH secretion.

Pegvisomant treatment in gigantism caused by a growth hormone-secreting giant pituitary adenoma.

PubMed

Müssig, K; Gallwitz, B; Honegger, J; Strasburger, C J; Bidlingmaier, M; Machicao, F; Bornemann, A; Ranke, M B; Häring, H-U; Petersenn, S

2007-03-01

Gigantism is rare with the majority of cases caused by a growth hormone (GH)-secreting pituitary adenoma. Treatment options for GH-secreting pituitary adenomas have been widened with the availability of long-acting dopamine agonists, depot preparations of somatostatin analogues, and recently the GH receptor antagonist pegvisomant. A 23-year-old male patient presented with continuous increase in height during the past 6 years due to a GH-secreting giant pituitary adenoma. Because of major intracranial extension and failure of octreotide treatment to shrink the tumour, the tumour was partially resected by a trans-frontal surgical approach. At immunohistochemistry, the tumour showed a marked expression of GH and a sparsely focal expression of prolactin. Somatostatin receptors (sst) 1-5 were not detected. Tumour tissue weakly expressed dopamine receptor type 2. The Gs alpha subunit was intact. Conversion from somatostatin analogue to pegvisomant normalized insulin-like-growth-factor-I (IGF-I) levels and markedly improved glucose tolerance. Pegvisomant is a potent treatment option in patients with pituitary gigantism. In patients who do not respond to somatostatin analogues, knowledge of the SST receptor status may shorten the time to initiation of pegvisomant treatment.

Questioning the role of pituitary oxytocin in parturition: spontaneous onset of labor in women with panhypopituitarism--a case series.

PubMed

Shinar, Shiri; Many, Ariel; Maslovitz, Sharon

2016-02-01

Oxytocin, a nanopeptide secreted by the posterior pituitary gland, has well-established uterotonic activity. Its role in initiating the vigorous and regular contractions of the first stage of labor is still controversial. We report four cases of panhypopituitarism who had spontaneous onset of labor, undermining the role of maternal oxytocin in the first phase of labor. Four women with no residual pituitary function conceived through ovulation induction and were treated throughout pregnancy with thyroid replacement therapy, desmopressin and glucocorticoids. In all cases pituitary function was undetectable in repeated blood tests. We report their course of pregnancy and delivery. All four pregnancies progressed to term with hormonal replacement therapy. All cases went into spontaneous labor. Two women delivered vaginally unassisted by pharmacological intervention and two delivered by cesarean sections during active labor due to obstetrical indications. Three suffered postpartum hemorrhage. Lactation did not ensue in all four cases. Endogenous pituitary oxytocin is probably not obligatory for initiation of labor in the first phase of parturition. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Separation of cells from the rat anterior pituitary gland

NASA Technical Reports Server (NTRS)

Hymer, W. C.; Hatfield, J. Michael

1984-01-01

Data concerned with analyzing the cellular organization of the rat anterior pituitary gland are examined. The preparation of the cell suspensions and the methods used to separate pituitary cell types are described. Particular emphasis is given to velocity sedimentation at unit gravity, density gradient centrifugation, affinity methods, fluorescence activated cell sorting, and density gradient and continuous-flow electrophoresis. The difficulties encountered when attempting to compare data from different pituitary cell separation studies are discussed, and results from various experiments are presented. The functional capabilities of the separated cell populations can be tested in various culture systems.

Pituitary gland in psychiatric disorders: a review of neuroimaging findings.

PubMed

Atmaca, Murad

2014-08-01

In this paper, it was reviewed neuroimaging results of the pituitary gland in psychiatric disorders, particularly schizophrenia, mood disorders, anxiety disorders, and somatoform disorders. The author made internet search in detail by using PubMed database including the period between 1980 and 2012 October. It was included in the articles in English, Turkish and French languages on pituitary gland in psychiatric disorders through structural or functional neuroimaging results. After searching mentioned in the Methods section in detail, investigations were obtained on pituitary gland neuroimaging in a variety of psychiatric disorders. There have been so limited investigations on pituitary neuroimaging in psychiatric disorders including major psychiatric illnesses like schizophrenia and mood disorders. Current findings are so far from the generalizability of the results. For this reason, it is required to perform much more neuroimaging studies of pituitary gland in all psychiatric disorders to reach the diagnostic importance of measuring it.

LHRH-pituitary plasma membrane binding: the presence of specific binding sites in other tissues.

PubMed

Marshall, J C; Shakespear, R A; Odell, W D

1976-11-01

Two specific binding sites for LHRH are present on plasma membranes prepared from rat and bovine anterior pituitary glands. One site is of high affinity (K = 2X108 1/MOL) and the second is of lower affinity (8-5X105 1/mol) and much greater capacity. Studies on membrane fractions prepared from other tissues showed the presence of a single specific site for LHRH. The kinetics and specificity of this site were similar to those of the lower affinity pituitary receptor. These results indicate that only pituitary membranes possess the higher affinity binding site and suggest that the low affinity site is not of physiological importance in the regulation of gonadotrophin secretion. After dissociation from membranes of non-pituitary tissues 125I-LHRH rebound to pituitary membrane preparations. Thus receptor binding per se does not result in degradation of LHRH and the function of these peripheral receptors remains obscure.

TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction.

PubMed

Topaloglu, A Kemal; Reimann, Frank; Guclu, Metin; Yalin, Ayse Serap; Kotan, L Damla; Porter, Keith M; Serin, Ayse; Mungan, Neslihan O; Cook, Joshua R; Imamoglu, Sazi; Akalin, N Sema; Yuksel, Bilgin; O'Rahilly, Stephen; Semple, Robert K

2009-03-01

The timely secretion of gonadal sex steroids is essential for the initiation of puberty, the postpubertal maintenance of secondary sexual characteristics and the normal perinatal development of male external genitalia. Normal gonadal steroid production requires the actions of the pituitary-derived gonadotropins, luteinizing hormone and follicle-stimulating hormone. We report four human pedigrees with severe congenital gonadotropin deficiency and pubertal failure in which all affected individuals are homozygous for loss-of-function mutations in TAC3 (encoding Neurokinin B) or its receptor TACR3 (encoding NK3R). Neurokinin B, a member of the substance P-related tachykinin family, is known to be highly expressed in hypothalamic neurons that also express kisspeptin, a recently identified regulator of gonadotropin-releasing hormone secretion. These findings implicate Neurokinin B as a critical central regulator of human gonadal function and suggest new approaches to the pharmacological control of human reproduction and sex hormone-related diseases.

The pituitary growth hormone cell in space

NASA Technical Reports Server (NTRS)

Hymer, Wesley C.; Grindeland, R.

1989-01-01

Growth hormone (GH), produced and secreted from specialized cells in the pituitary gland, controls the metabolism of protein, fat, and carbohydrate. It is also probably involved in the regulation of proper function of bone, muscle and immune systems. The behavior of the GH cell system was studied by flying either isolated pituitary cells or live rats. In the latter case, pituitary GH cells are prepared on return to earth and then either transplanted into hypophysectomized rats or placed into cell culture so that function of GH cells in-vivo vs. in-vitro can be compared. The results from three flights to date (STS-8, 1983; SL-3, 1985; Cosmos 1887, 1987) established that the ability of GH cells to release hormone, on return to earth, is compromised. The mechanism(s) responsible for this attenuation response is unknown. However, the data are sufficiently positive to indicate that the nature of the secretory defect resides directly within the GH cells.

Immunohistochemical localization of anterior pituitary hormones in S-100 protein-positive cells in the rat pituitary gland.

PubMed

Kikuchi, Motoshi; Yatabe, Megumi; Tando, Yukiko; Yashiro, Takashi

2011-09-01

In the anterior and intermediate lobes of the rat pituitary gland, non-hormone-producing cells that express S-100 protein coexist with various types of hormone-producing cells and are believed to function as phagocytes, supporting and paracrine-controlling cells of hormone-producing cells and stem cells, among other functions; however, their cytological characteristics are not yet fully understood. Using a transgenic rat that expresses green fluorescent protein under the promoter of the S100β protein gene, we immunohistochemically detected expression of the luteinizing hormone, thyroid-stimulating hormone, prolactin, growth hormone and proopiomelanocortin by S-100 protein-positive cells located between clusters of hormone-producing cells in the intermediate lobe. These findings lend support to the hypothesis that S-100 protein-positive cells are capable of differentiating into hormone-producing cells in the adult rat pituitary gland.

Physiological basis for the etiology, diagnosis, and treatment of adrenal disorders: Cushing's syndrome, adrenal insufficiency, and congenital adrenal hyperplasia.

PubMed

Raff, Hershel; Sharma, Susmeeta T; Nieman, Lynnette K

2014-04-01

The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing's syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing's syndrome). Endogenous Cushing's syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing's syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control. © 2014 American Physiological Society.

Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing’s Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia

PubMed Central

Raff, Hershel; Sharma, Susmeeta T.; Nieman, Lynnette K.

2014-01-01

The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing’s syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing’s syndrome). Endogenous Cushing’s syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing’s syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control. PMID:24715566

Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP-fas(Ipr) mice.

PubMed

Lechner, O; Dietrich, H; Oliveira dos Santos, A; Wiegers, G J; Schwarz, S; Harbutz, M; Herold, M; Wick, G

2000-06-01

The immune system interacts with the hypothalamo-pituitary-adrenal axis via so-called glucocorticoid increasing factors, which are produced by the immune system during immune reactions, causing an elevation of systemic glucocorticoid levels that contribute to preservation of the immune reactions specificities. Previous results from our laboratory had already shown an altered immuno-neuroendocrine dialogue via the hypothalamo-pituitary-adrenal axis in autoimmune disease-prone chicken and mouse strains. In the present study, we further investigated the altered glucocorticoid response via the hypothalamo-pituitary-adrenal axis in murine lupus. We established the circadian rhythms of corticosterone, dehydroepiandrosterone-sulfate, adrenocorticotropic hormone and melatonin, as well as the time response curves after injection of interleukin-1 of the first three parameters in normal SWISS and lupus-prone MRL/MP-fas(Ipr) mice. The results show that lupus-prone MRL/ MP-fas(Ipr) mice do not react appropriately to changes of the light/dark cycle, circadian melatonin rhythms seem to uncouple from the light/dark cycle, and plasma corticosterone levels are elevated during the resting phase. Diurnal changes of dehydroepiandrosterone-sulfate and adrenocorticotropic hormone were normal compared to healthy controls. These data indicate that MRL/ MP-fas(Ipr) mice not only show an altered glucocorticoid response mediated via the hypothalamo pituitary adrenal axis to IL-1, but are also affected by disturbances of corticosterone and melatonin circadian rhythms. Our findings may have implications for intrathymic T cell development and the emergence of autoimmune disease.

Somatotropinomas, but not nonfunctioning pituitary adenomas, maintain a functional apoptotic RET/Pit1/ARF/p53 pathway that is blocked by excess GDNF.

PubMed

Diaz-Rodriguez, Esther; Garcia-Rendueles, Angela R; Ibáñez-Costa, Alejandro; Gutierrez-Pascual, Ester; Garcia-Lavandeira, Montserrat; Leal, Alfonso; Japon, Miguel A; Soto, Alfonso; Venegas, Eva; Tinahones, Francisco J; Garcia-Arnes, Juan A; Benito, Pedro; Angeles Galvez, Maria; Jimenez-Reina, Luis; Bernabeu, Ignacio; Dieguez, Carlos; Luque, Raul M; Castaño, Justo P; Alvarez, Clara V

2014-11-01

Acromegaly is caused by somatotroph cell adenomas (somatotropinomas [ACROs]), which secrete GH. Human and rodent somatotroph cells express the RET receptor. In rodents, when normal somatotrophs are deprived of the RET ligand, GDNF (Glial Cell Derived Neurotrophic Factor), RET is processed intracellularly to induce overexpression of Pit1 [Transcription factor (gene : POUF1) essential for transcription of Pituitary hormones GH, PRL and TSHb], which in turn leads to p19Arf/p53-dependent apoptosis. Our purpose was to ascertain whether human ACROs maintain the RET/Pit1/p14ARF/p53/apoptosis pathway, relative to nonfunctioning pituitary adenomas (NFPAs). Apoptosis in the absence and presence of GDNF was studied in primary cultures of 8 ACROs and 3 NFPAs. Parallel protein extracts were analyzed for expression of RET, Pit1, p19Arf, p53, and phospho-Akt. When GDNF deprived, ACRO cells, but not NFPAs, presented marked level of apoptosis that was prevented in the presence of GDNF. Apoptosis was accompanied by RET processing, Pit1 accumulation, and p14ARF and p53 induction. GDNF prevented all these effects via activation of phospho-AKT. Overexpression of human Pit1 (hPit1) directly induced p19Arf/p53 and apoptosis in a pituitary cell line. Using in silico studies, 2 CCAAT/enhancer binding protein alpha (cEBPα) consensus-binding sites were found to be 100% conserved in mouse, rat, and hPit1 promoters. Deletion of 1 cEBPα site prevented the RET-induced increase in hPit1 promoter expression. TaqMan qRT-PCR (real time RT-PCR) for RET, Pit1, Arf, TP53, GDNF, steroidogenic factor 1, and GH was performed in RNA from whole ACRO and NFPA tumors. ACRO but not NFPA adenomas express RET and Pit1. GDNF expression in the tumors was positively correlated with RET and negatively correlated with p53. In conclusion, ACROs maintain an active RET/Pit1/p14Arf/p53/apoptosis pathway that is inhibited by GDNF. Disruption of GDNF's survival function might constitute a new therapeutic route in acromegaly.

Role of hormonal and inflammatory alterations in obesity-related reproductive dysfunction at the level of the hypothalamic-pituitary-ovarian axis.

PubMed

Goldsammler, Michelle; Merhi, Zaher; Buyuk, Erkan

2018-05-09

Besides being a risk factor for multiple metabolic disorders, obesity could affect female reproduction. While increased adiposity is associated with hormonal changes that could disrupt the function of the hypothalamus and the pituitary, compelling data suggest that obesity-related hormonal and inflammatory changes could directly impact ovarian function. To review the available data related to the mechanisms by which obesity, and its associated hormonal and inflammatory changes, could affect the female reproductive function with a focus on the hypothalamic-pituitary-ovarian (HPO) axis. PubMed database search for publications in English language until October 2017 pertaining to obesity and female reproductive function was performed. The obesity-related changes in hormone levels, in particular leptin, adiponectin, ghrelin, neuropeptide Y and agouti-related protein, are associated with reproductive dysfunction at both the hypothalamic-pituitary and the ovarian levels. The pro-inflammatory molecules advanced glycation end products (AGEs) and monocyte chemotactic protein-1 (MCP-1) are emerging as relatively new players in the pathophysiology of obesity-related ovarian dysfunction. There is an intricate crosstalk between the adipose tissue and the inflammatory system with the HPO axis function. Understanding the mechanisms behind this crosstalk could lead to potential therapies for the common obesity-related reproductive dysfunction.

Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Role of a TSH-T3-Shunt and Sensitivity Analysis.

PubMed

Berberich, Julian; Dietrich, Johannes W; Hoermann, Rudolf; Müller, Matthias A

2018-01-01

Despite significant progress in assay technology, diagnosis of functional thyroid disorders may still be a challenge, as illustrated by the vague upper limit of the reference range for serum thyrotropin ( TSH ). Diagnostical problems also apply to subjects affected by syndrome T, i.e., those 10% of hypothyroid patients who continue to suffer from poor quality of life despite normal TSH concentrations under substitution therapy with levothyroxine ( L - T 4 ). In this paper, we extend a mathematical model of the pituitary-thyroid feedback loop in order to improve the understanding of thyroid hormone homeostasis. In particular, we incorporate a TSH - T 3 -shunt inside the thyroid, whose existence has recently been demonstrated in several clinical studies. The resulting extended model shows good accordance with various clinical observations, such as a circadian rhythm in free peripheral triiodothyronine ( FT 3 ). Furthermore, we perform a sensitivity analysis of the derived model, revealing the dependence of TSH and hormone concentrations on different system parameters. The results have implications for clinical interpretation of thyroid tests, e.g., in the differential diagnosis of subclinical hypothyroidism.

Infertility in transgenic mice overexpressing the bovine growth hormone gene: luteal failure secondary to prolactin deficiency.

PubMed

Cecim, M; Kerr, J; Bartke, A

1995-05-01

Overexpression of growth hormone (GH) in transgenic mice is associated with various degrees of impairment of female reproductive functions. Transgenic PEPCK.bGH mice express high GH levels, and only around 20% of the females will carry gestation to Day 7. The objective of the present study was to investigate luteal function in PEPCK.bGH mice during early pregnancy, when CL are fully dependent on the pituitary. Plasma progesterone levels measured on Days 2 or 7 postcoitum (p.c.) were lower in transgenic than in normal females. In transgenic females with a previous history of infertility, daily injections of 1 mg progesterone starting on Day 2 p.c. significantly increased the proportion of animals pregnant on Day 7. When ovaries from transgenic mice were transplanted into ovariectomized normal littermates, the recipients exhibited normal vaginal cycles and responded to mating by vaginal cytology changes consistent with pseudopregnancy. In contrast, ovariectomized transgenic females bearing transplants of ovaries from normal mice had slightly prolonged estrous cycles and failed to become pseudopregnant after mating. Plasma progesterone levels on Days 2 and 7 p.c. in normal females with transgenic ovaries were not different from plasma progesterone levels measured in normal females into which normal ovaries had been transplanted. Twice-daily injections of 100 micrograms of prolactin (PRL) in saline or in polyvinylpyrrolidone starting on the evening of Day 2 p.c. were able to rescue luteal function. The proportion of PRL-injected transgenic animals that were pregnant on Day 7 was significantly higher than that of saline-injected transgenic controls and resembled the pregnancy rate of normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

The thyroid axis in ageing.

PubMed

Leitol, Holger; Behrends, Jens; Brabant, Georg

2002-01-01

The hypothalmo-pituitary thyroid axis, among various endocrine systems, undergoes physiological alterations associated with the ageing process. Directly age-related changes have to be distinguished from indirect modifications which are caused by simultaneous thyroidal or non-thyroidal illness or other physiological or pathophysiological states whose incidence increases with age. In summary, direct changes of the hypothalmo-pituitary-thyroid axis seem to be subtle and suggestive of a decreased hypothalamic stimulation of thyroid function. In parallel, disease-specific alterations such as the development of thyroid autonomy or changes in energy intake or sleep lead to pronounced alterations of thyroid function with age which may dominate the underlying ageing of the hypothalmo-pituitary thyroid axis itself. The following article attempts to delineate some aspects of the interplay of the regulation of thyroid function and the ageing process.

Mid-term prognosis of non-functioning pituitary adenomas with high proliferative potential: really an aggressive variant?

PubMed

Ogawa, Yoshikazu; Jokura, Hidefumi; Niizuma, Kuniyasu; Tominaga, Teiji

2018-05-01

Pituitary adenomas with high proliferation rate and rapid growth are well known, but the clinical characteristics, prognosis, and treatment algorithm remain unclear. The clinical characteristics and mid-term prognosis of patients with non-functioning pituitary adenomas with high proliferative potential were retrospectively investigated. This study identified 53 patients with Ki-67 labeling index of > 3% among 845 patients with non-functioning pituitary adenoma (6.3%) initially treated by surgery. Prophylactic treatment was not applied for patients with residual tumor, but salvage treatment was performed if tumor progression was identified within the follow-up period. Twenty-two patients remained progression-free, whereas 31 patients suffered tumor progression. Comparison of gross total removal (n = 22) and non-total removal (n = 31) groups showed significantly longer progression-free period in the former group (P < 0.001). As salvage treatment gamma knife radiosurgery was applied for 11 patients resulting in 10 patients remaining progression-free and regrowth in 1 patient. Fractionated irradiation was applied for 10 patients, resulting in 2 patients remaining progression-free, deaths in 5 patients including 3 of transformation to pituitary carcinoma, dementia in 1 patient caused by frontal lobe dysfunction, and progression in 2 patients requiring additional surgery and gamma knife radiosurgery. Temozolomide was administered in 2 patients, resulting in deaths in both patients including 1 transformation to pituitary carcinoma. Total removal and gamma knife radiosurgery can result in good outcome. However, the prognosis is extremely poor for patients inadequate for gamma knife radiosurgery. Development of new salvage treatments is essential.

Diagnosis and treatment of pituitary adenomas.

PubMed

Chanson, P; Salenave, S

2004-12-01

Pituitary tumors cause symptoms by secreting hormones (prolactin, PRL, responsible for amenorrhea-galactorrhea in women and decreased libido in men; growth hormone, GH, responsible for acromegaly; adrenocorticotropic hormone, ACTH, responsible for Cushing's syndrome; thyroid-stimulating hormone, TSH, responsible for hyperthyroidism), depressing the secretion of hormones (hypopituitarism), or by mass-related effects (headaches, visual field abnormalities...). All patients with pituitary tumors should be evaluated for gonadal, thyroid and adrenal function as well as PRL and GH secretion. Specific stimulation and suppression tests for pituitary hormones are performed in selected situations for detecting the type of hypersecretion or the response to treatment. Imaging procedures (mainly magnetic resonance imaging, MRI, nowadays) determine the presence, size and extent of the lesion. The classification of pituitary tumors is based on the staining properties of the cell cytoplasm viewed by light microscopy and immunocytochemistry revealing the secretory pattern of the adenoma. Treatment of pituitary adenomas consists of surgery (performed in more than 99% of cases via a transphenoidal route) and radiotherapy, generally fractionated or, in selected cases, using stereotactic techniques such as gamma-knife. The availability of medical treatment (dopamine, DA, agonists, somatostatin analogs, GH-receptor antagonists...) has profoundly modified the indications of radiotherapy, drugs being now generally used as a second-line treatment, after surgery (or even as first-line treatment). Based on the results of the different treatment modalities for each type of pituitary adenoma, recommendations will be proposed. They may be summarized as follows. For treatment of GH-secreting adenomas, trans-sphenoidal surgery is the first-line therapy except when the macroadenoma is giant or if surgery is contra-indicated; postoperative radiation therapy (fractionated, or by gamma-knife) is performed for partially resected tumors or when GH levels remain elevated (eventually after a trial of somatostatin analog). Somatostatin analogs, now available in slow release form, are proposed when surgery is contra-indicated, or has failed to normalize GH levels, or in waiting for the delayed effects of radiation therapy. If the probability of surgical cure is low (e.g. in patients with very large and/or invasive tumors), then somatostatin analogs may be reasonable primary therapeutic modality provided that the tumor does not threaten vision or neurological function. Pegvisomant, the new GH-receptor antagonist, is indicated in case of resistance to somatostatin analogs. Patients with PRL-secreting microadenomas may be treated either with trans-sphenoidal surgery or medically with DA agonists. In patients with macroadenomas, even in the presence of chiasmatic syndrome, DA agonists are now proposed as primary treatment. Indeed, effects on visual disturbances are often very rapid (within a few hours or days) and tumoral shrinkage is usually very significant. For patients with ACTH-secreting adenomas, primary therapy is generally trans-sphenoidal surgery by a skilled surgeon, whether or not a microadenoma is visible on MRI. Radiotherapy is reserved for patients who are subtotally resected or remain hyper-secretory after surgery. In waiting for the effects of radiotherapy, adrenal steroidogenesis inhibitors (mitotane, ketoconazole) may be indicated. If drugs are not available or not tolerated, bilateral adrenalectomy may be proposed. For patients with clinically non functioning adenomas (generally gonadotropin-secreting adenomas on immunocytochemistry), trans-sphenoidal surgery with or without postoperative radiation therapy is performed for almost all patients whether or not they have visual consequences of their tumor. Selected patients with small, incidentally discovered microadenomas may be carefully followed without immediate therapy.

Cyclic 3',5'-adenosine monophosphate (cAMP) signaling in the anterior pituitary gland in health and disease.

PubMed

Hernández-Ramírez, Laura C; Trivellin, Giampaolo; Stratakis, Constantine A

2018-03-05

The cyclic 3',5'-adenosine monophosphate (cAMP) was the first among the so-called "second messengers" to be described. It is conserved in most organisms and functions as a signal transducer by mediating the intracellular effects of multiple hormones and neurotransmitters. In this review, we first delineate how different members of the cAMP pathway ensure its correct compartmentalization and activity, mediate the terminal intracellular effects, and allow the crosstalk with other signaling pathways. We then focus on the pituitary gland, where cAMP exerts a crucial function by controlling the responsiveness of the cells to hypothalamic hormones, neurotransmitters and peripheral factors. We discuss the most relevant physiological functions mediated by cAMP in the different pituitary cell types, and summarize the defects affecting this pathway that have been reported in the literature. We finally discuss how a deregulated cAMP pathway is involved in the pathogenesis of pituitary disorders and how it affects the response to therapy. Copyright © 2017. Published by Elsevier B.V.

The pituitary gland: a brief history.

PubMed

Kaplan, Solomon Alexander

2007-01-01

The functions of the pituitary gland as an important constituent of the endocrine system were not understood until the latter part of the nineteenth century and the first half of the 20th century. At one time, the pituitary was deemed to be the "leader of the endocrine orchestra," but more recent studies have shown that its secretions are influenced by external stimuli and that it is largely under the control of the hypothalamus.

Pit-1/growth hormone factor 1 splice variant expression in the rhesus monkey pituitary gland and the rhesus and human placenta.

PubMed

Schanke, J T; Conwell, C M; Durning, M; Fisher, J M; Golos, T G

1997-03-01

We have examined the expression of Pit-1 messenger RNA (mRNA) splice variants in the nonhuman primate pituitary and in rhesus and human placenta. Full-length complementary DNAs (cDNAs) representing Pit-1 and the Pit-1 beta splice variants were cloned from a rhesus monkey pituitary cDNA library and were readily detectable by RT-PCR with rhesus pituitary gland RNA. The Pit-1T variant previously reported in mouse pituitary tumor cell lines was not detectable in normal rhesus pituitary tissue, although two novel splice variants were detected. A cDNA approximating the rat Pit-1 delta 4 variant was cloned but coded for a truncated and presumably nonfunctional protein. Only by using a nested RT-PCR approach were Pit-1 and Pit-1 beta variants consistently detectable in both human and rhesus placental tissue. The Pit-1 beta variant mRNA was not detectable in JEG-3 choriocarcinoma cells unless the cells were stimulated with 8-Br-cAMP. Immunoblot studies with nuclear extracts from primary rhesus syncytiotrophoblast cultures or JEG-3 choriocarcinoma cells indicated that although mRNA levels were very low, Pit-1 protein was detectable in differentiated cytotrophoblasts, and levels increased after treatment with 8-Br-cAMP. Two major species of Pit-1 protein were detected that corresponded to the two major bands in rat pituitary GH3 cell nuclear extracts. Low levels of slightly larger bands also were seen, which may represent Pit-1 beta protein or phosphorylated species. We conclude that Pit-1 splice variants expressed in the primate pituitary gland differ from those in the rodent gland and that the Pit-1 and Pit-1 beta mRNAs expressed in the placenta give rise to a pattern of protein expression similar to that seen in pituitary cells, which is inducible by treatment with 8-Br-cAMP.

Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic-pituitary-adrenal axis.

PubMed

Johnson, Elizabeth O; Kamilaris, Themis C; Calogero, Aldo E; Gold, Philip W; Chrousos, George P

2005-07-01

Previous studies on the effects of altered thyroid function on the secretion and metabolism of adrenocortical hormones suggest a degree of adrenocortical hyperactivity in hyperthyroidism. We have previously shown that experimentally-induced hyperthyroidism is associated with significant alterations in pituitary-adrenal responsiveness to synthetic ovine corticotropin-releasing hormone (oCRH) that are contingent upon the duration of the altered thyroid function. The purpose of this study was to assess the time-dependent effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis by in vivo stimulation of the hypothalamic CRH neuron and adrenal cortex. The functional integrity of the HPA axis was examined in vivo in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given 50 mug of thyroxine every day for 7 or 60 days. Responses to insulin-induced hypoglycemia and IL-1alpha stimulation were used to assess the hypothalamic CRH neuron. Adrenocortical reserve was assessed in response to low-dose adrenocorticotropic hormone (ACTH), following suppression of the HPA axis with dexamethasone. Adrenal and thymus tissue weight, in addition to basal plasma ACTH, corticosterone and thyroid indices were also determined. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days, cerebrospinal fluid (CSF) corticosterone levels were significantly increased. Basal plasma ACTH levels were similar to controls. Although plasma ACTH responses to hypoglycemic stress and IL-1alpha administration in both short- and long-term hyperthyroidism were normal, corticosterone responses to the ACTH release during the administration of these stimuli were significantly increased. The adrenal reserve was significantly elevated in short-term hyperthyroidsim. Long-term hyperthyroidism, however, was associated with a significant reduction in adrenocortical reserve. A significant increase in adrenal weights and a decrease in thymus weights were observed in both short- and long-term hyperthyroidism. The available data confirms that hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally affected still remains unclear. Despite the sustained hyperactivity of the HPA axis, long-term experimentally-induced hyperthyroidism is associated with diminished adrenal functional reserve. The alterations in HPA function in states of disturbed thyroid function were found to be somewhat more pronounced as the duration of thyroid dysfunction increased.

Regulatory System for Stem/Progenitor Cell Niches in the Adult Rodent Pituitary

PubMed Central

Yoshida, Saishu; Kato, Takako; Kato, Yukio

2016-01-01

The anterior lobe of the pituitary gland is a master endocrine tissue composed of five types of endocrine cells. Although the turnover rate of pituitary endocrine cells is as low as about 1.6% per day, recent studies have demonstrated that Sex-determining region Y-box 2 (SOX2)+-cells exist as pituitary stem/progenitor cells in the adult anterior lobe and contribute to cell regeneration. Notably, SOX2+-pituitary stem/progenitor cells form two types of niches in this tissue: the marginal cell layer (MCL-niche) and the dense cell clusters scattering in the parenchyma (parenchymal-niche). However, little is known about the mechanisms and factors for regulating the pituitary stem/progenitor cell niches, as well as the functional differences between the two types of niches. Elucidation of the regulatory mechanisms in the niches might enable us to understand the cell regeneration system that acts in accordance with physiological demands in the adult pituitary. In this review, so as to reveal the regulatory mechanisms of the two types of niche, we summarize the regulatory factors and their roles in the adult rodent pituitary niches by focusing on three components: soluble factors, cell surface proteins and extracellular matrixes. PMID:26761002

Central diabetes insipidus in children and young adults: etiological diagnosis and long-term outcome of idiopathic cases.

PubMed

Di Iorgi, Natascia; Allegri, Anna Elsa Maria; Napoli, Flavia; Calcagno, Annalisa; Calandra, Erika; Fratangeli, Nadia; Vannati, Marianna; Rossi, Andrea; Bagnasco, Francesca; Haupt, Riccardo; Maghnie, Mohamad

2014-04-01

Central diabetes insipidus (CDI) is considered idiopathic in 20% to 50% of affected subjects. The purpose of this study was to determine whether a systematic diagnostic workup could achieve better etiologic diagnosis in children and adolescents presenting with polyuria and polydipsia. This is a prospective study conducted at a tertiary referral center. Patients underwent clinical and endocrine evaluations every 6 months and neuroimaging every 6 months for 2 years and yearly for 3 years. Endocrine function and neuroimaging were also reassessed after adult height achievement. A total of 85 consecutive patients with CDI were enrolled at a median age of 7.5 years; those with idiopathic CDI were stratified based on pituitary stalk thickness. To establish the etiology of CDI, we determined the time lag between its onset and the specific diagnosis, the long-term impact on pituitary function, and the overall long-term outcomes. Of the subjects, 24 (28.2%) received an etiologic diagnosis at presentation and 11 (13%) within 2.5 years (n = 7 germinomas and n = 4 Langerhans cell histiocytosis), 7 (8.2%) were lost to follow-up, and 43 (50.6%) were considered to have idiopathic disease and were followed until the median age of 17.3 years. Neuroimaging identified 40 of 43 patients with self-limited inflammatory/autoimmune pituitary stalk thickness within the first 6 months, the severity of which was significantly correlated to pituitary dysfunction. The probability of >10-year-survival without an anterior pituitary defect was related to the severity of pituitary stalk thickness, and 53% showed permanent anterior pituitary defects. Three patients developed Langerhans cell histiocytosis and 1 developed Hodgkin lymphoma after a median of 9 and 13 years, respectively. A diagnostic etiology was achieved in 96% of patients with CDI. Risk stratification based on the degree of pituitary stalk thickness is of prognostic value for long-term outcomes including permanent pituitary dysfunction. New guidance is provided for the management of these patients.

Ghrelin and cancer progression.

PubMed

Lin, Tsung-Chieh; Hsiao, Michael

2017-08-01

Ghrelin is a small peptide with 28 amino acids, and has been characterized as the ligand of the growth hormone secretagogue receptor (GHSR). In addition to its original function in stimulating pituitary growth hormone release, ghrelin is multifunctional and plays a role in the regulation of energy balance, gastric acid release, appetite, insulin secretion, gastric motility and the turnover of gastric and intestinal mucosa. The discovery of ghrelin and GHSR expression beyond normal tissues suggests its role other than physiological function. Emerging evidences have revealed ghrelin's function in regulating several processes related to cancer progression, especially in metastasis and proliferation. We further show the relative GHRL and GHSR expression in pan-cancers from The Cancer Genome Atlas (TCGA), suggesting the potential pathological role of the axis in cancers. This review focuses on ghrelin's biological function in cancer progression, and reveals its clinical significance especially the impact on cancer patient outcome. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Absence of detectable immunoreactive alpha melanocyte stimulating hormone in plasma in various types of Cushing's disease.

PubMed

Croughs, R J; Thijssen, J H; Mol, J A

1991-03-01

We have measured alpha-MSH in plasma of normal subjects and subjects with various diseases of the pituitary-adrenocortical system using a radioimmunoassay with a sensitivity of 1.2 pmol/l. No alpha-MSH could be detected in plasma of normal subjects (n = 6), in plasma of patients with Addison's disease (n = 3), Nelson's syndrome (n = 2), bromocriptine responsive (n = 2) and unresponsive (n = 5) Cushing's disease and in plasma of psychiatric patients on chronic treatment with the dopamine antagonist haloperidol (n = 5). Plasma alpha-MSH remained undetectable in 2 patients with Cushing's disease after iv injection of 60 micrograms/kg haloperidol. In contrast, alpha-MSH was detectable in plasma of normal dogs (n = 2) and dogs with pituitary dependent hyperadrenocorticism (n = 2), whereas the iv injection of halo peridol was associated with a rise of plasma alpha-MSH. Thus we are unable to detect circulating alpha-MSH in man despite the use of a sensitive radioimmunoassay.

Stress, fighting and neuroendocrine function.

NASA Technical Reports Server (NTRS)

Conner, R. L.; Levine, S.; Vernikos-Danellis, J.

1971-01-01

Plasma concentrations of pituitary adrenocorticotrophic hormone (ACTH) and adrenocortical steroids in rats after testing in the shock-induced fighting paradigm were examined. The investigations provide data consistent with the view that psychological aspects of the stressful situation are important in determining the effects of shock on physiological function. The data indicate that the pituitary-adrenal response can be attenuated by the expression of an organized pattern of behavior.

Growth and adult height in GH-treated children with nonacquired GH deficiency and idiopathic short stature: the influence of pituitary magnetic resonance imaging findings.

PubMed

Coutant, R; Rouleau, S; Despert, F; Magontier, N; Loisel, D; Limal, J M

2001-10-01

We analyzed the final height of 146 short children with either nonacquired GH deficiency or idiopathic short stature. Our purpose was 1) to assess growth according to the pituitary magnetic resonance imaging findings in the 63 GH-treated children with GH deficiency and 2) to compare the growth of the GH-deficient patients with normal magnetic resonance imaging (n = 48) to that of 32 treated and 51 untreated children with idiopathic short stature (GH peak to provocative tests >10 microg/liter). The mean GH dose was 0.44 IU/kg.wk (0.15 mg/kg.wk), given for a mean duration of 4.6 yr. Among the GH-deficient children, 15 had hypothalamic-pituitary abnormalities (stalk agenesis), all with total GH deficiency (GH peak <5 microg/liter). They were significantly shorter and younger at the time of diagnosis than those with normal magnetic resonance imaging, had better catch-up growth (+2.7 +/- 0.9 vs. +1.3 +/- 0.8 SD score; P < 0.01), and reached greater final height (-1.1 +/- 1.0 vs. -1.7 +/- 1.0 SD score; P < 0.05). Among patients with normal magnetic resonance imaging, there was no difference in catch-up growth and final height between partial and total GH deficiencies. GH-deficient subjects with normal magnetic resonance imaging and treated and untreated patients with idiopathic short stature had comparable auxological characteristics, age at evaluation, and target height. Although they had different catch-up growth (+1.3 +/- 0.8, +0.9 +/- 0.6, and +0.7 +/- 0.9 SD score, respectively; P < 0.01, by ANOVA), these patients reached a similar final height (-1.7 +/- 1.0, -2.1 +/- 0.8, and -2.1 +/- 1.0 SD score, respectively; P = 0.13). Pituitary magnetic resonance imaging findings show the heterogeneity within the group of nonacquired GH deficiency and help to predict the response to GH treatment in these patients. The similarities in growth between the GH-deficient children with normal magnetic resonance imaging and those with idiopathic short stature suggest that the short stature in the former subjects is at least partly due to factors other than GH deficiency.

Random Secretion of Growth Hormone in Humans

NASA Astrophysics Data System (ADS)

Prank, Klaus; Kloppstech, Mirko; Nowlan, Steven J.; Sejnowski, Terrence J.; Brabant, Georg

1996-08-01

In normal humans, growth hormone (GH) is secreted from a gland located adjacent to the brain (pituitary) into the blood in distinct pulses, but in patients bearing a tumor within the pituitary (acromegaly) GH is excessively secreted in an irregular manner. It has been hypothesized that GH secretion in the diseased state becomes random. This hypothesis is supported by demonstrating that GH secretion in patients with acromegaly cannot be distinguished from a variety of linear stochastic processes based on the predictability of the fluctuations of GH concentration in the bloodstream.

Incidence of Diabetes Insipidus in Postoperative Period among the Patients Undergoing Pituitary Tumour Surgery.

PubMed

Kadir, M L; Islam, M T; Hossain, M M; Sultana, S; Nasrin, R; Hossain, M M

2017-07-01

Post operative complications after pituitary tumour surgery vary according to procedure. There are several surgical procedures being done such as transcranial, transsphenoidal microsurgical and transsphenoidal endoscopic approaches. One of the commonest complications is diabetes insipidus (DI). Our main objective was to find out the incidence of diabetes insipidus in post operative period among patients undergoing surgical intervention for pituitary tumour in our institute. The presence of diabetes insipidus in the postoperative period was established by measuring serum Na+ concentration, hourly urine output and urinary specific gravity to find out the incidence of diabetes insipidus in postoperative period in relation to age, gender, tumour diameter, function of tumour (i.e., either hormone secreting or not) and operative procedure used for surgical resection of pituitary tumor. As it is the most common postoperative complication so, in this study we tried to find out how many of the patients develop diabetes insipidus in postoperative period following surgical resection of pituitary tumour. This cross sectional type of observational study was carried out in the department of Neurosurgery, BSMMU from May 2014 to October 2015 on 33 consecutive patients who underwent surgical intervention for pituitary tumour for the first time. Data was collected by using a data collection sheet. The incidence of diabetes insipidus was found 23.1% of patients in <30 year age group, 38.5% of patients in 31-40 year age group and 38.5% of patients in ≥40 year age group (p=0.764). In case of distribution of patients according to gender 38.5% of male and 61.5% of female developed diabetes insipidus (p=0.073). Regarding tumour size 30.8% and 69.2% of patients developed diabetes insipidus having tumour diameter <30mm and ≥30mm respectively (p=0.590). In case of operative procedure 69.2% of patients developed diabetes insipidus who was operated by transsphenoidal endoscopic approach, 23.1% and 7.7% of patients developed diabetes insipidus who underwent pituitary tumour resection through transsphenoidal microscopic approach and transcranial microscopic approach respectively (p=0.432). 17.6% of patients develop DI having functioning pituitary macroadenoma and 62.5% of patients develop DI having nonfunctioning pituitary macroadenoma. This observational study has been performed to find out the incidence of diabetes insipidus. Incidence of postoperative DI is more at or around the age of 40 years. It is slightly predominant in female. Most of the patients manifest DI in the first 24 hours of surgical intervention. Incidence of DI is low among patients having functioning pituitary macroadenoma.

The Ubiquitin Ligase Component Siah1a Is Required for Completion of Meiosis I in Male Mice

PubMed Central

Dickins, Ross A.; Frew, Ian J.; House, Colin M.; O'Bryan, Moira K.; Holloway, Andrew J.; Haviv, Izhak; Traficante, Nadia; de Kretser, David M.; Bowtell, David D. L.

2002-01-01

The mammalian Siah genes encode highly conserved proteins containing a RING domain. As components of E3 ubiquitin ligase complexes, Siah proteins facilitate the ubiquitination and degradation of diverse protein partners including β-catenin, N-CoR, and DCC. We used gene targeting in mice to analyze the function of Siah1a during mammalian development and reveal novel roles in growth, viability, and fertility. Mutant animals have normal weights at term but are postnatally growth retarded, despite normal levels of pituitary growth hormone. Embryonic fibroblasts isolated from mutant animals grow normally. Most animals die before weaning, and few survive beyond 3 months. Serum gonadotropin levels are normal in Siah1a mutant mice; however, females are subfertile and males are sterile due to a block in spermatogenesis. Although spermatocytes in mutant mice display normal meiotic prophase and meiosis I spindle formation, they accumulate at metaphase to telophase of meiosis I and subsequently undergo apoptosis. The requirement of Siah1a for normal progression beyond metaphase I suggests that Siah1a may be part of a novel E3 complex acting late in the first meiotic division. PMID:11884614

New trends in combined use of gonadotropin-releasing hormone antagonists with gonadotropins or pulsatile gonadotropin-releasing hormone in ovulation induction and assisted reproductive technologies.

PubMed

Gordon, K; Danforth, D R; Williams, R F; Hodgen, G D

1992-10-01

The use of gonadotropin-releasing hormone agonists as adjunctive therapy with gonadotropins for ovulation induction in in vitro fertilization and other assisted reproductive technologies has become common clinical practice. With the recent advent of potent gonadotropin-releasing hormone antagonists free from the marked histamine-release effects that stymied earlier compounds, an attractive alternative method may be available. We have established the feasibility of combining gonadotropin-releasing hormone antagonist-induced inhibition of endogenous gonadotropins with exogenous gonadotropin therapy for ovulation induction in a nonhuman primate model. Here, the principal benefits to be gained from using the gonadotropin-releasing hormone antagonist rather than the gonadotropin-releasing hormone agonist are the immediate inhibition of pituitary gonadotropin secretion without the "flare effect," which brings greater safety and convenience for patients and the medical team and saves time and money. We have also recently demonstrated the feasibility of combining gonadotropin-releasing hormone antagonist with pulsatile gonadotropin-releasing hormone therapy for the controlled restoration of gonadotropin secretion and gonadal steroidogenesis culminating in apparently normal (singleton) ovulatory cycles. This is feasible only with gonadotropin-releasing hormone antagonists because, unlike gonadotropin-releasing hormone agonists, they achieve control of the pituitary-ovarian axis without down regulation of the gonadotropin-releasing hormone receptor system. This capacity to override gonadotropin-releasing hormone antagonist-induced suppression of pituitary-ovarian function may allow new treatment modalities to be employed for women who suffer from chronic hyperandrogenemia with polycystic ovarian disease.

Nocturnal growth hormone and gonadotrophin secretion in growth retarded children with Crohn's disease.

PubMed Central

Farthing, M J; Campbell, C A; Walker-Smith, J; Edwards, C R; Rees, L H; Dawson, A M

1981-01-01

Although impaired growth hormone secretion in response to pharmacological stimuli occurs in some growth retarded children with Crohn's disease, its relationship to past and future th is uncertain. We have therefore determined the growth hormone and gonadotrophin response to the physiological stimulus of sleep by continuous venous sampling in five severely gonadotrophin profiles, the mean plasma hormone concentrations during the first five hours of sleep were determined. In three of the five patients, five hour mean growth hormone levels were reduced (3.8, 5.0, and 8.5 mU/l) compared with levels reported previously in normal short children (10-43 mU/l), although the pulsatile pattern of growth hormone secretion was preserved in all. Nocturnal growth hormone secretion was unrelated to the growth velocities of these children during both pre- and post-treatment assessment periods but a significant correlation was found between growth hormone concentration and a disease activity score (r = 0.79, P less than 0.05), suggesting that growth hormone release by the pituitary was influenced by the severity of the disease. Nocturnal growth hormone secretion was also correlated with gonadotrophin secretion (luteinising hormones, r = 0.99, and follicle stimulating hormone, r = 0.96; p less than 0.01) indicating more extensive hypothalamic-pituitary disturbance. These findings suggest that hypothalamic-pituitary function is depressed in growth retarded children with Crohn's disease, but that abnormalities of growth hormone secretion are unlikely to be directly involved in the growth retardation seen in this condition. PMID:7308847

Maturation of human hypothalamic-pituitary-thyroid function and control.

PubMed

Fisher, D A; Nelson, J C; Carlton, E I; Wilcox, R B

2000-03-01

Measurements of serum thyrotropin (TSH) and free thyroxine (T4) concentrations were conducted in infants, children, and adults to assess maturation of the hypothalamic-pituitary-thyroid (HPT) feedback control axis. Serum free T4 and TSH concentration data were collated for cord blood of the midgestation fetus, for premature and term infants, and for peripheral blood from newborn infants, children, and adults. Mean values were plotted on a nomogram developed to characterize the reference ranges of the normal axis quantitatively based on data from 522 healthy subjects, 2 weeks to 54 years of age; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patients. Samples for 75 patients with thyroid hormone resistance were also plotted. The characterized pattern of HPT maturation included a progressive decrease in the TSH/free T4 ratio with age, from 15 in the midterm fetus, to 4.7 in term infants, and 0.97 in adults. Maturation plotted on the nomogram was complex, suggesting increasing hypothalamic-pituitary T4 resistance during fetal development, probably secondary to increasing thyrotropin-releasing hormone (TRH) secretion, the marked, cold-stimulated TRH-TSH surge at birth with reequilibration by 2-20 weeks, and a final maturation phase characterized by a decreasing serum TSH with minimal change in free T4 concentration during childhood and adolescence. The postnatal maturative phase during childhood and adolescence correlates with the progressive decrease in thyroxine secretion rate (on a microg/kg per day basis) and metabolic rate and probably reflects decreasing TRH secretion.

Quantitative evaluation of vision-related and health-related quality of life after endoscopic transsphenoidal surgery for pituitary adenoma.

PubMed

Wolf, Amparo; Coros, Alexandra; Bierer, Joel; Goncalves, Sandy; Cooper, Paul; Van Uum, Stan; Lee, Donald H; Proulx, Alain; Nicolle, David; Fraser, J Alexander; Rotenberg, Brian W; Duggal, Neil

2017-08-01

OBJECTIVE Endoscopic resection of pituitary adenomas has been reported to improve vision function in up to 80%-90% of patients with visual impairment due to these adenomas. It is unclear how these reported rates translate into improvement in visual outcomes and general health as perceived by the patients. The authors evaluated self-assessed health-related quality of life (HR-QOL) and vision-related QOL (VR-QOL) in patients before and after endoscopic resection of pituitary adenomas. METHODS The authors prospectively collected data from 50 patients who underwent endoscopic resection of pituitary adenomas. This cohort included 32 patients (64%) with visual impairment preoperatively. Twenty-seven patients (54%) had pituitary dysfunction, including 17 (34%) with hormone-producing tumors. Patients completed the National Eye Institute Visual Functioning Questionnaire and the 36-Item Short Form Health Survey preoperatively and 6 weeks and 6 months after surgery. RESULTS Patients with preoperative visual impairment reported a significant impact of this condition on VR-QOL preoperatively, including general vision, near activities, and peripheral vision; they also noted vision-specific impacts on mental health, role difficulties, dependency, and driving. After endoscopic resection of adenomas, patients reported improvement across all these categories 6 weeks postoperatively, and this improvement was maintained by 6 months postoperatively. Patients with preoperative pituitary dysfunction, including hormone-producing tumors, perceived their general health and physical function as poorer, with some of these patients reporting improvement in perceived general health after the endoscopic surgery. All patients noted that their ability to work or perform activities of daily living was transiently reduced 6 weeks postoperatively, followed by significant improvement by 6 months after the surgery. CONCLUSIONS Both VR-QOL and patient's perceptions of their ability to do work and perform other daily activities as a result of their physical health significantly improved by 6 months after endoscopic resection of pituitary adenoma. The use of multidimensional QOL questionnaires provides a precise assessment of perceived outcomes after endoscopic surgery.

Auxologic parameters and response to 2-year therapy with recombinant human growth hormone in growth hormone deficient children with an ectopic posterior pituitary.

PubMed

Kalina, Maria; Kalina-Faska, Barbara; Gruszczyńska, Katarzyna; Baron, Jan; Cisowska, Anita; Morawiec, Karolina; Biel-Lewandowska, Paulina; Małecka-Tendera, Ewa

2015-01-01

Structural defects of the hypothalamic-pituitary area in MRI are suggested as being a more accurate marker of growth hormone deficiency (GHD) than laboratory assays. To compare auxological characteristics in GHD children with normal pituitary (NP) function and with ectopic posterior pituitary (EPP), prior to therapy with recombinant human growth hormone (rhGH), extending the follow-up to two years following treatment. Eighty-six (86) GHD patients were divided into two groups depending on the pituitary MRI: the EPP (23 children, 3.2-16.8 years old) and the NP group (63 children, 3.3-14.8 years old). Height deficits in the population (hSD) and parents (hSD-mpSD) and the change of hSD and bone/chronological age ratio were assessed before and after 12 and 24 months of rhGH therapy. Height deficits before treatment were significantly greater in EPP compared to NP [median -4.07 (-7.06, -2.75) vs -3.15 (-4.9, -2.35) for hSD, and -3.65 (-7.06, -1.21) vs -1.83 (-4.31, -0.28) for hSD-mpSD; p<0.05]. Bone age was significantly delayed in the EPP group [0.62 (0.27, 0.92) vs 0.75 (0.21, 0.71); p<0.05]; differences remained significant during follow-up. After 12 months of rhGH therapy, EPP showed significantly greater catch-up growth compared to NP [ΔhSD=1.2 (0.42, 2.69) vs 0.74 (0.05, 1.48); p<0.05]. In the 2nd year, height velocity slowed down and was comparable in the two groups. At the conclusion of the study, hSD was similar in both groups, but hSD-mpSD was more deviated in EPP [-1.79 (-3.71, -1.21) vs -1.1 (0.98, -0.07); p<0.05]. The study showed relevant auxologic differences between EPP and NP children, as well as beneficial effects of rhGH therapy in both groups.

Ras-dva Is a Novel Pit-1- and Glucocorticoid-Regulated Gene in the Embryonic Anterior Pituitary Gland

PubMed Central

Ellestad, Laura E.

2013-01-01

Glucocorticoids play a role in functional differentiation of pituitary somatotrophs and lactotrophs during embryogenesis. Ras-dva was identified as a gene regulated by anterior neural fold protein-1/homeobox expressed in embryonic stem cells-1, a transcription factor known to be critical in pituitary development, and has an expression profile in the chicken embryonic pituitary gland that is consistent with in vivo regulation by glucocorticoids. The objective of this study was to characterize expression and regulation of ras-dva mRNA in the developing chicken anterior pituitary. Pituitary ras-dva mRNA levels increased during embryogenesis to a maximum on embryonic day (e) 18 and then decreased and remained low or undetectable after hatch. Ras-dva expression was highly enriched in the pituitary gland on e18 relative to other tissues examined. Glucocorticoid treatment of pituitary cells from mid- and late-stage embryos rapidly increased ras-dva mRNA, suggesting it may be a direct transcriptional target of glucocorticoids. A reporter construct driven by 4 kb of the chicken ras-dva 5′-flanking region, containing six putative pituitary-specific transcription factor-1 (Pit-1) binding sites and two potential glucocorticoid receptor (GR) binding sites, was highly activated in embryonic pituitary cells and up-regulated by corticosterone. Mutagenesis of the most proximal Pit-1 site decreased promoter activity in chicken e11 pituitary cells, indicating regulation of ras-dva by Pit-1. However, mutating putative GR binding sites did not substantially reduce induction of ras-dva promoter activity by corticosterone, suggesting additional DNA elements within the 5′-flanking region are responsible for glucocorticoid regulation. We have identified ras-dva as a glucocorticoid-regulated gene that is likely expressed in cells of the Pit-1 lineage within the developing anterior pituitary gland. PMID:23161868

Ras-dva is a novel Pit-1- and glucocorticoid-regulated gene in the embryonic anterior pituitary gland.

PubMed

Ellestad, Laura E; Porter, Tom E

2013-01-01

Glucocorticoids play a role in functional differentiation of pituitary somatotrophs and lactotrophs during embryogenesis. Ras-dva was identified as a gene regulated by anterior neural fold protein-1/homeobox expressed in embryonic stem cells-1, a transcription factor known to be critical in pituitary development, and has an expression profile in the chicken embryonic pituitary gland that is consistent with in vivo regulation by glucocorticoids. The objective of this study was to characterize expression and regulation of ras-dva mRNA in the developing chicken anterior pituitary. Pituitary ras-dva mRNA levels increased during embryogenesis to a maximum on embryonic day (e) 18 and then decreased and remained low or undetectable after hatch. Ras-dva expression was highly enriched in the pituitary gland on e18 relative to other tissues examined. Glucocorticoid treatment of pituitary cells from mid- and late-stage embryos rapidly increased ras-dva mRNA, suggesting it may be a direct transcriptional target of glucocorticoids. A reporter construct driven by 4 kb of the chicken ras-dva 5'-flanking region, containing six putative pituitary-specific transcription factor-1 (Pit-1) binding sites and two potential glucocorticoid receptor (GR) binding sites, was highly activated in embryonic pituitary cells and up-regulated by corticosterone. Mutagenesis of the most proximal Pit-1 site decreased promoter activity in chicken e11 pituitary cells, indicating regulation of ras-dva by Pit-1. However, mutating putative GR binding sites did not substantially reduce induction of ras-dva promoter activity by corticosterone, suggesting additional DNA elements within the 5'-flanking region are responsible for glucocorticoid regulation. We have identified ras-dva as a glucocorticoid-regulated gene that is likely expressed in cells of the Pit-1 lineage within the developing anterior pituitary gland.

Biological Stress Systems, Adverse Life Events, and the Improvement of Chronic Multisite Musculoskeletal Pain Across a 6-Year Follow-Up.

PubMed

Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Dekker, Joost; Penninx, Brenda W J H

2017-02-01

Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1) function of biological stress systems, 2) adverse life events, and 3) their combination predict the improvement of chronic multisite musculoskeletal pain. Subjects of the Netherlands Study of Depression and Anxiety (NESDA) with chronic multisite musculoskeletal pain at baseline (N = 665) were followed-up 2, 4, and 6 years later. The Chronic Pain Grade Questionnaire was used to determine improvement (not meeting the criteria) of chronic multisite musculoskeletal pain at follow-up. Baseline assessment of biological stress systems included function of hypothalamic-pituitary-adrenal axis (1-hour cortisol awakening response, evening level, and post dexamethasone level), the immune system (basal and lipopolysaccharide-stimulated inflammatory markers), the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, and respiratory sinus arrhythmia). The number of adverse life events were assessed at baseline and 2-year follow-up using the List of Threatening Events Questionnaire. We showed that hypothalamic-pituitary-adrenal axis, immune system, and autonomic nervous system functioning and adverse life events were not associated with the improvement of chronic multisite musculoskeletal pain, either as a main effect or in interaction. This longitudinal study could not confirm that biological stress system dysfunction and adverse life events affect the course of chronic multisite musculoskeletal pain. Biological stress systems and adverse life events are not associated with the improvement of chronic multisite musculoskeletal pain over 6 years of follow-up. Other determinants should thus be considered in future research to identify in which persons pain symptoms will improve. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Evaluation of clinical hypothyroidism risk due to irradiation of thyroid and pituitary glands in radiotherapy of nasopharyngeal cancer patients.

PubMed

Lin, Zhixiong; Wang, Xiaoyan; Xie, Wenjia; Yang, Zhining; Che, Kaijun; Wu, Vincent W C

2013-12-01

Radiation-induced thyroid dysfunction after radiotherapy for nasopharyngeal cancer (NPC) has been reported. This study investigated the radiation effects of the thyroid and pituitary glands on thyroid function after radiotherapy for NPC. Sixty-five NPC patients treated with radiotherapy were recruited. Baseline thyroid hormone levels comprising free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) were taken before treatment and at 3, 6, 12 and 18 months. A seven-beam intensity-modulated radiotherapy plan was generated for each patient. Thyroid and pituitary gland dose volume histograms were generated, dividing the patients into four groups: high (>50 Gy) thyroid and pituitary doses (HTHP group); high thyroid and low pituitary doses (HTLP group); low thyroid and high pituitary doses; and low thyroid and pituitary doses. Incidence of hypothyroidism was analysed. Twenty-two (34%) and 17 patients (26%) received high mean thyroid and pituitary doses, respectively. At 18 months, 23.1% of patients manifested various types of hypothyroidism. The HTHP group showed the highest incidence (83.3%) of hypothyroidism, followed by the HTLP group (50%). NPC patients with high thyroid and pituitary gland doses carried the highest risk of abnormal thyroid physiology. The dose to the thyroid was more influential than the pituitary dose at 18 months after radiotherapy, and therefore more attention should be given to the thyroid gland in radiotherapy planning. © 2013 The Royal Australian and New Zealand College of Radiologists.

Pituitary gland volumes in bipolar disorder.

PubMed

Clark, Ian A; Mackay, Clare E; Goodwin, Guy M

2014-12-01

Bipolar disorder has been associated with increased Hypothalamic-Pituitary-Adrenal axis function. The mechanism is not well understood, but there may be associated increases in pituitary gland volume (PGV) and these small increases may be functionally significant. However, research investigating PGV in bipolar disorder reports mixed results. The aim of the current study was twofold. First, to assess PGV in two novel samples of patients with bipolar disorder and matched healthy controls. Second, to perform a meta-analysis comparing PGV across a larger sample of patients and matched controls. Sample 1 consisted of 23 established patients and 32 matched controls. Sample 2 consisted of 39 medication-naïve patients and 42 matched controls. PGV was measured on structural MRI scans. Seven further studies were identified comparing PGV between patients and matched controls (total n; 244 patients, 308 controls). Both novel samples showed a small (approximately 20mm(3) or 4%), but non-significant, increase in PGV in patients. Combining the two novel samples showed a significant association of age and PGV. Meta-analysis showed a trend towards a larger pituitary gland in patients (effect size: .23, CI: -.14, .59). While results suggest a possible small difference in pituitary gland volume between patients and matched controls, larger mega-analyses with sample sizes greater even than those used in the current meta-analysis are still required. There is a small but potentially functionally significant increase in PGV in patients with bipolar disorder compared to controls. Results demonstrate the difficulty of finding potentially important but small effects in functional brain disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Differential regulation of thyrotropin subunit apoprotein and carbohydrate biosynthesis by thyroid hormone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, T.; Weintraub, B.D.

1985-04-01

The regulation of TSH apoprotein and carbohydrate biosynthesis by thyroid hormone was studied by incubating pituitaries from normal and hypothyroid (3 weeks post-thyroidectomy) rats in medium containing (/sup 14/C)alanine and (/sup 3/H) glucosamine. After 6 h, samples were sequentially treated with anti-TSH beta to precipitate TSH and free TSH beta, anti-LH beta to clear the sample of LH and free LH beta, then anti-LH alpha to precipitate free alpha-subunit. Total proteins were acid precipitated. All precipitates were subjected to electrophoresis on sodium dodecyl sulfate-polyacrylamide gels, which were then sliced and assayed by scintillation spectrometry. In hypothyroid pituitaries plus medium, (/supmore » 14/C)alanine incorporation in combined and free beta-subunits was 26 times normal and considerably greater than the 3.4-fold increase seen in total protein; combined and free alpha-subunits showed no specific increase in apoprotein synthesis. (/sup 3/H)Glucosamine incorporation in combined alpha- and beta-subunits in hypothyroid samples was 13 and 21 times normal, respectively, and was greater than the 1.9-fold increase in total protein; free alpha-subunit showed no specific increase in carbohydrate synthesis. The glucosamine to alanine ratio, reflecting relative glycosylation of newly synthesized molecules, was increased in hypothyroidism for combined alpha-subunits, but not for combined beta-subunits, free alpha-subunits, or total proteins. In summary, short term hypothyroidism selectively stimulated TSH beta apoprotein synthesis and carbohydrate synthesis of combined alpha- and beta-subunits. Hypothyroidism also increased the relative glycosylation of combined alpha-subunit. Thus, thyroid hormone deficiency appears to alter the rate-limiting step in TSH assembly (i.e. beta-subunit synthesis) as well as the carbohydrate structure of TSH, which may play important roles in its biological function.« less

Behaviour problems and cortisol levels in very-low-birth-weight children.

PubMed

Wadsby, Marie; Nelson, Nina; Ingemansson, Fredrik; Samuelsson, Stefan; Leijon, Ingemar

2014-11-01

Abstract Background. There are still diverging results concerning the behaviour of children with very-low-birth-weight (VLBW) and they have been questioned to display different levels of stress hormone than normal-birth-weight (NBW) children. Aims. This study examined behaviour and the stress hormone cortisol in children with VLBW at the ages of 7 and 9 years compared with children with NBW. Results. Fifty-one VLBW and 50 NBW children were studied with the Child Behavior Checklist. Cortisol rhythm was measured through saliva samples three times a day for 2 days. VLBW children displayed more behavioural problems than NBW children, specifically social and attention problems, although still within normal ranges. They showed lower cortisol levels both at 7 and 9 years of age. No strong association between behaviour and cortisol levels was shown. Conclusion. VLBW children display more behaviour problems compared with NBW children but both groups score are within the normal range. Down-regulation of their hypothalamic-pituitary-adrenal (HPA) function in terms of lower cortisol levels is also noted.

Modification of hormonal secretion in clinically silent pituitary adenomas.

PubMed

Daems, Tania; Verhelst, Johan; Michotte, Alex; Abrams, Pascale; De Ridder, Dirk; Abs, Roger

2009-01-01

Silent pituitary adenomas are a subtype of adenomas characterized by positive immunoreactivity for one or more hormones classically secreted by normal pituitary cells but without clinical expression, although in some occasions enhanced or changed secretory activity can develop over time. Silent corticotroph adenomas are the classical example of this phenomenon. A series of about 500 pituitary adenomas seen over a period of 20 years were screened for modification in hormonal secretion. Biochemical and immunohistochemical data were reviewed. Two cases were retrieved, one silent somatotroph adenoma and one thyrotroph adenoma, both without specific clinical features or biochemical abnormalities, which presented 20 years after initial surgery with evidence of acromegaly and hyperthyroidism, respectively. While the acromegaly was controlled by a combination of somatostatin analogs and growth hormone (GH) receptor antagonist therapy, neurosurgery was necessary to manage the thyrotroph adenoma. Immunohistochemical examination demonstrated an increase in the number of thyroid stimulating hormone (TSH)-immunoreactive cells compared to the first tissue. Apparently, the mechanisms responsible for the secretory modifications are different, being a change in secretory capacity in the silent somatotroph adenoma and a quantitative change in the silent thyrotroph adenoma. These two cases, one somatotroph and one thyrotroph adenoma, are an illustration that clinically silent pituitary adenomas may in rare circumstances evolve over time and become active, as previously demonstrated in silent corticotroph adenomas.

Reassembly of Anterior Pituitary Organization by Hanging Drop Three-Dimensional Cell Culture

PubMed Central

Tsukada, Takehiro; Kouki, Tom; Fujiwara, Ken; Ramadhani, Dini; Horiguchi, Kotaro; Kikuchi, Motoshi; Yashiro, Takashi

2013-01-01

The anterior pituitary gland comprises 5 types of hormone-producing cells and non-endocrine cells, such as folliculostellate (FS) cells. The cells form a lobular structure surrounded by extracellular matrix (ECM) but are not randomly distributed in each lobule; hormone-producing cells have affinities for specific cell types (topographic affinity), and FS cells form a homotypic meshwork. To determine whether this cell and ECM organization can be reproduced in vitro, we developed a 3-dimensional (3D) model that utilizes hanging drop cell culture. We found that the topographic affinities of hormone-producing cells were indeed maintained (ie, GH to ACTH cells, GH to TSH cells, PRL to LH/FSH cells). Fine structures in hormone-producing cells retained their normal appearance. In addition, FS cells displayed well-developed cytoplasmic protrusions, which interconnected with adjacent FS cells to form a 3D meshwork. In addition, reassembly of gap junctions and pseudofollicles among FS cells was observed in cell aggregates. Major ECM components—collagens and laminin—were deposited and distributed around the cells. In sum, the dissociated anterior pituitary cells largely maintained their in vivo anterior pituitary architectures. This culture system appears to be a powerful experimental tool for detailed analysis of anterior pituitary cell organization. PMID:24023396

Reassembly of anterior pituitary organization by hanging drop three-dimensional cell culture.

PubMed

Tsukada, Takehiro; Kouki, Tom; Fujiwara, Ken; Ramadhani, Dini; Horiguchi, Kotaro; Kikuchi, Motoshi; Yashiro, Takashi

2013-08-29

The anterior pituitary gland comprises 5 types of hormone-producing cells and non-endocrine cells, such as folliculostellate (FS) cells. The cells form a lobular structure surrounded by extracellular matrix (ECM) but are not randomly distributed in each lobule; hormone-producing cells have affinities for specific cell types (topographic affinity), and FS cells form a homotypic meshwork. To determine whether this cell and ECM organization can be reproduced in vitro, we developed a 3-dimensional (3D) model that utilizes hanging drop cell culture. We found that the topographic affinities of hormone-producing cells were indeed maintained (ie, GH to ACTH cells, GH to TSH cells, PRL to LH/FSH cells). Fine structures in hormone-producing cells retained their normal appearance. In addition, FS cells displayed well-developed cytoplasmic protrusions, which interconnected with adjacent FS cells to form a 3D meshwork. In addition, reassembly of gap junctions and pseudofollicles among FS cells was observed in cell aggregates. Major ECM components-collagens and laminin-were deposited and distributed around the cells. In sum, the dissociated anterior pituitary cells largely maintained their in vivo anterior pituitary architectures. This culture system appears to be a powerful experimental tool for detailed analysis of anterior pituitary cell organization.

PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex.

PubMed

Kiefer, Florian W; Winhofer, Yvonne; Iacovazzo, Donato; Korbonits, Márta; Wolfsberger, Stefan; Knosp, Engelbert; Trautinger, Franz; Höftberger, Romana; Krebs, Michael; Luger, Anton; Gessl, Alois

2017-08-01

Carney complex (CNC) is an autosomal dominant condition caused, in most cases, by an inactivating mutation of the PRKAR1A gene, which encodes for the type 1 alpha regulatory subunit of protein kinase A. CNC is characterized by the occurrence of endocrine overactivity, myxomas and typical skin manifestations. Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine disease observed in CNC. Here, we describe the first case of a patient with CNC and adrenocorticotropic hormone (ACTH)-dependent Cushing disease due to a pituitary corticotroph adenoma. Loss-of-heterozygosity analysis of the pituitary tumour revealed loss of the wild-type copy of PRKAR1A , suggesting a role of this gene in the pituitary adenoma development. PRKAR1A loss-of-function mutations can rarely lead to ACTH-secreting pituitary adenomas in CNC patients. Pituitary-dependent disease should be considered in the differential diagnosis of Cushing syndrome in CNC patients. © 2017 European Society of Endocrinology.

Management of type 2 diabetes mellitus associated with pituitary gigantism.

PubMed

Ali, Omar; Banerjee, Swati; Kelly, Daniel F; Lee, Phillip D K

2007-01-01

Pituitary gigantism, a condition of endogenous growth hormone (GH) hypersecretion prior to epiphyseal closure, is a rare condition. In the adult condition of GH excess, acromegaly, the occurrence of type 2 diabetes mellitus (T2DM) and diabetic ketoacidosis (DKA) have been reported, with resolution following normalization of GH levels. We report the case of a 16-year-old male with pituitary gigantism due to a large invasive suprasellar adenoma who presented with T2DM and DKA. Despite surgical de-bulking, radiotherapy and medical treatment with cabergoline and pegvisomant, GH and insulin-like growth factor-I (IGF-I) levels remained elevated. However, the T2DM and recurrent DKA were successfully managed with metformin and low-dose glargine insulin, respectively. We review the pathophysiology of T2DM and DKA in growth hormone excess and available treatment options.

Spreading the Clinical Window for Diagnosing Fetal-Onset Hypogonadism in Boys

PubMed Central

Grinspon, Romina P.; Loreti, Nazareth; Braslavsky, Débora; Valeri, Clara; Schteingart, Helena; Ballerini, María Gabriela; Bedecarrás, Patricia; Ambao, Verónica; Gottlieb, Silvia; Ropelato, María Gabriela; Bergadá, Ignacio; Campo, Stella M.; Rey, Rodolfo A.

2014-01-01

In early fetal development, the testis secretes – independent of pituitary gonadotropins – androgens and anti-Müllerian hormone (AMH) that are essential for male sex differentiation. In the second half of fetal life, the hypothalamic–pituitary axis gains control of testicular hormone secretion. Follicle-stimulating hormone (FSH) controls Sertoli cell proliferation, responsible for testis volume increase and AMH and inhibin B secretion, whereas luteinizing hormone (LH) regulates Leydig cell androgen and INSL3 secretion, involved in the growth and trophism of male external genitalia and in testis descent. This differential regulation of testicular function between early and late fetal periods underlies the distinct clinical presentations of fetal-onset hypogonadism in the newborn male: primary hypogonadism results in ambiguous or female genitalia when early fetal-onset, whereas it becomes clinically undistinguishable from central hypogonadism when established later in fetal life. The assessment of the hypothalamic–pituitary–gonadal axis in male has classically relied on the measurement of gonadotropin and testosterone levels in serum. These hormone levels normally decline 3–6 months after birth, thus constraining the clinical evaluation window for diagnosing male hypogonadism. The advent of new markers of gonadal function has spread this clinical window beyond the first 6 months of life. In this review, we discuss the advantages and limitations of old and new markers used for the functional assessment of the hypothalamic–pituitary–testicular axis in boys suspected of fetal-onset hypogonadism. PMID:24847309

Ghrelin increases intracellular Ca²⁺ concentration in the various hormone-producing cell types of the rat pituitary gland.

PubMed

Yamazaki, Mami; Aizawa, Sayaka; Tanaka, Toru; Sakai, Takafumi; Sakata, Ichiro

2012-09-20

Ghrelin, isolated from the stomach as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), has potent growth hormone release ability in vivo and in vitro. Although GHS-R is abundantly expressed in the pituitary gland, there is no direct evidence of a relationship between hormone-producing cells and functional GHS-R in the pituitary gland. The aim of this study was to determine which anterior pituitary cells respond to ghrelin stimulation in male rats. We performed Fura-2 Ca(2+) imaging analysis using isolated pituitary cells, and performed immunocytochemistry to identify the type of pituitary hormone-producing cells. In Fura-2 Ca(2+) imaging analysis, ghrelin administration increased the intracellular Ca(2+) concentration in approximately 50% of total isolated anterior pituitary cells, and 20% of these cells strongly responded to ghrelin. Immunocytochemical analysis revealed that 82.9 ± 1.3% of cells that responded to ghrelin stimulation were GH-immunopositive. On the other hand, PRL-, LH-, and ACTH-immunopositive cells constituted 2.0 ± 0.3%, 12.6 ± 0.3%, and 2.5 ± 0.8% of ghrelin-responding pituitary cells, respectively. TSH-immunopositive cells did not respond to ghrelin treatment. These results suggest that ghrelin directly acts not only on somatotrophs, but also on mammotrophs, gonadotrophs, and corticotrophs in the rat pituitary gland. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Dopamine D2-like receptors (DRD2 and DRD4) in chickens: Tissue distribution, functional analysis, and their involvement in dopamine inhibition of pituitary prolactin expression.

PubMed

Lv, Can; Mo, Chunheng; Liu, Haikun; Wu, Chao; Li, Zhengyang; Li, Juan; Wang, Yajun

2018-04-20

Dopamine (DA) D2-like (and D1-like) receptors are suggested to mediate the dopamine actions in the anterior pituitary and/or CNS of birds. However, the information regarding the structure, functionality, and expression of avian D2-like receptors have not been fully characterized. In this study, we cloned two D2-like receptors (cDRD2, cDRD4) from chicken brain using RACE PCR. The cloned cDRD4 is a 378-amino acid receptor, which shows 57% amino acid (a.a.) identity with mouse DRD4. As in mammals, two cDRD2 isoforms, cDRD2L (long isoform, 437 a.a.) and cDRD2S (short isoform, 408 a.a.), which differ in their third intracellular loop, were identified in chickens. Using cell-based luciferase reporter assays or Western blot, we demonstrated that cDRD4, cDRD2L and cDRD2S could be activated by dopamine and quinpirole (a D2-like receptor agonist) dose-dependently, and their activation inhibits cAMP signaling pathway and stimulates MAPK/ERK signaling cascade, indicating that they are functional receptors capable of mediating dopamine actions. Quantitative real-time PCR revealed that cDRD2 and cDRD4 are widely expressed in chicken tissues with abundant expression noted in anterior pituitary, and their expressions are likely controlled by their promoters near exon 1, as demonstrated by dual-luciferase reporter assays in DF-1 cells. In accordance with cDRD2/cDRD4 expression in the pituitary, DA or quinpirole could partially inhibit vasoactive intestinal peptide-induced prolactin expression in cultured chick pituitary cells. Together, our data proves the functionality of DRD2 and DRD4 in birds and aids to uncover the conserved roles of DA/D2-like receptor system in vertebrates, such as its action on the pituitary. Copyright © 2018. Published by Elsevier B.V.

Surgical Outcome of Endoscopic Endonasal Surgery for Non-Functional Pituitary Adenoma by a Team of Neurosurgeons and Otolaryngologists Adenoma by a Team of Neurosurgeons and Otolaryngologists.

PubMed

Kikuchi, Ryogo; Toda, Masahiro; Tomita, Toshiki; Ogawa, Kaoru; Yoshida, Kazunari

2017-01-01

This study aimed to assess the efficacy of endoscopic endonasal surgery, conducted by a team of neurosurgeons and otolaryngologists. We studied 40 patients who were undergoing surgery for primary non-functional pituitary adenomas with Knosp grades 1 to 3, at Keio University Hospital between 2005 and 2012. We compared the endoscopic endonasal transsphenoidal approach (team-eTSS; T-eTSS), with a microscopic transsphenoidal approach (mTSS). Analyses were conducted for differences between the two groups in tumor resection rates, operating durations, and complications from the non-functional pituitary adenomas. We also compared the heminostril and binostril approaches for T-eTSS. Tumor resection rates were higher when the surgeries were conducted by T-eTSS than mTSS. In particular, when the maximum tumor diameter was more than 25 mm, resection rates were significantly higher for T-eTSS than for mTSS. There were no unexpected complications in either group. There was no significant difference in resection rates between the heminostril and binostril approaches when T-eTSS was performed. T-eTSS is an efficacious surgical option for non-functional pituitary adenomas, particularly when the adenoma is of large size. Benefits of the heminostril approach are evident.

Advanced virtual endoscopy for endoscopic transsphenoidal pituitary surgery.

PubMed

Wolfsberger, Stefan; Neubauer, André; Bühler, Katja; Wegenkittl, Rainer; Czech, Thomas; Gentzsch, Stephan; Böcher-Schwarz, Hans-Gerd; Knosp, Engelbert

2006-11-01

Virtual endoscopy (vE) is the navigation of a camera through a virtual anatomical space that is computationally reconstructed from radiological image data. Inside this three-dimensional space, arbitrary movements and adaptations of viewing parameters are possible. Thereby, vE can be used for noninvasive diagnostic purposes and for simulation of surgical tasks. This article describes the development of an advanced system of vE for endoscopic transsphenoidal pituitary surgery and its application to teaching, training, and in the routine clinical setting. The vE system was applied to a series of 35 patients with pituitary pathology (32 adenomas, three Rathke's cleft cysts) operated endoscopically via the transsphenoidal route at the Department of Neurosurgery of the Medical University Vienna between 2004 and 2006. The virtual endoscopic images correlated well with the intraoperative view. For the transsphenoidal approach, vE improved intraoperative orientation by depicting anatomical landmarks and variations. For planning a safe and tailored opening of the sellar floor, transparent visualization of the pituitary adenoma and the normal gland in relation to the internal carotid arteries was useful. According to our experience, vE can be a valuable tool for endoscopic transsphenoidal pituitary surgery for training purposes and preoperative planning. For the novice, it can act as a simulator for endoscopic anatomy and for training surgical tasks. For the experienced pituitary surgeon, vE can depict the individual patient's anatomy, and may, therefore, improve intraoperative orientation. By prospectively visualizing unpredictable anatomical variations, vE may increase the safety of this surgical procedure.

Distinct functions of neuromedin u and neuromedin s in orange-spotted grouper.

PubMed

Li, Shuisheng; Xiao, Ling; Liu, Qiongyu; Zheng, Binbin; Chen, Huapu; Liu, Xiaochun; Zhang, Yong; Lin, Haoran

2015-10-01

Neuromedin U (NMU) and neuromedin S (NMS) play inhibitory roles in the regulation of food intake and energy homeostasis in mammals. However, their functions are not clearly established in teleost fish. In the present study, nmu and nms homologs were identified in several fish species. Subsequently, their cDNA sequences were cloned from the orange-spotted grouper (Epinephelus coioides). Sequence analysis showed that the orange-spotted grouper Nmu proprotein contains a 21-amino acid mature Nmu peptide (Nmu-21). The Nms proprotein lost the typical mature Nms peptide, but it retains a putative 34-amino acid peptide (Nmsrp). In situ hybridization revealed that nmu- and nms-expressing cells are mainly localized in the hypothalamic regions associated with appetite regulation. Food deprivation decreased the hypothalamic nmu mRNA levels but induced an increase of nms mRNA levels. Periprandial expression analysis showed that hypothalamic expression of nmu increased significantly at 3 h post-feeding, while nms expression was elevated at the normal feeding time. I.p. injection of synthetic Nmu-21 peptide suppressed the hypothalamic neuropeptide y (npy) expression, while Nmsrp administration significantly increased the expression of npy and orexin in orange-spotted grouper. Furthermore, the mRNA levels of LH beta subunit (lhβ) and gh in the pituitary were significantly down-regulated after Nmu-21 peptide administration, while Nmsrp was able to significantly stimulate the expression of FSH beta subunit (fshβ), prolactin (prl), and somatolaction (sl). Our results indicate that nmu and nms possess distinct neuroendocrine functions and pituitary functions in the orange spotted grouper. © 2015 Society for Endocrinology.

Analysis of differential gene expression by bead-based fiber-optic array in nonfunctioning pituitary adenomas.

PubMed

Jiang, Z; Gui, S; Zhang, Y

2011-05-01

Nonfunctioning pituitary adenomas (NFPAs) are relatively common, accounting for 30% of all pituitary adenomas; however, their pathogenesis remains enigmatic. To explore the possible pathogenesis of NFPAs, we used fiber-optic BeadArray to examine gene expression in 5 NFPAs compared with 3 normal pituitaries. 4 differentially expressed genes were chosen randomly for validation by reverse transcriptase-real time quantitative polymerase chain reaction (RT-qPCR). We then analyzed the differentially expressed gene profile with Kyoto Encyclopedia of Genes and Genomes (KEGG). The array analysis indentified significant increases in the expression of 1,402 genes and 383 expressed sequence tags (ESTs), and decreases in 1,697 genes and 113 ESTs in the NFPAs. Bioinformatic and pathway analysis showed that the genes HIGD1B, FAM5C, PMAIP1 and the pathway cell-cycle regulation may play an important role in tumorigenesis and progression of NFPAs. Our data suggest fiber-optic BeadArray combined with pathway analysis of differential gene expression profile appears to be a valid approach for investigating the pathogenesis of tumors. © Georg Thieme Verlag KG Stuttgart · New York.

Identification and characterisation of side population cells in the canine pituitary gland.

PubMed

van Rijn, Sarah J; Gremeaux, Lies; Riemers, Frank M; Brinkhof, Bas; Vankelecom, Hugo; Penning, Louis C; Meij, Björn P

2012-06-01

To date, stem/progenitor cells have not been identified in the canine pituitary gland. Cells that efficiently exclude the vital dye Hoechst 33342 can be visualised and identified using fluorescence activated cell sorting (FACS) as a 'side population' (SP), distinct from the main population (MP). Such SPs have been identified in several tissues and display stem/progenitor cell characteristics. In this study, a small SP (1.3%, n=6) was detected in the anterior pituitary glands of healthy dogs. Quantitative PCR indicated significantly higher expression of CD34 and Thy1 in this SP, but no differences in the expression of CD133, Bmi-1, Axin2 or Shh. Pro-opiomelanocortin (POMC) and Lhx3 expression were significantly higher in the MP than in the SP, but no differences in the expression of Tpit, GH or PRL were found. The study demonstrated the existence of an SP of cells in the normal canine pituitary gland, encompassing cells with stem cell characteristics and without POMC expression. Copyright © 2011 Elsevier Ltd. All rights reserved.

Somatotroph hypoplasia and dwarfism in transgenic mice expressing a non-phosphorylatable CREB mutant.

PubMed

Struthers, R S; Vale, W W; Arias, C; Sawchenko, P E; Montminy, M R

1991-04-18

Most of the transcriptional effects of cyclic AMP are mediated by the cAMP response element binding protein (CREB). After activation of cAMP-dependent protein kinase A, the catalytic subunits of this enzyme apparently mediate the phosphorylation and activation of CREB. As cAMP serves as a mitogenic signal for anterior pituitary somatotrophic cells, we investigated whether CREB similarly regulates proliferation of these cells. We prepared transgenic mice expressing a transcriptionally inactive mutant of CREB (CREBM1), which cannot be phosphorylated, in cells of the anterior pituitary. If CREB activity is required for proliferation, the overexpressed mutant protein would effectively compete with wild-type CREB activity and thereby block the response to cAMP. As predicted, the CREBM1 transgenic mice exhibited a dwarf phenotype with atrophied pituitary glands markedly deficient in somatotroph but not other cell types. We conclude that transcriptional activation of CREB is necessary for the normal development of a highly restricted cell type, and that environmental cues, possibly provided by the hypothalamic growth hormone-releasing factor, are necessary for population of the pituitary by somatotrophic cells.

[Unconsciousness due to hyponatremia in a patient with short stature with panhypopituitarism].

PubMed

Notsu, K; Takagi, C; Umaki, I

1995-03-20

An unconscious woman of short stature (141 cm) was admitted to our hospital in March, 1994. She had hyponatremia (120 mEq/l) and had experienced massive bleeding during delivery. No increment of either plasma ACTH or cortisol levels was observed after insulin-induced hypoglycemia. However, urinary 17OHCS levels gradually increased after repeated intramuscular injections of ACTH. Plasma free T3 and free T4 levels were low. Neither plasma TSH nor prolactin (PRL) levels increased after an intravenous injection of TRH. Basal plasma LH, FSH and growth hormone (GH) levels were low and there were no observable responses to any of the stimulation tests. A magnetic resonance image (MRI) of her pituitary gland showed an empty sella. These results showed that she had a panhypopituitarism with primary empty sella. Replacement therapy with glucocorticoid was started and serum sodium levels normalized immediately. Levothyroxine was also administered. The possibility of pituitary dwarfism during her youth and a gradual postpartum reduction of other pituitary hormones may have caused an impairment of the hypothalamo-pituitary-adrenal axis.

Serotonin and pituitary-adrenal function. [in rat under stress

NASA Technical Reports Server (NTRS)

Berger, P. A.; Barchas, J. D.; Vernikos-Danellis, J.

1974-01-01

An investigation is conducted to evaluate the response of the pituitary-adrenal system to a stress stimulus in the rat. In the investigation brain serotonin synthesis was inhibited with p-chlorophenylalanine. In other tests the concentration of serotonin was enhanced with precursors such as tryptophan or 5-hydroxytryptophan. On the basis of the results obtained in the study it is speculated that in some disease states there is a defect in serotonergic neuronal processes which impairs pituitary-adrenal feedback mechanisms.

Evaluation of diffusivity in the anterior lobe of the pituitary gland: 3D turbo field echo with diffusion-sensitized driven-equilibrium preparation.

PubMed

Hiwatashi, A; Yoshiura, T; Togao, O; Yamashita, K; Kikuchi, K; Kobayashi, K; Ohga, M; Sonoda, S; Honda, H; Obara, M

2014-01-01

3D turbo field echo with diffusion-sensitized driven-equilibrium preparation is a non-echo-planar technique for DWI, which enables high-resolution DWI without field inhomogeneity-related image distortion. The purpose of this study was to evaluate the feasibility of diffusion-sensitized driven-equilibrium turbo field echo in evaluating diffusivity in the normal pituitary gland. First, validation of diffusion-sensitized driven-equilibrium turbo field echo was attempted by comparing it with echo-planar DWI. Five healthy volunteers were imaged by using diffusion-sensitized driven-equilibrium turbo field echo and echo-planar DWI. The imaging voxel size was 1.5 × 1.5 × 1.5 mm(3) for diffusion-sensitized driven-equilibrium turbo field echo and 1.5 × 1.9 × 3.0 mm(3) for echo-planar DWI. ADCs measured by the 2 methods in 15 regions of interests (6 in gray matter and 9 in white matter) were compared by using the Pearson correlation coefficient. The ADC in the pituitary anterior lobe was then measured in 10 volunteers by using diffusion-sensitized driven-equilibrium turbo field echo, and the results were compared with those in the pons and vermis by using a paired t test. The ADCs from the 2 methods showed a strong correlation (r = 0.79; P < .0001), confirming the accuracy of the ADC measurement with the diffusion-sensitized driven-equilibrium sequence. The ADCs in the normal pituitary gland were 1.37 ± 0.13 × 10(-3) mm(2)/s, which were significantly higher than those in the pons (1.01 ± 0.24 × 10(-3) mm(2)/s) and the vermis (0.89 ± 0.25 × 10(-3) mm(2)/s, P < .01). We demonstrated that diffusion-sensitized driven-equilibrium turbo field echo is feasible in assessing ADC in the pituitary gland.

Somatic GPR101 Duplication Causing X-Linked Acrogigantism (XLAG)—Diagnosis and Management

PubMed Central

Rodd, Celia; Millette, Maude; Iacovazzo, Donato; Stiles, Craig E.; Barry, Sayka; Evanson, Jane; Albrecht, Steffen; Caswell, Richard; Bunce, Benjamin; Jose, Sian; Trouillas, Jacqueline; Roncaroli, Federico; Sampson, Julian; Ellard, Sian

2016-01-01

Context: Recent reports have proposed that sporadic or familial germline Xq26.3 microduplications involving the GPR101 gene are associated with early-onset X-linked acrogigantism (XLAG) with a female preponderance. Case Description: A 4-year-old boy presented with rapid growth over the previous 2 years. He complained of sporadic headaches and had coarse facial features. His height Z-score was +4.89, and weight Z-score was +5.57. Laboratory testing revealed elevated serum prolactin (185 μg/L; normal, <18 μg/L), IGF-1 (745 μg/L; normal, 64–369 μg/L), and fasting GH > 35.0 μg/L. Magnetic resonance imaging demonstrated a homogenous bulky pituitary gland (18 × 15 × 13 mm) without obvious adenoma. A pituitary biopsy showed hyperplastic pituitary tissue with enlarged cords of GH and prolactin cells. Germline PRKAR1A, MEN1, AIP, DICER1, CDKN1B, and somatic GNAS mutations were negative. Medical management was challenging until institution of continuous sc infusion of short-acting octreotide combined with sc pegvisomant and oral cabergoline. The patient remains well controlled with minimal side effects 7 years after presentation. His phenotype suggested XLAG, but his peripheral leukocyte-, saliva-, and buccal cell-derived DNA tested negative for microduplication in Xq26.3 or GPR101. However, DNA isolated from the pituitary tissue and forearm skin showed duplicated dosage of GPR101, suggesting that he is mosaic for this genetic abnormality. Conclusions: Our patient is the first to be described with somatic microduplication leading to typical XLAG phenotype. This patient demonstrates that a negative test for Xq26.3 microduplication or GPR101 duplication on peripheral blood DNA does not exclude the diagnosis of XLAG because it can result from a mosaic mutation affecting the pituitary. PMID:26982009

Giant pituitary adenoma: histological types, clinical features and therapeutic approaches.

PubMed

Iglesias, Pedro; Rodríguez Berrocal, Víctor; Díez, Juan José

2018-06-16

Giant pituitary adenomas comprise about 6-10% of all pituitary tumors. They are mostly clinically non-functioning adenomas and occur predominantly in males. The presenting symptoms are usually secondary to compression of neighboring structures, but also due to partial or total hypopituitarism. Functioning adenomas give rise to specific symptoms of hormonal hypersecretion. The use of dopamine agonists is considered a first-line treatment in patients with giant macroprolactinomas. Somatostatin analogs can also be used as primary treatment in cases of growth hormone and thyrotropin producing giant adenomas, although remission of the disease is not achieved in the vast majority of these patients. Neurosurgical treatment, either through transsphenoidal or transcranial surgery, continues to be the treatment of choice in the majority of patients with giant pituitary adenomas. The intrinsic complexity of these tumors requires the use of different therapies in a combined or sequential way. A multimodal approach and a therapeutic strategy involving a multidisciplinary team of expert professionals form the basis of the therapeutic success in these patients.

Development and sexual dimorphism of the pituitary gland.

PubMed

MacMaster, Frank P; Keshavan, Matcheri; Mirza, Yousha; Carrey, Normand; Upadhyaya, Ameet R; El-Sheikh, Rhonda; Buhagiar, Christian J; Taormina, S Preeya; Boyd, Courtney; Lynch, Michelle; Rose, Michelle; Ivey, Jennifer; Moore, Gregory J; Rosenberg, David R

2007-02-13

The pituitary gland plays a central role in sexual development and brain function. Therefore, we examined the effect of age and gender on pituitary volume in a large sample of healthy children and adults. Volumetric magnetic resonance imaging (MRI) was conducted in one hundred and fifty four (77 males and 77 females) healthy participants. Males were between the ages of 7 to 35 years (16.91+/-5.89 years) and females were 7 to 35 years of age (16.75+/-5.75 years). Subjects were divided into subgroups of age (7 to 9, 10 to 13, 14 to 17, 18 to 21, 22 and older) and sex (male/female). Pituitary gland volume differed between sexes when comparing the age groups (F=3.55, df=2, 143, p=0.03). Females demonstrated larger pituitary glands than males in the age 14 to 17 year old groups (p=0.04). Young (19 years and under) and old (20 years and older) females demonstrated a correlation between pituitary volume and age. Males did not show this relationship. These findings provide additional evidence for gender differences in the normative anatomy of the pituitary and may have relevance for the study of various childhood onset neuropsychiatric disorders in which pituitary dysfunction has been implicated.

Pituitary Volumes Are Reduced in Patients with Somatization Disorder

PubMed Central

Yildirim, Hanefi; Sirlier, Burcu; Kayali, Alperen

2012-01-01

Objective Despite of the suggested physiological relationship between somatoform disorder and disturbances in HPA axis function no volumetric study of pituitary volumes in somatization disorder has been carried out. Therefore, we aimed to use structural MRI to evaluate the pituitary volumes of the patients with somatization disorder. Methods Eighteen female patients with somatization disorder according to DSM-IV and same number of healthy controls were included into the study. All subjects were scanned using a 1.5-T General Electric (GE; Milwaukee, USA) scanner. Pituitary volume measurements were determined by using manuallly tracings according to standard antomical atlases. Results It was found significantly smaller pituitary volumes of the whole group of somatization patients compared to healthy (t=-3.604, p=0.001). ANCOVA predicting pituitary volumes demonstrated a significant main effect of diagnostic group (F=13.530, p<0.001) but TBV (F=1.924, p>0.05) or age (F=1.159, p>0.05). It was determined that there was no significant correlation between smaller pituitary volumes and the duration of illness (r=0.16, p>0.05) in the patient group. Conclusion In conclusion, we suggest that the patients with somatization disorder might have significantly smaller pituitary volumes compared to healthy control subjects. PMID:22993528

Hypothalamic-pituitary cytokine network.

PubMed

Kariagina, Anastasia; Romanenko, Dmitry; Ren, Song-Guang; Chesnokova, Vera

2004-01-01

Cytokines expressed in the brain and involved in regulating the hypothalamus-pituitary-adrenal (HPA) axis contribute to the neuroendocrine interface. Leukemia inhibitory factor (LIF) and LIF receptors are expressed in human pituitary cells and murine hypothalamus and pituitary. LIF potently induces pituitary proopiomelanocortin (POMC) gene transcription and ACTH secretion and potentiates CRH induction of POMC. In vivo, LIF, along with CRH, enhances POMC expression and ACTH secretion in response to emotional and inflammatory stress. To further elucidate specific roles for both CRH and LIF in activating the inflammatory HPA response, double-knockout mice (CRH/LIFKO) were generated by breeding the null mutants for each respective single gene. Inflammation produced by ip injection of lipopolysaccharide (1 microg/mouse) to double CRH and LIF-deficient mice elicited pituitary POMC induction similar to wild type and markedly higher than in single null animals (P<0.0.01). Double-knockout mice also demonstrated robust corticosterone response to inflammation. High pituitary POMC mRNA levels may reflect abundant TNFalpha, IL-1beta, and IL-6 activation observed in the hypothalamus and pituitary of these animals. Our results suggest that increased central proinflammatory cytokine expression can compensate for the impaired HPA axis function and activates inflammatory ACTH and corticosterone responses in mice-deficient in both CRH and LIF.

Height, shape and anterior-posterior diameter of pituitary gland on magnetic resonance imaging among patients with multiple sclerosis compared to normal individuals.

PubMed

Saba, Mohammad; Ebrahimi, Hossein Ali; Ahmadi-Pour, Habibeh; Khodadoust, Mohammad

2017-10-07

Background: Several studies indicate contribution of hypothalamus-pituitary-adrenal (HPA) axis in multiple sclerosis (MS) disease. This study was designed to determine whether there is an effective difference in pituitary height, shape, and anterior-posterior diameter (APD) between patients with MS and the control group. Methods: In this study, sagittal pituitary height and APD of 134 men and women (64 patients with MS and 70 healthy subjects as control group) were measured by T1 sequence magnetic resonance imaging (MRI). All the subjects were free of sellar or parasellar pathology without a history of surgical intervention or prolactin affecting drugs like bromocriptine and cabergoline or corticosteroid consumption. Results: Mean height of pituitary gland was 6.62 ± 1.43 and 5.78 ± 1.15 mm for patients and the control group, respectively, and the difference between the two groups was statistically significant (P = 0.001). Mean APD was 10.40 ± 1.29 mm for the group of patients and 10.25 ± 1.41 mm for the control group, respectively, without significant differences. 46.9%, 37.5%, and 15.6% of patients had flat, convex, and concave hypophyseal surfaces, respectively. This rate was 50%, 30%, and 20% among the control group, respectively. There was no significant difference between our measurements among patients on whom imaging study was performed at time of disease onset with others. Conclusion: Mean height of pituitary gland among patients with MS was significantly greater than the control group (P = 0.001). So can we consider the same etiology for pituitary hypertrophy among patients with MS as a hypothesis?

PITUITARY GIGANTISM--EXPERIENCE OF A SINGLE CENTER FROM WESTERN INDIA.

PubMed

Patt, Hiren P; Bothra, Nikita; Goel, Atul H; Kasaliwal, Rajeev; Lila, Anurag R; Bandgar, Tushar R; Shah, Nalini S

2015-06-01

Limited data are available on pituitary gigantism, as it is a rare disorder. This study was carried out to assess the clinical, hormonal, and radiologic profiles and management outcomes of patients with pituitary gigantism. We conduced a retrospective analysis of 14 patients with pituitary gigantism who presented to a single tertiary care institute from 1990 to 2014. Thirteen patients were male, and 1 was female. The mean age at diagnosis was 21.9 ± 6.1 years, with a mean lag period of 6.5 ± 5.6 years. The mean height SD score at the time of diagnosis was 3.2 ± 0.6. Symptoms of tumor mass effect were the chief presenting complaint in the majority (50%) of patients, while 2 patients were asymptomatic. Six patients had hyperprolactinemia. At presentation, the nadir PGGH (postglucose GH) and insulin-like growth factor (IGF 1)-ULN (× upper limit of normal) were 63.2 ± 94.9 ng/mL and 1.98 ± 0.5, respectively. All (except 1 with mild pituitary hyperplasia) had pituitary macroadenoma. Six patients had invasive pituitary adenoma. Transsphenoidal surgery (TSS) was the primary modality of treatment in 13/14 patients, and it achieved remission in 4/13 (30.76%) patients without recurrence over a median follow-up of 7 years. Post-TSS radiotherapy (RT) achieved remission in 3/5 (60%) patients over a median follow-up of 3.5 years. None of the patients received medical management at any point of time. Gigantism is more common in males, and remission can be achieved in the majority of the patients with the help of multimodality treatment (TSS and RT).

Rethinking the Stalk Effect: A New Hypothesis Explaining Suprasellar Tumor-Induced Hyperprolactinemia

PubMed Central

Skinner, Donal C.

2009-01-01

The pars tuberalis is a distinct subdivision of the pituitary gland but its function remains poorly understood. Suprasellar tumors in this pars tuberalis region are frequently accompanied by hyperprolactinemia. As these tumors do not immunoreact for any of the established pituitary hormones, they are classified as non-secretory. It has been postulated that these suprasellar tumors induce hyperprolactinemia by compressing the pituitary stalk, resulting in impaired dopamine delivery to the pituitary and, consequently, disinhibition of the lactotropes. An alternative hypothesis proposed is that suprasellar tumors secrete a specific pars tuberalis factor that stimulates prolactin secretion. Hypothesized candidates are the preprotachykinin A derived tachykinins, substance P and/or neurokinin A. PMID:19028420

Evaluation of the Olfactory Function With the "Sniffin' Sticks" Test After Endoscopic Transsphenoidal Pituitary Surgery.

PubMed

Cingoz, Ilker Deniz; Kizmazoglu, Ceren; Guvenc, Gonul; Sayin, Murat; Imre, Abdulkadir; Yuceer, Nurullah

2018-06-01

The aim of this study was to evaluate the olfactory function of patients who had undergone endoscopic transsphenoidal pituitary surgery. In this prospective study, the "Sniffin' Sticks" test was performed between June 2016 and April 2017 at Izmir Katip Celebi University Ataturk Training and Research Hospital. Thirty patients who were scheduled to undergo endoscopic transsphenoidal pituitary surgery were evaluated preoperatively and 8 weeks postoperatively using the Sniffin' Sticks test battery for olfactory function, odor threshold, smell discrimination, and odor identification. The patients were evaluated preoperatively by an otolaryngologist. The patients' demographic data and olfactory functions were analyzed with a t test and Wilcoxon-labeled sequential test. The study group comprised 14 women (46.7%) and 16 men (53.3%) patients. The mean age of the patients was 37.50 ± 9.43 years (range: 16-53 years). We found a significant difference in the preoperative and postoperative values of the odor recognition test (P = 0.017); however, there was no significant difference between the preoperative and postoperative odor threshold values (P = 0.172) and odor discrimination values (P = 0.624). The threshold discrimination identification test scores were not significant (P = 0.110). The olfactory function of patients who were normosmic preoperatively was not affected postoperatively. This study shows that the endoscopic transsphenoidal technique for pituitary surgery without nasal flap has no negative effect on the olfactory function.

Hypogonadotropic Hypogonadism and Short Stature in Patients with Diabetes Due to Neurogenin 3 Deficiency

PubMed Central

Rubio-Cabezas, Oscar; Gómez, José Luis; Gleisner, Andrea; Hattersley, Andrew T.

2016-01-01

Context: Biallelic mutations in NEUROG3 are known to cause early-onset malabsorptive diarrhea due to congenital anendocrinosis and diabetes mellitus at a variable age. No other endocrine disorders have been described so far. We report four patients with homozygous NEUROG3 mutations who presented with short stature and failed to show any signs of pubertal development. Case Description: Four patients (two males, two females) were diagnosed with homozygous mutations in NEUROG3 on the basis of congenital malabsorptive diarrhea and diabetes. All four had severe short stature and failed to develop secondary sexual characteristics at an appropriate age, despite some having normal body mass index. The absence of gonadal function persisted into the third decade in one patient. Upon testing, both basal and stimulated LH and FSH levels were low, with the remaining pituitary hormones within the normal range. Magnetic resonance imaging scans of the hypothalamic-pituitary axis did not reveal structural abnormalities. A diagnosis of hypogonadotropic hypogonadism was made, and replacement therapy with sex hormones was started. Conclusions: The high reproducibility of this novel phenotype suggests that central hypogonadism and short stature are common findings in patients with mutations in NEUROG3. Growth rate needs to be carefully monitored in these patients, who also should be routinely screened for hypogonadism when they reach the appropriate age. NEUROG3 mutations expand on the growing number of genetic causes of acquired hypogonadotropic hypogonadism. PMID:27533310

New male contraceptive entering clinical trials worldwide.

PubMed

1989-10-01

250 men are participating in a clinical trial of a reversible male testosterone contraceptive at the University of Washington in Seattle and at 9 other centers in Europe, Asia, and Australia. Clinicians inject the WHO-developed testosterone enanthate (200 mg) into these men once a week. The testosterone contraceptive instructs the pituitary gland to deactivate 2 hormones which normally maintain the testes' function resulting in a temporary stop of spermatogenesis just like the female oral contraceptive instructs the pituitary gland to suppress ovulation. Tests of 5 ejaculates in preliminary trials have indicated that 50-60% of the men experience azoospermia. Investigators are concerned with the possibility that ejaculates during normal intercourse may contain enough sperm to impregnate the partner. An investigator at the University of Washington believes this clinical trial of 250 men will determine whether this is indeed the case. The concern about contraceptive failure is the main problem with contraceptive testosterone. The minor side effects include weight gain which may be due to increased muscle mass and some sodium retention, acne, and possible reduction of libido but that has not yet occurred in the 250 men in the clinical trial. This contraceptive testosterone does not remain active for long periods of time if administered orally. Researchers are now developing a newer form of the contraceptive which will increase the intervals between administrations from 1 week to 3 months. An investigator from Seattle guesses that this male contraceptive will not be available for marketing in the US until at least 1994.

Development and Clinical Application of a New Method for the Radioimmunoassay of Arginine Vasopressin in Human Plasma

PubMed Central

Robertson, Gary L.; Mahr, Ermelinda A.; Athar, Shahid; Sinha, Tushar

1973-01-01

A radioimmunoassay has been developed that permits reliable measurements of plasma arginine vasopressin (AVP) at concentrations as low as 0.5 pg/ml in sample volumes of 1 ml or less. Nonhormonal immunoreactivity associated with the plasma proteins is eliminated by acetone precipitation before assay, leaving unaltered a component that is immunologically and chromatographically indistinguishable from standard AVP. Storage of plasma results in a decline in AVP concentration and, thus, must be carefully regulated. The plasma AVP values obtained by our method approximate the anticipated levels and vary in accordance with physiologic expections. In recumbent normal subjects, plasma AVP ranged from (mean ±SD) 5.4±3.4 pg/ml after fluid deprivation to 1.4±0.8 pg/ml after water loading, and correlated significantly with both plasma osmolality (r=0.52; P<0.001) and urine osmolality (r=0.77; P<0.001). After fluid restriction, plasma AVP was uniformly normal relative to plasma osmolality in patients with nephrogenic diabetes insipidus and primary polydipsia but was distinctly subnormal in all patients with pituitary diabetes insipidus. The infusion of physiologic amounts of posterior pituitary extract caused a dose-related rise in plasma vasopressin that afterwards declined at the expected rate (t½=22.5±4 min). We conclude that, when used appropriately, our radioimmunoassay method provides a useful way of assessing AVP function in man. PMID:4727463

Clinical and laboratory parameters predicting a requirement for the reevaluation of growth hormone status during growth hormone treatment: Retesting early in the course of GH treatment.

PubMed

Vuralli, Dogus; Gonc, E Nazli; Ozon, Z Alev; Alikasifoglu, Ayfer; Kandemir, Nurgun

2017-06-01

We aimed to define the predictive criteria, in the form of specific clinical, hormonal and radiological parameters, for children with growth hormone deficiency (GHD) who may benefit from the reevaluation of GH status early in the course of growth hormone (GH) treatment. Two hundred sixty-five children with growth hormone deficiency were retested by GH stimulation at the end of the first year of GH treatment. The initial clinical and laboratory characteristics of those with a normal (GH≥10ng/ml) response and those with a subnormal (GH<10ng/ml) response were compared to predict a normal GH status during reassessment. Sixty-nine patients (40.6%) out of the 170 patients with isolated growth hormone deficiency (IGHD) had a peak GH of ≥10ng/ml during the retest. None of the patients with multiple pituitary hormone deficiency (MPHD) had a peak GH of ≥10ng/ml. Puberty and sex steroid priming in peripubertal cases increased the probability of a normal GH response. Only one patient with IGHD who had an ectopic posterior pituitary without stalk interruption on MRI analysis showed a normal GH response during the retest. Patients with a peak GH between 5 and 10ng/ml, an age at diagnosis of ≥9years or a height gain below 0.61 SDS during the first year of treatment had an increased probability of having a normal GH response at the retest. Early reassessment of GH status during GH treatment is unnecessary in patients who have MPHD with at least 3 hormone deficiencies. Retesting at the end of the first year of therapy is recommended for patients with IGHD who have a height gain of <0.61 SDS in the first year of treatment, especially those with a normal or 'hypoplastic' pituitary on imaging. Priming can increase the likelihood of a normal response in patients in the pubertal age group who do not show overt signs of pubertal development. Copyright © 2017. Published by Elsevier Ltd.

Testosterone Regulates NUCB2 mRNA Expression in Male Mouse Hypothalamus and Pituitary Gland

PubMed Central

Seon, Sojeong; Jeon, Daun; Kim, Heejeong; Chung, Yiwa; Choi, Narae; Yang, Hyunwon

2017-01-01

ABSTRACT Nesfatin-1/NUCB2 is known to take part in the control of the appetite and energy metabolism. Recently, many reports have shown nesfatin-1/NUCB2 expression and function in various organs. We previously demonstrated that nesfatin-1/NUCB2 expression level is higher in the pituitary gland compared to other organs and its expression is regulated by 17β-estradiol and progesterone secreted from the ovary. However, currently no data exist on the expression of nesfatin-1/NUCB2 and its regulation mechanism in the pituitary of male mouse. Therefore, we examined whether nesfatin-1/NUCB2 is expressed in the male mouse pituitary and if its expression is regulated by testosterone. As a result of PCR and western blotting, we found that a large amount of nesfatin-1/NUCB2 was expressed in the pituitary and hypothalamus. The NUCB2 mRNA expression level in the pituitary was decreased after castration, but not in the hypothalamus. In addition, its mRNA expression level in the pituitary was increased after testosterone treatment in the castrated mice, whereas, the expression level in the hypothalamus was significantly decreased after the treatment with testosterone. The in vitro experiment to elucidate the direct effect of testosterone on NUCB2 mRNA expression showed that NUCB2 mRNA expression was significantly decreased with testosterone in cultured hypothalamus tissue, but increased with testosterone in cultured pituitary gland. The present study demonstrated that nesfatin-1/NUCB2 was highly expressed in the male mouse pituitary and was regulated by testosterone. This data suggests that reproductive-endocrine regulation through hypothalamus-pituitary-testis axis may contribute to NUCB2 mRNA expression in the mouse hypothalamus and pituitary gland. PMID:28484746

The extracellular matrix component laminin promotes gap junction formation in the rat anterior pituitary gland.

PubMed

Horiguchi, Kotaro; Kouki, Tom; Fujiwara, Ken; Kikuchi, Motoshi; Yashiro, Takashi

2011-03-01

Folliculo-stellate (FS) cells in the anterior pituitary gland are believed to have multifunctional properties. FS cells connect to each other not only by mechanical means, but also by gap junctional cell-to-cell communication. Using transgenic rats that express green fluorescent protein (GFP) specifically in FS cells in the anterior pituitary gland (S100b-GFP rats), we recently revealed that FS cells in primary culture markedly change their shape, and form numerous interconnections with neighboring FS cells in the presence of laminin, an extracellular matrix (ECM) component of the basement membrane. Morphological and functional changes in cells are believed to be partly modified by matricrine signaling, by which ECM components function as cellular signals. In the present study, we examined whether gap junction formation between FS cells is affected by matricrine cues. A cell sorter was used to isolate FS cells from male S100b-GFP rat anterior pituitary for primary culture. We observed that mRNA and protein levels of connexin 43 in gap junction channels were clearly higher in the presence of laminin. In addition, we confirmed the formation of gap junctions between FS cells in primary culture by electron microscopy. Interestingly, we also observed that FS cells in the presence of laminin displayed well-developed rough endoplasmic reticulum and Golgi apparatus. Our findings suggest that, in anterior pituitary gland, FS cells may facilitate functional roles such as gap junctional cell-to-cell communication by matricrine signaling.

Neurotrophins, their receptors and KI-67 in human GH-secreting pituitary adenomas: an immunohistochemical analysis.

PubMed

Artico, M; Bianchi, E; Magliulo, G; De Vincentiis, M; De Santis, E; Orlandi, A; Santoro, A; Pastore, F S; Giangaspero, F; Caruso, R; Re, M; Fumagalli, L

2012-01-01

Pituitary adenomas are a diverse group of tumors arising from the pituitary gland. Typically, they are small, slow-growing, hormonally inactive lesions that come to light as incidental findings on radiologic or postmortem examinations, although some small, slow-growing lesions with excessive hormonal activity may manifest with a clinical syndrome. The family of neurotrophins plays a key role in the development and maintenance of the pituitary endocrine cell function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. The objective of our experimental study is to investigate the localization of the neurotrophins, their relative receptors and to detect the expression level of Ki-67 to determine whether all these factors participate in the transformation and development of human pituitary adenomas. A very strong expression of Neurotrophin-3 (NT-3) and its receptor TrKC was observed in the extracellular matrix (ECM) and vessel endothelium, together with a clear/marked presence of Brain-derived neurotrophic factor (BDNF), and its receptor TrKB, thus confirming their direct involvement in the progression of pituitary adenomas. On the contrary, NGF (Nerve growth factor) and its receptor TrKA and p75NTR were weakly expressed in the epithelial gland cells and the ECM.

Expression and Roles of Pannexins in ATP Release in the Pituitary Gland

PubMed Central

Li, Shuo; Bjelobaba, Ivana; Yan, Zonghe; Kucka, Marek; Tomić, Melanija

2011-01-01

Pannexins are a newly discovered three-member family of proteins expressed in the brain and peripheral tissues that belong to the superfamily of gap junction proteins. However, in mammals pannexins do not form gap junctions, and their expression and function in the pituitary gland have not been studied. Here we show that the rat pituitary gland expresses mRNA and protein transcripts of pannexins 1 and 2 but not pannexin 3. Pannexin 1 was more abundantly expressed in the anterior lobe, whereas pannexin 2 was more abundantly expressed in the intermediate and posterior pituitary. Pannexin 1 was identified in corticotrophs and a fraction of somatotrophs, the S100-positive pituicytes of the posterior pituitary and AtT-20 (mouse pituitary adrenocorticotropin-secreting cells) and rat immortalized pituitary cells secreting prolactin, whereas pannexin 2 was detected in the S100-positive folliculostellate cells of the anterior pituitary, melanotrophs of the intermediate lobe, and vasopressin-containing axons and nerve endings in the posterior lobe. Overexpression of pannexins 1 and 2 in AtT-20 pituitary cells enhanced the release of ATP in the extracellular medium, which was blocked by the gap junction inhibitor carbenoxolone. Basal ATP release in At-T20 cells was also suppressed by down-regulating the expression of endogenous pannexin 1 but not pannexin 2 with their short interfering RNAs. These results indicate that pannexins may provide a pathway for delivery of ATP, which is a native agonist for numerous P2X cationic channels and G protein-coupled P2Y receptors endogenously expressed in the pituitary gland. PMID:21467198

Expression and roles of pannexins in ATP release in the pituitary gland.

PubMed

Li, Shuo; Bjelobaba, Ivana; Yan, Zonghe; Kucka, Marek; Tomic, Melanija; Stojilkovic, Stanko S

2011-06-01

Pannexins are a newly discovered three-member family of proteins expressed in the brain and peripheral tissues that belong to the superfamily of gap junction proteins. However, in mammals pannexins do not form gap junctions, and their expression and function in the pituitary gland have not been studied. Here we show that the rat pituitary gland expresses mRNA and protein transcripts of pannexins 1 and 2 but not pannexin 3. Pannexin 1 was more abundantly expressed in the anterior lobe, whereas pannexin 2 was more abundantly expressed in the intermediate and posterior pituitary. Pannexin 1 was identified in corticotrophs and a fraction of somatotrophs, the S100-positive pituicytes of the posterior pituitary and AtT-20 (mouse pituitary adrenocorticotropin-secreting cells) and rat immortalized pituitary cells secreting prolactin, whereas pannexin 2 was detected in the S100-positive folliculostellate cells of the anterior pituitary, melanotrophs of the intermediate lobe, and vasopressin-containing axons and nerve endings in the posterior lobe. Overexpression of pannexins 1 and 2 in AtT-20 pituitary cells enhanced the release of ATP in the extracellular medium, which was blocked by the gap junction inhibitor carbenoxolone. Basal ATP release in At-T20 cells was also suppressed by down-regulating the expression of endogenous pannexin 1 but not pannexin 2 with their short interfering RNAs. These results indicate that pannexins may provide a pathway for delivery of ATP, which is a native agonist for numerous P2X cationic channels and G protein-coupled P2Y receptors endogenously expressed in the pituitary gland.

Clinical characteristics of pain in patients with pituitary adenomas.

PubMed

Dimopoulou, C; Athanasoulia, A P; Hanisch, E; Held, S; Sprenger, T; Toelle, T R; Roemmler-Zehrer, J; Schopohl, J; Stalla, G K; Sievers, C

2014-11-01

Clinical presentation of pituitary adenomas frequently involves pain, particularly headache, due to structural and functional properties of the tumour. Our aim was to investigate the clinical characteristics of pain in a large cohort of patients with pituitary disease. In a cross-sectional study, we assessed 278 patients with pituitary disease (n=81 acromegaly; n=45 Cushing's disease; n=92 prolactinoma; n=60 non-functioning pituitary adenoma). Pain was studied using validated questionnaires to screen for nociceptive vs neuropathic pain components (painDETECT), determine pain severity, quality, duration and location (German pain questionnaire) and to assess the impact of pain on disability (migraine disability assessment, MIDAS) and quality of life (QoL). We recorded a high prevalence of bodily pain (n=180, 65%) and headache (n=178, 64%); adrenocorticotropic adenomas were most frequently associated with pain (n=34, 76%). Headache was equally frequent in patients with macro- and microadenomas (68 vs 60%; P=0.266). According to painDETECT, the majority of the patients had a nociceptive pain component (n=193, 80%). Despite high prevalence of headache, 72% reported little or no headache-related disability (MIDAS). Modifiable factors including tumour size, genetic predisposition, previous surgery, irradiation or medical therapy did not have significant impact neither on neuropathic pain components (painDETECT) nor on headache-related disability (MIDAS). Neuropathic pain and pain-related disability correlated significantly with depression and impaired QoL. Pain appears to be a frequent problem in pituitary disease. The data suggest that pain should be integrated in the diagnostic and therapeutic work-up of patients with pituitary disease in order to treat them appropriately and improve their QoL. © 2014 European Society of Endocrinology.

Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

PubMed

Genazzani, Alessandro D; Podfigurna-Stopa, Agnieszka; Czyzyk, Adam; Katulski, Krzysztof; Prati, Alessia; Despini, Giulia; Angioni, Stefano; Simoncini, Tommaso; Meczekalski, Blazej

2016-01-01

To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 μg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.

Evidence that obesity and androgens have independent and opposing effects on gonadotropin production from puberty to maturity

PubMed Central

Rosenfield, Robert L; Bordini, Brian

2010-01-01

Optimal fat mass is necessary for normal gonadotropin levels in adults, and both undernutrition and overnutrition suppress gonadotropins: thus, the gonadotropin response to relative adipose mass is biphasic. Adult obesity is associated with blunted luteinizing hormone (LH) pulse amplitude that is partially attributable to increased LH clearance rate. Testosterone appears to have a biphasic effect on gonadotropin production in females. Moderate elevations of testosterone appear to stimulate LH production at both the hypothalamic and pituitary level, while very high levels of testosterone suppress LH. Thus, obesity per se appears to suppress gonadotropin production, and moderate hyperandrogenemia in women appears to stimulate LH. The ordinary hypergonadotropic hyperandrogenism of obese women appears to be an exception to this model because it is usually due to polycystic ovary syndrome (PCOS), a condition in which intrinsic functional ovarian hyperandrogenism and excess adiposity share a common origin that involves insulin-resistant hyperinsulinemia. LH elevation seems to be secondary to hyperandrogenemia and is absent in the most obese cases. Overweight early pubertal girls have significant blunting of sleep-related LH production, which is the first hormonal change of puberty. The data are compatible with the possibility that excess adiposity may paradoxically subtly suppress hypothalamic-pituitary-gonadal function in early puberty although it is known to contribute to the early onset of puberty. PMID:20816944

[Disorders of endocrine function after brain tumor therapy in childhood].

PubMed

Marx, M; Langer, T; Beck, J D; Dörr, H G

1999-07-01

Advances in the therapy of malignant brain tumors in children have led to a significant improvement in survival rates over the last few decades. As a result, the recognition and treatment of late effects have become more important. In addition to secondary tumors and deficiencies in cognitive and intellectual skills, the resulting endocrine disturbances play an important role. Own data and literature review. Deviations from the normal growth hormone secretion are usually recognized first and are most common, and have already been observed after conventional whole brain irradiation with 18 Gy. With some delay, other hypothalamo-pituitary deficiencies may occur, including panhypopituitarism. Puberty may come too early or too late or may not appear at all. Girls in particular, frequently experience an early and rapid pubertal development after brain tumor therapy, which may lead to further reduction in height due to an accelerated bone maturation. Functional disturbances of the thyroid and adrenal glands due to hypothalamic or pituitary deficiency are less common, and usually seen only after a radiation dose of over 40 Gy. Survivors of childhood brain tumors must be considered as long-term survivors, in whom the first therapy-induced long-term side effects appear almost immediately after the end of therapy. Maximum quality of life for the individual patient can only be achieved by long-term care and close cooperation of specialists in the different medical disciplines involved.

Multi-chaperone function modulation and association with cytoskeletal proteins are key features of the function of AIP in the pituitary gland

PubMed Central

Hernández-Ramírez, Laura C.; Morgan, Rhodri M.L.; Barry, Sayka; D’Acquisto, Fulvio; Prodromou, Chrisostomos; Korbonits, Márta

2018-01-01

Despite the well-recognized role of loss-of-function mutations of the aryl hydrocarbon receptor interacting protein gene (AIP) predisposing to pituitary adenomas, the pituitary-specific function of this tumor suppressor remains an enigma. To determine the repertoire of interacting partners for the AIP protein in somatotroph cells, wild-type and variant AIP proteins were used for pull-down/quantitative mass spectrometry experiments against lysates of rat somatotropinoma-derived cells; relevant findings were validated by co-immunoprecipitation and co-localization. Global gene expression was studied in AIP mutation positive and negative pituitary adenomas via RNA microarrays. Direct interaction with AIP was confirmed for three known and six novel partner proteins. Novel interactions with HSPA5 and HSPA9, together with known interactions with HSP90AA1, HSP90AB1 and HSPA8, indicate that the function/stability of multiple chaperone client proteins could be perturbed by a deficient AIP co-chaperone function. Interactions with TUBB, TUBB2A, NME1 and SOD1 were also identified. The AIP variants p.R304* and p.R304Q showed impaired interactions with HSPA8, HSP90AB1, NME1 and SOD1; p.R304* also displayed reduced binding to TUBB and TUBB2A, and AIP-mutated tumors showed reduced TUBB2A expression. Our findings suggest that cytoskeletal organization, cell motility/adhesion, as well as oxidative stress responses, are functions that are likely to be involved in the tumor suppressor activity of AIP. PMID:29507682

Hypopituitarism.

PubMed

Higham, Claire E; Johannsson, Gudmundur; Shalet, Stephen M

2016-11-12

Hypopituitarism refers to deficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary. Hypopituitarism is associated with excess mortality, a key risk factor being cortisol deficiency due to adrenocorticotropic hormone (ACTH) deficiency. Onset can be acute or insidious, and the most common cause in adulthood is a pituitary adenoma, or treatment with pituitary surgery or radiotherapy. Hypopituitarism is diagnosed based on baseline blood sampling for thyroid stimulating hormone, gonadotropin, and prolactin deficiencies, whereas for ACTH, growth hormone, and antidiuretic hormone deficiency dynamic stimulation tests are usually needed. Repeated pituitary function assessment at regular intervals is needed for diagnosis of the predictable but slowly evolving forms of hypopituitarism. Replacement treatment exists in the form of thyroxine, hydrocortisone, sex steroids, growth hormone, and desmopressin. If onset is acute, cortisol deficiency should be replaced first. Modifications in replacement treatment are needed during the transition from paediatric to adult endocrine care, and during pregnancy. Copyright © 2016 Elsevier Ltd. All rights reserved.

The pituitary gland under infrared light - in search of a representative spectrum for homogeneous regions.

PubMed

Banas, A; Banas, K; Furgal-Borzych, A; Kwiatek, W M; Pawlicki, B; Breese, M B H

2015-04-07

The pituitary gland is a small but vital organ in the human body. It is located at the base of the brain and is often described as the master gland due to its multiple functions. The pituitary gland secretes and stores hormones, such as the thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), growth hormone (hGH), prolactin, gonadotropins, and luteinizing hormones, as well as the antidiuretic hormone (ADH). A proper diagnosis of pituitary disorders is of utmost importance as this organ participates in regulating a variety of body functions. Typical histopathological analysis provides much valuable information, but it gives no insight into the biochemical background of the changes that occur within the gland. One approach that could be used to evaluate the biochemistry of tissue sections obtained from pituitary disorders is Fourier Transform Infra-Red (FTIR) spectromicroscopy. In order to collect diagnostically valuable information large areas of tissue must be investigated. This work focuses on obtaining a unique and representative FTIR spectrum characteristic of one type of cell architecture within a sample. The idea presented is based on using hierarchical cluster analysis (HCA) for data evaluation to search for uniform patterns within samples from the perspective of FTIR spectra. The results obtained demonstrate that FTIR spectromicroscopy, combined with proper statistical evaluation, can be treated as a complementary method for histopathological analysis and ipso facto can increase the sensitivity and specificity for detecting various disorders not only for the pituitary gland, but also for other human tissues.

Transformation of a MGUS to overt multiple myeloma: the possible role of a pituitary macroadenoma secreting high levels of insulin-like growth factor 1 (IGF-1).

PubMed

Tucci, Alessandra; Bonadonna, Stefania; Cattaneo, Chiara; Ungari, Marco; Giustina, Andrea; Guiseppe, Rossi

2003-03-01

We present a female patient with monoclonal gammopathy of undetermined significance who has remained stable for five years but evolved to overt myeloma in strict temporal relationship with the diagnosis of GH-secreting pituitary macroadenoma. IGF-I serum levels correlated with serum and urine M component. Since the in vitro role of IGF-I on proliferation and survival of normal and neoplastic plasma cells has been recently emphasized, the pathogenetic link between acromegaly and transformation of gammopathy to overt myeloma in this case is discussed.

The accuracy of the glucagon test compared to the insulin tolerance test in the diagnosis of adrenal insufficiency in young children with growth hormone deficiency.

PubMed

di Iorgi, Natascia; Napoli, Flavia; Allegri, Anna; Secco, Andrea; Calandra, Erika; Calcagno, AnnaLisa; Frassinetti, Costanza; Ghezzi, Michele; Ambrosini, Linda; Parodi, Stefano; Gastaldi, Roberto; Loche, Sandro; Maghnie, Mohamad

2010-05-01

The accuracy of the glucagon test in the diagnosis of central adrenal insufficiency in young children has not yet been definitively established. The aim of this study was to investigate the diagnostic accuracy of the glucagon test as an alternative to the insulin tolerance test (ITT) in children with GH deficiency under 6 yr of age. This was a prospective study conducted in two Pediatric Endocrinology Centers. Forty-eight children (median age, 4.2 yr) with GH deficiency confirmed by a peak GH to ITT and arginine less than 10 microg/liter were enrolled: 24 with normal hypothalamic-pituitary anatomy, seven with isolated anterior pituitary hypoplasia, and 17 with structural hypothalamic-pituitary abnormalities at magnetic resonance imaging. Twelve subjects had central adrenal insufficiency defined by a peak cortisol response of less than 20 microg/dl to ITT. All children underwent a glucagon stimulation test with blood sampling for cortisol and glucose (time 0 to 180 min) after the im administration of 30 microg/kg of glucagon. The mean peak cortisol after glucagon was not significantly different from that obtained after ITT in the whole cohort (25.9 vs. 26.0 microg/dl; P = 0.908), and it was significantly reduced in patients with structural hypothalamic-pituitary abnormalities (P < 0.001). Receiver operating characteristic curve analysis showed that the best diagnostic accuracy was obtained with a peak cortisol cutoff to glucagon of 14.6 microg/dl (sensitivity, 66.67%; specificity, 100%; area under the curve = 0.91; 95% confidence interval, 0.82-0.99). Using this cutoff, 91.67% of the patients were correctly classified. This study shows that glucagon is an accurate and safe diagnostic test for adrenal function in young children who are at risk for adrenal insufficiency.

Neuropsychiatric and metabolic aspects of dopaminergic therapy: perspectives from an endocrinologist and a psychiatrist

PubMed Central

Athanasoulia-Kaspar, Anastasia P; Popp, Kathrin H; Stalla, Gunter Karl

2018-01-01

The dopaminergic treatment represents the primary treatment in prolactinomas, which are the most common pituitary adenomas and account for about 40% of all pituitary tumours with an annual incidence of six to ten cases per million population. The dopaminergic treatment includes ergot and non-ergot derivatives with high affinity for the dopamine receptors D1 or/and D2. Through the activation of the dopaminergic pathway on pituitary lactotrophs, the dopamine agonists inhibit the prolactin synthesis and secretion, therefore normalizing the prolactin levels and restoring eugonadism, but they also lead to tumour shrinkage. Treatment with dopamine agonists has been associated – apart from the common side effects such as gastrointestinal symptoms, dizziness and hypotension – with neuropsychiatric side effects such as impulse control disorders (e.g. pathological gambling, compulsive shopping, hypersexuality and binge eating) and also with behavioral changes from low mood, irritability and verbal aggressiveness up to psychotic and manic symptoms and paranoid delusions not only in patients with prolactinomas but also in patients with Parkinson’s disease and restless leg syndrome. They usually have de novo onset after initiation of the dopaminergic treatment and have been mainly reported in patients with Parkinson’s disease, who are being treated with higher doses of dopamine agonists. Moreover, dopamine and prolactin seem to play an essential role in the metabolic pathway. Patients with hyperprolactinemia tend to have increased body weight and an altered metabolic profile with hyperinsulinemia and increased prevalence of diabetes mellitus in comparison to healthy individuals and patients with non-functioning pituitary adenomas. Treatment with dopamine agonists in these patients in short-term studies seems to lead to weight loss and amelioration of the metabolic changes. Together these observations provide evidence that dopamine and prolactin have a crucial role both in the regard and metabolic system, findings that merit further investigation in long-term studies. PMID:29378769

Endoscopic Endonasal Transsphenoidal Approach

PubMed Central

Cappabianca, Paolo; Alfieri, Alessandra; Colao, Annamaria; Ferone, Diego; Lombardi, Gaetano; de Divitiis, Enrico

1999-01-01

The outcome of endoscopic endonasal transsphenoidal surgery in 10 patients with pituitary adenomas was compared with that of traditional transnasal transsphenoidal approach (TTA) in 20 subjects. Among the 10 individuals subjected to “pure endoscopy,” 2 had a microadenoma, 1 an intrasellar macroadenoma, 4 had a macroadenoma with suprasellar expansion, 2 had a macroadenoma with supra-parasellar expansion, and 1 a residual tumor; 5 had acromegaly and 5 had a nonfunctioning adenoma (NFA). Among the patients subjected to TTA, 4 had a microadenoma, 2 had an intrasellar macroadenoma, 6 had a macroadenoma with suprasellar expansion, 4 had a macroadenoma with supra-parasellar expansion, and 4 had a residual tumor; 9 patients had acromegaly, 1 hyperprolactinemia, 1 Cushing's disease, and 9 a NFA. At the macroscopic evaluation, tumor removal was total (100%) after endoscopy in 9 patients and after TTA in 14 patients. Six months after surgery, magnetic resonance imaging (MRI) confirmed the total tumor removal in 21 of 23 patients (91.3%). Circulating growth hormone (GH) and insulin-like growth factor-I (IGF-I) significantly decreased 6 months after surgery in all 14 acromegalic patients: normalization of plasma IGF-I levels was obtained in 4 of 5 patients after the endoscopic procedure and in 4 of 9 patients after TTA. Before surgery, pituitary hormone deficiency was present in 14 out of 30 patients: pituitary function improved in 4 patients, remaining unchanged in the other 10 patients. Visual field defects were present before surgery in 4 patients, and improved in all. Early surgical results in the group of 10 patients who underwent endoscopic pituitary tumor removal were at least equivalent to those of standard TTA, with excellent postoperative course. Postsurgical hospital stay was significantly shorter (3.1 ± 0.4 vs. 6.2 ± 0.3 days, p < 0.001) after endoscopy as compared to TTA. ImagesFigure 1Figure 2 PMID:17171126

A rare challenging case of co-existent craniopharyngioma, acromegaly and squamous cell lung cancer.

PubMed

Fountas, Athanasios; Chai, Shu Teng; Ayuk, John; Gittoes, Neil; Chavda, Swarupsinh; Karavitaki, Niki

2018-01-01

Co-existence of craniopharyngioma and acromegaly has been very rarely reported. A 65-year-old man presented with visual deterioration, fatigue and frontal headaches. Magnetic resonance imaging revealed a suprasellar heterogeneous, mainly cystic, 1.9 × 2 × 1.9 cm mass compressing the optic chiasm and expanding to the third ventricle; the findings were consistent with a craniopharyngioma. Pituitary hormone profile showed hypogonadotropic hypogonadism, mildly elevated prolactin, increased insulin-like growth factor 1 (IGF-1) and normal thyroid function and cortisol reserve. The patient had transsphenoidal surgery and pathology of the specimen was diagnostic of adamantinomatous craniopharyngioma. Post-operatively, he had diabetes insipidus, hypogonadotropic hypogonadism and adrenocorticotropic hormone and thyroid-stimulating hormone deficiency. Despite the hypopituitarism, his IGF-1 levels remained elevated and subsequent oral glucose tolerance test did not show complete growth hormone (GH) suppression. Further review of the pre-operative imaging revealed a 12 × 4 mm pituitary adenoma close to the right carotid artery and no signs of pituitary hyperplasia. At that time, he was also diagnosed with squamous cell carcinoma of the left upper lung lobe finally managed with radical radiotherapy. Treatment with long-acting somatostatin analogue was initiated leading to biochemical control of the acromegaly. Latest imaging has shown no evidence of craniopharyngioma regrowth and stable adenoma. This is a unique case report of co-existence of craniopharyngioma, acromegaly and squamous lung cell carcinoma that highlights diagnostic and management challenges. Potential effects of the GH hypersecretion on the co-existent tumours of this patient are also briefly discussed. Although an extremely rare clinical scenario, craniopharyngioma and acromegaly can co-exist; aetiopathogenic link between these two conditions is unlikely.Meticulous review of unexpected biochemical findings is vital for correct diagnosis of dual pituitary pathology.The potential adverse impact of GH excess due to acromegaly in a patient with craniopharyngioma (and other neoplasm) mandates adequate biochemical control of the GH hypersecretion.

Prevalence of hypopituitarism after intracranial operations not directly associated with the pituitary gland.

PubMed

Fleck, Steffen Kristian; Wallaschofski, Henri; Rosenstengel, Christian; Matthes, Marc; Kohlmann, Thomas; Nauck, Matthias; Schroeder, Henry Werner Siegfried; Spielhagen, Christin

2013-11-04

Over the last few years, awareness and detection rates of hypopituitarism following traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) has steadily increased. Moreover, recent studies have found that a clinically relevant number of patients develop pituitary insufficiency after intracranial operations and radiation treatment for non-pituitary tumors. But, in a substantial portion of more than 40%, the hypopituitarism already exists before surgery. We sought to determine the frequency, pattern, and severity of endocrine disturbances using basal and advanced dynamic pituitary testing following non-pituitary intracranial procedures. 51 patients (29 women, 22 men) with a mean age of 55 years (range of 20 to 75 years) underwent prospective evaluation of basal parameters and pituitary function testing (combined growth hormone releasing hormone (GHRH)/arginine test, insulin tolerance test (ITT), low dose adrenocorticotropic hormone (ACTH) test), performed 5 to 168 months (median 47.2 months) after intracranial operation (4 patients had additional radiation and 2 patients received additional radiation combined with chemotherapy). We discovered an overall rate of hypopituitarism with distinct magnitude in 64.7% (solitary in 45.1%, multiple in 19.6%, complete in 0%). Adrenocorticotropic hormone insufficiency was found in 51.0% (partial in 41.2%, complete in 9.8%) and growth hormone deficiency (GHD) occurred in 31.4% (partial in 25.5%, severe in 5.9%). Thyrotropic hormone deficiency was not identified. The frequency of hypogonadism was 9.1% in men. Pituitary deficits were associated with operations both in close proximity to the sella turcica and more distant regions (p = 0.91). Age (p = 0.76) and gender (p = 0.24) did not significantly differ across patients with versus those without hormonal deficiencies. Groups did not significantly differ across pathology and operation type (p = 0.07). Hypopituitarism occurs more frequently than expected in patients who have undergone neurosurgical intracranial procedures for conditions other then pituitary tumors or may already exists in a neurosurgical population before surgery. Pituitary function testing and adequate substitution may be warranted for neurosurgical patients with intracranial pathologies at least if unexplained symptoms like fatigue, weakness, altered mental activity, and decreased exercise tolerance are present.

Absence of growth hormone (GH) secretion after the administration of either GH-releasing hormone (GHRH), GH-releasing peptide (GHRP-6), or GHRH plus GHRP-6 in children with neonatal pituitary stalk transection.

PubMed

Pombo, M; Barreiro, J; Peñalva, A; Peino, R; Dieguez, C; Casanueva, F F

1995-11-01

GH-releasing peptide (GHRP-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic compound that releases GH in a specific and dose-related manner through mechanisms and a point of action that are mostly unknown, but different from those of GHRH. In man, GHRP-6 is more efficacious than GHRH, and a striking synergistic action occurs when both compounds are administered together. To explain such a synergistic effect, it has been postulated, but not proven, that GHRP-6 acts through a double mechanism, with actions exerted at the pituitary and the hypothalamic level. On the other hand, patients with the syndrome of GH deficiency due to perinatal pituitary stalk transection have any hypothalamic factor nonoperandi. The aim of the present study was 3-fold: 1) to further understand how relevant, if at all, the hypothalamic action of GHRP-6 is for GH regulation; 2) to evaluate whether GHRP-6 plus GHRH could be a suitable diagnostic tool in children with pituitary stalk transection; and 3) to compare these results with similar published studies performed in patients with hypothalamo-pituitary disconnection, who developed the disease as adults. Seven patients with GH deficiency and different degrees of panhypopituitarism due to perinatal pituitary stalk transection and 7 age- and sex-matched normal controls were studied. The subjects underwent 3 different tests on separate occasions, being challenged with GHRH (1 microgram/kg, iv), GHRP-6 (1 microgram/kg, iv), or GHRH plus GHRP-6. GH was analyzed as the area under the curve (mean +/- SE; micrograms per L/90 min). In normal subjects, GH secretion was 1029 +/- 202 after GHRH treatment, 1221 +/- 345 after GHRP-6, and 3542 +/- 650 after GHRH plus GHRP-6; the latter value was significantly (P < 0.05) higher than the secretion elicited by GHRH or GHRP-6 alone. In the group of patients with perinatal pituitary stalk transection, the level of GH after GHRH treatment was 116 +/- 22 and was even more reduced (P < 0.05) after GHRP-6 treatment (37 +/- 8). After GHRH plus GHRP-6, GH secretion in those patients was 177 +/- 27, significantly higher (P < 0.05) than the secretion induced by either GHRH or GHRP-6 alone. Individually examined, none of the patients tested with the most potent stimulus known to date (GHRH plus GHRP-6) exhibited GH secretion greater than 5 micrograms/L.(ABSTRACT TRUNCATED AT 400 WORDS)

Transsphenoidal pituitary resection with intraoperative MR guidance: preliminary results

NASA Astrophysics Data System (ADS)

Pergolizzi, Richard S., Jr.; Schwartz, Richard B.; Hsu, Liangge; Wong, Terence Z.; Black, Peter M.; Martin, Claudia; Jolesz, Ferenc A.

1999-05-01

The use of intraoperative MR image guidance has the potential to improve the precision, extent and safety of transsphenoidal pituitary resections. At Brigham and Women's Hospital, an open-bore configuration 0.5T MR system (SIGNA SP, GE Medical Systems, Milwaukee, WI) has been used to provide image guidance for nine transsphenoidal pituitary adenoma resections. The intraoperative MR system allowed the radiologist to direct the surgeon toward the sella turcica successfully while avoiding the cavernous sinus, optic chiasm and other sensitive structures. Imaging performed during the surgery monitored the extent of resection and allowed for removal of tumor beyond the surgeon's view in five cases. Dynamic MR imaging was used to distinguish residual tumor from normal gland and postoperative changes permitting more precise tumor localization. A heme-sensitive long TE gradient echo sequence was used to evaluate for the presence of hemorrhagic debris. All patients tolerated the procedure well without significant complications.

Central hypothyroidism and its role for cardiovascular risk factors in hypopituitary patients.

PubMed

Feldt-Rasmussen, Ulla; Klose, Marianne

2016-10-01

Hypothyroidism is characterized by hypometabolism, and may be seen as a part of secondary failure due to pituitary insufficiency or tertiary due to hypothalamic disease. Secondary and tertiary failures are also referred to as central hypothyroidism. Whereas overt primary hypothyroidism has a well-known affection on the heart and cardiovascular system, and may result in cardiac failure, cardiovascular affection is less well recognized in central hypothyroidism. Studies on central hypothyroidism and cardiovascular outcome are few and given the rarity of the diseases often small. Further, there are several limitations given vast difficulties in diagnosing the condition correctly biochemically, and difficulties monitoring the treatment because normal thyroid-pituitary feedback interrelationships are disrupted. The present review summarizes available studies of central adult hypothyroidism and its possible influence on the cardiovascular system, describe differences from primary thyroid failure and seek evidence for performing guidelines for clinical management of this particular thyroid and hypothalamo-pituitary disorder.

Hyperthyroidism due to inappropriate secretion of thyroid-stimulating hormone: diagnosis and management.

PubMed

Hermus, A; Ross, H; van Liessum, P; Naber, A; Smals, A; Kloppenborg, P

1991-06-01

The case histories of three patients with hyperthyroidism due to overproduction of thyroid-stimulating hormone (TSH) by the pituitary gland are described. In the first patient treatment with the T3-metabolite 3,5,3'-triiodothyroacetic acid (TRIAC) led to complete clinical and biochemical normalization. In the second patient treatment with the dopaminergic agonist bromocriptine led to a temporal amelioration of hyperthyroidism. In the third patient, who was the only one with a proven pituitary adenoma, hypersecretion of TSH could be controlled by administration of the somatostatin analogue octreotide. It is emphasized that patients with this disorder should preferably not be treated with thyrostatic drugs, radioactive iodine or thyroid surgery. The success rate of these treatment modalities is lower than normal, they may lead to an increase of goiter size, and they potentially may promote growth or development of a TSH-producing adenoma. Treatment should be aimed at diminishing TSH hypersecretion.

Purinergic signaling pathways in endocrine system.

PubMed

Bjelobaba, Ivana; Janjic, Marija M; Stojilkovic, Stanko S

2015-09-01

Adenosine-5'-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5'-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5'-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5'-triphosphate hydrolysis to adenosine-5'-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. Published by Elsevier B.V.

Purinergic Signaling Pathways in Endocrine System

PubMed Central

Bjelobaba, Ivana; Janjic, Marija M.; Stojilkovic, Stanko S.

2015-01-01

Adenosine-5′-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5′-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5′-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5′-triphosphate hydrolysis to adenosine-5′-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. PMID:25960051

Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system.

PubMed

Budak, Erdal; Fernández Sánchez, Manuel; Bellver, José; Cerveró, Ana; Simón, Carlos; Pellicer, Antonio

2006-06-01

To summarize the effects of novel hormones (leptin, ghrelin, adiponectin, resistin, and PYY3-36) secreted from adipose tissue and the gastrointestinal tract that have been discovered to exert different effects on several reproductive functions, such as the hypothalamic-pituitary-gonadal axis, embryo development, implantation physiology, and clinically relevant conditions. A MEDLINE computer search was performed to identify relevant articles. Leptin and ghrelin exert important roles on body weight regulation, eating behavior, and reproduction, acting on the central nervous system and target reproductive organs. As a marker of adequate nutritional stores, these hormones may act on the central nervous system to initiate the complex process of puberty and maintain normal reproductive function. In addition, leptin and ghrelin and their receptors are involved in reproductive events such as gonadal function, embryo development, and embryo-endometrial interaction. Leptin and ghrelin and other adipose tissue-secreted hormones have significant effects on reproduction. Acting through the brain, these hormones may serve as links between adipose tissue and the reproductive system to supply and regulate energy needs for normal reproduction and pregnancy. Future studies are needed to further clarify the role of these hormones in reproductive events and other related gynecological conditions.

[The interactions of functional systems at the homeostatic level in normal children and adolescents and in a radioecologically unfavorable environment].

PubMed

Glazachev, O S; Sudakov, K V

1999-01-01

In the article theoretical and application development of one of postulates of the Anokhin's theory of functional systems--the principle of multiparametric interaction is attempted in study of singularities of intersystem relationships of a number of leading functional homeostatic systems in a developing adolescent's organism living in radioecological unfavorable conditions and during rehabilitational procedures with application of interval dosed normobaric hypoxia. On the basis of a dynamic research of parameters cardiorespiratory and vegetative-humoral homeostasis is established, that the acclimatization of a children's organism to the factors of ecological and social risk in regions under small doses of radionuclides contamination is exhibited in reorganization of multiparametric relations of functional systems: a) increase of "rigidity" of intrasystem links separate cardiovascular effectors, b) of maximum activation sympathetic, pituitary-adrenal and pituitary-thyroid axes of a system stress-response, c) lack of intersystem consolidation of cardiorespiratory functional systems at a level of useful adaptive results. Thus character of interaction of homeostatic functional systems, their stability depend on personal combination of typological singularities in "the integral constitution" of the child-types of a vegetative regulation, somatic constitution, versions of emotional uneasiness. Principally important that it is revealed the capability of a correction in intersystem relations of homeostatic parameters, in particular, with the use of interval normobaric hypoxia of training (IHT). Hypoxic indorsements rendering the influence first of all through an exterior link of a functional system of breathing is carry on to recovery of integration of functional systems defining a homeostasis for children as at a level useful adaptive results. Thus the role initially high neurohumoral activity in achievement of best values cerebral, peripheral blood flow, lung ventilation is reduced, the contribution of separate effectors to security of physical functionality and aerobic capabilities of a children's organism "is equilibrated".

Inhibin binding protein in rats: alternative transcripts and regulation in the pituitary across the estrous cycle.

PubMed

Bernard, D J; Woodruff, T K

2001-04-01

Inhibin binding protein (InhBP) and the transforming growth factor-beta (TGF beta) type III receptor, beta glycan, have been identified as putative inhibin coreceptors. Here we cloned the InhBP cDNA in rats and predict that it encodes a large membrane-spanning protein that is part of the Ig superfamily, as has been described for humans. Two abundant InhBP transcripts (4.4 and 1.8 kb) were detected in the adult rat pituitary. The larger transcript encodes the full-length protein while the 1.8-kb transcript (InhBP-short or InhBP-S) corresponds to a splice variant of the receptor. This truncated isoform contains only the N-terminal signal peptide and first two (of 12) Ig-like domains observed in the full-length InhBP (InhBP-long or InhBP-L). InhBP-S does not contain a transmembrane domain and is predicted to be a soluble protein. Beta glycan was also detected in the pituitary; however, it was most abundant within the intermediate lobe. Although we also observed beta glycan immunopositive cells in the anterior pituitary, they rarely colocalized with FSH beta-producing cells. We next examined physiological regulation of the coreceptors across the rat estrous cycle. Like circulating inhibin A and inhibin B levels, pituitary InhBP-L and InhBP-S mRNA levels were dynamically regulated across the cycle and were negatively correlated with serum FSH levels. Expression of both forms of InhBP was also positively correlated with serum inhibin B, but not inhibin A, levels. These data are particularly interesting in light of our in vitro observations that InhBP may function as an inhibin B-specific coreceptor. Pituitary beta glycan mRNA levels did not fluctuate across the cycle nor did they correlate with serum FSH. These observations, coupled with its pattern of expression within the pituitary, indicate that beta glycan likely functions as more than merely an inhibin coreceptor within the pituitary. A direct role for InhBP or beta glycan in regulation of pituitary FSH by inhibin in vivo has yet to be determined, but the demonstration of dynamic regulation of pituitary InhBP and its negative relation to serum FSH across the estrous cycle is an important step in this direction.

Rathke's cyst with ectopic neurohypophysis presenting as severe short stature with delayed puberty.

PubMed

Dutta, Deep; Roy, Ajitesh; Ghosh, Sujoy; Mukhopadhyay, Pradip; Dasgupta, Ranen; Mukhopadhyay, Satinath; Chowdhury, Subhankar

2012-12-01

Ectopic neurohypophysis (EN) is found in nearly half of children with growth hormone deficiency (GHD). Rathke's cyst (RC) is uncommon in children and when present, hypopituitarism is found in nearly half of them. We present a fourteen and half-year-old girl with severe short stature and delayed puberty who on evaluation was found to have GHD, secondary hypocortisolism, and hypogonadism. Imaging revealed hypoplastic anterior pituitary, stalk agenesis, EN at tuber cinereum and intrapituitary RC. This is perhaps the first report of simultaneous occurrence of EN and RC, which was seen in a girl with multiple pituitary hormone deficiency. A primary defect in pituitary development may explain this simultaneous occurrence of EN and RC and hence this severe anterior pituitary function deficit.

[Effects of electroacupuncture with branch-foundation acupoint combination on the pituitary-target gland axis in aging rats with yang deficiency].

PubMed

Hao, Qing; Wu, Song; Liu, Jian-min; Wang, Hua

2014-10-01

To observe the effects of electroacupuncture (EA) with branch-foundation acupoint combination on the indices regarding pituitary-target gland axis in aging rats with yang deficiency, so as to explore its regulating mechanism on aging rats with yang deficiency. Forty healthy Sprague-Dawley female rats were randomly divided into a normal control group, a model group, an EA group and an EA control group, 10 rats in each group. Except the normal control group, the rats in the rest 3 groups were all treated with subcutaneous injection of D-galactose for 40 d, followed by intramuscular injection of hydrocortisone for 7 d to establish aging model with yang deficiency. After the successful establishment of model, the EA group was treated with EA at "Guanyuan" (CV 4), "Housanli" (ST 36) and "Baihui "(GV 20) while the EA control group was treated with EA at "Zhongji" (CV 3) "Yinlingquan" (SP 9) and "Yintang" (GV 29); the rats in the normal control group and model group were immobilized and fixed during the same time period. The treatments were given 6 times per week totally for 4 weeks. With radiation immunity analysis method, the 8 biological indices of pituitary-target gland axis, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), tetraiodothyronine-4 (T4), adrenocorticotropic hormone (ACTH), corticosterone (CORT), estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were detected to observe the changes of their content. Compared with the normal control group, the serum level of TSH, T3, T4 and E2 were reduced in the model group (P<0.05, P< 0.01) while those of ACTH, CORT, FSH and LH were increased (P<0.05, P<0.01). Compared with the model group, the serum level of TSH, T3, T4 and E2 were increased in the EA group (P<0.05, P<0.01) while those of ACTH, CORT, FSH and LH were significantly reduced (P<0.05, P<0.01). Compared with the EA control group, the content of TSH was increased in the EA group without statistical significance (P>0.05), that of T3, T4 and E2 was increased (all P<0.05) and that of ACTH, CORT, FSH and LH was significantly reduced (all P<0.05). The electroacupuncture with branch-foundation acupoint combination has benign regulating effects on the key hormones of pituitary-target gland axis, which could effectively improve the dysfunction of pituitary-target gland axis that is caused by aging with yang deficiency; the efficacy of electroacupuncture with branch-foundation acupoint combination is superior to that of adjacent control acupoint combination.

Modulating the pituitary-adrenal response to stress

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.

1975-01-01

Serotonin is believed to be a transmitter or regulator of neuronal function. A possible relationship between the pituitary-adrenal secretion of steroids and brain serotonin in the rat was investigated by evaluating the effects of altering brain 5-hydroxy tryptamine (HT) levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. The approach was either to inhibit brain 5-HT synthesis with para-chlorophenyl alanine or to raise its level with precursors such as tryptophan or 5-hydroxy tryptophan.

Adrenal tuberculosis in Cushing's disease with bilateral macronodular adrenocortical hyperplasia.

PubMed

Kwon, Hyuk-Sang; Kim, Sang-Il; Yoo, Soon-Jib; Yoon, Kun-Ho; Lee, Kwang-Woo; Kang, Moon-Won; Son, Ho-Young; Kang, Sung-Koo; Cha, Bong-Yun

2006-04-01

Cushing's disease is a disorder of hypercortisolism caused by a pituitary micro- or macro-adenoma. Most patients with Cushing's disease have a bilateral adrenal enlargement, which depends on the duration of the disease, as a result of the long standing ACTH stimulation of both adrenal glands. However, in macronodular adrenocortical hyperplasia (MNH) that is caused by Cushing's disease, if the MNH gains autonomy, a bilateral adrenalectomy, as well as the removal of pituitary adenoma, is often essential. We encountered a patient diagnosed with Cushing's disease with bilateral adrenal tuberculosis simulating MNH. She had taken anti-tuberculosis medications one year prior to admission due to spinal tuberculosis. Sellar MRI revealed a pituitary macroadenoma, but adrenal CT showed enlargement in both adrenal glands that appeared to be MNH. A hormonal study and bilateral inferior petrosal sinus sampling revealed Cushing's disease. Therefore, she underwent trans-sphenoidal surgery of the pituitary mass. The pituitary surgery was successful and the serum cortisol returned to normal range. However, the adrenal mass rapidly enlarged after removing the pituitary tumor without showing evidence of a recurrence or adrenal autonomy of hypercortisolism. Accordingly, a laparoscopic left adrenalectomy was performed to examine the nature of the mass. The resected left adrenal gland was pathologically determined to have a lesion of tuberculosis with some part of the intact cortex. So we assumed that the cause of rapid adrenal enlargement might be due to adrenal tuberculosis. In summary, to the best of our knowledge, this is the first case of Cushing's disease coexisting with both adrenal tuberculosis simulating a bilateral MNH.

Dexmedetomidine could enhance surgical satisfaction in Trans-sphenoidal resection of pituitary adenoma.

PubMed

Salimi, Alireza; Sharifi, Guive; Bahrani, Houshang; Mohajerani, Seyed A; Jafari, Alireza; Safari, Farhad; Jalessi, Maryam; Mirkheshti, Alireza; Mottaghi, Kamran

2017-02-01

Excessive bleeding is an unwanted complication of trans-sphenoidal resection of pituitary adenoma due to increases in intracranial pressure (ICP) and hemodynamic instability. Dexmedetomidine (Dex) anα2-agonists is the drug of choice in intensive care units (ICU) and cardiac surgeries to control abrupt changes in hemodynamic. Severe cardiovascular responses occur during trans-sphenoidal resection (TSR) of the pituitary adenoma despite adequate depth of anesthesia. The aim of this paper was to determine the effect of Dexmedetomidine on bleeding as primary outcome, and surgeon's satisfaction and hemodynamic stability as secondary outcomes in patients undergoing trans-sphenoidal resection of pituitary adenoma. Total numbers of 60 patients between 18-65 years old and candidate for elective trans-sphenoidal resection of pituitary adenoma were randomLy allocated to two groups; Dexmedetomidine infusion (0.6µg/kg/hour) or normal saline infusion. Mean arterial pressure (MAP), heart rate (HR), dose of hypnotics and narcotics during surgery, bleeding, and surgeon's satisfaction were recorded. Propofol maintenance dose (µg/kg/min) and total Fentanyl use (µg) were significantly lower in Dex group compare to control group (P=0.01 and 0.003, respectively). Total bleeding amount during operation in Dex group was significantly lower than control group (P=0.012). Surgeon's satisfaction was significantly higher in Dex group at the end of surgery. MAP and heart rate throughout surgery were significantly lower in Dex group compare to control group (P=0.001). Dexmedetomidine infusion (0.6µg/kg/hour) could reduce bleeding and provide surgeon's satisfaction during trans-sphenoidal resection of pituitary adenoma.

Radiofrequency (RF) effects on blood cells, cardiac, endocrine, and immunological functions.

PubMed

Black, David R; Heynick, Louis N

2003-01-01

Effects of radiofrequency electromagnetic fields (RFEMF) on the pituitary adrenocortical (ACTH), growth (GH), and thyroid (TSH) hormones have been extensively studied, and there is coherent research on reproductive hormones (FSH and LH). Those effects which have been identified are clearly caused by heating. The exposure thresholds for these effects in living mammals, including primates, have been established. There is limited evidence that indicates no interaction between RFEMF and the pineal gland or an effect on prolactin from the pituitary gland. Studies of RFEMF exposed blood cells have shown that changes or damage do not occur unless the cells are heated. White cells (leukocytes) are much more sensitive than red cells (erythrocytes) but white cell effects remain consistent with normal physiological responses to systemic temperature fluctuation. Lifetime studies of RFEMF exposed animals show no cumulative adverse effects in their endocrine, hematological, or immune systems. Cardiovascular tissue is not directly affected adversely in the absence of significant RFEMF heating or electric currents. The regulation of blood pressure is not influenced by ultra high frequency (UHF) RFEMF at levels commonly encountered in the use of mobile communication devices. Copyright 2003 Wiley-Liss, Inc.