Sample records for adrenal medullary hyperplasia

  1. Adrenal medullary hyperplasia. Hyperplasia-pheochromocytoma sequence.

    PubMed

    Kurihara, K; Mizuseki, K; Kondo, T; Ohoka, H; Mannami, M; Kawai, K

    1990-09-01

    We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.

  2. Adrenal medullary hyperplasia is a precursor lesion for pheochromocytoma in MEN2 syndrome.

    PubMed

    Korpershoek, Esther; Petri, Bart-Jeroen; Post, Edward; van Eijck, Casper H J; Oldenburg, Rogier A; Belt, Eric J T; de Herder, Wouter W; de Krijger, Ronald R; Dinjens, Winand N M

    2014-10-01

    Adrenal medullary hyperplasias (AMHs) are adrenal medullary proliferations with a size < 1 cm, while larger lesions are considered as pheochromocytoma (PCC). This arbitrary distinction has been proposed decades ago, although the biological relationship between AMH and PCC has never been investigated. Both lesions are frequently diagnosed in multiple endocrine neoplasia type 2 (MEN2) patients in whom they are considered as two unrelated clinical entities. In this study, we investigated the molecular relationship between AMH and PCC in MEN2 patients. Molecular aberrations of 19 AMHs and 13 PCCs from 18 MEN2 patients were determined by rearranged during transfection (RET) proto-oncogene mutation analysis and loss of heterozygosity (LOH) analysis for chromosomal regions 1p13, 1p36, 3p, and 3q, genomic areas covering commonly altered regions in RET-related PCC. Identical molecular aberrations were found in all AMHs and PCCs, at similar frequencies. LOH was seen for chromosomes 1p13 in 8 of 18 (44%), 1p36 in 9 of 15 (60%), 3p12-13 in 12 of 18 (67%), and 3q23-24 in 10 of 16 (63%) of AMHs, and for chromosome 1p13 in 13 of 13 (100%), 1p36 in 7 of 11 (64%), 3p12-13 in 4 of 11 (36%), and 3q23-24 in 11 of 12 (92%) of PCCs. Our results indicate that AMHs are not hyperplasias and, in clinical practice, should be regarded as PCCs, which has an impact on diagnosis and treatment of MEN2 patients. We therefore propose to replace the term AMH by micro-PCC to indicate adrenal medullary proliferations of less than 1 cm.

  3. Frequency of Cushing's syndrome due to ACTH-secreting adrenal medullary lesions: a retrospective study over 10 years from a single center.

    PubMed

    Falhammar, Henrik; Calissendorff, Jan; Höybye, Charlotte

    2017-01-01

    Cushing's syndrome due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions has occasionally been described. We retrospectively reviewed all 164 cases of Cushing's syndrome and 77 cases of pheochromocytomas during 10 years. Of all cases with Cushing's syndrome, only two cases (1.2 %) were due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions (one case of pheochromocytoma and one case of adrenal medullary hyperplasia). Of all pheochromocytomas only the above-mentioned case (1.3 %) also gave rise to an ectopic adrenocorticotropic hormone syndrome. The clinical presentation of adrenocorticotropic hormone-secreting pheochromocytoma and adrenal medullary hyperplasia can be anything from mild to dramatic. These are rare conditions important to bear in mind in the workup of a patient with Cushing's syndrome or with pheochromocytoma. The identification of ectopic adrenocorticotropic hormone secretion from adrenal medullary lesions can be life-saving.

  4. Management of adolescents with congenital adrenal hyperplasia

    PubMed Central

    Merke, Deborah P; Poppas, Dix P

    2014-01-01

    The management of congenital adrenal hyperplasia involves suppression of adrenal androgen production, in addition to treatment of adrenal insufficiency. Management of adolescents with congenital adrenal hyperplasia is especially challenging because changes in the hormonal milieu during puberty can lead to inadequate suppression of adrenal androgens, psychosocial issues often affect adherence to medical therapy, and sexual function plays a major part in adolescence and young adulthood. For these reasons, treatment regimen reassessment is indicated during adolescence. Patients with non-classic congenital adrenal hyperplasia require reassessment regarding the need for glucocorticoid drug treatment. No clinical trials have compared various regimens for classic congenital adrenal hyperplasia in adults, thus therapy is individualised and based on the prevention of adverse outcomes. Extensive patient education is key during transition from paediatric care to adult care and should include education of females with classic congenital adrenal hyperplasia regarding their genital anatomy and surgical history. Common issues for these patients include urinary incontinence, vaginal stenosis, clitoral pain, and cosmetic concerns; for males with classic congenital adrenal hyperplasia, common issues include testicular adrenal rest tumours. Transition from paediatric to adult care is most successful when phased over many years. Education of health-care providers on how to successfully transition patients is greatly needed. PMID:24622419

  5. Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia.

    PubMed

    Louiset, Estelle; Duparc, Céline; Young, Jacques; Renouf, Sylvie; Tetsi Nomigni, Milène; Boutelet, Isabelle; Libé, Rossella; Bram, Zakariae; Groussin, Lionel; Caron, Philippe; Tabarin, Antoine; Grunenberger, Fabienne; Christin-Maitre, Sophie; Bertagna, Xavier; Kuhn, Jean-Marc; Anouar, Youssef; Bertherat, Jérôme; Lefebvre, Hervé

    2013-11-28

    Bilateral macronodular adrenal hyperplasia is a rare cause of primary adrenal Cushing's syndrome. In this form of hyperplasia, hypersecretion of cortisol suppresses the release of corticotropin by pituitary corticotrophs, which results in low plasma corticotropin levels. Thus, the disease has been termed corticotropin-independent macronodular adrenal hyperplasia. We examined the abnormal production of corticotropin in these hyperplastic adrenal glands. We obtained specimens of hyperplastic macronodular adrenal tissue from 30 patients with primary adrenal disease. The corticotropin precursor proopiomelanocortin and corticotropin expression were assessed by means of a polymerase-chain-reaction assay and immunohistochemical analysis. The production of corticotropin and cortisol was assessed in 11 specimens with the use of incubated explants and cell cultures coupled with hormone assays. Corticotropin levels were measured in adrenal and peripheral venous blood samples from 2 patients. The expression of proopiomelanocortin messenger RNA (mRNA) was detected in all samples of hyperplastic adrenal tissue. Corticotropin was detected in steroidogenic cells arranged in clusters that were disseminated throughout the adrenal specimens. Adrenal corticotropin levels were higher in adrenal venous blood samples than in peripheral venous samples, a finding that was consistent with local production of the peptide within the hyperplastic adrenals. The release of adrenal corticotropin was stimulated by ligands of aberrant membrane receptors but not by corticotropin-releasing hormone or dexamethasone. A semiquantitative score for corticotropin immunostaining in the samples correlated with basal plasma cortisol levels. Corticotropin-receptor antagonists significantly inhibited in vitro cortisol secretion. Cortisol secretion by the adrenals in patients with macronodular hyperplasia and Cushing's syndrome appears to be regulated by corticotropin, which is produced by a subpopulation of

  6. Effect of Space Flight on Adrenal Medullary Function

    NASA Technical Reports Server (NTRS)

    Lelkes, Peter I.

    1999-01-01

    We hypothesize that microgravity conditions during space flight alter the expression and specific activities of the adrenal medullary CA synthesizing enzymes (CASE). Previously, we examined adrenals from six rats flown for six days aboard STS 54 and reported that microgravity induced a decrease in the expression and specific activity of rat adrenal medullary tyrosine hydroxylase, the rate limiting enzyme of CA synthesis, without affecting the expression of other CASE. In the past, we analyzed some of the > 300 adrenals from two previous Space Shuttle missions (PARE 03 and SLS 2). The preliminary results (a) attest to the good state of tissue preservation, thus proving the feasibility of subsequent large-scale evaluation, and (b) confirm and extend our previous findings. With this grant we will be able to expeditiously analyze all our specimens and to complete our studies in a timely fashion.

  7. Congenital adrenal hyperplasia

    MedlinePlus

    ... body produces more androgen, a type of male sex hormone. This causes male characteristics to appear early (or inappropriately). Congenital adrenal hyperplasia can affect both boys and girls. About 1 in 10,000 to ...

  8. [Primary hyperaldosteronism due to unilateral adrenal hyperplasia with surgical resolution].

    PubMed

    Rubio-Puchol, O; Garzón-Pastor, S; Salom-Vendrell, C; Hernández-Mijares, A

    Unilateral adrenal hyperplasia is a rare cause of primary hyperaldosteronism (around a 3%) that has surgical treatment. A case of a patient with hypertension resistant to conventional therapy in treatment with 7 drugs who presented with primary hyperaldosteronism due to unilateral adrenal hyperplasia is presented. A left adrenalectomy was performed, and the patient had a good clinical response, with no need of any drug after 2 years of surgery. Unilateral adrenal hyperplasia is a different entity and it is not an asymmetric variant of the bilateral adrenal hyperplasia. In the study of patients with primary hyperaldosteronism and imaging tests with absence of adenoma is a diagnosis that must be considered before cataloguing patients with bilateral adrenal hyperplasia and start a medical treatment, because unilateral adrenal hyperplasia would have a surgical resolution. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Adrenomegaly and septic adrenal hemorrhage (Waterhouse-Friderichsen syndrome) in the setting of congenital adrenal hyperplasia.

    PubMed

    Saad, Amin F; Ford, Kenneth L; Deprisco, Gregory; Smerud, Michael J

    2013-07-01

    Congenital adrenal hyperplasia refers to a spectrum of autosomal recessive inherited disorders of steroidogenesis most commonly identified on newborn screenings. We describe a young woman who presented with abdominal pain and on subsequent imaging was found to have features of congenital adrenal hyperplasia. Imaging findings, treatment, and potential complications are discussed.

  10. Adrenomegaly and septic adrenal hemorrhage (Waterhouse-Friderichsen syndrome) in the setting of congenital adrenal hyperplasia

    PubMed Central

    Ford, Kenneth L.; dePrisco, Gregory; Smerud, Michael J.

    2013-01-01

    Congenital adrenal hyperplasia refers to a spectrum of autosomal recessive inherited disorders of steroidogenesis most commonly identified on newborn screenings. We describe a young woman who presented with abdominal pain and on subsequent imaging was found to have features of congenital adrenal hyperplasia. Imaging findings, treatment, and potential complications are discussed. PMID:23814386

  11. Nonclassic Congenital Adrenal Hyperplasia

    PubMed Central

    Witchel, Selma Feldman; Azziz, Ricardo

    2010-01-01

    Nonclassic congenital adrenal hyperplasia (NCAH) due to P450c21 (21-hydroxylase deficiency) is a common autosomal recessive disorder. This disorder is due to mutations in the CYP21A2 gene which is located at chromosome 6p21. The clinical features predominantly reflect androgen excess rather than adrenal insufficiency leading to an ascertainment bias favoring diagnosis in females. Treatment goals include normal linear growth velocity and “on-time” puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and fertility. This paper will review key aspects regarding pathophysiology, diagnosis, and treatment of NCAH. PMID:20671993

  12. Decreased adrenal medullary tyrosine hydroxylase mRNA in DMBA (7,12-dimethylbenz(a)anthracene)-induced mammary carcinoma

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

    Bunce, O.R.; Badary, O.A.; Abou El-Ela, S.

    1991-03-15

    Adrenal cortical hormones suppress initiation and promotion of DMBA-induced mammary tumorigenesis. The authors found a positive correlation between presence of DMBA-induced adrenal cortical necrosis and mammary tumor incidence. Because they find adrenal medullary as well as cortical lesions in tumor bearing (TB) DMBA-treated rats, they evaluated medullary function by quantitating hybridized cDNA- TH-S{sup 35} with in situ TH-mRNA u sing computer assisted quantitative autoradiographic technique. Virgin female Sprague-Dawley rats were given a 10 mg i.g. dose of DMBA. Three wks later, rats were placed on 20% polyunsaturated (PUFA) fat diets containing omega-6 and omega-3 fatty acids. All were killed 15more » wks post-DMBA. TH-mRNA levels in adrenal medullae of TB animals were decreased compared to non-TB rats. Histopathology indicated a high incidence of medullary necrosis in TB rats, whereas, adrenal necrosis did not occur in non-TB animals. Adrenal necrosis correlated positively with tumor burden, but no correlation was found between incidence of adrenal lesions and type of PUFA in the diet. The authors suggest that DMBA adrenal necrosis may reduce TH-mRNA in the medulla, compromise its catecholamine synthetic capability, and thereby contribute to the overall metabolic stress condition of TB rats.« less

  13. Morphometric study of the avian adrenal gland.

    PubMed Central

    Aire, T A

    1980-01-01

    The interrenal and medullary cords as well as the blood vessels and connective tissue proportions in the adrenal glands of the male Nigerian fowl (Gallus domesticus) and guinea-fowl (Numida meleagris) were studied by microstereological techniques. Laying domestic fowl of the Rhode Island Red breed were entirely defeathered and maintained in a hot, humid pen for a period of three months, after which the adrenal glands were also studied microstereologically. Interrenal cord width was also measured in all the birds studied. The interrenal cords of the subscapular zone were consistently wider than those cords in the inner zone of the adrenal glands. This clearly suggested morphological zoning. The proportion of interrenal tissue was significantly greater in the guinea-fowl than in the Nigerian fowl, but the medullary tissue and the blood vessels and connective tissue were not significantly different. Interrenal hypoplasia or medullary hyperplasia occurred in the defeathered Rhode Island Red fowl as compared to the control birds of the same breed and sex. The significance of these findings is discussed. PMID:7440402

  14. Early Hormonal Influences on Cognitive Functioning in Congenital Adrenal Hyperplasia.

    ERIC Educational Resources Information Center

    Resnick, Susan M.; And Others

    1986-01-01

    Reports the results of cognitive test performance and early childhood activities in individuals with congenital adrenal hyperplasia, an autosomal recessive disorder associated with elevated prenatal adrenal androgen levels, demonstrating the effects of early exposure to excess androgenizing hormones on sexually dimorphic cognitive functioning.…

  15. Prenatal Diagnosis of Congenital Adrenal Hyperplasia.

    PubMed

    Yau, Mabel; Khattab, Ahmed; New, Maria I

    2016-06-01

    Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is a monogenic disorder of adrenal steroidogenesis. To prevent genital ambiguity, in girls, prenatal dexamethasone treatment is administered early in the first trimester. Prenatal genetic diagnosis of CAH and fetal sex determination identify affected female fetuses at risk for genital virilization. Advancements in prenatal diagnosis are owing to improved understanding of the genetic basis of CAH and improved technology. Cloning of the CYP21A2 gene ushered in molecular genetic analysis as the current standard of care. Noninvasive prenatal diagnosis allows for targeted treatment and avoids unnecessary treatment of males and unaffected females. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Classic congenital adrenal hyperplasia and puberty.

    PubMed

    Charmandari, Evangelia; Brook, Charles G D; Hindmarsh, Peter C

    2004-11-01

    Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders resulting from deficiency of one of the five enzymes required for synthesis of cortisol in the adrenal cortex. The most common form of the disease is classic 21-hydroxylase deficiency, which is characterized by decreased synthesis of glucocorticoids and often mineralocorticoids, adrenal hyperandrogenism and impaired development and function of the adrenal medulla. The clinical management of classic 21-hydroxylase deficiency is often suboptimal, and patients are at risk of developing in tandem iatrogenic hypercortisolism and/or hyperandogenism. Limitations of current medical therapy include the inability to control hyperandrogenism without employing supraphysiologic doses of glucocorticoid, hyperresponsiveness of the hypertrophied adrenal glands to adrenocorticotropic hormone (ACTH) and difficulty in suppressing ACTH secretion from the anterior pituitary. Puberty imposes increased difficulty in attaining adrenocortical suppression despite optimal substitution therapy and adherence to medical treatment. Alterations in the endocrine milieu at puberty may influence cortisol pharmacokinetics and, consequently, the handling of hydrocortisone used as replacement therapy. Recent studies have demonstrated a significant increase in cortisol clearance at puberty and a shorter half-life of free cortisol in pubertal females compared with males. Furthermore, children with classic CAH have elevated fasting serum insulin concentrations and insulin resistance. The latter may further enhance adrenal and/or ovarian androgen secretion, decrease the therapeutic efficacy of glucocorticoids and contribute to later development of the metabolic syndrome and its complications.

  17. A Case of a Composite Adrenal Medullary Tumor of Pheochromocytoma and Ganglioneuroma Masquerading as Acute Pancreatitis

    PubMed Central

    Choi, Eun-Kyoung; Kim, Wan-Ho

    2006-01-01

    Composite adrenal medullary tumors, composed of both pheochromocytoma and ganglioneuroma, are extremely rare, as are pheochromocytomas masquerading as acute relapsing pancreatitis. We recently experienced a case of a 48-year-old male with both these phenomena. The patient complained of an acute onset of intense abdominal discomfort. At the same time, pancreatic enzymes were increased in concentration. An abdominal computed tomographic scan revealed an enlarged pancreas and a 3-cm left adrenal incidentaloma. Biochemical and 131I-MIBG scintigraphic findings were compatible with a pheochromocytoma. Yet, he had no clinical manifestations suggesting pheochromocytoma. An adrenalectomy was performed and a composite adrenal medullary tumor of pheochromocytoma and ganglioneuroma was confirmed during a pathologic examination. This case illustrates two points: 1) acute abdominal intense discomfort and hyperamylasemia may be unusual presentations of pheochromocytomas; and 2) the possibility of the pheochromocytoma, albeit rare, should be considered when a relapsing pancreatitis of uncertain etiology develops. PMID:16913447

  18. Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats: effects on cardiovascular parameters

    PubMed Central

    Trevenzoli, I H; Valle, M M R; Machado, F B; Garcia, R M G; Passos, M C F; Lisboa, P C; Moura, E G

    2007-01-01

    Epidemiological studies have shown a strong correlation between stressful events (nutritional, hormonal or environmental) in early life and development of adult diseases such as obesity, diabetes and cardiovascular failure. It is known that gestation and lactation are crucial periods for healthy growth in mammals and that the sympathoadrenal system is markedly influenced by environmental conditions during these periods. We previously demonstrated that neonatal hyperleptinaemia in rats programmes higher body weight, higher food intake and hypothalamic leptin resistance in adulthood. Using this model of programming, we investigated adrenal medullary function and effects on cardiovascular parameters in male rats in adulthood. Leptin treatment during the first 10 days of lactation (8μg 100 g−1 day−1, s.c.) resulted in lower body weight (6.5%, P < 0.05), hyperleptinaemia (10-fold, P < 0.05) and higher catecholamine content in adrenal glands (18.5%, P < 0.05) on the last day of treatment. In adulthood (150 days), the rats presented higher body weight (5%, P < 0.05), adrenal catecholamine content (3-fold, P < 0.05), tyrosine hydroxylase expression (35%, P < 0.05) and basal and caffeine-stimulated catecholamine release (53% and 100%, respectively, P < 0.05). Systolic blood pressure and heart rate were also higher in adult rats (7% and 6%, respectively, P < 0.05). Our results show that hyperleptinaemia in early life increases adrenal medullary function in adulthood and that this may alter cardiovascular parameters. Thus, we suggest that imprinting factors which increase leptin and catecholamine levels during the neonatal period could be involved in development of adult chronic diseases. PMID:17218354

  19. Mistaken gender identity in non-classical congenital adrenal hyperplasia.

    PubMed

    Kukreti, Prerna; Kandpal, Manish; Jiloha, R C

    2014-04-01

    Gender identity is the sense of belonging that one feels for a particular sex psychologically and socially, independent of one's biological sex. There is much less systematic data on gender identity in females with congenital adrenal hyperplasia (CAH). We report a case of non-classical CAH presenting as a case of gender identity disorder.

  20. Mistaken gender identity in non-classical congenital adrenal hyperplasia

    PubMed Central

    Kukreti, Prerna; Kandpal, Manish; Jiloha, R. C.

    2014-01-01

    Gender identity is the sense of belonging that one feels for a particular sex psychologically and socially, independent of one's biological sex. There is much less systematic data on gender identity in females with congenital adrenal hyperplasia (CAH). We report a case of non-classical CAH presenting as a case of gender identity disorder. PMID:24891708

  1. 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.

  2. Diagnosis and management of classical congenital adrenal hyperplasia.

    PubMed

    Marumudi, Eunice; Khadgawat, Rajesh; Surana, Vineet; Shabir, Iram; Joseph, Angela; Ammini, Ariachery C

    2013-08-01

    Congenital adrenal hyperplasia (CAH) is among the most common genetic disorders. Deficiency of adrenal steroid 21-hydroxylase deficiency due to mutations in the CYP21A2 gene accounts for about 95% cases of CAH. This disorder manifests with androgen excess with or without salt wasting. It also is a potentially life threatening disorder; neonatal screening with 17-hydroxyprogesterone measurement can diagnose the condition in asymptomatic children. Carefully monitored therapy with glucocorticoid and mineralocorticoid supplementation will ensure optimal growth and development for children with CAH. Genital surgery may be required for girls with CAH. Continued care is required for individuals with CAH as adults to prevent long-term adverse consequences of the disease, including infertility, metabolic syndrome and osteoporosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Sonographic Appearance of Testicular Adrenal Rest Tumour in a Patient with Congenital Adrenal Hyperplasia.

    PubMed

    Deshpande, Saurabh S; Shetty, Devdas; Saifi, Shenaz

    2017-01-01

    Testicular adrenal rest tumours (TARTs) are benign testicular masses that are found in inadequately treated patients with congenital adrenal hyperplasia (CAH). Recognizing this association and identifying characteristic ultrasound features of TARTs is important so as to avoid misdiagnosing them as malignancies, which can lead to unnecessary interventions. We describe a case of a 9-year-old boy, with a diagnosis of CAH and precocious puberty, who was referred to our department for an ultrasound evaluation of the abdomen and scrotum. On ultrasound, there were well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses in both testes. Taking into account the presence of CAH and a typical sonographic appearance of bilateral testicular masses, a diagnosis of testicular adrenal rest tumour was made; biopsy was deferred and hormonal treatment was modified. Prompt diagnosis of testicular adrenal rest tumours is essential, as it only indicates inadequate hormonal control. Moreover, it can prevent unnecessary biopsies and orchidectomies, and can maintain fertility. TARTs have a typical imaging appearance that every radiologist must be aware of.

  4. Sonographic Appearance of Testicular Adrenal Rest Tumour in a Patient with Congenital Adrenal Hyperplasia

    PubMed Central

    Shetty, Devdas; Saifi, Shenaz

    2017-01-01

    Summary Background Testicular adrenal rest tumours (TARTs) are benign testicular masses that are found in inadequately treated patients with congenital adrenal hyperplasia (CAH). Recognizing this association and identifying characteristic ultrasound features of TARTs is important so as to avoid misdiagnosing them as malignancies, which can lead to unnecessary interventions. Case Report We describe a case of a 9-year-old boy, with a diagnosis of CAH and precocious puberty, who was referred to our department for an ultrasound evaluation of the abdomen and scrotum. On ultrasound, there were well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses in both testes. Taking into account the presence of CAH and a typical sonographic appearance of bilateral testicular masses, a diagnosis of testicular adrenal rest tumour was made; biopsy was deferred and hormonal treatment was modified. Conclusions Prompt diagnosis of testicular adrenal rest tumours is essential, as it only indicates inadequate hormonal control. Moreover, it can prevent unnecessary biopsies and orchidectomies, and can maintain fertility. TARTs have a typical imaging appearance that every radiologist must be aware of. PMID:29662583

  5. 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

  6. Congenital Adrenal Hyperplasia: Unresolved Issues.

    PubMed

    Yau, Mabel; Khattab, Ahmed; Poppas, Dix; Ghizzoni, Lucia; New, Maria

    2016-01-01

    Congenital adrenal hyperplasia (CAH) describes a family of disorders that comes from enzymatic deficiencies in cortisol production, with 21-hydroxylase deficiency causing ∼90% of cases. Distinction is made between the severe classical form and milder nonclassical form of CAH. Molecular genetic analysis is used to confirm the hormonal diagnosis. A high rate of genotype-phenotype disconcordance has been found in 21-hydroxylase deficiency. The goal of treatment is to replace with synthetic glucocorticoids and mineralocorticoids and suppress adrenal androgen production. The treatment of patients affected with nonclassical CAH, particularly males, remains controversial. Variable synthetic glucocorticoids are used and new modes of glucocorticoid delivery are under investigation. To improve height, growth hormone and other adjuvant therapies are employed. Long-term outcomes of genital surgery using modern techniques in females affected with classical CAH continue to be investigated. Prenatal treatment with dexamethasone is available to avoid ambiguous genitalia in these females. Although studies have shown its safety to mother and fetus, prenatal treatment is still regarded as experimental. Currently, prenatal diagnosis of CAH can only be obtained through invasive methods. Recently, the detection of cell-free fetal DNA in maternal plasma has made it possible to make this diagnosis earlier and noninvasively. © 2016 S. Karger AG, Basel.

  7. Clinical and molecular profile of newborns with confirmed or suspicious congenital adrenal hyperplasia detected after a public screening program implementation.

    PubMed

    Kopacek, Cristiane; Prado, Mayara J; da Silva, Claudia M D; de Castro, Simone M; Beltrão, Luciana A; Vargas, Paula R; Grandi, Tarciana; Rossetti, Maria L R; Spritzer, Poli Mara

    2018-04-30

    To describe the results obtained in a neonatal screening program after its implementation and to assess the clinical and molecular profiles of confirmed and suspicious congenital adrenal hyperplasia cases. A cross-sectional study was conducted. Newborns with suspected disease due to high 17-hydroxyprogesterone levels and adjusted for birth weight were selected. Classical congenital adrenal hyperplasia (salt-wasting and simple virilizing forms) was diagnosed by an increase in 17-hydroxyprogesterone levels as confirmed in the retest, clinical evaluation, and genotype determined by SNaPshot and multiplex ligation-dependent probe amplification. After 24 months, 15 classic congenital adrenal hyperplasia cases were diagnosed in a total of 217,965 newborns, with an estimated incidence of 1:14,531. From 132 patients, seven non-classical and 14 heterozygous patients were screened for CYP21A2 mutations, and 96 patients presented false positives with wild type CYP21A2. On retest, increased 17-hydroxyprogesterone levels were found in classical congenital adrenal hyperplasia patients and showed significant correlation with genotype-related classical genital adrenal hyperplasia. The most frequent mutations were IVS2-13A/C>G followed by gene deletion or rearrangement events in the classical form. In non-classical and heterozygous diseases, p.Val282Leu was the most common mutation. The results underscore the effectiveness of congenital adrenal hyperplasia neonatal screening in the public health system and indicate that the adopted strategy was appropriate. The second sample collection along with genotyping of suspected cases helped to properly diagnose both severe and milder cases and delineate them from false positive patients. Copyright © 2018. Published by Elsevier Editora Ltda.

  8. Fetal endocrine therapy for congenital adrenal hyperplasia should not be done.

    PubMed

    Miller, Walter L

    2015-06-01

    Prenatal treatment of congenital adrenal hyperplasia by administering dexamethasone to a woman presumed to be carrying an at-risk fetus remains a controversial experimental treatment. Review of data from animal experimentation and human trials indicates that dexamethasone cannot be considered safe for the fetus. In animals, prenatal dexamethasone decreases birth weight, affects renal, pancreatic beta cell and brain development, increases anxiety and predisposes to adult hypertension and hyperglycemia. In human studies, prenatal dexamethasone is associated with orofacial clefts, decreased birth weight, poorer verbal working memory, and poorer self-perception of scholastic and social competence. Numerous medical societies have cautioned that prenatal treatment of adrenal hyperplasia with dexamethasone is not appropriate for routine clinical practice and should only be done in Institutional Review Board approved, prospective clinical research settings with written informed consent. The data indicate that this treatment is inconsistent with the classic medical ethical maxim to 'first do no harm'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. 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.

  10. Parental management of adrenal crisis in children with congenital adrenal hyperplasia

    PubMed Central

    Fleming, Louise; Knafl, Kathleen; Knafl, George; Van Riper, Marcia

    2018-01-01

    Purpose Congenital adrenal hyperplasia (CAH) requires parents to inject their child with hydro-cortisone intramuscularly during times of illness and adrenal crisis. The purpose of this study was to describe circumstances surrounding adrenal crisis events in children with CAH; to explore parents’ perceptions of the consequences of having a child with a life-threatening condition; and to examine a relationship between parents’ perceived management ability and the impact CAH has on the family. Methods In Phase 1 of this mixed-methods, cross-sectional study, 77 parents were asked to complete questionnaires comprising measures of family life in the context of childhood illness. Descriptive statistics were computed with four separate analyses using linear mixed models allowing for correlation between responses from parents of the same family and for the variance to be different for fathers and mothers. The following relationships were examined: (1) parental management ability and type of provider instruction on how to manage adrenal crises; (2) parental management ability and child age; (3) the perceived impact of the condition on the family and management ability; and (4) the age of the child and number of adrenal crisis events. In Phase 2, 16 semi-structured interviews were conducted to elicit detailed descriptions of parents’ experiences in managing crises. Results There was a significant, positive relationship between detailed provider instruction to parents on adrenal crisis management and perceived management ability (p = .02), additionally the stronger the perceived management ability, the less impact CAH had on the family (p < .001). From birth to age 5, parents reported more frequent crisis events and less perceived ability to manage the condition when compared with parents of older children (p = .009). The threat of an adrenal crisis event is a pervasive concern for parents, especially when they are not being properly prepared by providers. Practice

  11. Parental management of adrenal crisis in children with congenital adrenal hyperplasia.

    PubMed

    Fleming, Louise; Knafl, Kathleen; Knafl, George; Van Riper, Marcia

    2017-10-01

    Congenital adrenal hyperplasia (CAH) requires parents to inject their child with hydrocortisone intramuscularly during times of illness and adrenal crisis. The purpose of this study was to describe circumstances surrounding adrenal crisis events in children with CAH; to explore parents' perceptions of the consequences of having a child with a life-threatening condition; and to examine a relationship between parents' perceived management ability and the impact CAH has on the family. In Phase 1 of this mixed-methods, cross-sectional study, 77 parents were asked to complete questionnaires comprising measures of family life in the context of childhood illness. Descriptive statistics were computed with four separate analyses using linear mixed models allowing for correlation between responses from parents of the same family and for the variance to be different for fathers and mothers. The following relationships were examined: (1) parental management ability and type of provider instruction on how to manage adrenal crises; (2) parental management ability and child age; (3) the perceived impact of the condition on the family and management ability; and (4) the age of the child and number of adrenal crisis events. In Phase 2, 16 semi-structured interviews were conducted to elicit detailed descriptions of parents' experiences in managing crises. There was a significant, positive relationship between detailed provider instruction to parents on adrenal crisis management and perceived management ability (p = .02), additionally the stronger the perceived management ability, the less impact CAH had on the family (p < .001). From birth to age 5, parents reported more frequent crisis events and less perceived ability to manage the condition when compared with parents of older children (p = .009). The threat of an adrenal crisis event is a pervasive concern for parents, especially when they are not being properly prepared by providers. Provider support is needed for these parents

  12. Early diagnosis of salt-losing congenital adrenal hyperplasia in a newborn boy.

    PubMed Central

    Hughes, I. A.; Winter, J. S.

    1977-01-01

    Assays of serum 17-hydroxyprogesterone concentration may be relied upon to establish a diagnosis of congenital adrenal hyperplasia within a few hours of birth. In a male infant the concentration of 17-hydroxyprogesterone was increased in cord serum and remained elevated until glucocorticoid therapy was started on the 5th day of life. Plasma renin activity was increased only slightly in the first few days, but a striking increase on day 5, along with a gradual increase in the serum potassium concentration, confirmed that the infant had the salt-losing form of congenital adrenal hyperplasia. It was not possible to demonstrate an increased concentration of 17-hydroxyprogesterone, in amniotic fluid obtained at 30 weeks' gestation, presumably because of interference in this assay by cross-reacting steroids. Studies of the mother's serum concentration of 17-hydroxyprogesterone and cortisol during delivery did not disclose any deviation from normal. PMID:890632

  13. Feminising genitoplasty: one-stage genital reconstruction in congenital adrenal hyperplasia: 30 years' experience.

    PubMed

    Roll, M F; Kneppo, C; Roth, H; Bettendorf, M; Waag, K-L; Holland-Cunz, S

    2006-10-01

    The study objective is to evaluate the results of our surgical technique for children with congenital adrenal hyperplasia and ambiguous genitalia at the University Hospital of Heidelberg, Department of Paediatric Surgery. The records of 19 patients with congenital adrenal hyperplasia treated between 1972 and 2004 were reviewed with respect to age at surgery, operative procedures and outcome. We describe the recession clitoroplasty technique currently used in our hospital and highlight the importance of short and long-term follow-up results with respect to appearance, position and size of the clitoris and quality of the vagina. One-stage recession clitoroplasty and vaginoplasty gives very satisfactory cosmetic and functional results, with few complications and a reduced need for secondary surgical interventions. The results of this study support the assumption that total correction can be achieved through a single-stage operation, performed in infancy.

  14. Receptor stimulated formation of inositol phosphates in cultures of bovine adrenal medullary cells: the effects of bradykinin, bombesin and neurotensin.

    PubMed

    Bunn, S J; Marley, P D; Livett, B G

    1990-04-01

    The ability of a number of drugs and neuropeptides to stimulate phosphoinositide metabolism in cultured bovine adrenal medullary cells has been assessed. Low concentrations (10 nM) of angiotensin II, bradykinin, histamine, arginine-vasopressin, and bombesin, and high (10 microM) concentrations of oxytocin, prostaglandins E1, and E2, beta-endorphin, and neurotensin stimulated significant accumulation of [3H]inositol phosphates in adrenal medullary cells preloaded with [3H)]inositol. Bradykinin stimulated a significant response at concentration as low as 10pM, with an EC50 of approximately 0.5 nM. The response was markedly inhibited by the bradykinin B2 antagonist [Thi5,8,D-Phe7] bradykinin but not the B1 antagonist [Des-Arg9,Leu8] bradykinin. Higher concentrations of bombesin and neurotensin were required to elicit a response (10 nM and 10 microM respectively). The bombesin response was sensitive to inhibition by the bombesin antagonist [D-Arg1,D-Pro2,D-Trp7,9Leu11]-substance P. In contrast, the neurotensin response was not reduced by the NT1 antagonist [D-Trp11]-neurotensin. These results indicate there are a number of agents that can stimulate phosphatidylinositide hydrolysis in the adrenal medullary cells by acting on different classes of receptors. Such a range of diverse agonists that stimulate inositol phosphate formation will facilitate further analysis of the phosphatidylinositide breakdown in chromaffin cell function.

  15. Congenital adrenal hyperplasia with localized aggressive periodontitis and amelogenesis imperfecta.

    PubMed

    Ajlan, Sumaiah Abdulbaqi

    2015-11-01

    Congenital adrenal hyperplasia (CAH) is an inherited medical condition that implies defects in steroid biosynthesis. The dental findings of a female patient with CAH are reported. The patient suffered from severe periodontal tissue destruction, obvious enamel defects, as well as some occlusal problems. The management approach is presented and the possibility of interrelation of her dental findings with her medical condition is discussed. © 2015 Japanese Teratology Society.

  16. Magnetic Resonance Imaging of the Vocal Folds in Women with Congenital Adrenal Hyperplasia and Virilized Voices

    ERIC Educational Resources Information Center

    Nygren, Ulrika; Isberg, Bengt; Arver, Stefan; Hertegård, Stellan; Södersten, Maria; Nordenskjöld, Agneta

    2016-01-01

    Purpose: Women with congenital adrenal hyperplasia (CAH) may develop a virilized voice due to late diagnosis or suboptimal suppression of adrenal androgens. Changes in the vocal folds due to virilization have not been studied in vivo. The purpose was to investigate if the thyroarytenoid (TA) muscle is affected by virilization and correlate…

  17. [Medullary layer activity of the rat adrenals after a flight on the Kosmos-1129 biosatellite].

    PubMed

    Kvetnanský, R; Blazicek, P; Tigranian, R A

    1982-01-01

    After a 18.5-day space flight on Cosmos-1129 rat adrenals were investigated for the concentration of catecholamines and activity of enzymes involved in their synthesis, i.e. tyrosine hydroxylase, dopamine-beta-hydroxylase, and phenyl ethanol amine-N-methyl transferase. It was found that inflight the sympatho-adreno-medullary system of rats was not exposed to a prolonged or strong stressogenic effect. Postflight the rats showed an increased reactivity to the immobilization stress.

  18. Adrenal venous sampling in a patient with adrenal Cushing syndrome

    PubMed Central

    Villa-Franco, Carlos Andrés; Román-Gonzalez, Alejandro; Velez-Hoyos, Alejandro; Echeverri-Isaza, Santiago

    2015-01-01

    The primary bilateral macronodular adrenal hyperplasia or the independent adrenocorticotropic hormone bilateral nodular adrenal hyperplasia is a rare cause hypercortisolism, its diagnosis is challenging and there is no clear way to decide the best therapeutic approach. Adrenal venous sampling is commonly used to distinguish the source of hormonal production in patients with primary hyperaldosteronism. It could be a useful tool in this context because it might provide information to guide the treatment. We report the case of a patient with ACTH independent Cushing syndrome in whom the use of adrenal venous sampling with some modifications radically modified the treatment and allowed the diagnosis of a macronodular adrenal hyperplasia. PMID:26309345

  19. Cell-To-Cell Communication in Bilateral Macronodular Adrenal Hyperplasia Causing Hypercortisolism

    PubMed Central

    Lefebvre, Hervé; Duparc, Céline; Prévost, Gaëtan; Bertherat, Jérôme; Louiset, Estelle

    2015-01-01

    It has been well established that, in the human adrenal gland, cortisol secretion is not only controlled by circulating corticotropin but is also influenced by a wide variety of bioactive signals, including conventional neurotransmitters and neuropeptides, released within the cortex by various cell types such as chromaffin cells, neurons, cells of the immune system, adipocytes, and endothelial cells. These different types of cells are present in bilateral macronodular adrenal hyperplasia (BMAH), a rare etiology of primary adrenal Cushing’s syndrome, where they appear intermingled with adrenocortical cells in the hyperplastic cortex. In addition, the genetic events, which cause the disease, favor abnormal adrenal differentiation that results in illicit expression of paracrine regulatory factors and their receptors in adrenocortical cells. All these defects constitute the molecular basis for aberrant autocrine/paracrine regulatory mechanisms, which are likely to play a role in the pathophysiology of BMAH-associated hypercortisolism. The present review summarizes the current knowledge on this topic as well as the therapeutic perspectives offered by this new pathophysiological concept. PMID:25941513

  20. Should male gender assignment be considered in the markedly virilized patient With 46,XX and congenital adrenal hyperplasia?

    PubMed

    Lee, Peter A; Houk, Christopher P; Husmann, Douglas A

    2010-10-01

    We assess the outcome in 46,XX men with congenital adrenal hyperplasia who were born with Prader 4 or 5 genitalia and assigned male gender at birth. After receiving institutional review board approval and subject consent we reviewed the medical records of 12 men 35 to 69 years old with 46,XX congenital adrenal hyperplasia, of whom 6 completed social and gender issue questionnaires. All subjects were assigned male gender at birth, were diagnosed with virilizing congenital adrenal hyperplasia at age greater than 3 years and indicated a male gender identity with sexual orientation to females. Ten of the 12 subjects had always lived as male and 2 who were reassigned to female gender in childhood subsequently self-reassigned as male. Nine of the 12 men had long-term female partners, including 7 married 12 years or more. The 3 subjects without a long-term female partner included 1 priest, 1 who was reassigned female gender, married, divorced and self-reassigned as male, and 1 with a girlfriend and sexual activity. All except the priest and the subject who was previously married when female indicated a strong libido and frequent orgasmic sexual activity. Responses to self-esteem, masculinity, body image, social adjustment and symptom questionnaires suggested adjustments related to the extent of familial and social support. Outcome data on severely masculinized 46,XX patients with congenital adrenal hyperplasia who were assigned male gender at birth indicate male gender identity in adulthood with satisfactory male sexual function in those retaining male genitalia. In men who completed questionnaires results were poorer in those lacking familial/social support. Male gender of rearing may be a viable option for parents whose children are born with congenital adrenal hyperplasia, a 46,XX karyotype and male genitalia, although positive parental and other support, and counseling are needed for adjustment. Copyright © 2010 American Urological Association Education and Research

  1. p.R182C mutation in Korean twin with congenital lipoid adrenal hyperplasia

    PubMed Central

    Park, Hye Won; Kwak, Byung Ok; Kim, Gu-Hwan; Yoo, Han-Wook

    2013-01-01

    Congenital lipoid adrenal hyperplasia (CLAH) is the most severe form of congenital adrenal hyperplasia which is caused by mutations in the steroidogenic acute regulatory protein (StAR). The mutations in StAR gene resulted in failure of the transport cholesterol into mitochondria for steroidogenesis in the adrenal gland. Twin sisters (A, B) with normal 46, XX were born at 36+2 gestational week, premature to nonrelated parents. They had symptoms as hyperpigmentation, slightly elevated potassium level and low level of sodium. Laboratory finding revealed normal 17-hydroxyprogesterone level, elevated adrenocorticotropin hormone (A, 4,379.2 pg/mL; B, 11,616.1 pg/mL), and high plasma renin activity (A, 49.02 ng/mL/hr; B, 52.7 ng mL/hr). However, the level of plasma cortisol before treatment was low (1.5 µg/dL) in patient B but normal (8.71 µg/dL) in patient A. Among them, only patient A was presented with adrenal insufficiency symptoms which was suggestive of CLAH and prompted us to order a gene analysis in both twin. The results of gene analysis of StAR in twin revealed same heterozygous conditions for c.544C>T (Arg182Cys) in exon 5 and c.722C>T (Gln258*) in exon 7. We report the first case on the mutation of p.R182C in exon 5 of the StAR gene in Korea. PMID:24904850

  2. Mechanisms and roles of muscarinic activation in guinea-pig adrenal medullary cells.

    PubMed

    Inoue, Masumi; Harada, Keita; Matsuoka, Hidetada; Nakamura, Jun; Warashina, Akira

    2012-09-15

    Muscarinic receptors are expressed in the adrenal medullary (AM) cells of various mammals, but their physiological roles are controversial. Therefore, the ionic mechanism for muscarinic receptor-mediated depolarization and the role of muscarinic receptors in neuronal transmission were investigated in dissociated guinea-pig AM cells and in the perfused guinea-pig adrenal gland. Bath application of muscarine induced an inward current at -60 mV. This inward current was partially suppressed by quinine with an IC(50) of 6.1 μM. The quinine-insensitive component of muscarine-induced currents changed the polarity at -78 mV and was inhibited by bupivacaine, a TWIK-related acid-sensitive K(+) (TASK) channel inhibitor. Conversely, the current-voltage relationship for the bupivacaine-insensitive component of muscarine currents showed a reversal potential of -5 mV and a negative slope below -40 mV. External application of La(3+) had a double action on muscarine currents of both enhancement and suppression. Immunoblotting and immunocytochemistry revealed expression of TASK1 channels and cononical transient receptor potential channels 1, 4, 5, and 7 in guinea-pig AM cells. Retrograde application of atropine reversibly suppressed transsynaptically evoked catecholamine secretion from the adrenal gland. The results indicate that muscarinic receptor stimulation in guinea-pig AM cells induces depolarization through inhibition of TASK channels and activation of nonselective cation channels and that muscarinic receptors are involved in neuronal transmission from the splanchnic nerve.

  3. Mechanisms and roles of muscarinic activation in guinea-pig adrenal medullary cells

    PubMed Central

    Harada, Keita; Matsuoka, Hidetada; Nakamura, Jun; Warashina, Akira

    2012-01-01

    Muscarinic receptors are expressed in the adrenal medullary (AM) cells of various mammals, but their physiological roles are controversial. Therefore, the ionic mechanism for muscarinic receptor-mediated depolarization and the role of muscarinic receptors in neuronal transmission were investigated in dissociated guinea-pig AM cells and in the perfused guinea-pig adrenal gland. Bath application of muscarine induced an inward current at −60 mV. This inward current was partially suppressed by quinine with an IC50 of 6.1 μM. The quinine-insensitive component of muscarine-induced currents changed the polarity at −78 mV and was inhibited by bupivacaine, a TWIK-related acid-sensitive K+ (TASK) channel inhibitor. Conversely, the current-voltage relationship for the bupivacaine-insensitive component of muscarine currents showed a reversal potential of −5 mV and a negative slope below −40 mV. External application of La3+ had a double action on muscarine currents of both enhancement and suppression. Immunoblotting and immunocytochemistry revealed expression of TASK1 channels and cononical transient receptor potential channels 1, 4, 5, and 7 in guinea-pig AM cells. Retrograde application of atropine reversibly suppressed transsynaptically evoked catecholamine secretion from the adrenal gland. The results indicate that muscarinic receptor stimulation in guinea-pig AM cells induces depolarization through inhibition of TASK channels and activation of nonselective cation channels and that muscarinic receptors are involved in neuronal transmission from the splanchnic nerve. PMID:22744007

  4. Impaired adrenal medullary function in a mouse model of depression induced by unpredictable chronic stress.

    PubMed

    Santana, Magda M; Rosmaninho-Salgado, Joana; Cortez, Vera; Pereira, Frederico C; Kaster, Manuella P; Aveleira, Célia A; Ferreira, Marisa; Álvaro, Ana Rita; Cavadas, Cláudia

    2015-10-01

    Stress has been considered determinant in the etiology of depression. The adrenal medulla plays a key role in response to stress by releasing catecholamines, which are important to maintain homeostasis. We aimed to study the adrenal medulla in a mouse model of depression induced by 21 days of unpredictable chronic stress (UCS). We observed that UCS induced a differential and time-dependent change in adrenal medulla. After 7 days of UCS, mice did not show depressive-like behavior, but the adrenal medullae show increased protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH and PNMT), Neuropeptide Y, the SNARE protein SNAP-25, the catecholamine transporter VMAT2 and the chromaffin progenitor cell markers, Mash1 and Phox2b. Moreover, 7 days of UCS induced a decrease in the chromaffin progenitor cell markers, Sox9 and Notch1. This suggests an increased capacity of chromaffin cells to synthesize, store and release catecholamines. In agreement, after 7 days, UCS mice had higher NE and EP levels in adrenal medulla. Opposite, when mice were submitted to 21 days of UCS, and showed a depressive like behavior, adrenal medullae had lower protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH, PNMT), catecholamine transporters (NET, VMAT1), SNARE proteins (synthaxin1A, SNAP25, VAMP2), catecholamine content (EP, NE), and lower EP serum levels, indicating a reduction in catecholamine synthesis, re-uptake, storage and release. In conclusion, this study suggests that mice exposed to UCS for a period of 21 days develop a depressive-like behavior accompanied by an impairment of adrenal medullary function. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  5. Adrenal malignant melanoma masquerading as a pheochromocytoma in a patient with a history of a multifocal papillary and medullary thyroid carcinoma.

    PubMed

    Barmpari, Maria E; Savvidis, Christos; Dede, Anastasia D; Markogiannakis, Haridimos; Dikoglou, Christina; Xekouki, Paraskevi; Stratakis, Constantine A; Manouras, Andreas; Malaktari-Skarantavou, Sofia

    2016-04-01

    Adrenal masses usually represent benign and nonfunctional adrenal adenomas; however, primary or metastatic malignancy should also be considered. Discovery of an adrenal mass needs further evaluation in order to exclude malignancy and hormonal secretion. We present a rare case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. A 61-year-old male farmer was referred for evaluation of a mass in the right supraclavicular region and a left adrenal lesion. The patient had a history of a multifocal papillary and medullary thyroid carcinoma. Laboratory tests revealed increased 24hour urinary dopamine and also increased serum calcitonin and neuron specific enolase. A pathology report of the resected right supraclavicular mass and left adrenal showed a malignant melanoma. This is a case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. Although this case is very rare and there are rigid diagnostic criteria for the diagnosis of primary adrenal melanoma, it underlines the fact that the differential diagnosis of a dopamine secreting adrenal mass should include primary or metastatic malignant melanoma in order to determine the best diagnostic approach for the patient and select the most appropriate surgical management.

  6. Pathological and Genetic Characterization of Bilateral Adrenomedullary Hyperplasia in a Patient with Germline MAX Mutation.

    PubMed

    Romanet, Pauline; Guerin, Carole; Pedini, Pascal; Essamet, Wassim; Castinetti, Frédéric; Sebag, Fréderic; Roche, Philippe; Cascon, Alberto; Tischler, Arthur S; Pacak, Karel; Barlier, Anne; Taïeb, David

    2017-12-01

    In recent years, familial pheochromocytoma (PHEO) with germline mutations in the MAX (MYC associated factor X) gene has been reported in a few cases. Here, we investigated a 25-year-old patient with multiple PHEOs associated with a non-sense germline MAX mutation. Preoperative 18 F-FDOPA PET/CT revealed bilateral adrenal involvement with multiple tumors. In addition, both adrenal glands were found to have diffuse or nodular adrenal medullary hyperplasia (AMH), a histopathological feature previously described as a precursor of MEN2- and SDHB-related PHEOs but not MAX. After bilateral adrenalectomy, different paraffin-embedded and frozen samples were analyzed for allelic imbalances of the MAX gene using allelic quantification by pyrosequencing. The expression of the protein MAX was studied by immunohistochemistry. All PHEOs but also nodular AMH exhibited a loss of the normal allele. By contrast, the diffuse AMH did not show loss-of-heterozygosity. Nevertheless, immunohistochemistry demonstrated loss of protein MAX expression in all samples including diffuse hyperplasia, suggesting a causative role of MAX mutation for both PHEOs and AMH. The present case shows that both nodular and diffuse AMH belongs to the spectrum of MAX-related disease. These data support the possible continuum between nodular AMH and PHEO, expanding the qualification of micro-PHEO to nodular AMH.

  7. Adrenal rest tissue in gonads of patients with classical congenital adrenal hyperplasia: multicenter study of 45 French male patients.

    PubMed

    Pierre, Peggy; Despert, François; Tranquart, François; Coutant, Régis; Tardy, Véronique; Kerlan, Véronique; Sonnet, Emmanuel; Baron, Sabine; Lorcy, Yannick; Emy, Philippe; Delavierre, Dominique; Monceaux, Françoise; Morel, Yves; Lecomte, Pierre

    2012-12-01

    Several cases of testicular adrenal rest tumours have been reported in men with congenital adrenal hyperplasia (CAH) due to the classical form of 21-hydroxylase deficiency but the prevalence has not been established. The aims of this report were to evaluate the frequency of testicular adrenal rest tissue in this population in a retrospective multicentre study involving eight endocrinology centres, and to determine whether treatment or genetic background had an impact on the occurrence of adrenal rest tissue. Testicular adrenal rest tissue (TART) was sought clinically and with ultrasound examination in forty-five males with CAH due to the classical form of 21-hydroxylase deficiency. When the diagnosis of testicular adrenal rest tumours was sought, good observance of treatment was judged on biological concentrations of 17-hydroxyprogesterone (17OHP), delta4-androstenedione, active renin and testosterone. The results of affected and non-affected subjects were compared. TART was detected in none of the 18 subjects aged 1 to 15years but was detected in 14 of the 27 subjects aged more than 15years. Five patients with an abnormal echography result had no clinical signs. Therapeutic control evaluated at diagnosis of TART seemed less effective when diagnosis was made in patients with adrenal rest tissue compared to TART-free subjects. Various genotypes were observed in patients with or without TART. Due to the high prevalence of TART in classical CAH and the delayed clinical diagnosis, testicular ultrasonography must be performed before puberty and thereafter regularly during adulthood even if the clinical examination is normal. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  8. HYDROCORTISONE THERAPY AND GROWTH TRAJECTORY IN CHILDREN WITH CLASSICAL CONGENITAL ADRENAL HYPERPLASIA.

    PubMed

    Bizzarri, Carla; Improda, Nicola; Maggioli, Chiara; Capalbo, Donatella; Roma, Silvia; Porzio, Ottavia; Salerno, Mariacarolina; Cappa, Marco

    2017-05-01

    Poor linear growth is one of the main concerns in children with congenital adrenal hyperplasia (CAH). We aimed to analyze factors affecting growth trajectory in children with classical CAH. Clinical records of children followed from infancy up to the end of growth at two Italian tertiary referral hospitals were reviewed. Fifty-seven patients (31 males), treated with hydrocortisone and fludrocortisone only, were included. Clinical observations were divided into three groups: 0 to 2 years, 172 observations; from 2 years to puberty onset, 813 observations; after puberty onset, 527 observations. Height velocity, pubertal growth spurt, and final height were evaluated as outcomes. Final height standard deviation score (SDS) was lower than target height SDS (-0.74 ± 1.1 versus -0.31 ± 1.01; P<.001). Target-adjusted final height SDS was -0.44 ± 1.8 in males and -0.13 ± 1.1 in females (P = .001). Total pubertal growth was 21.9 ± 7.3 cm in males and 19.2 ± 8.2 cm in females (P = .19). Hydrocortisone dose increased and height-velocity SDS decreased during puberty. At multivariable analysis, height-velocity SDS was adversely affected by hydrocortisone dose (P = .038) and directly related to adrenocorticotropic hormone (ACTH) levels (P = .023). Target-adjusted final-height SDS was adversely affected by hydrocortisone dose (P<.001) and positively related to mineralocorticoid therapy (P = .001) and ACTH levels (P = .02). Total pubertal growth (cm) was positively related to ACTH levels (P = .01). Height outcome of CAH patients is now better than previously reported. During puberty, the lowest effective dose of hydrocortisone should be used to optimize pubertal growth spurt and final height. 17-OHP = 17-alpha-hydroxyprogesterone ACTH = adrenocorticotropic hormone BMI = body mass index CAH = congenital adrenal hyperplasia GH = growth hormone HPA = hypothalamus-pituitary-adrenal PRA = plasma renin activity SDS = standard deviation score SV = simple virilizing SW = salt-wasting.

  9. [National screening for phenylketonuria, congenital hypothyroidism and congenital adrenal hyperplasia].

    PubMed

    Osório, R V; Vilarinho, L; Soares, J P

    1992-03-01

    In Portugal the screening for phenylketonuria (PKU) and congenital hypothyroidism (CH) was begun towards the end of 1979, and by 1990 59 cases of PKU and 227 cases of CH had been detected. The early initiation of treatment and the observed mental and motor development, point towards a normal development in these children. A trial screen for congenital adrenal hyperplasia was carried out in 100.000 newborns, from which it was concluded that, under the present conditions, screening at a national level is not justified. A similar study is currently being undertaken for biotinidase deficiency and cystic fibrosis. The results ares discussed, as are the cost/benefits evaluations.

  10. High Background Incidence of Spontaneous Subcapsular Adrenal Gland Hyperplasia of Tg.rasH2 Mice Used in 26-week Carcinogenicity Studies.

    PubMed

    Boyle, Molly H; Paranjpe, Madhav G; Creasy, Dianne M

    2018-06-01

    The Tg.rasH2 model was accepted by regulatory agencies worldwide for 26-week carcinogenicity assays as an alternative to the standard 2-year assays in conventional mice in 2003. Several references documenting spontaneous nonneoplastic findings and incidences of spontaneous tumors in the Tg.rasH2 mice have been published. The purpose of this publication is to add adrenal gland subcapsular hyperplasia to the database pertaining to spontaneous lesions noted in Tg.rasH2 mice, review physiology related to this finding, and discuss its significance. The incidence of spontaneous subcapsular adrenal gland hyperplasia was determined in control Tg.rasH2 mice from nine 26-week carcinogenicity studies carried out within the last 5 years at two contract research organizations. Incidence of this finding ranged from 56% to 79% in males and 88% to 100% in females, with an incidence average of 62% in males and 93% in females. Adrenal gland subcapsular hyperplasia is a common finding in male and female Tg.rasH2 mice that did not progress to neoplasia in Tg.rasH2 mice. In general, it tends to be more frequent and severe in females in comparison to males.

  11. Diagnosis of pheochromocytoma in the setting of Parkinson disease.

    PubMed

    Mehta, Shyamal H; Prakash, Rajan; Prisant, L Michael; Isales, Carlos M; Morgan, John C; Williams, Hadyn; Sethi, Kapil D

    2009-06-01

    A 59-year-old man with a 7-year history of Parkinson disease (PD) presented with episodes of sudden, severe headaches with neck pain, tachycardia, sweating and pallor. During these episodes, the patient showed marked elevations in blood pressure, regardless of posture. This was unusual, given that he had no prior history of hypertension. The array of symptoms raised suspicions of pheochromocytoma, but diagnosis was challenging, as the standard diagnostic biochemical tests were confounded by dopaminergic medications. Further work-up revealed left adrenal medullary hyperplasia. Several reports exist of pseudopheochromocytoma in patients on dopaminergic therapy, but this is the first documented case of pheochromocytoma syndrome due to adrenal medullary hyperplasia in a patient with PD. This case highlights the challenges of performing a diagnostic work-up in a PD patient with symptoms suggestive of pheochromocytoma, and illustrates the utility of (123)I-metaiodobenzylguanidine ((123)I-MIBG) single-photon emission CT in making a diagnosis.Investigations. Physical examination, laboratory tests, abdominal MRI scan, abdominal (123)I-MIBG scan, abdominal (18)F-fluorodeoxyglucose PET scan. Pheochromocytoma syndrome due to adrenal medullary hyperplasia.Management. Surgical excision of the left adrenal gland.

  12. GLUCOCORTICOID TREATMENT—EFFECT ON ADRENAL MEDULLARY CATECHOLAMINE PRODUCTION

    PubMed Central

    Sharara-Chami, Rana I.; Joachim, Maria; Pacak, Karel; Majzoub, Joseph A.

    2016-01-01

    Glucocorticoid and epinephrine are important stress hormones secreted from the adrenal gland during critical illness. Adrenal glucocorticoid stimulates phenylethanolamine N-methyltransferase (PNMT) to convert norepinephrine to epinephrine in the adrenal medulla. Glucocorticoid is sometimes used in catecholamine-resistant septic shock in critically ill patients. By suppressing adrenal glucocorticoid production, glucocorticoid therapy might also reduce the secretion of epinephrine during stress. To investigate this, we used a mouse model subjected to glucocorticoid therapy under basal conditions (experiment 1) and during stress (experiment 2). In experiment 1, pellets containing 0% to 8% dexamethasone were implanted subcutaneously in mice for 4 weeks. In experiment 2, animals received 14 days of intraperitoneal injections of normal saline, low- or high-dose dexamethasone, followed by 2 h of restraint. We found that in experiment 1, adrenal corticosterone did not differ with dexamethasone treatment. Phenylethanolamine N-methyltransferase messenger RNA levels and adrenal catecholamines were highest in the 8% dexamethasone group. Compared with experiment 1, restrained control mice in experiment 2 had high adrenal corticosterone, which decreased with dexamethasone. Phenylethanolamine N-methyltransferase messenger RNA content doubled with restraint but decreased with dexamethasone treatment. As in experiment 1, adrenal catecholamine content increased significantly with dexamethasone treatment. We conclude that without stress, when adrenocorticotropic hormone is low, high doses of exogenous dexamethasone stimulate PNMT and catecholamine synthesis, likely independently of adrenal corticosterone concentration. After stress, adrenocorticotropic hormone levels are elevated, and exogenous dexamethasone suppresses endogenous corticosterone and PNMT production. Nonetheless, catecholamines increase, possibly due to direct neural stimulation, which may override the hormonal

  13. [Final height in symptomatic boys with late-onset adrenal hyperplasia (LOCAH), treated with glucocorticoids. Clinical cases].

    PubMed

    Pasqualini, Titania; Alonso, Guillermo; Fernández, Cecilia; Buzzalino, Noemí; Dain, Liliana

    2013-04-01

    Although corticoid replacement is recommended for those late-onset adrenal hyperplasia with clinical manifestations, asymptomatic patients do not need treatment. We describe clinical features at diagnosis, treatment, and growth till adult- height, in 4 boys. At diagnosis, age ranged from 9.2-11.6 years. The initial symptoms/signs were: precocious pubarche (n = 2), accelerated bone age (n = 1) and precocious puberty (n = 1). All of them presented elevated 17 hydroxyprogesterone levels and were compound heterozygotes carrying p.V281L mutation. Since, at diagnosis, bone age was significantly advanced for chronological age (13.1 ± 0.5 vs. 10.2 ± 1.1 p = 0.008), hydrocortisone therapy was initiated. During follow-up, mean height Z score decreased 1.4 ± 0.4 SDS (p = 0.007), though adult mean height was not different from target height (-0.39 ± 0.7 vs. -0.04 ± 0.5 SDS, p = 0.054). In conclusion, in 4 symptomatic patients, accurate treatment of late-onset adrenal hyperplasia led to an adult mean height not different from target height. Advanced bone age at diagnosis and the loss of height during pubertal development suggest the need of therapy.

  14. Noninvasive Prenatal Diagnosis of Congenital Adrenal Hyperplasia.

    PubMed

    Khattab, Ahmed; Yuen, Tony; Sun, Li; Yau, Mabel; Barhan, Ariella; Zaidi, Mone; Lo, Y M Dennis; New, Maria I

    2016-01-01

    A major hallmark of classical congenital adrenal hyperplasia (CAH) is genital ambiguity noted at birth in affected females, which leads to psychological and psychosexual issues in adult life. Attempts to correct genital ambiguity through surgical intervention have been partially successful. Fetal hyperandrogenemia and genital ambiguity have been shown to be preventable by prenatal administration of low-dose dexamethasone initiated before the 9th week of gestation. In 7 of 8 at-risk pregnancies, the unaffected fetus is unnecessarily exposed to dexamethasone for weeks until the diagnosis of classical CAH is ruled out by invasive procedures. This therapeutic dilemma calls for early prenatal diagnosis so that dexamethasone treatment can be directed to affected female fetuses only. We describe the utilization of cell-free fetal DNA in mothers carrying at-risk fetuses as early as 6 gestational weeks by targeted massively parallel sequencing of the genomic region including and flanking the CYP21A2 gene. Our highly personalized and innovative approach should permit the diagnosis of CAH before genital development begins, therefore restricting the purposeful administration of dexamethasone to mothers carrying affected females. © 2016 S. Karger AG, Basel.

  15. [Diffuse hypertrichosis revealing non-classical congenital adrenal hyperplasia].

    PubMed

    Berthin, C; Sibilia, P; Martins-Hericher, J; Donzeau, A; Martin, L

    2018-04-01

    Non-classical congenital adrenal hyperplasia (NC-CAH) is a recessive autosomal disease caused by a deficiency of adrenal steroidogenesis enzymes. It must be distinguished from classical CAH, either simple virilising or salt-wasting, diagnosed during the neonatal period and responsible for potentially lethal disorders of sexual differentiation. NC-CAH presents a simpler and less specific clinical picture. Herein, we present two cases comprising twin girls consulting for diffuse hypertrichosis. Two 5-year-old twin girls were seen at our consultation for increased pilosity on all four limbs, but with no facial pilosity or synophrys, as well as comedones on the chin. Their height and weight and psychomotor development was normal, with no signs of precocious puberty and no clitoral hypertrophy. Levels of 17OH-P and SDHA were high, while FSH and LH were low and IGF1 and TSH were normal. Analysis of gene CYP21 associated with NC-CAH showed mutations p.V281L and IVS2-13A/C>G. Mutation p.V281L was present in the heterozygous state in the older sister and the father, together with moderate hyperpilosity but without hirsutism or acne. No mutations were found in the mother, indicating either de novo appearance of mutation IVS2-13A/C>G in the twins or germline mosaicism in the mother. We diagnosed NC-CAH as the cause of diffuse hypertrichosis in these twins. This disease is not rare, with a prevalence of 1/1000 to 1500 among peoples of European descent. It is often diagnosed late since routine neonatal screening is not performed. In some cases, NC-CAH remains asymptomatic. The appearance of pubic hair at around 5 to 7 years is the initial reason for consultation, particularly with a dermatologist. Hyperandrogenism varies, involving hirsutism, acne, fertility disorders and premature ageing of bone. Cortisol and aldosterone levels are generally normal. The risk of acute adrenal insufficiency is extremely low. Differential diagnosis concerns ovarian or adrenal tumors and

  16. Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions

    PubMed Central

    Lefebvre, Hervé; Thomas, Michaël; Duparc, Céline; Bertherat, Jérôme; Louiset, Estelle

    2016-01-01

    In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells and, thus, indirectly regulates steroid production through modulation of the adrenal blood flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit molecular and cellular defects that tend to reinforce the influence of paracrine regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of adrenocortical cells that express gonadal markers. This observation suggests that ectopic production of ACTH may result from impaired embryogenesis leading to abnormal maturation of the adrenogonadal primordium. Globally, the current literature indicates that ACTH is a major player in the autocrine/paracrine processes occurring in the adrenal gland in both physiological and pathological conditions. PMID:27489549

  17. [Class I HLA antigens in children from families with congenital adrenal hyperplasia].

    PubMed

    Turowska-Heydel, D; Pietrzyk, J J; Turowski, G

    1995-02-01

    Congenital adrenal hyperplasia (CAH) is a syndrome of adrenal steroid metabolism errors with an autosomal inheritance model. The most common metabolic defect is 21-hydroxylase deficiency. It has been demonstrated that 21-hydroxylase genes are in close association with HLA antigens. I HLA antigens were typed in a group of 32 families of children with CAH-type 21-hydroxylase deficiency with salt loss. The antigen frequencies were determined and compared to those of the control population. The studies revealed that two HLA antigens determined by the B Locus, i.e. HLA-B47 and HLA-B61, showed a highly significant frequency (chi 2 corresponding to 404,5259 and 23,7808, respectively). The calculated relative risk and etiologic fraction values were extremely high, distinguishing the population of patients and their parents. The RR value among patients was 427.1 for HLA-B47 and 7.8 for HLA-B61 antigen. Studies on the correlation between HLA and CAH indicate an association with HLA-B47 and HLA-B61 antigens.

  18. Suppression of Prostate Tumors by INK4C and PTEN

    DTIC Science & Technology

    2007-12-01

    or Pten/ single mutant mice developed tumors in both lobes (Fig. 2). Pheochromocytomas developed in the adrenals of 84% of p18/ Pten/ mice...0 1 (13) 14 (74) Adrenal Normal 14 6 8 3 5 4 4 3 1 Medullary hyperplasia 1 0 4 4 2 2 1 1 2 Pheochromocytoma 0 0 2 (14)e 2 (22) 13 (65)f 2 (25) 12 (71...Hematoxylin and eosin staining of adrenal glands from different genotypes. Hyperplasia (H) and pheochromocytoma (T) of the adrenal medulla (AM

  19. Cushing's syndrome and the nodular adrenal gland.

    PubMed

    Samuels, M H; Loriaux, D L

    1994-09-01

    This article examines Cushing's syndrome in four main categories as associated with nodular adrenal glands: adrenal adenoma, adrenal carcinoma, primary pigmented nodular adrenal dysplasia, and macronodular adrenal hyperplasia. A summary of clinical features of these four categories is presented.

  20. Management issues of congenital adrenal hyperplasia during the transition from pediatric to adult care.

    PubMed

    Choi, Jin-Ho; Yoo, Han-Wook

    2017-02-01

    Steroid 21-hydroxylase deficiency is the most prevalent form of congenital adrenal hyperplasia (CAH), accounting for approximately 95% of cases. With the advent of newborn screening and hormone replacement therapy, most children with CAH survive into adulthood. Adolescents and adults with CAH experience a number of complications, including short stature, obesity, infertility, tumor, osteoporosis, and reduced quality of life. Transition from pediatric to adult care and management of long-term complications are challenging for both patients and health-care providers. Psychosocial issues frequently affect adherence to glucocorticoid treatment. Therefore, the safe transition of adolescents to adult care requires regular follow-up of patients by a multidisciplinary team including pediatric and adult endocrinologists. The major goals for management of adults with 21-hydroxylase deficiency are to minimize the long-term complications of glucocorticoid therapy, reduce hyperandrogenism, prevent adrenal or testicular adrenal rest tumors, maintain fertility, and improve quality of life. Optimized medical or surgical treatment strategies should be developed through coordinated care, both during transition periods and throughout patients' lifetimes. This review will summarize current knowledge on the management of adults with CAH, and suggested appropriate approaches to the transition from pediatric to adult care.

  1. Confirmation of congenital adrenal hyperplasia by adrenal steroid profiling of filter paper dried blood samples using ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Rossi, Claudia; Calton, Lisa; Brown, Heather A; Gillingwater, Scott; Wallace, A Michael; Petrucci, Francesca; Ciavardelli, Domenico; Urbani, Andrea; Sacchetta, Paolo; Morris, Michael

    2011-04-01

    The specificity of screening for congenital adrenal hyperplasia by direct measurement of 17-hydroxyprogesterone in filter paper dried blood spot samples by immunoassay is low and has a high false-positive rate. In order to reduce the false-positive rate of this test, we developed a rapid, robust, specific confirmatory procedure in which cortisol, 4-androstene-3,17-dione and 17-hydroxyprogesterone were measured simultaneously by ultra-performance liquid chromatography-tandem mass spectrometry. After extraction, samples were analysed by ultra-performance liquid chromatography-tandem mass spectrometry and 17-hydroxyprogesterone was quantified accurately. Other steroids were determined using stable deuterated internal standards. In total, 25 patient blood spot samples and 92 control samples were analysed. The assay was linear for 17-hydroxyprogesterone, with a coefficient of determination >0.997 and imprecision ≤ 6.5%. An upper limit of normal for 17-hydroxyprogester-one of 4.45 nmol/L was established by analysing a cohort of samples from unaffected newborns. In addition, a cut-off of 3.5 for the peak areas ratio (17-hydroxyprogesterone+4-androstene-3,17-dione)/cortisol, allows confirmation of the affected steroidogenic enzyme. A high throughput method for the detection of steroids related to congenital adrenal hyperplasia has been developed, allowing the false-positive rate associated with screening for 17-hydroxyprogesterone by immunoassay to be determined.

  2. [Recommendations for the diagnosis and treatment of classic forms of 21-hydroxylase-deficient congenital adrenal hyperplasia].

    PubMed

    Rodríguez, Amparo; Ezquieta, Begoña; Labarta, José Igancio; Clemente, María; Espino, Rafael; Rodriguez, Amaia; Escribano, Aranzazu

    2017-08-01

    Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations in the CYP21A2 gene. Cortisol and aldosterone synthesis are impaired in the classic forms (adrenal insufficiency and salt-wasting crisis). Females affected are virilised at birth, and are at risk for genital ambiguity. In this article we give recommendations for an early as possible diagnosis and an appropriate and individualised treatment. A patient and family genetic study is essential for the diagnosis of the patient, and allows genetic counselling, as well as a prenatal diagnosis and treatment for future pregnancy. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Psychological evaluation of treated females with virilizing congenital adrenal hyperplasia.

    PubMed

    Hurtig, A L; Radhakrishnan, J; Reyes, H M; Rosenthal, I M

    1983-12-01

    The psychological development of females with congenital adrenal hyperplasia (CAH) has been previously studied by Money, et al, who found that psychological development of sex identity was consistent with sex assignment despite virilizing adrenal hormones and abnormal external genitalia requiring surgical correction. In this study, using a variety of psychological tests, we assessed the sex-dimorphic behavior, body image, cognitive functioning, and sex-role identity of nine patients ranging in age from 13 to 21, all treated with glucocorticoids and surgical correction. Four of the nine showed moderate virilization despite treatment. Psychological measures included the Wechsler Intelligence Scale for Children-Revised (WISC-R), the Bem Sex-Role Inventory, the Draw-A-Person (DAP) and an interview with patient and family. Results indicate that patients fall within the normal expectable range for this developmental period in visual-spatial and verbal cognitive functioning, in sex-role identity, and in social interpersonal early behaviors. In two areas of functioning these patients demonstrated some variance from the norms, specifically in sexual identity and early activity levels. This suggests that sexual identity and physical activity are most prone to hormonal and psychological impact but that cognition and sex-role identity are not affected. Future studies of this sample will look at personality dimensions such as ego functioning, defense and affect to consider the impact of body image concerns and conflicts.

  4. Congenital Adrenal Hyperplasia: Review from a Surgeon’s Perspective in the Beginning of the Twenty-First Century

    PubMed Central

    Piaggio, Lisandro Ariel

    2013-01-01

    Congenital adrenal hyperplasia (CAH) most commonly due to 21-hydroxylase deficiency is the most common type of disorder of sex development. This review will focus on CAH addressing historical and current surgical techniques with their anatomical foundations, with special attention to long-term results and outcomes on sexual function, patient satisfaction, patient attitude toward surgery, and ongoing controversies in management of these patients. PMID:24400298

  5. Ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppressing nicotinic acetylcholine receptor-ion channels in cultured bovine adrenal medullary cells.

    PubMed

    Li, Xiaojia; Toyohira, Yumiko; Horisita, Takafumi; Satoh, Noriaki; Takahashi, Keita; Zhang, Han; Iinuma, Munekazu; Yoshinaga, Yukari; Ueno, Susumu; Tsutsui, Masato; Sata, Takeyoshi; Yanagihara, Nobuyuki

    2015-12-01

    Ikarisoside A is a natural flavonol glycoside derived from plants of the genus Epimedium, which have been used in Traditional Chinese Medicine as tonics, antirheumatics, and aphrodisiacs. Here, we report the effects of ikarisoside A and three other flavonol glycosides on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that ikarisoside A (1-100 μM), but not icariin, epimedin C, or epimedoside A, concentration-dependently inhibited the secretion of catecholamines induced by acetylcholine, a physiological secretagogue and agonist of nicotinic acetylcholine receptors. Ikarisoside A had little effect on catecholamine secretion induced by veratridine and 56 mM K(+). Ikarisoside A (1-100 μM) also inhibited (22)Na(+) influx and (45)Ca(2+) influx induced by acetylcholine in a concentration-dependent manner similar to that of catecholamine secretion. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, ikarisoside A (0.1-100 μM) directly inhibited the current evoked by acetylcholine. It also suppressed (14)C-catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine at 1-100 μM and 10-100 μM, respectively. The present findings suggest that ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells.

  6. Localization and characterization of carbohydrates in adrenal medullary cells

    PubMed Central

    1975-01-01

    The localization and characterization of carbohydrates in adrenal medullary cells were studied by histochemical and cytochemical methods. Adrenaline (A)-and noradrenaline (N)-storing granules were argentaphobic when ultrathin sections of Araldite-embedded medullae were stained according to the periodic acid-thiocarbohydrazide-silver proteinate technique of Thiery. A small amount of glycogen in the form of single beta-particles as well as lysosomes were, however, visualized by this technique. The entire core of the A granules was markedly positive after ultrathin sections of glutaraldehyde-fixed, glycol methacrylate (GMA)-embedded medullae were stained with phosphotungstic acid (PTA) at low pH (0.3). The N granules, in contrast, were mostly unreactive. In the A cells, PTA stained a large part of the Golgi complex, whereas in the N cells the Golgi complex was mostly unstained. In both cell types, the cell coat, lysosomes, and multivesticular bodies reacted to PTA. The periodic acid-Schiff (PAS) technique showed A but not N granules in semithin sections of GMA- or Araldite-embedded medullae. The PTA and PAS stains were abolished by acetylation, restored by saponification, unchanged by methylation, and greatly diminished by sulfation. In ultrathin sections of GMA- or Araldite- embedded medullae incubated with colloidal iron according to various techniques, the cell coat and lysosomes of both cell types were stained, unlike all the other cytoplasmic organelles. These results indicate that A granules and the Golgi complex of A cells, unlike the same structures in N cells, are rich in glycoproteins which are probably not acidic. PMID:47862

  7. Autologous Adrenal Medullary, Fetal Mesencephalic, and Fetal Adrenal Brain Transplantation in Parkinson's Disease: A Long-Term Postoperative Follow-Up

    PubMed Central

    Madrazo, Ignacio; Franco-Bourland, Rebecca; Aguilera, Maricarmen; Ostrosky-Solis, Feggy; Madrazo, Mario; Cuevas, Carlos; Catrejon, Hugo; Guizar-Zahagun, Gabriel; Magallon, Eduardo

    1991-01-01

    We report on the clinical status of 5 patients with Parkinson's disease (PD) 3 years after autologous adrenal medullary (AM)-to-caudate nucleus (CN) implanfion, and of 2 PD patients, 2 years after fetal ventral mesencephalon (VM)- and fetal adrenal (A)-to-CN homotransplantation. Current clinical evaluation of 4 of the AM grafted patients revealed sustained bilateral amelioration of their PD signs, most notably of rgidity, postural imbalance and gait disturbances, resulting in a substantial improvement in their quality of life. the disease-related dystonia of one of them disappeared only 2 years after surgery. The levodopa requirements of 2 of these patients and the anticholinergic therapy of another have been reduced. In agreement with the satisfactory clinical evaluation of these 4 patients, their neuropsychological and electrophysiological improvements, initially registered 3 months after surgery, have been maintained for 3 years. After 1 year of significant recovery, the 5th patient of this group has almost returned to her preoperative state. The 2 homotransplanted patients also showed sustained bilateral improvement of their PD signs. Two years after surgery, the most improved signs of the fetal VM case were rigidity, bradykinesia, postural imbalance, gait disturbances and facial expression. The fetal A case has only shown amelioration of rigidity and bradykinesia. Neither of them has shown significant neuropsychological changes. Their current levodopa requirements are less than before surgery. The improvements shown here by PD patients after brain tissue grafts go beyond those obtained using any other therapeutic approach, when levodopa fails. Although more studies and the development of these procedures are obviously required, these initial human trials appear to be resisting the test of time. PMID:1782251

  8. Woman with virilizing congenital adrenal hyperplasia and Leydig cell tumor of the ovary.

    PubMed

    Fernández-García Salazar, Rosario; Muñoz-Darias, Carmen; Haro-Mora, Juan Jesús; Almaraz, M Cruz; Audí, Laura; Martínez-Tudela, Juana; Yahyaoui, Raquel; Esteva, Isabel

    2014-08-01

    We report the case of a 36-year-old woman with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, and corticosteroid replacement therapy since birth. She manifested persistent virilization and high testosterone levels that were attributed to nonadherence to medical treatment. The patient was referred to our gender unit for genitoplastic surgery. We recommended the patient for left oophorectomy after detecting an ovarian mass. Pathologic findings confirmed an ovarian hilus cell tumor. Testosterone levels fell back to normal and masculinization disappeared but ACTH remained elevated. This case represents a very rare type of primary ovarian tumor that must be considered in persistent virilizing symptoms in women with CAH.

  9. Prenatal Androgens and Gender-Typed Behavior: A Study of Girls with Mild and Severe Forms of Congenital Adrenal Hyperplasia.

    ERIC Educational Resources Information Center

    Servin, Anna; Nordenstrom, Anna; Larsson, Agne; Bohlin, Gunilla

    2003-01-01

    Examined gender-typed behavior and interests in 2- to 10-year-old girls with congenital adrenal hyperplasia (CAH) and in unaffected girls matched for age. Found that, compared with unaffected girls, girls with CAH were more interested in masculine toys and less interested in feminine toys and were more likely to report having male playmates and…

  10. Iatrogenic Cushing's Disease in a Boy after Misdiagnosis of Salt-Losing Virilizing Adrenal Hyperplasia: Impaired Metyrapone Response with Failure of Catch-Up Growth

    ERIC Educational Resources Information Center

    Mendilaharzu, Hernan; And Others

    1973-01-01

    A boy misdiagnosed as having the sodium-losing form of virilizing adrenal hyperplasia was treated with large doses of glucocorticoids and mineralocorticoids from the newborn period until he was more than 4 years of age. (Author)

  11. PC12 Cells Differentiate into Chromaffin Cell-Like Phenotype in Coculture with Adrenal Medullary Endothelial Cells

    NASA Astrophysics Data System (ADS)

    Mizrachi, Yaffa; Naranjo, Jose R.; Levi, Ben-Zion; Pollard, Harvey B.; Lelkes, Peter I.

    1990-08-01

    Previously we described specific in vitro interactions between PC12 cells, a cloned, catecholamine-secreting pheochromocytoma cell line derived from the rat adrenal medulla, and bovine adrenal medullary endothelial cells. We now demonstrate that these interactions induce the PC12 cells to acquire physical and biochemical characteristics reminiscent of chromaffin cells. Under coculture conditions involving direct cell-cell contact, the endothelial cells and the PC12 cells reduced their rates of proliferation; upon prolonged coculture PC12 cells clustered into nests of cells similar to the organization of chromaffin cells seen in vivo. Within 3 days in coculture with endothelial cells, but not with unrelated control cells, PC12 cells synthesized increased levels of [Met]enkephalin. In addition, PC12 cells, growing on confluent endothelial monolayers, failed to extend neurites in response to nerve growth factor. Neither medium conditioned by endothelial cells nor fixed endothelial cells could by themselves induce all of these different phenomena in the PC12 cells. These results suggest that under coculture conditions PC12 cells change their state of differentiation toward a chromaffin cell-like phenotype. The rapid, transient increase in the expression of the protooncogene c-fos suggests that the mechanism(s) inducing the change in the state of differentiation in PC12 cells in coculture with the endothelial cells may be distinct from that described for the differentiation of PC12 cells--e.g., by glucocorticoids. We propose that similar interactions between endothelial cells and chromaffin cell precursors may occur during embryonic development and that these interactions might be instrumental for the organ-specific differentiation of the adrenal medulla in vivo.

  12. Angiotensin II receptors in cortical and medullary adrenal tumors.

    PubMed

    Opocher, G; Rocco, S; Cimolato, M; Vianello, B; Arnaldi, G; Mantero, F

    1997-03-01

    Several pieces of evidences suggest that angiotensin II (Ang II) has mitogenic effects, and a link between Ang II receptors and adrenal tumors can be suggested. In various adrenal tumors, aldosterone-producing adenoma (APA), Cushing's adrenal adenomas (Cush), pheochromocytomas (Pheo), and adrenal carcinomas, we studied the density, affinity, and subtype of Ang II receptors. Ang II binding was tested in cell membrane homogenates. [125I]Ang II was used as ligand, and Losartan and CGP 42112 were used as selective Ang II type 1 and type 2 antagonists, respectively. In APA, Ang II receptor density was 178.5 +/- 82.7 fmol/mg: however, due to the high degree of variability, the receptor density was not significantly higher than that in nontumorous adrenal cortex (59.3 +/- 8.4 fmol/mg). In Cush, the receptor density (27.6 +/- 8.2 fmol/mg; P < 0.05) was significantly lower than that in controls, whereas in Pheo and cortical carcinoma, Ang II binding was very low and in several cases almost undetectable. There was no remarkable difference in the Ang II receptor affinity among all tissues tested. The ratio between type 1 and type 2 Ang II receptors showed a large prevalence of type 1 in controls, APA, and three cases of Cush; in two cases of Cush, this ratio was reversed. In conclusion, our data indicate that Ang II receptors are normally expressed in APA and can also be detected in Cush, whereas they have a very low density in Pheo and adrenal carcinoma. Therefore, Ang II receptors are not involved in the lack of response to Ang II that is characteristic of APA; additionally, a reduction of Ang II receptors can be associated with dedifferentiation or malignancy of adrenal tumors. Further investigation of the expression and functional characterization of Ang II receptors is required to better clarify their possible role in adrenal tumorigenesis.

  13. Prenatal Hormones and Postnatal Socialization by Parents as Determinants of Male-Typical Toy Play in Girls With Congenital Adrenal Hyperplasia

    ERIC Educational Resources Information Center

    Pasterski, Vickie L.; Geffner, Mitchell E.; Brain, Caroline; Hindmarsh, Peter; Brook, Charles; Hines, Melissa

    2005-01-01

    Toy choices of 3- to 10-year-old children with congenital adrenal hyperplasia (CAH) and of their unaffected siblings were assessed. Also assessed was parental encouragement of sex-typed toy play. Girls with CAH displayed more male-typical toy choices than did their unaffected sisters, whereas boys with and without CAH did not differ. Mothers and…

  14. Growth in disorders of adrenal hyperfunction.

    PubMed

    Magiakou, Maria Alexandra

    2004-08-01

    This article reviews how growth is affected in disorders of adrenal hyperfunction. Growth is disturbed by adrenal hypersecretion of androgens or cortisol. Adrenal androgens, when in excess, lead to advanced linear growth and skeletal maturation, and prolonged hypercortisolemia leads to the suppression of growth hormone (GH) secretion and inhibition of somatomedin C and other growth factor effects on their target tissues. In virilizing adrenal tumors height is increased at diagnosis, but after surgical cure the final height is usually in the normal range. In congenital adrenal hyperplasia height is usually compromised by advanced skeletal maturation or by suppressed growth, particularly in the first years of life, due to excess glucocorticoid treatment. The final height is reduced in both clinical forms (salt wasting and simple virilizing) and sexes in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Growth impairment is also the hallmark of Cushing syndrome of whatever etiology when it occurs in children and growing adolescents, and the final height of these patients, even after surgical cure, remains compromised. This is apparently due to direct or indirect growth impairment by the hypercortisolism during the disease, followed by inadequate catch-up growth. Although it seems that GH treatment might be beneficial for improving final height both in patients with congenital adrenal hyperplasia who have poor height predictions and in patients with Cushing disease and GH deficiency, a larger number of studies is needed to confirm this suggestion.

  15. Regulation of α3-containing GABAA receptors in guinea-pig adrenal medullary cells by adrenal steroids.

    PubMed

    Inoue, M; Harada, K; Nakamura, J; Matsuoka, H

    2013-12-03

    GABA is thought to function as a paracrine factor in adrenal medullary (AM) cells. Thus, we electrophysiologically and immunologically examined the properties of GABAA receptors (GABAARs) in guinea-pig AM cells. Bath application of GABA produced an inward current at -60 mV in a dose-dependent manner with an EC50 of 32.3 μM. This GABA-induced current was enhanced by allopregnanolone at concentrations of 0.01 μM and more. A prior exposure to allopregnanolone resulted in a decrease in an EC50 for GABA in activating GABAARs. The GABA-induced current was suppressed by Zn(2+) in a dose-dependent manner with an IC50 of 18 μM, whereas it was enhanced by 100 μM La(3+). The benzodiazepine analog diazepam was three times more potent than zolpidem in enhancing the GABA current, and it was also augmented by L-838,417, which has no action on α1-containing GABAARs. The GABAAR α3, but not α1, and γ2 subunits were immunologically detected at the cell periphery. The expression of α3 subunits in PC12 cells was enhanced by glucocorticoid activity. The results indicated that GABAARs in guinea-pig AM cells mainly comprise α3, β, and γ2 subunits and are enhanced by allopreganalone and glucocorticoids may play a major role in the expression of α3 subunits. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Immunocytochemical localization of metabotropic (mGluR2/3 and mGluR4a) and ionotropic (GluR2/3) glutamate receptors in adrenal medullary ganglion cells.

    PubMed

    Sarría, R; Díez, J; Losada, J; Doñate-Oliver, F; Kuhn, R; Grandes, P

    2006-02-01

    The localization of metabotropic glutamate receptors of groups II (mGluR2/3) and III (mGluR4a) and the subunits 2 and 3 of alfa-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) ionotropic glutamate receptors (GluR2/3) was investigated with immunocytochemical methods in the rat adrenal gland. MGluR2/3, mGluR4a and GluR2/3 immunoreactivities were observed in large-sized, centrally located type I adrenal medullary ganglion neurons. Furthermore, the small-sized type II adrenal ganglion neurons identified by their immunoreactivity to brain nitric oxide synthase (bNOS), also expressed mGluR2/3, mGluR4a and GluR2/3. These cells were disposed in the peripheral portion of the adrenal medulla. None of the type I neurons were positively labeled for bNOS. These morphological observations suggest that activation of glutamate receptors in ganglion neurons may be instrumental in the control of adrenal endocrine systems as well as blood regulation.

  17. A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in Adults With Congenital Adrenal Hyperplasia.

    PubMed

    Nella, Aikaterini A; Mallappa, Ashwini; Perritt, Ashley F; Gounden, Verena; Kumar, Parag; Sinaii, Ninet; Daley, Lori-Ann; Ling, Alexander; Liu, Chia-Ying; Soldin, Steven J; Merke, Deborah P

    2016-12-01

    Classic congenital adrenal hyperplasia (CAH) management remains challenging, given that supraphysiologic glucocorticoid doses are often needed to optimally suppress the ACTH-driven adrenal androgen overproduction. This study sought to approximate physiologic cortisol secretion via continuous subcutaneous hydrocortisone infusion (CSHI) and evaluate the safety and efficacy of CSHI in patients with difficult-to-treat CAH. Eight adult patients with classic CAH participated in a single-center open-label phase I-II study comparing CSHI to conventional oral glucocorticoid treatment. All patients had elevated adrenal steroids and one or more comorbidities at study entry. Assessment while receiving conventional therapy at baseline and 6 months following CSHI included: 24-hour hormonal sampling, metabolic and radiologic evaluation, health-related quality-of-life (HRQoL), and fatigue questionnaires. The ability of CSHI to approximate physiologic cortisol secretion and the percent of patients with 0700-hour 17-hydroxyprogesterone (17-OHP) ≤1200 ng/dL was measured. CSHI approximated physiologic cortisol secretion. Compared with baseline, 6 months of CSHI resulted in decreased 0700-hour and 24-hour area under the curve 17-OHP, androstenedione, ACTH, and progesterone, increased osteocalcin, c-telopeptide and lean mass, and improved HRQoL (and SF-36 Vitality Score), and fatigue. One of three amenorrheic women resumed menses. One man had reduction of testicular adrenal rest tissue. CSHI is a safe and well-tolerated modality of cortisol replacement that effectively approximates physiologic cortisol secretion in patients with classic CAH poorly controlled on conventional therapy. Improved adrenal steroid control and positive effects on HRQoL suggest that CSHI should be considered a treatment option for classic CAH. The long-term effect on established comorbidities requires further study.

  18. Inhibitory effects of pine nodule extract and its component, SJ-2, on acetylcholine-induced catecholamine secretion and synthesis in bovine adrenal medullary cells.

    PubMed

    Li, Xiaojia; Horishita, Takafumi; Toyohira, Yumiko; Shao, Hui; Bai, Jie; Bo, Haixia; Song, Xinbo; Ishikane, Shin; Yoshinaga, Yukari; Satoh, Noriaki; Tsutsui, Masato; Yanagihara, Nobuyuki

    2017-04-01

    Extract of pine nodules (matsufushi) formed by bark proliferation on the surface of trees of Pinus tabulaeformis or Pinus massoniana has been used as an analgesic for joint pain, rheumatism, neuralgia, dysmenorrhea and other complaints in Chinese traditional medicine. Here we report the effects of matsufushi extract and its components on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that matsufushi extract (0.0003-0.005%) and its component, SJ-2 (5-hydroxy-3-methoxy-trans-stilbene) (0.3-100 μM), but not the other three, concentration-dependently inhibited catecholamine secretion induced by acetylcholine, a physiological secretagogue. Matsufushi extract (0.0003-0.005%) and SJ-2 (0.3-100 μM) also inhibited 45 Ca 2+ influx induced by acetylcholine in a concentration-dependent manner, similar to its effect on catecholamine secretion. They also suppressed 14 C-catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, matsufushi extract (0.00003-0.001%) and SJ-2 (1-100 μM) directly inhibited the current evoked by acetylcholine. The present findings suggest that SJ-2, as well as matsufushi extract, inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  19. Reconstructive surgery for females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a review from the Prince of Wales Hospital.

    PubMed

    Houben, C H; Tsui, S Y; Mou, J W; Chan, K W; Tam, Y H; Lee, K H

    2014-12-01

    To present the results of feminising genitoplasty done in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Case series. A tertiary referral centre in Hong Kong. Female patients with congenital adrenal hyperplasia undergoing corrective surgery for virilisation between 1993 and 2012. The operative result was judged with a scoring system (1-3) for four areas: appearance of clitoris, labia and vagina, plus requirement for revision surgery. A total of 23 female patients with congenital adrenal hyperplasia with a median age of 17.5 (range, 1.5-33.8) years were identified. Of these individuals, 17 presented in the neonatal period and early infancy, of which four had an additional salt-losing crisis. Six patients-including four migrants from mainland China-were late presenters at a median age of 2 (range, 0.5-14) years. Twenty-two patients had corrective surgery at a median age of 2 (range, 1-14) years. Clitoral reduction was performed in all, and further surgery in 21 patients. The additional surgery was flap vaginoplasty in 10 patients, a modified Passerini procedure in six, and a labial reconstruction in five; one patient with prominent clitoris was for observation only. Minor revision surgery (eg mucosal trimming) was required in three patients; a revision vaginoplasty was done in one individual. Of the 23 patients, 18 (78%) with a median age of 20 (range, 9.3-33.8) years participated in the outcome evaluation: a 'good' outcome (4 points) was seen in 12 patients and a 'satisfactory' (5-9 points) result in five patients. Nearly three quarters of our cohort (n=17) presented with classic virilising form of 21-hydroxylase deficiency. Only four (25%) patients experienced a salt-losing crisis. Female gender assignment at birth was maintained for all individuals in this group. 'Good' and 'satisfactory' outcomes of surgery were reported in nearly all participants.

  20. Clinicopathological correlates of adrenal Cushing's syndrome.

    PubMed

    Duan, Kai; Hernandez, Karen Gomez; Mete, Ozgur

    2015-06-01

    Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Clinicopathological correlates of adrenal Cushing's syndrome.

    PubMed

    Duan, Kai; Gomez Hernandez, Karen; Mete, Ozgur

    2015-03-01

    Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in Adults With Congenital Adrenal Hyperplasia

    PubMed Central

    Mallappa, Ashwini; Perritt, Ashley F.; Gounden, Verena; Kumar, Parag; Sinaii, Ninet; Daley, Lori-Ann; Ling, Alexander; Liu, Chia-Ying; Soldin, Steven J.; Merke, Deborah P.

    2016-01-01

    Context: Classic congenital adrenal hyperplasia (CAH) management remains challenging, given that supraphysiologic glucocorticoid doses are often needed to optimally suppress the ACTH-driven adrenal androgen overproduction. Objective: This study sought to approximate physiologic cortisol secretion via continuous subcutaneous hydrocortisone infusion (CSHI) and evaluate the safety and efficacy of CSHI in patients with difficult-to-treat CAH. Design: Eight adult patients with classic CAH participated in a single-center open-label phase I–II study comparing CSHI to conventional oral glucocorticoid treatment. All patients had elevated adrenal steroids and one or more comorbidities at study entry. Assessment while receiving conventional therapy at baseline and 6 months following CSHI included: 24-hour hormonal sampling, metabolic and radiologic evaluation, health-related quality-of-life (HRQoL), and fatigue questionnaires. Main Outcome Measures: The ability of CSHI to approximate physiologic cortisol secretion and the percent of patients with 0700-hour 17-hydroxyprogesterone (17-OHP) ≤1200 ng/dL was measured. Results: CSHI approximated physiologic cortisol secretion. Compared with baseline, 6 months of CSHI resulted in decreased 0700-hour and 24-hour area under the curve 17-OHP, androstenedione, ACTH, and progesterone, increased osteocalcin, c-telopeptide and lean mass, and improved HRQoL (and SF-36 Vitality Score), and fatigue. One of three amenorrheic women resumed menses. One man had reduction of testicular adrenal rest tissue. Conclusions: CSHI is a safe and well-tolerated modality of cortisol replacement that effectively approximates physiologic cortisol secretion in patients with classic CAH poorly controlled on conventional therapy. Improved adrenal steroid control and positive effects on HRQoL suggest that CSHI should be considered a treatment option for classic CAH. The long-term effect on established comorbidities requires further study. PMID:27680873

  3. Genotype-Phenotype Correlation in 153 Adult Patients With Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: Analysis of the United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE) Cohort

    PubMed Central

    Krone, Nils; Rose, Ian T.; Willis, Debbie S.; Hodson, James; Wild, Sarah H.; Doherty, Emma J.; Hahner, Stefanie; Parajes, Silvia; Stimson, Roland H.; Han, Thang S.; Carroll, Paul V.; Conway, Gerry S.; Walker, Brian R.; MacDonald, Fiona; Arlt, Wiebke

    2013-01-01

    Context: In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a strong genotype-phenotype correlation exists in childhood. However, similar data in adults are lacking. Objective: The objective of the study was to test whether the severity of disease-causing CYP21A2 mutations influences the treatment and health status in adults with CAH. Research Design and Methods: We analyzed the genotype in correlation with treatment and health status in 153 adults with CAH from the United Kingdom Congenital adrenal Hyperplasia Adult Study Executive cohort. Results: CYP21A2 mutations were distributed similarly to previously reported case series. In 7 patients a mutation was identified on only 1 allele. Novel mutations were detected on 1.7% of alleles (5 of 306). Rare mutations were found on 2.3% of alleles (7 of 306). For further analysis, patients were categorized into CYP21A2 mutation groups according to predicted residual enzyme function: null (n = 34), A (n = 42), B (n = 36), C (n = 34), and D (n = 7). Daily glucocorticoid dose was highest in group null and lowest in group C. Fludrocortisone was used more frequently in patients with more severe genotypes. Except for lower female height in group B, no statistically significant associations between genotype and clinical parameters were found. Androgens, blood pressure, lipids, blood glucose, and homeostasis model assessment of insulin resistance were not different between groups. Subjective health status was similarly impaired across groups. Conclusions: In adults with classic CAH and women with nonclassic CAH, there was a weak association between genotype and treatment, but health outcomes were not associated with genotype. The underrepresentation of males with nonclassic CAH may reflect that milder genotypes result in a milder condition that is neither diagnosed nor followed up in adulthood. Overall, our results suggest that the impaired health status of adults with CAH coming to medical attention is

  4. Growth and development in children with classic congenital adrenal hyperplasia.

    PubMed

    Bonfig, Walter

    2017-02-01

    Final height outcome in classic congenital adrenal hyperplasia (CAH) has been of interest for many years. With analysis of growth patterns and used glucocorticoid regimens, enhanced treatment strategies have been developed and are still under development. Most of the current reports on final height outcome are confirmative of previous results. Final height data is still reported in cohorts that were diagnosed clinically and not by newborn screening. Clinical diagnosis of CAH leads to delayed diagnosis especially of simple virilizing CAH with significantly advanced bone age resulting in early pubertal development and reduced final height. In contrast salt-wasting CAH is diagnosed at an earlier stage in most cases resulting in better final height outcome in some cohorts. Nevertheless, final height outcome in patients with CAH treated with glucocorticoids is lower than the population norm and also at the lower end of genetic potential. Achievement of regular adult height is still a challenge with conventional glucocorticoid treatment in patients with CAH, which is why new hydrocortisone formulations and new treatment options for CAH are underway.

  5. Congenital Adrenal Hyperplasia in an Elite Female Soccer Player; What Sports Medicine Clinicians Should Know about This?

    PubMed

    Angoorani, Hooman; Haratian, Zohreh; Halabchi, Farzin

    2012-09-01

    Congenital Adrenal Hyperplasia (CAH) refers to a group of congenital conditions characterized by disordered cortisol synthesis. The correlation between CAH and sports performance has been less studied before and there is very limited information regarding the impacts of this congenital disease on sports performance. Probably, there are some limitations for patients who suffer from CAH in sports, but at the same time, they may enjoy some advantage due to the probable effect of endogenous hyperandrogenism on their exercise performance. The case is a 14 - year old girl with male phenotype who is a known case of congenital adrenal hyperplasia. She plays in the women's national soccer team of under 16. She has been in the first division league of indoor soccer for 4 years and was also selected in the preparation training camp of women's football team for Singapore's youth Olympic Games. Her illness and dependence on corticosteroid have caused some concerns for her participation in the international competitions of women. However, following consultations with the Therapeutic Use Exemption (TUE) Committee of games organization, she received TUE to use corticosteroid only within the games period. Despite all her problems, she is now playing in the Second Division League of indoor soccer. A female adolescent with CAH may compete at the high level of outdoor and indoor soccer. However, there are many questions regarding the advantages and disadvantages of this congenital disorder and its treatment on sports related issues.

  6. Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy.

    PubMed

    Pina, Christian; Khattab, Ahmed; Katzman, Philip; Bruckner, Lauren; Andolina, Jeffrey; New, Maria; Yau, Mabel

    2015-05-01

    A 14-year-old female with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency underwent bilateral adrenalectomy at 6 years of age as a result of poor hormonal control. Because the patient was adrenalectomized, extra adrenal androgen production was suspected. Imaging studies including pelvic ultrasound and pelvic magnetic resonance imaging (MRI) were obtained to evaluate for adrenal rest tumors of the ovaries. Abdominal MRI was obtained to evaluate for residual adrenal tissue. A cystic lesion arising from her right ovary suspicious for ovarian neoplasm was noted on pelvic MRI. Right salpingo-oophorectomy was performed and histopathological examination revealed ovarian serous adenocarcinoma, low-grade, and well-differentiated. Tumor marker CA-125 was elevated and additional ovarian cancer staging workup confirmed stage IIIC due to one lymph node positive for carcinoma. The patient then developed a large left ovarian cyst, which led to a complete total abdominal hysterectomy and removal of the left ovary and fallopian tube. Pathology confirmed ovarian serous adenocarcinoma with microscopic focus of carcinoma in the left ovary. After numerous complications, the patient responded well to chemotherapy, CA-125 levels fell and no evidence of carcinoma was observed on subsequent imaging. To our knowledge, this is the first reported case of an ovarian serous adenocarcinoma in a patient with CAH. Although rare, we propose that the ovaries were the origin of androgen production and not residual adrenal tissue. The relationship between CAH and ovarian carcinomas has yet to be established, but further evaluation is needed given the poor survival rate of high-grade serous ovarian carcinoma.

  7. Gender reversal in 46XX congenital virilizing adrenal hyperplasia.

    PubMed

    Sripathi, V; Ahmed, S; Sakati, N; al-Ashwal, A

    1997-05-01

    To review the results of gender reversal in six patients with 46XX congenital virilizing adrenal hyperplasia (CVAH). Fifty-one patients with 46XX CVAH were seen in an 8 year period; 45 were managed by conventional feminizing genitoplasty, but six underwent gender reversal and were managed as males. The clinical decision for gender reversal was made after appropriate counselling and was based primarily on parental choice, this being influenced significantly by a delayed diagnosis in four patients. Surgical management consisted of gonadectomy, excision of Müllerian structures and staged hypospadias repair/ chordee correction in four patients, and circumcision in two completely masculinized children. All six boys are well adjusted to their gender of rearing, with ages ranging from 3 years to 16.5 years (mean 8.5) at the time of review. Two children have normal penises and four have a satisfactory result after two-stage repair of hypospadias/chordee. Most patients with 46XX CVAH are preferably raised as females and require a feminizing genitoplasty. However, the clinical decision may be influenced by many factors, including delay in diagnosis, social bias and the premium on male rearing in certain communities. When male rearing is chosen, early gonadectomy and excision of Müllerian structures, together with staged hypospadias repair, gives satisfactory results.

  8. Steroid hormone receptors ERalpha and PR characterised by immunohistochemistry in the mare adrenal gland.

    PubMed

    Alm, Ylva Hedberg; Sukjumlong, Sayamon; Kindahl, Hans; Dalin, Anne-Marie

    2009-07-22

    Sex steroid hormone receptors have been identified in the adrenal gland of rat, sheep and rhesus monkey, indicating a direct effect of sex steroids on adrenal gland function. In the present study, immunohistochemistry using two different mouse monoclonal antibodies was employed to determine the presence of oestrogen receptor alpha (ERalpha) and progesterone receptor (PR) in the mare adrenal gland. Adrenal glands from intact (n = 5) and ovariectomised (OVX) (n = 5) mares, as well as uterine tissue (n = 9), were collected after euthanasia. Three of the OVX mares were treated with a single intramuscular injection of oestradiol benzoate (2.5 mg) 18-22 hours prior to euthanasia and tissue collection (OVX+Oe). Uterine tissue was used as a positive control and showed positive staining for both ERalpha and PR. ERalpha staining was detected in the adrenal zona glomerulosa, fasciculata and reticularis of all mare groups. Ovariectomy increased cortical ERalpha staining intensity. In OVX mares and one intact mare, positive ERalpha staining was also detected in adrenal medullary cells. PR staining of weak intensity was present in a low proportion of cells in the zona fasciculata and reticularis of all mare groups. Weak PR staining was also found in a high proportion of adrenal medullary cells. In contrast to staining in the adrenal cortex, which was always located within the cell nuclei, medullary staining for both ERalpha and PR was observed only in the cell cytoplasm. The present results show the presence of ERalpha in the adrenal cortex, indicating oestradiol may have a direct effect on mare adrenal function. However, further studies are needed to confirm the presence of PR as staining in the present study was only weak and/or minor. Also, any possible effect of oestradiol treatment on the levels of steroid receptors cannot be determined by the present study, as treatment time was of a too short duration.

  9. Lipoid congenital adrenal hyperplasia due to STAR mutations in a Caucasian patient.

    PubMed

    Kaur, Jasmeet; Casas, Luis; Bose, Himangshu S

    2016-01-01

    Lipoid congenital adrenal hyperplasia (lipoid CAH), the most severe form of CAH, is most commonly caused by mutations in steroidogenic acute regulatory protein (STAR), which is required for the movement of cholesterol from the outer to the inner mitochondrial membranes to synthesize pregnenolone. This study was performed to evaluate whether the salt-losing crisis and the adrenal inactivity experienced by a Scandinavian infant is due to a de novo STAR mutation. The study was conducted at the University of North Dakota, the Mercer University School of Medicine and the Memorial University Medical Center to identify the cause of this disease. The patient was admitted to a pediatric endocrinologist at the Sanford Health Center for salt-losing crisis and possible adrenal failure. Lipoid CAH is an autosomal recessive disease, we identified two de novo heterozygous mutations (STAR c.444C>A (STAR p.N148K) and STAR c.557C>T (STAR p.R193X)) in the STAR gene, causing lipoid CAH. New onset lipoid CAH can occur through de novo mutations and is not restricted to any specific region of the world. This Scandinavian family was of Norwegian descent and had lipoid CAH due to a mutation in S TAR exons 4 and 5. Overexpression of the STAR p.N148K mutant in nonsteroidogenic COS-1 cells supplemented with an electron transport system showed activity similar to the background level, which was ∼10% of that observed with wild-type (WT) STAR. Protein-folding analysis showed that the finger printing of the STAR p.N148K mutant is also different from the WT protein. Inherited STAR mutations may be more prevalent in some geographical areas but not necessarily restricted to those regions. STAR mutations cause lipoid CAH.This is a pure population from a caucasian family.Mutation ablated STAR activity.The mutation resulted in loosely folded conformation of STAR.

  10. Adrenal venous sampling for stratifying patients for surgery of adrenal nodules detected using dynamic contrast enhanced CT

    PubMed Central

    Kim, Jin Young; Kim, See Hyung; Lee, Hee Jung; Kim, Young Hwan; Kim, Mi Jeong; Cho, Seung Hyun

    2014-01-01

    PURPOSE We aimed to assess the value of adrenal venous sampling (AVS) for diagnosing primary aldosteronism (PA) subtypes in patients with a unilateral nodule detected on adrenal computed tomography (CT) and scheduled for adrenalectomy. MATERIALS AND METHODS This retrospective study included 80 consecutive patients with PA undergoing CT and AVS. Different lateralization indices were assessed, and a cutoff established using receiver operating characteristic curve analysis. The value of CT alone versus CT with AVS for differentiating PA subtypes was compared. The adrenalectomy outcome was assessed, and predictors of cure were determined using univariate analysis. RESULTS AVS was successful in 68 patients. A cortisol-corrected aldosterone affected-to-unaffected ratio cutoff of 2.0 and affected-to-inferior vena cava ratio cutoff of 1.4 were the best lateralization indices, with accuracies of 82.5% and 80.4%, respectively. CT and AVS diagnosed 38 patients with aldosterone-producing adenomas, five patients with unilateral adrenal hyperplasia, and 25 patients with bilateral adrenal hyperplasia. Of the 52 patients with a nodule detected on CT, subsequent AVS diagnosed bilateral adrenal hyperplasia in 14 patients (27%). Compared to the results of combining CT with AVS, the accuracy of CT alone for diagnosing aldosterone-producing adenomas was 71.1% (P < 0.001). The cure rate for hypertension after adrenalectomy was 39.2%, with improvement in 53.5% of patients. On univariate analysis, predictors of persistent hypertension were male gender and preoperative systolic blood pressure. CONCLUSION To avoid inappropriate surgery, AVS is necessary for diagnosing unilateral nodules with aldosterone hypersecretion detected by CT. PMID:24047720

  11. Identification of five novel STAR variants in ten Chinese patients with congenital lipoid adrenal hyperplasia.

    PubMed

    Huang, Zhuo; Ye, Jun; Han, Lianshu; Qiu, Wenjuan; Zhang, Huiwen; Yu, Yongguo; Liang, Lili; Gong, Zhuwen; Gu, Xuefan

    2016-04-01

    Congenital lipoid adrenal hyperplasia (CLAH) is a rare autosomal recessive disorder caused by defective synthesis of all steroids. This disorder is characterized by 46,XY sex reversal, skin hyperpigmentation, early-onset adrenal crisis and enlarged adrenal with fatty accumulation. CLAH is caused by mutations in the STAR gene. The clinical features and STAR gene mutation spectrum of a large cohort of Chinese patients with CLAH were not reported previously. We performed clinical retrospective review and genetic analysis of the STAR gene in ten unrelated Chinese phenotypic female patients who were clinically diagnosed with CLAH and followed up in our hospital from 2006 to 2015. All ten patients, including two 46,XY females and eight 46,XX females, presented skin hyperpigmentation and early salt-wasting episode, and showed normal growth and development after steroid replacement treatment. Totally 20 mutant alleles containing 11 different STAR gene mutations were identified in these ten patients, including five novel variants (two missense and three null variants), all predicted to be pathogenic in bioinformatics analysis, and six mutations described in previous literature. Among these 11 mutations, a reported mutation c.772C>T and a novel variant c.707_708delinsCTT were most frequent, accounting for 35% and 15% of the total mutant alleles, respectively. This is the first report of a large Chinese cohort with CLAH, presenting the mutation spectrum of the STAR gene and two possible founder mutations in the Chinese population, which may contribute to better genetic counseling and prenatal diagnosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. The effect of bedrest on adrenal function

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Hulley, S. B.; Rambaut, P. C.; Dietlein, L. F.

    1973-01-01

    Eight male subjects were subjected to continuous bedrest for 24-80 weeks for the purpose of studying metabolic responses. Three of the subjects did supine exercises daily during part of the study. Adrenal function was examined in relation to adrenal cortical and medullary excretions. The results reveal an increase in hydrocortisone throughout the test period, a decrease in norepinephrine and no change in epinephrine. These data suggest that exercise could decrease the severity of deconditioning caused by bedrest.

  13. Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing's syndrome.

    PubMed

    Lecoq, Anne-Lise; Stratakis, Constantine A; Viengchareun, Say; Chaligné, Ronan; Tosca, Lucie; Deméocq, Vianney; Hage, Mirella; Berthon, Annabel; Faucz, Fabio R; Hanna, Patrick; Boyer, Hadrien-Gaël; Servant, Nicolas; Salenave, Sylvie; Tachdjian, Gérard; Adam, Clovis; Benhamo, Vanessa; Clauser, Eric; Guiochon-Mantel, Anne; Young, Jacques; Lombès, Marc; Bourdeau, Isabelle; Maiter, Dominique; Tabarin, Antoine; Bertherat, Jérôme; Lefebvre, Hervé; de Herder, Wouter; Louiset, Estelle; Lacroix, André; Chanson, Philippe; Bouligand, Jérôme; Kamenický, Peter

    2017-09-21

    GIP-dependent Cushing's syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing's syndrome and one patient with GIP-dependent aldosteronism. GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had a 19q duplication only. We demonstrated that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in adenoma cells. Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing's syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations.

  14. Unilateral Adrenalectomy as a First-Line Treatment of Cushing's Syndrome in Patients With Primary Bilateral Macronodular Adrenal Hyperplasia.

    PubMed

    Debillon, Emmanuelle; Velayoudom-Cephise, Fritz-Line; Salenave, Sylvie; Caron, Philippe; Chaffanjon, Philippe; Wagner, Tristan; Massoutier, Maximilien; Lambert, Benoit; Benoit, Marine; Young, Jacques; Tabarin, Antoine; Chabre, Olivier

    2015-12-01

    Bilateral adrenalectomy is the reference treatment for Cushing's syndrome (CS) related to primary bilateral macronodular adrenal hyperplasia (PBMAH). It is, however, responsible for definitive adrenal insufficiency. The objective of the study was to evaluate the clinical interest of unilateral adrenalectomy (UA) of the larger gland for the treatment of CS related to PBMAH. This was a retrospective study in four tertiary French centers including all 15 patients with PBMAH and CS who underwent UA of the larger gland between 2001 and 2015. Urinary free cortisol, plasma cortisol, ACTH, body mass index, blood pressure, plasma glucose, and lipids were registered pre- and postoperatively and on follow-up. Median follow-up was 60 months (interquartile range 39-105), including 8 of 15 patients followed up for at least 5 years. A normal or low urinary free cortisol was obtained in 15 of 15 patients (100%) postoperatively. Six patients (40%) became adrenal insufficient, of whom three of six recovered a quantitatively normal cortisol secretion on follow-up. Decrease of both body mass index and blood pressure were observed at 1 year, and decrease of blood pressure was persistent 5 years postoperatively. Diabetes was cured in four of six patients. Two patients experienced a recurrence of hypercortisolism, and one was treated with mitotane, whereas the other underwent a second adrenal surgery 9 years after initial UA. UA induced remission of hypercortisolism in all patients, with sustained significant clinical improvement. The rates of both definitive adrenal insufficiency and 5-year recurrence were low. UA appears an interesting alternative to bilateral adrenalectomy as a first-line treatment in PBMAH responsible for overt CS.

  15. Long-term follow-up of a female with congenital adrenal hyperplasia due to P450-oxidoreductase deficiency.

    PubMed

    Bonamichi, Beatriz D S F; Santiago, Stella L M; Bertola, Débora R; Kim, Chong A; Alonso, Nivaldo; Mendonca, Berenice B; Bachega, Tania A S S; Gomes, Larissa G

    2016-10-01

    P450 oxidoreductase deficiency (PORD) is a variant of congenital adrenal hyperplasia that is caused by POR gene mutations. The POR gene encodes a flavor protein that transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH) to all microsomal cytochrome P450 type II (including 21-hydroxylase, 17α-hydroxylase 17,20 lyase and aromatase), which is fundamental for their enzymatic activity. POR mutations cause variable impairments in steroidogenic enzyme activities that result in wide phenotypic variability ranging from 46,XX or 46,XY disorders of sexual differentiation, glucocorticoid deficiency, with or without skeletal malformations similar to Antley-Bixler syndrome to asymptomatic newborns diagnosed during neonatal screening test. Little is known about the PORD long-term evolution. We described a 46,XX patient with mild atypical genitalia associated with severe bone malformation, who was diagnosed after 13 years due to sexual infantilism. She developed large ovarian cysts and late onset adrenal insufficiency during follow-up, both of each regressed after hormone replacement therapies. We also described a late surgical approach for the correction of facial hypoplasia in a POR patient.

  16. Polycystic ovarian disease: the adrenal connection.

    PubMed

    Marouliss, George B; Triantafillidis, Ioannis K

    2006-01-01

    Polycystic ovarian disease (PCOD) is characterized by hyperandrogenemia, ovulatory dysfunction and polycystic ovaries (PCO). The increased androgen production in PCOD comes primarily from the ovaries. However, in about 40% of patients there is excessive adrenal androgen production (DHEA, DHEA-Sulfate, Androstenedione, Testosterone and Dihydrotestosterone). The contribution of the adrenal in the PCOD is suggested by the presence of adrenal androgen excess in PCO, the presence of PCO in women with enzymatic adrenal hyperplasia as well as in women with adrenal tumors. However, the cause of adrenal androgen hypersecretion is not yet fully understood but it may include endogenous hypersecretion of the zona reticularis of unclear cause, hypersecretion of cortical-androgen-stimulating hormone (CASH), stress, hyperprolactinemia, adrenal enzymatic defects etc. This short review covers the aspects of adrenal androgen hypersecretion in PCOD.

  17. [The effects of anterio-posterior and dorso-ventral inversions of the lateral mesoblast of the neurula on the formation of the mesonephric, medullary, and adrenal anlage of the common toad, Bufo bufo L. (Amphibia, Anoura)].

    PubMed

    Gipouloux, J D; Hakim, J

    1975-10-13

    The experimental results of cranio-caudal reversal and dorso-ventral reversal of the lateral mesoblast of the toad early neurula prove that, at this stage, the cranio-caudal polarity of this tissue is fixed but not the dorso-ventral one. External factors are responsible for the formation of mesonephric, adrenal and gonadal medullary anlage by the lateral mesoblast.

  18. Expression and regulation of CNTF receptor-alpha in the in situ and in oculo grafted adult rat adrenal medulla.

    PubMed

    Förander, P; Brené, S; Strömberg, I

    2000-02-28

    Cultured and transplanted adrenal medullary cells respond to ciliary neurotrophic factor (CNTF) with neurite formation and improved cell survival although the presence of the CNTF receptor-alpha (CNTFRalpha) has been unclear. This study show that CNTFRalpha mRNA was expressed in the postnatal day 1 as well as in the adult rat adrenal medulla. The highest CNTFRalpha mRNA signal was found in the ganglion cells of the adrenal medulla. After transplantation of adrenal medullary tissue the CNTFRalpha mRNA levels were down-regulated in the chromaffin cells. CNTF treatment of grafts did not normalize the receptor levels, but treatment with nerve growth factor (NGF) did. Thus, we demonstrate that CNTFRalpha mRNA is expressed in adrenal medulla, the levels becomes down-regulated after transplantation, but normalized after treatment with NGF.

  19. Coexistence of Cushing syndrome from functional adrenal adenoma and Addison disease from immune-mediated adrenalitis.

    PubMed

    Colucci, Randall; Jimenez, Rafael E; Farrar, William; Malgor, Ramiro; Kohn, Leonard; Schwartz, Frank L

    2012-06-01

    A 56-year-old woman presented with an incidental adrenal adenoma and physical examination findings that included moderate obesity, a slight cervicothoracic fat pad ("buffalo hump"), increased supraclavicular fat pads, and white abdominal striae. Biochemical workup revealed elevated levels of 24-hour urinary free cortisol but normal serum morning cortisol and suppressed levels of corticotropin, suggestive of adrenal-dependent Cushing syndrome. The resected adrenal gland revealed macronodular cortical hyperplasia with a dominant nodule. Other findings included an absent cortisol response to corticotropin stimulation, presence of serum anti-21-hydroxylase antibodies, and mononuclear cell infiltration--consistent with adrenalitis. The findings represent, to the authors' knowledge, the first known case of a patient with coexistent functional cortisol-secreting macronodular adrenal tumor resulting in Cushing syndrome and immune-mediated adrenalitis resulting in Addison disease.

  20. MANAGEMENT OF ENDOCRINE DISEASE: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: update on the management of adult patients and prenatal treatment.

    PubMed

    Bachelot, Anne; Grouthier, Virginie; Courtillot, Carine; Dulon, Jérôme; Touraine, Philippe

    2017-04-01

    Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by cortisol and in some cases aldosterone deficiency associated with androgen excess. Goals of treatment are to replace deficient hormones and control androgen excess, while avoiding the adverse effects of exogenous glucocorticoid. Over the last 5 years, cohorts of adults with CAH due to 21-hydroxylase deficiency from Europe and the United States have been described, allowing us to have a better knowledge of long-term complications of the disease and its treatment. Patients with CAH have increased mortality, morbidity and risk for infertility and metabolic disorders. These comorbidities are due in part to the drawbacks of the currently available glucocorticoid therapy. Consequently, novel therapies are being developed and studied in an attempt to improve patient outcomes. New management strategies in the care of pregnancies at risk for congenital adrenal hyperplasia using fetal sex determination and dexamethasone have also been described, but remain a subject of debate. We focused the present overview on the data published in the last 5 years, concentrating on studies dealing with cardiovascular risk, fertility, treatment and prenatal management in adults with classic CAH to provide the reader with an updated review on this rapidly evolving field of knowledge. © 2017 European Society of Endocrinology.

  1. Manifestations and characteristics of congenital adrenal hyperplasia-associated encephalopathy.

    PubMed

    Abe, Yuichi; Sakai, Tetsuro; Okumura, Akihisa; Akaboshi, Shinjiro; Fukuda, Mitsumasa; Haginoya, Kazuhiro; Hamano, Shin-Ichiro; Hirano, Kouichi; Kikuchi, Kenjiro; Kubota, Masaya; Lee, Sooyoung; Maegaki, Yoshihiro; Sanefuji, Masafumi; Shimozato, Sachiko; Suzuki, Motomasa; Suzuki, Yasuhiro; Takahashi, Mitsugi; Watanabe, Kenji; Mizuguchi, Masashi; Yamanouchi, Hideo

    2016-08-01

    This study aimed to clarify the characteristics of acute encephalopathic episodes in patients with congenital adrenal hyperplasia (CAH), which we termed "CAH-associated encephalopathy (CAHE)." This retrospective study was conducted using a questionnaire as a nationwide survey of patients with CAH with acute encephalopathy and related episodes. Fifteen patients were recruited on the bases of clinical data that supported a diagnosis of CAHE. Fourteen patients displayed seizures at onset, and 12 patients exhibited refractory seizures. Deep coma lasting >24h was noted in 12 patients. Neuroimaging studies revealed some heterogeneous features. Diffuse or focal edematous lesions in the cerebrum, which produce high signal intensity on diffusion-weighted magnetic resonance imaging or low density on computer tomography, were found in the acute period in all 15 patients. In the chronic period, 14 patients survived, 11 of whom had some degree of neurological sequelae. Moreover, various degrees of cerebral shrinkage were observed in 11 of 14 surviving patients. Surprisingly, there were no abnormal neuroimaging findings in the basal ganglia, brainstem, and cerebellum in any patient. Our results indicated that patients with CAH have a risk of developing CAHE, and thus, they should be followed closely because not only status epilepticus or deep coma but also minor symptoms, such as fever and nausea, may lead to CAHE. Because CAHE may feature some heterogeneous encephalopathic episodes, further validation is needed to clarify its etiology. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  2. Gender Identity in Patients with Congenital Adrenal Hyperplasia.

    PubMed

    Razzaghy-Azar, Maryam; Karimi, Sakineh; Shirazi, Elham

    2017-07-01

    Sex assignment in infancy for patients with disorder of sex development (DSD) is a challenging problem. Some of the patients with congenital adrenal hyperplasia (CAH) have DSD that may affect their gender identity. The study aimed to assess gender identity in patients with CAH. In this study, 52 patients with CAH, including 22 prepubertal children and 30 adolescents and adults, were assessed using two separate gender identity questionnaires for children and adults based on the criteria of diagnostic and statistical manual of mental disorders, 5th edition. In the children group, compatibility was seen between gender identity and rearing gender. In the adult group, there were three cases of mismatching between gender identity and sex assignment composed of two females with poor control and one male with good control with 21-hydroxylase deficiency (21-OHD). Three girls with 11-hydroxylase deficiency (11-OHD) were reared as boy. Two of them with late diagnosis at 5 and 6 years of age had pseudoprecocious puberty. Parents and children did not accept to change the gender. One of them is 36 years old now, is depressed and unsatisfied with her gender, another girl is still child and has male sexual identity. One girl with 11-OHD and early diagnosis at birth with Prader 5 virilization but with good hormonal control was changed to female gender at 12 years of age when female sexual characteristics appeared; she is 34-years-old now, married, and with two children, and she is satisfied with her gender. In patients with CAH, gender identity disorder is a rare finding. Hormonal control, social, familial, and religious beliefs have impacts on gender identity of these patients.

  3. Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome

    PubMed Central

    Lecoq, Anne-Lise; Stratakis, Constantine A.; Viengchareun, Say; Chaligné, Ronan; Tosca, Lucie; Hage, Mirella; Berthon, Annabel; Faucz, Fabio R.; Hanna, Patrick; Boyer, Hadrien-Gaël; Servant, Nicolas; Salenave, Sylvie; Tachdjian, Gérard; Adam, Clovis; Benhamo, Vanessa; Clauser, Eric; Guiochon-Mantel, Anne; Young, Jacques; Lombès, Marc; Bourdeau, Isabelle; Maiter, Dominique; Tabarin, Antoine; Bertherat, Jérôme; Lefebvre, Hervé; Louiset, Estelle; Lacroix, André; Bouligand, Jérôme; Kamenický, Peter

    2017-01-01

    GIP-dependent Cushing’s syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing’s syndrome and one patient with GIP-dependent aldosteronism. GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had a 19q duplication only. We demonstrated that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in adenoma cells. Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing’s syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations. PMID:28931750

  4. Transition of Care from Childhood to Adulthood: Congenital Adrenal Hyperplasia.

    PubMed

    Bachelot, Anne

    2018-01-01

    Deficiency of the 21-hydroxylase enzyme is the most common form of congenital adrenal hyperplasia (CAH), accounting for more than 95% of the cases. With the advent of newborn screening and hormone replacement therapy, most children with CAH survive into adulthood. Adolescents and adults with CAH experience a number of complications, including short stature, obesity, infertility, impaired bone mineral density, and reduced quality of life. Transition from pediatric to adult care and management of long-term complications are challenging for both patients and practitioners. In adulthood, the aims of the medical treatment are to substitute cortisol and, when necessary, aldosterone deficiency, to ensure normal fertility, and to avoid the long-term consequences of glucocorticoid use on bone, metabolism, and cardiovascular risk. Recent data suggest that poor health status is likely to begin in adolescence and persist into adulthood, highlighting the importance of this time period in a patient's endocrine care. During transition from pediatric to adult specific care, a shift in treatment goals is thus needed. Successful transition from pediatric to adult health care requires a regular follow-up of patients by a multidisciplinary team including pediatric endocrinologists, urologists, gynecologists, psychiatrists, and adult endocrinologists. All of this could be included in a specific therapeutic education program regarding transition and/or CAH. © 2018 S. Karger AG, Basel.

  5. Bilateral adrenal masses: a single-centre experience

    PubMed Central

    Bandgar, Tushar; Khare, Shruti; Jadhav, Swati; Lila, Anurag; Goroshi, Manjunath; Kasaliwal, Rajeev; Khadilkar, Kranti; Shah, Nalini S

    2016-01-01

    Background Bilateral adrenal masses may have aetiologies like hyperplasia and infiltrative lesions, besides tumours. Hyperplastic and infiltrative lesions may have coexisting hypocortisolism. Bilateral tumours are likely to have hereditary/syndromic associations. The data on clinical profile of bilateral adrenal masses are limited. Aims To analyse clinical, biochemical and radiological features, and management outcomes in patients with bilateral adrenal masses. Methods Retrospective analysis of 70 patients with bilateral adrenal masses presenting to a single tertiary care endocrine centre from western India (2002–2015). Results The most common aetiology was pheochromocytoma (40%), followed by tuberculosis (27.1%), primary adrenal lymphoma (PAL) (10%), metastases (5.7%), non-functioning adenomas (4.3%), primary bilateral macronodular adrenal hyperplasia (4.3%), and others (8.6%). Age at presentation was less in patients with pheochromocytoma (33 years) and tuberculosis (41 years) compared with PAL (48 years) and metastases (61 years) (P<0.001). The presenting symptoms for pheochromocytoma were hyperadrenergic spells (54%) and abdominal pain (29%), whereas tuberculosis presented with adrenal insufficiency (AI) (95%). The presenting symptoms for PAL were AI (57%) and abdominal pain (43%), whereas all cases of metastasis had abdominal pain. Mean size of adrenal masses was the largest in lymphoma (5.5cm) followed by pheochromocytoma (4.8cm), metastasis (4cm) and tuberculosis (2.1cm) (P<0.001). Biochemically, most patients with pheochromocytoma (92.8%) had catecholamine excess. Hypocortisolism was common in tuberculosis (100%) and PAL (71.4%) and absent with metastases (P<0.001). Conclusion In evaluation of bilateral adrenal masses, age at presentation, presenting symptoms, lesion size, and biochemical features are helpful in delineating varied underlying aetiologies. PMID:27037294

  6. Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 oxidoreductase deficiency.

    PubMed

    Idkowiak, Jan; O'Riordan, Stephen; Reisch, Nicole; Malunowicz, Ewa M; Collins, Felicity; Kerstens, Michiel N; Köhler, Birgit; Graul-Neumann, Luitgard Margarete; Szarras-Czapnik, Maria; Dattani, Mehul; Silink, Martin; Shackleton, Cedric H L; Maiter, Dominique; Krone, Nils; Arlt, Wiebke

    2011-03-01

    P450 oxidoreductase (POR) is a crucial electron donor to all microsomal P450 cytochrome (CYP) enzymes including 17α-hydroxylase (CYP17A1), 21-hydroxylase (CYP21A2) and P450 aromatase. Mutant POR causes congenital adrenal hyperplasia with combined glucocorticoid and sex steroid deficiency. P450 oxidoreductase deficiency (ORD) commonly presents neonatally, with disordered sex development in both sexes, skeletal malformations, and glucocorticoid deficiency. The aim of the study was to describe the clinical and biochemical characteristics of ORD during puberty. Clinical, biochemical, and genetic assessment of seven ORD patients (five females, two males) presenting during puberty was conducted. Predominant findings in females were incomplete pubertal development (four of five) and large ovarian cysts (five of five) prone to spontaneous rupture, in some only resolving after combined treatment with estrogen/progestin, GnRH superagonists, and glucocorticoids. Pubertal development in the two boys was more mildly affected, with some spontaneous progression. Urinary steroid profiling revealed combined CYP17A1 and CYP21A2 deficiencies indicative of ORD in all patients; all but one failed to mount an appropriate cortisol response to ACTH stimulation indicative of adrenal insufficiency. Diagnosis of ORD was confirmed by direct sequencing, demonstrating disease-causing POR mutations. Delayed and disordered puberty can be the first sign leading to a diagnosis of ORD. Appropriate testosterone production during puberty in affected boys but manifest primary hypogonadism in girls with ORD may indicate that testicular steroidogenesis is less dependent on POR than adrenal and ovarian steroidogenesis. Ovarian cysts in pubertal girls may be driven not only by high gonadotropins but possibly also by impaired CYP51A1-mediated production of meiosis-activating sterols due to mutant POR.

  7. Stigma Associated with Classical Congenital Adrenal Hyperplasia in Women's Sexual Lives.

    PubMed

    Meyer-Bahlburg, Heino F L; Khuri, Jananne; Reyes-Portillo, Jazmin; Ehrhardt, Anke A; New, Maria I

    2018-05-01

    The risk of intersex-related stigma often serves as social indication for "corrective" genital surgery, but has not been comprehensively documented. In preparation for the development of an intersex-specific stigma assessment tool, this qualitative project aimed to explore stigma in girls and women with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. As part of a comprehensive follow-up project, 62 adult women with classical CAH (age range 18-51 years) took part in an open-ended retrospective interview focusing on the impact of CAH and its treatment on various aspects of girls' and women's lives. Deductive qualitative content analysis (Patton, 2014) of de-identified transcripts involved categorization of three types of stigma: experienced, anticipated, and internalized. Two-fifths of the participants reported CAH-related stigma in romantic/sexual situations. Stigma enactment by romantic partners occurred in reaction to both genital and non-genital sex-atypical features of CAH and sometimes included explicit questioning of the women's true gender. Stigma anticipation by the women and their related avoidance of nudity, genital exposure, and romantic involvement altogether were frequent. Internalization of stigma occurred as well. In conclusion, the data suggest that many women with CAH experience, anticipate, and/or internalize intersex-related stigma in the context of their romantic/sexual lives.

  8. Gender Identity in Patients with Congenital Adrenal Hyperplasia

    PubMed Central

    Razzaghy-Azar, Maryam; Karimi, Sakineh; Shirazi, Elham

    2017-01-01

    Background Sex assignment in infancy for patients with disorder of sex development (DSD) is a challenging problem. Some of the patients with congenital adrenal hyperplasia (CAH) have DSD that may affect their gender identity. Objectives The study aimed to assess gender identity in patients with CAH. Methods In this study, 52 patients with CAH, including 22 prepubertal children and 30 adolescents and adults, were assessed using two separate gender identity questionnaires for children and adults based on the criteria of diagnostic and statistical manual of mental disorders, 5th edition. Results In the children group, compatibility was seen between gender identity and rearing gender. In the adult group, there were three cases of mismatching between gender identity and sex assignment composed of two females with poor control and one male with good control with 21-hydroxylase deficiency (21-OHD). Three girls with 11-hydroxylase deficiency (11-OHD) were reared as boy. Two of them with late diagnosis at 5 and 6 years of age had pseudoprecocious puberty. Parents and children did not accept to change the gender. One of them is 36 years old now, is depressed and unsatisfied with her gender, another girl is still child and has male sexual identity. One girl with 11-OHD and early diagnosis at birth with Prader 5 virilization but with good hormonal control was changed to female gender at 12 years of age when female sexual characteristics appeared; she is 34-years-old now, married, and with two children, and she is satisfied with her gender. Conclusions In patients with CAH, gender identity disorder is a rare finding. Hormonal control, social, familial, and religious beliefs have impacts on gender identity of these patients. PMID:29201068

  9. Recommendations for Treatment of Nonclassic Congenital Adrenal Hyperplasia (NCCAH): an Update

    PubMed Central

    Trapp, Christine M.; Oberfield, Sharon E.

    2013-01-01

    Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders. 21-hydroxylase deficiency, in which there are mutations in CYP21A2 (the gene encoding the adrenal 21-hydroxylase enzyme), is the most common form (90%) of CAH. In classic CAH there is impaired cortisol production with diagnostic increased levels of 17-OH progesterone. Excess androgen production results in virilization and in the newborn female may cause development of ambiguous external genitalia. Three-fourths of patients with classic CAH also have aldosterone insufficiency, which can result in salt-wasting; in infancy this manifests as shock, hyponatremia and hyperkalemia. CAH has a reported incidence of 1:10,000–1:20,000 births although there is an increased prevalence in certain ethnic groups. Nonclassic CAH (NCCAH) is a less severe form of the disorder, in which there is 20–50% of 21-hydroxylase enzyme activity (vs. 0–5% in classic CAH) and no salt wasting. The degree of symptoms related to androgen excess is variable and may be progressive with age, although some individuals are asymptomatic. NCCAH has an incidence of 1:1000–1:2000 births (0.1–0.2% prevalence) in the White population; an even higher prevalence is noted in certain ethnic groups such as Ashkenazi Jews (1–2%). As many as two-thirds of persons with NCCAH are compound heterozygotes and carry a severe and mild mutation on different alleles. This paper discusses the genetics of NCCAH, along with its variable phenotypic expression, and reviews the clinical course in untreated patients, which includes rapid early childhood growth, advanced skeletal age, premature adrenarche, acne, impaired reproductive function in both sexes and hirsutism as well as menstrual disorders in females. Finally, it addresses treatment with glucocorticoids vs. and other alternatives, particularly with respect to long term issues such as adult metabolic disease including insulin resistance, cardiovascular disease, metabolic syndrome

  10. Thyroid and adrenal relationships

    PubMed Central

    Parsons, Victor; Ramsay, Ian

    1968-01-01

    A brief review of the actions of adrenal medullary and thyroid hormones is presented and the ways in which they interact are examined. It is concluded that thyroid hormone produces the necessary intracellular environment without which the steady state and emergency actions of cathecholamines would be vitiated. In hyperthyroidism the increased concentration of thyroid hormones results in a lowering of the threshold for catecholamine action. For this reason it is possible to alleviate many of the symptoms of thyrotoxicosis by means of drugs which block β-adrenergic receptors. Attention is also drawn to the simultaneous occurrence of thyroid and adrenal disease, in the hope that this will encourage the search for further links in this field of endocrinology. PMID:5655216

  11. [Congenital adrenal hyperplasia due to lack of 17α-hydroxylase: a report of a new mutation in the gene CYP17A1].

    PubMed

    Perales Martínez, J I; Pina Marqués, B; de Arriba Muñoz, A; Mayayo Dehesa, E; Labarta Aizpún, J I; Loidi Fernández, L

    2015-01-01

    P450c17 enzyme catalyses two different reactions: the 17α-hydroxylation of progesterone and pregnenolone, and segmenting the carbon 17-20 binding from the 17,20lyase producing adrenal androgens. This enzyme is coded by the CYP17A1 gene. The case is presented of a 14 year old patient with delayed pubertal development and a high blood pressure for height and age. 46,XX karyotype. Hormonal studies highlighted hypergonadotropic hypogonadism, adrenal insufficiency and mineralocorticoid excess. Subsequent genetic studies showed a homozygous mutation in the CYP17A1 gene (c.753+G>A), not previously described, which is responsible for the pathophysiology of 17α-hydroxylase deficiency. This entity is a rare form of congenital adrenal hyperplasia. The disease often goes unnoticed until adolescence or early adult life, and should be suspected in 46,XY individuals with ambiguous genitalia or 46,XX with delayed puberty associated with hypertension and/or hypokalaemia. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  12. Congenital adrenal hyperplasia: as viewed by parents of affected children in India--a pilot study.

    PubMed

    Bhakhri, Bhanu Kiran; Jain, Vandana

    2011-01-01

    A spectrum of myths and misconceptions about congenital adrenal hyperplasia (CAH) is prevalent among the parents of affected children in India. The perceptions of parents may affect several aspects of these children's management, and to explore these perceptions we carried out a cross-sectional questionnaire-based descriptive study during May 2010. Twenty-eight individuals (17 males and 11 females), parents of 22 affected children aged < 5 years, completed the questionnaire. Their responses showed the prevalence among the parents of misconceptions about CAH. These misconceptions were resulting in potentially harmful practices, and in addition there was immense societal pressure on the families as a result of ignorance and myths about the disorder. There is a need for regular CAH education and interaction programs to provide an acceptable platform for the parents and patients, where their concerns can be expressed and shared and their requirements addressed appropriately by a multidisciplinary team.

  13. Motor development in individuals with congenital adrenal hyperplasia: strength, targeting, and fine motor skill.

    PubMed

    Collaer, Marcia L; Brook, Charles G D; Conway, Gerard S; Hindmarsh, Peter C; Hines, Melissa

    2009-02-01

    This study investigated early androgen influence on the development of human motor and visuomotor characteristics. Participants, ages 12-45 years, were individuals with congenital adrenal hyperplasia (CAH), a disorder causing increased adrenal androgen production before birth (40 females, 29 males) and their unaffected relatives (29 females, 30 males). We investigated grip strength and visuomotor targeting tasks on which males generally outperform females, and fine motor pegboard tasks on which females generally outperform males. Physical characteristics (height and weight) were measured to explore whether body parameters could explain differences in motor skills. Females with CAH were stronger and showed better targeting than unaffected females and showed reduced fine visuomotor skill on one pegboard measure, with no difference on the other. Males with CAH were weaker than unaffected males in grip strength but did not differ on the targeting or pegboard measures. Correction for body size could not explain the findings for females, but suggests that the reduced strength of males with CAH may relate to their smaller stature. Further, the targeting advantage in females with CAH persisted following adjustment for their greater strength. Results in females support the hypothesis that androgen may masculinize, or promote, certain motor characteristics at which males excel, and contribute to defeminization of certain fine motor characteristics at which females excel. Thus, these data suggest that organizational effects of androgens on behavior during prenatal life may extend to motor characteristics and may contribute to general sex differences in motor-related behaviors; however, alternative explanations based on activational influences of androgen or altered experiential factors cannot be excluded without further study.

  14. Genetics Home Reference: primary macronodular adrenal hyperplasia

    MedlinePlus

    ... too rapidly or in an uncontrolled way. ARMC5 gene mutations are believed to impair the protein's tumor-suppressor ... endocrine glands, including the adrenal glands. The GNAS gene mutations that cause PMAH are believed to result in ...

  15. Bilateral aldosterone-producing adenomas: differentiation from bilateral adrenal hyperplasia.

    PubMed

    Wu, V C; Chueh, S C; Chang, H W; Lin, W C; Liu, K L; Li, H Y; Lin, Y H; Wu, K D; Hsieh, B S

    2008-01-01

    Primary aldosteronism (PA) is a common curable disease of secondary hypertension. Most such patients have either idiopathic bilateral adrenal hyperplasia (BAH) or unilateral aldosterone-producing adenoma (APA). Bilateral APAs are reportedly extremely rare. To compare the distinctive characteristics, clinical course, and outcomes of bilateral APA vs. BAH. Retrospective record review. From July 1994 to Jan 2007, 190 patients diagnosed with PA underwent surgical intervention at our hospital. Bilateral APA was diagnosed in 7/164 patients with histologically-proven APA. Twenty-one patients diagnosed as BAH, and 21 randomly selected of unilateral APA patients, matched by age and sex served as controls. Patients with bilateral APA had similar blood pressure, arterial blood gas analysis, spot urinary potassium to creatinine ratio and clinical symptoms to those with BAH, but lower serum potassium levels (p = 0.027), lower plasma renin activity (p = 0.037), and higher plasma aldosterone concentrations (p = 0.029). Aldosterone-renin ratio (ARR) after administration of 50 mg captopril was higher in bilateral APA than in BAH patients (p = 0.023), but not different between unilateral APA and BAH (p = 0.218). A cut-off of ARR >100 ng/dl per ng/ml/h and plasma aldosterone >20 ng/dl after captopril significantly differentiated bilateral APA from BAH. Bilateral subtotal adrenalectomy normalized blood pressure and biochemistry in all patients with bilateral APA. Bilateral APA, presenting simultaneously or sequentially, may not be a rare disease, accounting for 4.3% of APA in this sample. The clinical presentations of bilateral functional adenoma are not different from BAH, but patients with low serum potassium and ARR >100 after captopril should be carefully evaluated for bilateral adenoma.

  16. Characterization of novel StAR (steroidogenic acute regulatory protein) mutations causing non-classic lipoid adrenal hyperplasia.

    PubMed

    Flück, Christa E; Pandey, Amit V; Dick, Bernhard; Camats, Núria; Fernández-Cancio, Mónica; Clemente, María; Gussinyé, Miquel; Carrascosa, Antonio; Mullis, Primus E; Audi, Laura

    2011-01-01

    Steroidogenic acute regulatory protein (StAR) is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH). StAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported. To report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature. Collaboration between the University Children's Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain. Two subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age. StAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (∼30%) and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol. StAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S) seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed.

  17. Characterization of Novel StAR (Steroidogenic Acute Regulatory Protein) Mutations Causing Non-Classic Lipoid Adrenal Hyperplasia

    PubMed Central

    Flück, Christa E.; Pandey, Amit V.; Dick, Bernhard; Camats, Núria; Fernández-Cancio, Mónica; Clemente, María; Gussinyé, Miquel; Carrascosa, Antonio; Mullis, Primus E.; Audi, Laura

    2011-01-01

    Context Steroidogenic acute regulatory protein (StAR) is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH). Objective StAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported. Design To report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature. Setting Collaboration between the University Children's Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain. Patients Two subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age. Results StAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (∼30%) and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol. Conclusions StAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S) seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed. PMID:21647419

  18. Neuropsychological assessment in prepubertal patients with congenital adrenal hyperplasia: preliminary study.

    PubMed

    Somajni, F; Sovera, V; Albizzati, A; Russo, G; Peroni, P; Seragni, G; Lenti, C

    2011-02-01

    Individuals with congenital adrenal hyperplasia (CAH) provide a test population for the theory that elevated testosterone levels alter pre-/perinatal brain development. Seven prepuberal girls with CAH and seven matched controls has been submitted to a neuropsychological evaluation. We measured abilities where gender differences repeatedly has been observed or that had earlier shown differences between CAH subjects and controls. The following cognitive functions were tested: general intelligence, attention, verbal and non-verbal abilities, cerebral dominance for verbal and non-verbal material, frontal functions, peripheral dominance and motor fluency. Since several animal studies shown hippocampal morphological changes induced by prolonged hydrocortisone exposure, we also investigated memory functions. No differences were recorded between two groups on those abilities that are not sexually dimorphic. The mean general intelligence level of the patients was significantly lower than the controls', in agreement with previous studies. The verbal and non-verbal tasks revealed an age-related male-like pattern (i.e., verbal disadvantage) and an inversion of the hemispheric dominances. The latter observation was supported by a right-to-left shift of the peripheral dominances. The patients memory performances were all inferior to the controls'. The results are discussed in the light of possible hormonal influences. Our main findings support the hypothesis that elevated pre-/perinatal androgen exposure can influence some cognitive pattern of specific sexual dimorphic abilities in prepubertal subjects.

  19. Mandibular pseudocarcinomatous hyperplasia.

    PubMed

    Warter, A; Walter, P; Meyer, C; Barrière, P; Galatir, L; Wilk, A

    2000-08-01

    Three unusual cases of pseudocarcinomatous (pseudoepitheliomatous) hyperplasia (PH) affecting chronic osteomyelitic mandibular sequestra are reported to highlight the differences with the various squamous neoplasms which occur in that site. In two patients carrying a mandibular graft following the excision of an ameloblastoma, mucosal ulcers resulted in chronic osteomyelitis. In a third patient, an apical dental infection was associated with fistulated osteomyelitis. Histology of the three sequestra showed an intraosseous squamous proliferation. It was characterized by a peripheral involvement of medullary spaces, the more mature epithelial layer covering the bone trabeculae without intervening stroma, and the basal type epithelial layer surrounding a central fibrovascular core. There were no histological or cytological signs of malignancy. PH shows an inverted pattern when compared with the centro-medullary tumoural islands seen in the various oral or odontogenic squamous neoplasms which occur in the jaws. The lack of signs of malignancy distinguish PH from common squamous cell carcinomas. A short clinical course is an important feature in the distinction of PH from the well differentiated squamous cell carcinomas which may develop in fistulated chronic osteomyelitis.

  20. Neonatal Bartter Syndrome in association with congenital adrenal hyperplasia in a neonate - a rare combination.

    PubMed

    Hussain, Shabbir

    2016-05-01

    Neonatal Bartter syndrome (NBS) is an autosomal recessive renal tubulopathy characterized by hypokalaemic, hypochloraemic metabolic alkalosis associated with increased urinary loss of sodium, potassium, calcium and chloride. There is hyperreninaemia and hyperaldosteronaemia but normotension. Congenital adrenal hyperplasia (CAH), another autosomal recessive condition, may present in the neonatal period with vomiting, hypovolaemia, failure to gain weight or ambiguous genitalia. We report a case of NBS and CAH combination in a neonate. A male neonate born at term was admitted with history of recurrent vomiting and dehydration episodes. Investigations revealed electrolytes imbalance, metabolic alkalosis, raised aldosterone and renin levels suggestive of NBS. He was treated successfully and discharged. He was re-admitted with the same symptoms. Further evaluation confirmed the presence of CAH as well. We report this case because of the rarity of this combination (NBS plus CAH) and to the best of our knowledge this is the first such case report from Pakistan.

  1. Relationship between final height and health outcomes in adults with congenital adrenal hyperplasia: United Kingdom congenital adrenal hyperplasia adult study executive (CaHASE).

    PubMed

    Han, T S; Conway, G S; Willis, D S; Krone, N; Rees, D A; Stimson, R H; Arlt, W; Walker, B R; Ross, R J

    2014-08-01

    Treatment of congenital adrenal hyperplasia (CAH) in childhood focuses on growth and development and adult final height (FH) is a measure of effective treatment. We hypothesized that shorter adults will have more severe underlying disease and worse health outcomes. This was a cross-sectional analysis of 199 adults with CAH. FH and quality of life were expressed as z-scores adjusted for midparental target height or UK population height. FH correlated inversely with age (men, r = -0.38; women, r = -0.26, P < .01). Men and women had z-scores adjusted for midparental target height of -2 and -1, respectively, and both groups had UK population height z-scores of -1 below the UK population (P < .01). In women, FH was shorter in non-salt-wasting than salt-wasting classic CAH (P < .05) and in moderately affected genotype group B women than either more severely affected groups null and A (P < .01) or the mildest group C (P < .001). Short stature and a higher prevalence of hypertension were observed in classic CAH patients diagnosed late (after 1 y) compared with those diagnosed early and in women treated with glucocorticoid only compared with those treated with both glucocorticoids and mineralocorticoids (P < .05). FH did not associate with insulin sensitivity, lipid profile, adiposity, or quality of life. Adult CAH patients remain short, although height prognosis has improved over time. The shortest adults are those diagnosed late with moderate severity CAH and are at increased risk of adult hypertension; we hypothesize that these patients are exposed in childhood to high androgens and/or excessive glucocorticoids with potential programming of hypertension. Another possibility is inadequate mineralocorticoid treatment early in life in the late-diagnosed patient group. Prospective studies are now required to examine these hypotheses.

  2. The Recalled Childhood Gender Questionnaire-Revised: a psychometric analysis in a sample of women with congenital adrenal hyperplasia.

    PubMed

    Meyer-Bahlburg, Heino F L; Dolezal, Curtis; Zucker, Kenneth J; Kessler, Suzanna J; Schober, Justine M; New, Maria I

    2006-11-01

    We administered the 18-item Recalled Childhood Gender Questionnaire-Revised (RCGQ-R), female version, to 147 adult women with congenital adrenal hyperplasia (CAH) representing three different degrees of prenatal androgenization due to 21-hydroxylase deficiency and to non-CAH controls. A principal components analysis generated three components accounting for 46%, 9%, and 6% of the variance, respectively. Corresponding unit-weighted scales (high scores = feminine) were labeled Gender Role (13 items; Cronbach alpha = .91), Physical Activity (3 items; alpha = .64), and Cross-Gender Desire (2 items; alpha = .47). Discriminant validity was demonstrated in terms of highly significant comparisons across the four groups. We conclude that the first 2 RCGQ-R scales show good psychometric qualities, but that the third scale needs to be further evaluated in a sample that includes women with gender identity disorder.

  3. Role of adrenals in the mobilization of carbohydrate and fat resources after overstimulation of rats

    NASA Technical Reports Server (NTRS)

    Khechninashvili, G. G.

    1980-01-01

    The role of the cortical and cerebral layers of the adrenal glands in mobilizing carbohydrate and fatty resources in response to the effect of an extreme stimulant was investigated. It is shown that following adrenodemedullation and adrenalectomy, the leading role is played by the secretion of the adrenal medullary layer, whereas the role of suprarenals in the mobilization of fats is only slightly pronounced.

  4. Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma

    PubMed Central

    Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

    2015-01-01

    Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC). PMID:26487970

  5. Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.

    PubMed

    Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

    2015-09-01

    Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC).

  6. Newborn screening for congenital adrenal hyperplasia in Cuba: six years of experience.

    PubMed

    González, Ernesto Carlos; Carvajal, Frank; Frómeta, Amarilys; Arteaga, Ana Luisa; Castells, Elisa María; Espinosa, Tania; Coto, Remigio; Pérez, Pedro Lucio; Tejeda, Yileidis; Del Río, Lesley; Segura, Mary Triny; Almenares, Pedro; Robaina, René; Fernández, José Luis

    2013-06-05

    Since 2005, a newborn screening program for congenital adrenal hyperplasia (CAH) by measuring 17-alpha-hydroxyprogesterone (17OHP) in dried blood spots was introduced in Cuba. The hormone was measured by the 17OHP Neonatal UMELISA method, in samples collected on the 5th day as average. Confirmatory test was performed to those neonates with 17OHP values above 55 nmol/l. Some perinatal factors that can influence on 17OHP levels were studied. From January 2005 to December 2010, 621,303 newborns were screened and 39 CAH cases were detected. Coverage of the program reached 98%. The incidence of CAH in Cuba was 1:15,931, similar to that reported by other programs. A recall for suspected CAH was performed in 10,799 cases (1.74%). Therapy in classical CAH patients was started at the mean age of 22 days. 17OHP levels were significantly higher in newborns with lower birth-weight (BW) and/or gestational age (GA). In addition, 17OHP values were affected by the gender, twin status or mode of delivery. In Cuba, the nationwide newborn screening program has allowed the early detection of CAH. The use of an optimized cut-off level for BW or GA could lead to a reduction in the percentage of recalled babies. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Pilot proficiency testing study for second tier congenital adrenal hyperplasia newborn screening.

    PubMed

    De Jesús, Víctor R; Simms, David A; Schiffer, Jarad; Kennedy, Meredith; Mei, Joanne V; Hannon, W Harry

    2010-11-11

    Congenital adrenal hyperplasia (CAH) is caused by inherited defects in steroid biosynthesis. The Newborn Screening Quality Assurance Program (NSQAP) initiated a pilot, dried-blood spot (DBS)-based proficiency testing program designed to investigate materials and laboratory performance for second tier CAH screening by tandem mass spectrometry (MS/MS). The ratio of 17-α-hydroxyprogesterone (17-OHP), androstenedione (4-AD) and cortisol is used as an indicator of CAH in laboratory protocols for second tier analysis of DBS specimens. DBS prepared by NSQAP contained a range of steroid concentrations resulting in different clinical ratios. Laboratories received blind-coded DBS specimens and reported results to NSQAP for evaluation. Quantitative values reported by participants for 17-OHP, 4-AD, and cortisol, reflected small differences in their analytical methods. Average quantitative values for 17-OHP increased from 81% to 107% recovery over the 3.5-year period; cortisol recoveries increased from 61.9% to 89.5%; and 4-AD recoveries decreased from 184% to 68%. Laboratory participation in the CAH second tier proficiency testing program has resulted in improved analyte recoveries and enhanced sample preparation methodologies. NSQAP services for the second tier CAH analysis in DBS demonstrate the need for surveillance to ensure harmonization and continuous improvements, and to achieve sustained high-performance of newborn screening laboratories worldwide. Published by Elsevier B.V.

  8. Association of leptin with cardiometabolic factors in schoolchildren and adolescents with congenital adrenal hyperplasia.

    PubMed

    Zurita-Cruz, Jessie Nallely; Villasís-Keever, Miguel Ángel; Damasio-Santana, Leticia; Manuel-Apolinar, Leticia; Ferrusca-Ceja, Rosalba; Nishimura-Meguro, Elisa; Rivera-Hernández, Aleida de J; Garrido-Magaña, Eulalia

    2018-01-01

    In congenital adrenal hyperplasia (CAH), obesity, hyperinsulinemia and leptin levels are increased. To identify the frequency of cardiometabolic risk factors (CRF) in children and adolescents with CAH and to explore the relationship with leptin levels. Cross-sectional study of 40 patients who underwent anthropometric measurements and had fasting glucose, insulin, triglycerides, 17-hidroxyprogesterone, leptin, HDL and LDL-cholesterol assessed. The patients were classified according to the number of CRFs, and leptin levels were analyzed with the Kruskal-Wallis test. Pearson's correlation was applied between leptin, body mass index (BMI) z-score and body fat percentage. Fifty percent of the patients had obesity and overweight, 59% had hypertriglyceridemia, 40%, hypoalphalipoproteinemia, 27.5%, high LDL-cholesterol and 22.5% insulin resistance. There was positive correlation between leptin and body fat percentage (r = 0.64), BMI z-score (r = 0.55) and the number of CRFs (r = 0.65). In the obesity-adjusted multivariate analysis, leptin levels were associated with the number of CRFs. CAH had a high frequency of CRFs and leptin appeared to be associated with a more adverse cardiometabolic profile in subjects with obesity and overweight. Copyright: © 2018 SecretarÍa de Salud.

  9. Ehlers-Danlos Syndrome Caused by Biallelic TNXB Variants in Patients with Congenital Adrenal Hyperplasia.

    PubMed

    Chen, Wuyan; Perritt, Ashley F; Morissette, Rachel; Dreiling, Jennifer L; Bohn, Markus-Frederik; Mallappa, Ashwini; Xu, Zhi; Quezado, Martha; Merke, Deborah P

    2016-09-01

    Some variants that cause autosomal-recessive congenital adrenal hyperplasia (CAH) also cause hypermobility type Ehlers-Danlos syndrome (EDS) due to the monoallelic presence of a chimera disrupting two flanking genes: CYP21A2, encoding 21-hydroxylase, necessary for cortisol and aldosterone biosynthesis, and TNXB, encoding tenascin-X, an extracellular matrix protein. Two types of CAH tenascin-X (CAH-X) chimeras have been described with a total deletion of CYP21A2 and characteristic TNXB variants. CAH-X CH-1 has a TNXB exon 35 120-bp deletion resulting in haploinsufficiency, and CAH-X CH-2 has a TNXB exon 40 c.12174C>G (p.Cys4058Trp) variant resulting in a dominant-negative effect. We present here three patients with biallelic CAH-X and identify a novel dominant-negative chimera termed CAH-X CH-3. Compared with monoallelic CAH-X, biallelic CAH-X results in a more severe phenotype with skin features characteristic of classical EDS. We present evidence for disrupted tenascin-X function and computational data linking the type of TNXB variant to disease severity. © 2016 WILEY PERIODICALS, INC.

  10. Mixed cortical adenoma and composite pheochromocytoma-ganglioneuroma: an unusual corticomedullary tumor of the adrenal gland.

    PubMed

    Lau, Sean K; Chu, Peiguo G; Weiss, Lawrence M

    2011-06-01

    Adrenal neoplasms composed of more than one cell type and demonstrating a mixed histologic appearance are exceedingly rare. We report the clinical and pathologic features of a morphologically distinctive tumor of the adrenal gland composed of cortical, chromaffin, and neural cells. Histologically, the tumor consisted of intermixed areas of proliferating cortical cells resembling adrenal cortical adenoma, neoplastic chromaffin cells consistent with pheochromocytoma, and a ganglioneuromatous stroma. The presence of the cortical, medullary, and neural components within the tumor was confirmed by immunohistochemical studies. The present case serves to broaden the morphologic spectrum of mixed tumors that may be encountered in the adrenal gland. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. A cAMP-specific phosphodiesterase (PDE8B) that is mutated in adrenal hyperplasia is expressed widely in human and mouse tissues: a novel PDE8B isoform in human adrenal cortex

    PubMed Central

    Horvath, Anelia; Giatzakis, Christoforos; Tsang, Kitman; Greene, Elizabeth; Osorio, Paulo; Boikos, Sosipatros; Libè, Rossella; Patronas, Yianna; Robinson-White, Audrey; Remmers, Elaine; Bertherat, Jerôme; Nesterova, Maria; Stratakis, Constantine A.

    2009-01-01

    Bilateral adrenocortical hyperplasia (BAH) is the second most common cause of corticotropin-independent Cushing syndrome (CS). Genetic forms of BAH have been associated with complex syndromes such as Carney Complex and McCune Albright syndrome or may present as isolated micronodular adrenocortical disease (iMAD) usually in children and young adults with CS. A genome-wide association study identified inactivating phosphodiesterase (PDE) 11A (PDE11A) sequencing defects as low-penetrance predisposing factors for iMAD and related abnormalities; we also described a mutation (c.914A>C/H305P) in cAMP-specific PDE8B, in a patient with iMAD. In this study we further characterize this mutation; we also found a novel PDE8B isoform, highly expressed in the adrenal gland. This mutation is shown to significantly affect the ability of the protein to degrade cAMP in vitro. Tumor tissues from patients with iMAD and no mutations in the coding PDE8B sequence or any other related genes (PRKAR1A, PDE11A) showed down-regulated PDE8B expression (compared to normal adrenal cortex). Pde8b is detectable in the adrenal gland of newborn mice and is widely expressed in other mouse tissues. We conclude that PDE8B is another PDE gene linked to iMAD; it is a candidate causative gene for other adrenocortical lesions linked to the cAMP-signaling pathway, and possibly for tumors in other tissues. PMID:18431404

  12. Changing perspectives in screening for congenital hypothyroidism and congenital adrenal hyperplasia.

    PubMed

    Mitchell, Marvin L; Hsu, Ho-Wen; Sahai, Inderneel

    2014-02-01

    The purpose of this review is to summarize recent information that has had a significant impact on the laboratory diagnosis and clinical management of newborns with congenital hypothyroidism and congenital adrenal hyperplasia (CAH). An approximate doubling of the incidence rate of congenital hypothyroidism in many parts of the world has been attributed to increased detection of infants with mild disease, delayed thyroid stimulating hormone elevations and demographic changes. A substantial number of children with modest thyroid stimulating hormone elevations on screening have permanent disease. Circulating levels of thyroxine may vary among hypothyroid children who are given identical dosages of medication. Treated infants should be monitored every 1-2 months during the first year of life. Although, generic and brand name thyroxine preparations may not be bioequivalent, children can be well controlled on generic formulations.Enzyme linked immunoassay assay for 17-hydroxyprogesterone is associated with a high rate of false positive specimens. In attempts to minimize this problem, some programs have resorted to two-tier screening of the initial specimen with steroid profiling as the second tier. Several programs are routinely testing second specimens in an effort to reduce the incidence of missed CAH cases. This review explains the uptick in incidence rate of congenital hypothyroidism and underscores issues in management that can affect developmental outcome. One specimen two-tier testing for CAH resulted in an increased false negative rate without significantly reducing the false positive rate. The benefit of collecting second specimens for CAH screening is problematic. Optimal treatment of CAH continues to pose a challenge.

  13. Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications.

    PubMed

    Charmandari, Evangelia; Weise, Martina; Bornstein, Stefan R; Eisenhofer, Graeme; Keil, Margaret F; Chrousos, George P; Merke, Deborah P

    2002-05-01

    Leptin is secreted by the white adipose tissue and modulates energy homeostasis. Nutritional, neural, neuroendocrine, paracrine, and autocrine factors, including the sympathetic nervous system and the adrenal medulla, have been implicated in the regulation of leptin secretion. Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in cortisol and aldosterone secretion, impaired development and function of the adrenal medulla, and adrenal hyperandrogenism. To examine leptin secretion in patients with classic CAH in relation to their adrenomedullary function and insulin and androgen secretion, we studied 18 children with classic CAH (12 boys and 6 girls; age range 2-12 yr) and 28 normal children (16 boys and 12 girls; age range 5-12 yr) matched for body mass index (BMI). Serum leptin concentrations were significantly higher in patients with CAH than in control subjects (8.1 +/- 2.0 vs. 2.5 +/- 0.6 ng/ml, P = 0.01), and this difference persisted when leptin values were corrected for BMI. When compared with their normal counterparts, children with CAH had significantly lower plasma epinephrine (7.1 +/- 1.3 vs. 50.0 +/- 4.2, P < 0.001) and free metanephrine concentrations (18.4 +/- 2.4 vs. 46.5 +/- 4.0, P < 0.001) and higher fasting serum insulin (10.6 +/- 1.4 vs. 3.2 +/- 0.2 microU/ml, P < 0.001) and testosterone (23.7 +/- 5.3 vs. 4.6 +/- 0.5 ng/dl, P = 0.003) concentrations. Insulin resistance determined by the homeostasis model assessment method was significantly greater in children with classic CAH than in normal children (2.2 +/- 0.3 vs. 0.7 +/- 0.04, P < 0.001). Leptin concentrations were significantly and negatively correlated with epinephrine (r = -0.50, P = 0.001) and free metanephrine (r = -0.48, P = 0.002) concentrations. Stepwise multiple linear regression analysis indicated that serum leptin concentrations were best predicted by BMI in both patients and controls. Gender predicted serum leptin concentrations in controls but not in patients

  14. Radioguided Adrenal Surgery

    PubMed Central

    Deus, Javier; Millera, Alfonso; Andrés, Alejandro; Prats, Enrique; Gil, Ismael; Suarez, Manuel; Salcini, José L.; Lahoz, Manuel

    2015-01-01

    Abstract The laparoscopic adrenalectomy is considered as the procedure of choice for the treatment of adrenal hyperplasia and tumor lesions. However, some special situations may limit the use of this method due to the difficulty to locate the gland and perform the lesion excision. We analyze 2 patients of a left adrenal tumor, explaining how they have overcome the difficulties in both situations. The first case was a patient with a history of intra-abdominal surgery and the other patient suffered from severe obesity. We performed with the use of the gamma probe, and the 2 cases, was of great help to access and glandular localization. The help of gamma probe test was achieved in the surgical bed, that removal was complete. The use of the portable gamma probe facilitated the access to the left adrenal gland as well as conducting the glandular excision without delay, despite the difficulties due to the intra abdominal surgery caused by the previous surgery, and in the case of severe obesity. PMID:26426608

  15. Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: description of a new mutation, R384X.

    PubMed

    Matallana-Rhoades, Audrey Mary; Corredor-Castro, Juan David; Bonilla-Escobar, Francisco Javier; Mecias-Cruz, Bony Valentina; Mejia de Beldjena, Liliana

    2016-09-30

    It is presented the phenotype of a new compound heterozygous mutation of the genes R384X and Q356X encoding the enzyme of 11-beta-hydroxylase. Severe virilization, peripheral hypertension, and early puberty. Managed with hormone replacement therapy (corticosteroid) and antihypertensive therapy (beta-blocker), resulting in the control of physical changes and levels of arterial tension. According to the phenotypic characteristics of the patient, it is inferred that the R384X mutation carries an additional burden on the Q356X mutation, with the latter previously described as a cause of 11-beta-hydroxylase deficiency. The description of a new genotype, as in this case, expands the understanding of the hereditary burden and deciphers the various factors that lead to this pathology as well as the other forms of congenital adrenal hyperplasia (CAH), presenting with a broad spectrum of clinical presentations. This study highlights the importance of a complete description of the patient's CAH genetic profile as well as their parents' genetic profile.

  16. STAR splicing mutations cause the severe phenotype of lipoid congenital adrenal hyperplasia: insights from a novel splice mutation and review of reported cases.

    PubMed

    Camats, Núria; Pandey, Amit V; Fernández-Cancio, Mónica; Fernández, Juan M; Ortega, Ana M; Udhane, Sameer; Andaluz, Pilar; Audí, Laura; Flück, Christa E

    2014-02-01

    The steroidogenic acute regulatory protein (StAR) transports cholesterol to the mitochondria for steroidogenesis. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH) which is characterized by impaired synthesis of adrenal and gonadal steroids causing adrenal insufficiency, 46,XY disorder of sex development (DSD) and failure of pubertal development. Partial loss of StAR activity may cause adrenal insufficiency only. A newborn girl was admitted for mild dehydration, hyponatremia, hyperkalemia and hypoglycaemia and had normal external female genitalia without hyperpigmentation. Plasma cortisol, 17OH-progesterone, DHEA-S, androstendione and aldosterone were low, while ACTH and plasma renin activity were elevated, consistent with the diagnosis of primary adrenal insufficiency. Imaging showed normal adrenals, and cytogenetics revealed a 46,XX karyotype. She was treated with fluids, hydrocortisone and fludrocortisone. Genetic studies revealed a novel homozygous STAR mutation in the 3' acceptor splice site of intron 4, c.466-1G>A (IVS4-1G>A). To test whether this mutation would affect splicing, we performed a minigene experiment with a plasmid construct containing wild-type or mutant StAR gDNA of exons-introns 4-6 in COS-1 cells. The splicing was assessed on total RNA using RT-PCR for STAR cDNAs. The mutant STAR minigene skipped exon 5 completely and changed the reading frame. Thus, it is predicted to produce an aberrant and shorter protein (p.V156GfsX19). Computational analysis revealed that this mutant protein lacks wild-type exons 5-7 which are essential for StAR-cholesterol interaction. STAR c.466-1A skips exon 5 and causes a dramatic change in the C-terminal sequence of the protein, which is essential for StAR-cholesterol interaction. This splicing mutation is a loss-of-function mutation explaining the severe phenotype of our patient. Thus far, all reported splicing mutations of STAR cause a severe impairment of protein function and phenotype.

  17. Gender role across development in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

    PubMed

    Long, Dominique N; Wisniewski, Amy B; Migeon, Claude J

    2004-10-01

    This study evaluated the degree of femininity and masculinity at different developmental stages in a group of adult women, some of whom were exposed to elevated prenatal adrenal androgens as a result of congenital adrenal hyperplasia (CAH) due to 21 hydroxylase (21-OH) deficiency. Women who had presented to the Johns Hopkins Hospital Pediatric Endocrine Clinic for treatment of CAH due to 21-OH deficiency were included. The control group consisted of sisters of CAH participants and women referred for evaluation of polycystic ovary syndrome. Study participants were given a questionnaire asking them to indicate their degree of masculinity and femininity during childhood, adolescence, and adulthood. In addition, participants were asked questions related to their play behavior during childhood, including playmate preferences, toy preferences, and admiration of male or female characters during fantasy play. Across participant groups, self-reported femininity decreased in a dose response manner, according to prenatal androgen exposure. For all groups, femininity increased through developmental stages. Women with salt-losing CAH remained less feminine than controls into adulthood. Conversely, self-reported masculinity increased in a dose-response manner, according to prenatal androgen exposure, across participant groups. Women with CAH showed a decrease in masculinity across developmental stages, such that by adulthood, there were no significant differences in masculinity between controls and the women with CAH. Women with salt-losing CAH were more likely to recall preferences for boy playmates, male-typical toys, and admiration for male characters during childhood than other study participants. Our data support the effect of both prenatal androgen exposure and socialization on gender role behavior in adult women with CAH due to 21-OH deficiency.

  18. Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.

    PubMed

    Khattab, Ahmed; Haider, Shozeb; Kumar, Ameet; Dhawan, Samarth; Alam, Dauood; Romero, Raquel; Burns, James; Li, Di; Estatico, Jessica; Rahi, Simran; Fatima, Saleel; Alzahrani, Ali; Hafez, Mona; Musa, Noha; Razzghy Azar, Maryam; Khaloul, Najoua; Gribaa, Moez; Saad, Ali; Charfeddine, Ilhem Ben; Bilharinho de Mendonça, Berenice; Belgorosky, Alicia; Dumic, Katja; Dumic, Miroslav; Aisenberg, Javier; Kandemir, Nurgun; Alikasifoglu, Ayfer; Ozon, Alev; Gonc, Nazli; Cheng, Tina; Kuhnle-Krahl, Ursula; Cappa, Marco; Holterhus, Paul-Martin; Nour, Munier A; Pacaud, Daniele; Holtzman, Assaf; Li, Sun; Zaidi, Mone; Yuen, Tony; New, Maria I

    2017-03-07

    Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1 , a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of CYP11B1 gene mutations in the largest international cohort of 108 patients with steroid 11β-hydroxylase deficiency CAH.

  19. Prenatal hormones and postnatal socialization by parents as determinants of male-typical toy play in girls with congenital adrenal hyperplasia.

    PubMed

    Pasterski, Vickie L; Geffner, Mitchell E; Brain, Caroline; Hindmarsh, Peter; Brook, Charles; Hines, Melissa

    2005-01-01

    Toy choices of 3- to 10-year-old children with congenital adrenal hyperplasia (CAH) and of their unaffected siblings were assessed. Also assessed was parental encouragement of sex-typed toy play. Girls with CAH displayed more male-typical toy choices than did their unaffected sisters, whereas boys with and without CAH did not differ. Mothers and fathers encouraged sex-typical toy play in children with and without CAH. However, girls with CAH received more positive feedback for play with girls' toys than did unaffected girls. Data show that increased male-typical toy play by girls with CAH cannot be explained by parental encouragement of male-typical toy play. Although parents encourage sex-appropriate behavior, their encouragement appears to be insufficient to override the interest of girls with CAH in cross-sexed toys.

  20. Immunohistochemistry of medullary thyroid carcinoma and C-cell hyperplasia by an affinity-purified anti-human calcitonin antiserum.

    PubMed

    Hayashida, C Y; Alves, V A; Kanamura, C T; Ezabella, M C; Abelin, N M; Nicolau, W; Bisi, H; Toledo, S P

    1993-08-15

    The diagnosis of medullary thyroid carcinoma (MTC) depends on the calcitonin immunohistochemistry. Familial MTC is associated with C-cell hyperplasia (CCH), whereas sporadic MTC is not. A specific and sensitive calcitonin immunohistochemistry is necessary for the diagnosis of MTC and CCH. An affinity-purified anti-calcitonin antiserum (APxCT) was used for immunohistochemistry of the thyroids of 15 patients with MTC. The thyroids of five patients with familial MTC were studied in detail, with each gland sectioned in 48 areas. Between three and ten independent MTC were found in each thyroid, and CCH was found in all five patients (24.2%, varying from 8.4-56.3% of the 48 areas from each thyroid). MTC and CCH were localized mainly in the middle third and in the central axis of the thyroid lobes. They often were found together in the same area (in a total of 21 areas for the five thyroids sectioned in 48 areas) but ten areas with MTC did not have CCH, and 37 areas with CCH did not have MTC. In ten thyroids partially studied, CCH was indicated in three patients thought to have sporadic MTC. In two thyroids, with follicular and papillary carcinoma, a higher density of C-cells was found around the tumors, but disease was not characterized as CCH. APxCT antiserum increased the immunohistochemical specificity and sensitivity. The distinction of the familial from the sporadic MTC requires a careful and extensive search of CCH. C-cells in high density may be found around follicular cell carcinomas, being a potential source of diagnostic error.

  1. A three-year follow-up of congenital adrenal hyperplasia newborn screening.

    PubMed

    Pezzuti, Isabela L; Barra, Cristina B; Mantovani, Rafael M; Januário, José N; Silva, Ivani N

    2014-01-01

    congenital adrenal hyperplasia (CAH) newborn screening can prevent neonatal mortality in children with the salt-wasting form of the disease and prevent incorrect gender assignments, which can occur in females. However, the occurrence of false-positive results in preterm or low-birth-weight newborns creates some diagnostic difficulties, with consequent therapeutic implications. This study aimed to report the results of a pilot project for neonatal CAH screening conducted in the state of Minas Gerais, Brazil from 09/2007 to 05/2008 with a three-year follow-up. dried blood specimens were collected on filter paper cards three to seven days after birth of all newborns in the period. Samples were analyzed for 17-hydroxyprogesterone using an enzyme-linked immunosorbent assay (ELISA). a total of 159,415 children were screened. The apparent incidence of the classic variant of the disease was 1:9,963, based on initial diagnoses following newborn screening. During the follow-up period, eight of 16 children initially diagnosed with CAH were reclassified as unaffected, resulting in a revised incidence of 1:19,927. The false-positive rate was 0.31%, and the positive predictive value was 2.1%. Sensitivity and specificity were 100% and 99.7%, respectively. newborn screening is an important public health policy in developing countries such as Brazil, where CAH remains underdiagnosed. It has great potential to identify children with the disease who otherwise cannot be diagnosed earlier. Long-term follow-up and monitoring of all children with positive screening results are crucial to ensure a correct diagnosis and to calculate a reliable incidence ratio of the disease. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  2. Congenital adrenal hyperplasia: problems with developmental anomalies of the external genitalia and sex assignment.

    PubMed

    Al-Maghribi, Hussein

    2007-09-01

    A retrospective study was performed on all patients with congenital adrenal hyperplasia (CAH) who were followed up at the King Hussein Medical Center (KHMC), Amman, Jordan, during the period from January 1996 to June 2006. The aim was to evaluate the clinical features, special problems, and corrective interventions for these patients. The records of 73 children (39 were genetic females and 34 were genetic males) with CAH were reviewed in the study. The age of the patients at last follow-up was between five months and 18 years. Diagnostic criteria for CAH were typical clinical features of the illness (salt loss, dehydration, virilization, macrogenitosomia, ambiguous genitalia, and accelerated growth) and typical hormonal abnormalities (decreased serum cortisol and elevated serum 17-hydroxyprogesterone). There were 62 patients with classical presentation; among them, salt-wasting (SW) form was seen in 41 patients (66%). There were 5 patients with the nonclassic form, while 6 others had cryptic presentation. Seven patients (9%) had hypertension, mostly due to salt-retaining CAH. Among the 39 females with CAH, 27 had developed mental anomalies of the external genitalia; 20 of them underwent surgical interventions of their external genitalia. Fourteen genetically female patients were wrongly diagnosed as 'male sex' at birth due to severe virilization. Seven of them were reassigned 'female sex' socially, legally, and surgically; the parents of one of them (a four-year-old girl) wanted the surgical intervention postponed for two to three years. Hysterectomy and gonadectomy were carried out for 6 of the other 7 patients who chose to keep the male gender. Our study indicates that newborns with developmental anomalies of the external genitalia should be diagnosed as early as possible so that medical, psychological, and social complications are minimized. A neonatal screening program for such a disorder can identify infants at risk for the development of life

  3. A new compound heterozygous frameshift mutation in the type II 3{beta}-hydroxysteroid dehydrogenase 3{beta}-HSD gene causes salt-wasting 3{beta}-HSD deficiency congenital adrenal hyperplasia

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

    Zhang, L.; Sakkal-Alkaddour, S.; Chang, Ying T.

    1996-01-01

    We report a new compound heterozygous frameshift mutation in the type II 3{Beta}-hydroxysteroid dehydrogenase (3{beta}-HSD) gene in a Pakistanian female child with the salt-wasting form of 3{Beta}-HSD deficiency congenital adrenal hyperplasia. The etiology for her congenital adrenal hyperplasia was not defined. Although the family history suggested possible 3{beta}-HSd deficiency disorder, suppressed adrenal function caused by excess glucocorticoid therapy in this child at 7 yr of age did not allow hormonal diagnosis. To confirm 3{beta}-HSD deficiency, we sequenced the type II 3{beta}-HSD gene in the patient, her family, and the parents of her deceased paternal cousins. The type II 3{beta}-HSD genemore » region of a putative promotor, exons I, II, III, and IV, and exon-intron boundaries were amplified by PCR and sequenced in all subjects. The DNA sequence of the child revealed a single nucleotide deletion at codon 318 [ACA(Thr){r_arrow}AA] in exon IV in one allele, and two nucleotide deletions at codon 273 [AAA(Lys){r_arrow}A] in exon IV in the other allele. The remaining gene sequences were normal. The codon 318 mutation was found in one allele from the father, brother, and parents of the deceased paternal cousins. The codon 273 mutation was found in one allele of the mother and a sister. These findings confirmed inherited 3{beta}-HSD deficiency in the child caused by the compound heterozygous type II 3{beta}-HSD gene mutation. Both codons at codons 279 and 367, respectively, are predicted to result in an altered and truncated type II 3{beta}-HSD protein, thereby causing salt-wasting 3{beta}-HSD deficiency in the patient. 21 refs., 2 figs., 1 tab.« less

  4. Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with an adrenal cortical carcinoma.

    PubMed

    Nadolski, Amy C; Markovich, Jessica E; Jennings, Samuel H; Mahony, Orla M

    2016-10-01

    A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior.

  5. Clinical features of congenital adrenal insufficiency including growth patterns and significance of ACTH stimulation test.

    PubMed

    Koh, Ji Won; Kim, Gu Hwan; Yoo, Han Wook; Yu, Jeesuk

    2013-11-01

    Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency.

  6. Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with an adrenal cortical carcinoma

    PubMed Central

    Nadolski, Amy C.; Markovich, Jessica E.; Jennings, Samuel H.; Mahony, Orla M.

    2016-01-01

    A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior. PMID:27708447

  7. A unique haplotype of RCCX copy number variation: from the clinics of congenital adrenal hyperplasia to evolutionary genetics

    PubMed Central

    Doleschall, Márton; Luczay, Andrea; Koncz, Klára; Hadzsiev, Kinga; Erhardt, Éva; Szilágyi, Ágnes; Doleschall, Zoltán; Németh, Krisztina; Török, Dóra; Prohászka, Zoltán; Gereben, Balázs; Fekete, György; Gláz, Edit; Igaz, Péter; Korbonits, Márta; Tóth, Miklós; Rácz, Károly; Patócs, Attila

    2017-01-01

    There is a difficulty in the molecular diagnosis of congenital adrenal hyperplasia (CAH) due to the c.955C>T (p.(Q319*), formerly Q318X, rs7755898) variant of the CYP21A2 gene. Therefore, a systematic assessment of the genetic and evolutionary relationships between c.955C>T, CYP21A2 haplotypes and the RCCX copy number variation (CNV) structures, which harbor CYP21A2, was performed. In total, 389 unrelated Hungarian individuals with European ancestry (164 healthy subjects, 125 patients with non-functioning adrenal incidentaloma and 100 patients with classical CAH) as well as 34 adrenocortical tumor specimens were studied using a set of experimental and bioinformatic methods. A unique, moderately frequent (2%) haplotypic RCCX CNV structure with three repeated segments, abbreviated to LBSASB, harboring a CYP21A2 with a c.955C>T variant in the 3′-segment, and a second CYP21A2 with a specific c.*12C>T (rs150697472) variant in the middle segment occurred in all c.955C>T carriers with normal steroid levels. The second CYP21A2 was free of CAH-causing mutations and produced mRNA in the adrenal gland, confirming its functionality and ability to rescue the carriers from CAH. Neither LBSASB nor c.*12C>T occurred in classical CAH patients. However, CAH-causing CYP21A2 haplotypes with c.955C>T could be derived from the 3′-segment of LBSASB after the loss of functional CYP21A2 from the middle segment. The c.*12C>T indicated a functional CYP21A2 and could distinguish between non-pathogenic and pathogenic genomic contexts of the c.955C>T variant in the studied European population. Therefore, c.*12C>T may be suitable as a marker to avoid this genetic confound and improve the diagnosis of CAH. PMID:28401898

  8. A unique haplotype of RCCX copy number variation: from the clinics of congenital adrenal hyperplasia to evolutionary genetics.

    PubMed

    Doleschall, Márton; Luczay, Andrea; Koncz, Klára; Hadzsiev, Kinga; Erhardt, Éva; Szilágyi, Ágnes; Doleschall, Zoltán; Németh, Krisztina; Török, Dóra; Prohászka, Zoltán; Gereben, Balázs; Fekete, György; Gláz, Edit; Igaz, Péter; Korbonits, Márta; Tóth, Miklós; Rácz, Károly; Patócs, Attila

    2017-06-01

    There is a difficulty in the molecular diagnosis of congenital adrenal hyperplasia (CAH) due to the c.955C>T (p.(Q319*), formerly Q318X, rs7755898) variant of the CYP21A2 gene. Therefore, a systematic assessment of the genetic and evolutionary relationships between c.955C>T, CYP21A2 haplotypes and the RCCX copy number variation (CNV) structures, which harbor CYP21A2, was performed. In total, 389 unrelated Hungarian individuals with European ancestry (164 healthy subjects, 125 patients with non-functioning adrenal incidentaloma and 100 patients with classical CAH) as well as 34 adrenocortical tumor specimens were studied using a set of experimental and bioinformatic methods. A unique, moderately frequent (2%) haplotypic RCCX CNV structure with three repeated segments, abbreviated to LBSASB, harboring a CYP21A2 with a c.955C>T variant in the 3'-segment, and a second CYP21A2 with a specific c.*12C>T (rs150697472) variant in the middle segment occurred in all c.955C>T carriers with normal steroid levels. The second CYP21A2 was free of CAH-causing mutations and produced mRNA in the adrenal gland, confirming its functionality and ability to rescue the carriers from CAH. Neither LBSASB nor c.*12C>T occurred in classical CAH patients. However, CAH-causing CYP21A2 haplotypes with c.955C>T could be derived from the 3'-segment of LBSASB after the loss of functional CYP21A2 from the middle segment. The c.*12C>T indicated a functional CYP21A2 and could distinguish between non-pathogenic and pathogenic genomic contexts of the c.955C>T variant in the studied European population. Therefore, c.*12C>T may be suitable as a marker to avoid this genetic confound and improve the diagnosis of CAH.

  9. Effects on gender identity of prenatal androgens and genital appearance: evidence from girls with congenital adrenal hyperplasia.

    PubMed

    Berenbaum, Sheri A; Bailey, J Michael

    2003-03-01

    To address questions about sex assignment in children with ambiguous genitalia, we studied gender identity in girls with congenital adrenal hyperplasia (CAH) in relation to characteristics of the disease and treatment, particularly genital appearance and surgery. A 9-item gender identity interview was administered to 43 girls with classical CAH ranging in age from 3-18 yr, 7 tomboys, and 29 sister control girls. Groups were compared on total score and on individual items. Results showed that, on the total gender identity score, 88% of girls with CAH had scores overlapping those of control girls, but the average score was intermediate between control girls and tomboys. On individual items of gender identity (discomfort as a girl, wish to be a boy), girls with CAH were similar to control girls. Gender identity in girls with CAH was not related to degree of genital virilization or age at which genital reconstructive surgery was done. Thus, moderate androgen excess early in development appears to produce a small increase in the risk of atypical gender identity, but this risk cannot be predicted from genital virilization.

  10. Unusual phenotype of congenital adrenal hyperplasia (CAH) with a novel mutation of the CYP21A2 gene.

    PubMed

    Raisingani, Manish; Contreras, Maria F; Prasad, Kris; Pappas, John G; Kluge, Michelle L; Shah, Bina; David, Raphael

    2016-07-01

    Gonadotropin independent sexual precocity (SP) may be due to congenital adrenal hyperplasia (CAH), and its timing usually depends on the type of mutation in the CYP21A2 gene. Compound heterozygotes are common and express phenotypes of varying severity. The objective of this case report was to investigate the hormonal pattern and unusual genetic profile in a 7-year-old boy who presented with pubic hair, acne, an enlarged phallus, slightly increased testicular volume and advanced bone age. Clinical, hormonal and genetic studies were undertaken in the patient as well as his parents. We found elevated serum 17-hydroxyprogesterone (17-OHP) and androstenedione that were suppressed with dexamethasone, and elevated testosterone that actually rose after giving dexamethasone, indicating activity of the hypothalamic-pituitary-gonadal (HPG) axis. An initial search for common mutations was negative, but a more detailed genetic analysis of the CYP21A2 gene revealed two mutations including R341W, a non-classical mutation inherited from his mother, and g.823G>A, a novel not previously reported consensus donor splice site mutation inherited from his father, which is predicted to be salt wasting. However, the child had a normal plasma renin activity. He was effectively treated with low-dose dexamethasone and a GnRH agonist. His father was an unaffected carrier, but his mother had evidence of mild non-classical CAH. In a male child presenting with gonadotropin independent SP it is important to investigate adrenal function with respect to the androgen profile, and to carry out appropriate genetic studies.

  11. Thyroid cancer - medullary carcinoma

    MedlinePlus

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... in children and adults. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...

  12. Prenatal androgens and gender-typed behavior: a study of girls with mild and severe forms of congenital adrenal hyperplasia.

    PubMed

    Servin, Anna; Nordenström, Anna; Larsson, Agne; Bohlin, Gunilla

    2003-05-01

    Gender-typed behaviors and interests were investigated in 26 girls, aged 2-10 years, affected with congenital adrenal hyperplasia (CAH) and in 26 unaffected girls matched for age. Girls with CAH were more interested in masculine toys and less interested in feminine toys and were more likely to report having male playmates and to wish for masculine careers. Parents of girls with CAH rated their daughters' behaviors as more boylike than did parents of unaffected girls. A relation was found between disease severity and behavior indicating that more severely affected CAH girls were more interested in masculine toys and careers. No parental influence could be demonstrated on play behavior, nor did the comparison of parents' ratings of wished for behavior versus perceived behavior in their daughters indicate an effect of parental expectations. The results are interpreted as supporting a biological contribution to differences in play behavior between girls with and without CAH.

  13. Nonsalt-losing congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency with normal glomerulosa function.

    PubMed

    Pang, S; Levine, L S; Stoner, E; Opitz, J M; Pollack, M S; Dupont, B; New, M I

    1983-04-01

    glucuronide, suggesting the presence of normal peripheral 3 beta-HSD activity. We propose that in these siblings, there is a deficiency of 3 beta-HSD in the adrenal zona fasciculata and zona reticularis, whereas 3 beta-HSD activity is intact in the zona glomerulosa. In addition, in these siblings, 3 beta-HSD deficiency was present in the gonads, while peripheral 3 beta-HSD activity appeared to be intact. These cases demonstrate further the heterogeneity of congenital adrenal hyperplasia due to 3 beta-HSD deficiency.

  14. Photosensitizer-induced fluorescence of the rat adrenal gland and rat pheochromocytoma cells (PC 12) by meso-tetra(hydroxyphenyl)chlorin (mTHPC)

    NASA Astrophysics Data System (ADS)

    Colombo-Benkmann, Mario; Muhm, Markus; Gahlen, Johannes; Heym, Christine; Senninger, Norbert

    1997-12-01

    Rat adrenal glands exhibit an intense mTHPC-induced fluorescence. The objective of our study was the identification of adrenal cells exhibiting mTHPC-induced fluorescence under normal conditions and under stimulation of adrenal proliferation by reserpine. Furthermore mTHPC-uptake of rat pheochromocytoma (PC 12) cells was investigated. Four male Wistar rats received 0.5 mg mTHPC/kg iv 48 hours before perfusion. Furthermore four rats received reserpine (2 mg/kg im od), bromo-deoxy-uridine (BrdU; 50 mg/kg ip od) each for one week and mTHPC (0.5 mg/kg) 48 hours before perfusion. BrdU was detected immunohistochemically. PC 12-cells were incubated with 0.5 mg mTHPC/l culture medium for 24 or 48 hours. Cells and tissues were examined by fluorescence microscopy. The adrenal cortex exhibited an intense mTHPC-induced fluorescence. The adrenal medulla fluoresced faintly. Reserpine increased fluorescence of intramedullary cells, not coinciding with adrenal proliferation. Cortical fluorescence remained unchanged. PC 12-cells lying singly or in small groups and differentiating cells showed a more intense mTHPC- induced fluorescence than confluent cells. Differences of cortical and medullary uptake of mTHPC are independent of proliferation and may be explained by lipophilia of mTHPC, since adrenocytes have an uptake mechanism for cholesterol. The difference of mTHPC-uptake between PC 12-cells and chromaffin cells implicate the possibility of photodynamic applications for medullary neoplasia.

  15. Guidelines for the Development of Comprehensive Care Centers for Congenital Adrenal Hyperplasia: Guidance from the CARES Foundation Initiative

    PubMed Central

    Auchus, Richard J.; Witchel, Selma Feldman; Leight, Kelly R.; Aisenberg, Javier; Azziz, Ricardo; Bachega, Tânia A.; Baker, Linda A.; Baratz, Arlene B.; Baskin, Laurence S.; Berenbaum, Sheri A.; Breault, David T.; Cerame, Barbara I.; Conway, Gerard S.; Eugster, Erica A.; Fracassa, Stephanie; Gearhart, John P.; Geffner, Mitchell E.; Harris, Katharine B.; Hurwitz, Richard S.; Katz, Aviva L.; Kalro, Brinda N.; Lee, Peter A.; Alger Lin, Gretchen; Loechner, Karen J.; Marshall, Ian; Merke, Deborah P.; Migeon, Claude J.; Miller, Walter L.; Nenadovich, Tamara L.; Oberfield, Sharon E.; Pass, Kenneth A.; Poppas, Dix P.; Lloyd-Puryear, Michele A.; Quigley, Charmian A.; Riepe, Felix G.; Rink, Richard C.; Rivkees, Scott A.; Sandberg, David E.; Schaeffer, Traci L.; Schlussel, Richard N.; Schneck, Francis X.; Seely, Ellen W.; Snyder, Diane; Speiser, Phyllis W.; Therrell, Bradford L.; VanRyzin, Carol; Vogiatzi, Maria G.; Wajnrajch, Michael P.; White, Perrin C.; Zuckerman, Alan E.

    2010-01-01

    Patients with rare and complex diseases such as congenital adrenal hyperplasia (CAH) often receive fragmented and inadequate care unless efforts are coordinated among providers. Translating the concepts of the medical home and comprehensive health care for individuals with CAH offers many benefits for the affected individuals and their families. This manuscript represents the recommendations of a 1.5 day meeting held in September 2009 to discuss the ideal goals for comprehensive care centers for newborns, infants, children, adolescents, and adults with CAH. Participants included pediatric endocrinologists, internal medicine and reproductive endocrinologists, pediatric urologists, pediatric surgeons, psychologists, and pediatric endocrine nurse educators. One unique aspect of this meeting was the active participation of individuals personally affected by CAH as patients or parents of patients. Representatives of Health Research and Services Administration (HRSA), New York-Mid-Atlantic Consortium for Genetics and Newborn Screening Services (NYMAC), and National Newborn Screening and Genetics Resource Center (NNSGRC) also participated. Thus, this document should serve as a “roadmap” for the development phases of comprehensive care centers (CCC) for individuals and families affected by CAH. PMID:21274448

  16. Fetal adrenal gland enlargement - prenatal and postnatal management.

    PubMed

    Lackova, Eliska; Cunderlik, Anton; Ticha, Lubica; Gabor, Maria

    2017-11-01

    The enlargement of suprarenal gland is related to preterm birth and the birth weight. The ultrasound measurement of fetal adrenal gland volume may identify women at risk for impending preterm birth. The aim of our study was to investigate the newborns in the region of western Slovakia followed up due to suprarenal gland enlargement. To set the ratio of prenatally diagnosed suprarenal gland enlargment, postnatal managment and treatment and interventions. The newborns with congenital adrenal hyperplasia were excluded. We have analyzed 6 years of medical records of all cases from the western Slovakia region of suprarenal gland enlargement encountered to 1st Pediatric Department, Children's University Hospital Bratislava Republic in the time period of January 2010 to Janurary 2016. The diagnosis of suprarenal gland enlargement was set by ultrasound examination performed on the 4th postnatal day as an overall screening test. Newborns with positive laboratory screening on congenital adrenal hyperplasia (CAH) were excluded from our study. We analyzed the origin of surarenal gland enlargement, gestation week on the due date, the birth weight and other comorbidities and genetic pathologies in newborns with the enlarged suprarenal glands. There were 6 newborns followed up due to suprarenal gland enlargement. All of the patients had diagnosed the adrenal haemorrhage. Adrenal lesions like adrenal cysts or neuroblastomas were not confirmed. All of the adrenal enlargements were benign with no need of other medical or surgical intervention. None of the newborn patients had other genetic abnormalities, mineral or hormonal imbalances, problems with arterial pressure or haemodynamic instability. All of the patients underwent at least 5 prenatal ultrasound tests and at least 2 postnatal ultrasound measurements. The avarage birth weight was 3030 grams (2700 grams - to 3750 grams). The avarage birth lenght was 50 cm (47 centimeter to 53 cm).The average gestation week (gw) on due date

  17. Trails on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Leading to Diagnosis of Testicular Adrenal Rest Tumor.

    PubMed

    Kashyap, Raghava

    2018-01-01

    Testicular adrenal rest tumors (TARTs) are secondary to hypertrophy of adrenal rest cells in the rete testis in settings of hypersecretion of androgens. We present a case of congenital adrenal hyperplasia with TART with clues to the diagnosis on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT). To the best of our knowledge, this is the first reported case on the role of 18 F-FDG PET/CT in TART.

  18. Gender of rearing and psychosocial aspect in 46 XX congenital adrenal hyperplasia

    PubMed Central

    Gangaher, Arushi; Jyotsna, Viveka P.; Chauhan, Vasundhera; John, Jomimol; Mehta, Manju

    2016-01-01

    Background: In congenital adrenal hyperplasia (CAH) with ambiguous genitalia, assigning gender of rearing can be complex, especially If genitalia is highly virilized. Apart from karyotype, prenatal androgen exposure, patient's gender orientation, sociocultural, and parental influences play a role. The aim of this study was to assess gender dysphoria and psychosocial issues in patients of CAH raised as males and females. Materials and Methods: This is a cross-sectional study that includes patients (old and new) with CAH who were treated by us in the last 6 months. A semi-structured interview proforma was used to elicit history and psychosocial background of the patients. The clinical and biochemical details were noted. For psychological analysis, patients were screened for gender dysphoria using Parent Report Gender Identity Questionnaire for children <12 years and Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults. Results: We analyzed 22 46 XX CAH patients among which, 3 were reared as males and 19 as females. Among the 19 patients reared as females, 17 patients showed no gender dysphoria. Two patients revealed gender dysphoria as indicated by their marginally low scores on the gender dysphoria assessment. However, in view of current literature and the age groups of the patients, behavior of the 6-year-old patient can be best understood as being tomboyish. Gender dysphoria in the 22-year-old can be explained by the dominance of psychosocial factors and not hormones alone. Among the three patients reared as males, two prepubertal were satisfied with their male gender identity. The third patient, aged 32 years, had gender dysphoria when reared as a male that resolved when gender was reassigned as female and feminizing surgery was done. Conclusion: Gender assignment in 46 XX CAH is guided by factors such as degree of virilization of genitalia, gender orientation, patient involvement, sociocultural, and parental influences. PMID:27867895

  19. Gender of rearing and psychosocial aspect in 46 XX congenital adrenal hyperplasia.

    PubMed

    Gangaher, Arushi; Jyotsna, Viveka P; Chauhan, Vasundhera; John, Jomimol; Mehta, Manju

    2016-01-01

    In congenital adrenal hyperplasia (CAH) with ambiguous genitalia, assigning gender of rearing can be complex, especially If genitalia is highly virilized. Apart from karyotype, prenatal androgen exposure, patient's gender orientation, sociocultural, and parental influences play a role. The aim of this study was to assess gender dysphoria and psychosocial issues in patients of CAH raised as males and females. This is a cross-sectional study that includes patients (old and new) with CAH who were treated by us in the last 6 months. A semi-structured interview proforma was used to elicit history and psychosocial background of the patients. The clinical and biochemical details were noted. For psychological analysis, patients were screened for gender dysphoria using Parent Report Gender Identity Questionnaire for children <12 years and Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults. We analyzed 22 46 XX CAH patients among which, 3 were reared as males and 19 as females. Among the 19 patients reared as females, 17 patients showed no gender dysphoria. Two patients revealed gender dysphoria as indicated by their marginally low scores on the gender dysphoria assessment. However, in view of current literature and the age groups of the patients, behavior of the 6-year-old patient can be best understood as being tomboyish. Gender dysphoria in the 22-year-old can be explained by the dominance of psychosocial factors and not hormones alone. Among the three patients reared as males, two prepubertal were satisfied with their male gender identity. The third patient, aged 32 years, had gender dysphoria when reared as a male that resolved when gender was reassigned as female and feminizing surgery was done. Gender assignment in 46 XX CAH is guided by factors such as degree of virilization of genitalia, gender orientation, patient involvement, sociocultural, and parental influences.

  20. Congenital adrenal hyperplasia clinical characteristics and genotype in newborn, childhood and adolescence.

    PubMed

    Pasqualini, Titania; Alonso, Guillermo; Tomasini, Rosangela; Galich, Ana Maria; Buzzalino, Noemi; Fernandez, Cecilia; Minutolo, Carolina; Alba, Liliana; Dain, Liliana

    2007-01-01

    Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disorder which can adopt three clinical expressions: two classical forms -salt-wasting (SW), with residual enzymatic activity (EA) < or = 1% and simple virilizing (SV), with EA 1-2%- and a mild late onset or nonclassical (NC) form, with EA 10-60%. Our objective is to describe clinical characteristics, growth, and bone mass in a group of patients affected by 21-hydroxylase deficiency. Besides, molecular genetics studies were performed in patients, and also when available in their parents and siblings. Nine patients with neonatal diagnosis and 8 with pre or postpubertal diagnosis were studied. Analyses of 10-point mutations in the CYP21A2 gene were performed. We found that all the patients with the classical expression, except one with a de novo mutation R356W in one allele, were fully genotyped with predictive < 2% EA mutations. Signs of hyperandrogenism were present in 5/6 NC patients; one was diagnosed by searching for mutations in asymptomatic siblings. All the NC patients were compound heterozygotes carrying V281L mutation in one allele and a predictive low EA in the other, except for one not yet determined. In patients with neonatal diagnosis, mean height was low at one year of age, though it showed a significant increase before the onset of puberty. We conclude that neonatal diagnosis of classical CAH allows an adequate follow up enhancing growth. Molecular analyses of all members of an affected family may disclose asymptomatic patients. The presence of de novo mutations, as well as, the presence of mutations with low predicted EA in NC patients reinforces the importance of genotyping for appropriate genetic counseling. In fully genotyped NC patients, the lowest value of ACTH-stimulated 17OHP was 14 ng/ml. Lower cut-off values might overestimate the diagnosis of the NC form.

  1. Ovarian hilus-cell hyperplasia and high serum testosterone in a patient with postmenopausal virilization.

    PubMed

    Delibasi, Tuncay; Erdogan, Murat F; Serinsöz, Ebru; Kaygusuz, Gulsah; Erdogan, Gurbuz; Sertçelik, Ayse

    2007-09-01

    To describe a woman with postmenopausal virilization and hirsutism caused by hilus-cell hyperplasia. We present a case report including laboratory, radiographic, and pathologic findings in a patient with postmenopausal hirsutism and virilization caused by ovarian hilus-cell hyperplasia as well as a brief review of the literature. A 60-year-old postmenopausal woman presented with extensive hirsutism, male-pattern hair loss, and clitoromegaly. The patient's plasma testosterone levels were very high, but computed tomography showed the adrenal glands to be normal in size. Pelvic ultrasonography revealed a cystic lesion in the left ovary. After bilateral salpingo-oophorectomy, histologic examination demonstrated a diffuse pattern of hilus-cell hyperplasia in the ovarian hilum. In the differential diagnosis of postmenopausal virilization, hilus-cell hyperplasia, although rare, should be considered.

  2. Update on the management of unusual neuroendocrine tumors: pheochromocytoma and paraganglioma, medullary thyroid cancer and adrenocortical carcinoma.

    PubMed

    Strosberg, Jonathan R

    2013-02-01

    Pheochromocytomas, paragangliomas, and medullary thyroid carcinomas (MTCs) originate in cells that share a common neuroectodermal origin. Like other neuroendocrine neoplasms, they are characterized by a propensity to secrete amines (epinephrine and norepinephrine) and peptide hormones (calcitonin). Improved understanding of underlying molecular pathways, such as mutations of the RET (rearranged during transfection) proto-oncogene, has led to new rational targeted therapies. Adrenocortical carcinomas (ACCs) originate in the steroid hormone-producing adrenal cortex. While tumors of the adrenal cortex are not, strictly speaking, part the "diffuse neuroendocrine system," they are often included in neuroendocrine tumor guidelines due to their orphan status. In this update on management of unusual neuroendocrine tumors, we review the biology and treatment of these rare neoplasms. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Quality of life in adults with congenital adrenal hyperplasia relates to glucocorticoid treatment, adiposity and insulin resistance: United Kingdom Congenital adrenal Hyperplasia Adult Study Executive (CaHASE)

    PubMed Central

    Han, Thang S; Krone, Nils; Willis, Debbie S; Conway, Gerard S; Hahner, Stefanie; Rees, D Aled; Stimson, Roland H; Walker, Brian R; Arlt, Wiebke; Ross, Richard J

    2013-01-01

    Context Quality of life (QoL) has been variously reported as normal or impaired in adults with congenital adrenal hyperplasia (CAH). To explore the reasons for this discrepancy we investigated the relationship between QoL, glucocorticoid treatment and other health outcomes in CAH adults. Methods Cross-sectional analysis of 151 adults with 21-hydroxylase deficiency aged 18–69 years in whom QoL (assessed using the Short Form Health Survey), glucocorticoid regimen, anthropometric and metabolic measures were recorded. Relationships were examined between QoL, type of glucocorticoid (hydrocortisone, prednisolone and dexamethasone) and dose of glucocorticoid expressed as prednisolone dose equivalent (PreDEq). QoL was expressed as z-scores calculated from matched controls (14 430 subjects from UK population). Principal components analysis (PCA) was undertaken to identify clusters of associated clinical and biochemical features and the principal component (PC) scores used in regression analysis as predictor of QoL. Results QoL scores were associated with type of glucocorticoid treatment for vitality (P=0.002) and mental health (P=0.011), with higher z-scores indicating better QoL in patients on hydrocortisone monotherapy (P<0.05). QoL did not relate to PreDEq or mutation severity. PCA identified three PCs (PC1, disease control; PC2, adiposity and insulin resistance and PC3, blood pressure and mutations) that explained 61% of the variance in observed variables. Stepwise multiple regression analysis demonstrated that PC2, reflecting adiposity and insulin resistance (waist circumference, serum triglycerides, homeostasis model assessment of insulin resistance and HDL-cholesterol), related to QoL scores, specifically impaired physical functioning, bodily pain, general health, Physical Component Summary Score (P<0.001) and vitality (P=0.002). Conclusions Increased adiposity, insulin resistance and use of prednisolone or dexamethasone are associated with impaired QoL in adults

  4. Molecular and clinical evidence for an ARMC5 tumor syndrome: concurrent inactivating germline and somatic mutations are associated with both primary macronodular adrenal hyperplasia and meningioma.

    PubMed

    Elbelt, Ulf; Trovato, Alessia; Kloth, Michael; Gentz, Enno; Finke, Reinhard; Spranger, Joachim; Galas, David; Weber, Susanne; Wolf, Cristina; König, Katharina; Arlt, Wiebke; Büttner, Reinhard; May, Patrick; Allolio, Bruno; Schneider, Jochen G

    2015-01-01

    Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing's syndrome, which may present in the context of different familial multitumor syndromes. Heterozygous inactivating germline mutations of armadillo repeat containing 5 (ARMC5) have very recently been described as cause for sporadic PMAH. Whether this genetic condition also causes familial PMAH in association with other neoplasias is unclear. The aim of the present study was to delineate the molecular cause in a large family with PMAH and other neoplasias. Whole-genome sequencing and comprehensive clinical and biochemical phenotyping was performed in members of a PMAH affected family. Nodules derived from adrenal surgery and pancreatic and meningeal tumor tissue were analyzed for accompanying somatic mutations in the identified target genes. PMAH presenting either as overt or subclinical Cushing's syndrome was accompanied by a heterozygous germline mutation in ARMC5 (p.A110fs*9) located on chromosome 16. Analysis of tumor tissue showed different somatic ARMC5 mutations in adrenal nodules supporting a second hit hypothesis with inactivation of a tumor suppressor gene. A damaging somatic ARMC5 mutation was also found in a concomitant meningioma (p.R502fs) but not in a pancreatic tumor, suggesting biallelic inactivation of ARMC5 as causal also for the intracranial meningioma. Our analysis further confirms inherited inactivating ARMC5 mutations as a cause of familial PMAH and suggests an additional role for the development of concomitant intracranial meningiomas.

  5. Comparison of one-tier and two-tier newborn screening metrics for congenital adrenal hyperplasia.

    PubMed

    Sarafoglou, Kyriakie; Banks, Kathryn; Gaviglio, Amy; Hietala, Amy; McCann, Mark; Thomas, William

    2012-11-01

    Newborn screening (NBS) for the classic forms of congenital adrenal hyperplasia (CAH) is mandated in all states in the United States. Compared with other NBS disorders, the false-positive rate (FPR) of CAH screening remains high and has not been significantly improved by adjusting 17α-hydroxyprogesterone cutoff values for birth weight and/or gestational age. Minnesota was the first state to initiate, and only 1 of 4 states currently performing, second-tier steroid profiling for CAH. False-negative rates (FNRs) for CAH are not well known. This is a population-based study of all Minnesota infants (769,834) born 1999-2009, grouped by screening protocol (one-tier with repeat screen, January 1999 to May 2004; two-tier with second-tier steroid profiling, June 2004 to December 2009). FPR, FNR, and positive predictive value (PPV) were calculated per infant, rather than per sample, and compared between protocols. Overall, 15 false-negatives (4 salt-wasting, 11 simple-virilizing) and 45 true-positives were identified from 1999 to 2009. With two-tier screening, FNR was 32%, FPR increased to 0.065%, and PPV decreased to 8%, but these changes were not statistically significant. Second-tier steroid profiling obviated repeat screens of borderline results (355 per year average). In comparing the 2 screening protocols, the FPR of CAH NBS remains high, the PPV remains low, and false-negatives occur more frequently than has been reported. Physicians should be cautioned that a negative NBS does not necessarily rule out classic CAH; therefore, any patient for whom there is clinical concern for CAH should receive immediate diagnostic testing.

  6. [Congenital adrenal hyperplasia: a qualitative study on sex definition and redesignation dilation surgery and psychological support (part II)].

    PubMed

    Telles-Silveira, Mariana; Tonetto-Fernandes, Vânia F; Schiller, Paulo; Kater, Claudio E

    2009-12-01

    To identify relevant questions related to sex definition and re-designation and reconstructive surgery in patients with congenital adrenal hyperplasia (CAH), and to understand the role of the psychologist in providing care for these patients. We selected 21 subjects: 7 pediatric endocrinologists from 5 Brazilian Public Health System institutions, 9 parents and 6 patients with CAH, according to a qualitative research model. In this paper, 3 of the studied categories are analyzed: 'sex definition and re-designation', 'reconstructive surgery/vaginal dilation', and 'psychology'. Parents' main anguish relates to the situation of an unnamed sex at birth, whereas sex re-designation was distressful to physicians. A sense of loneliness when dealing with the disease and treatment was a common anguish among patients; dilation procedures were the major complaint. In general, physicians recommend that genital reconstructive surgery be performed early on to avoid future trauma. In such a complex scenario, it is remarkable that not all the reference service staff have a psychologist on duty. Difficulties to deal with questions involving sexuality were evident and dilation procedures are an additional source of trauma for these patients.

  7. Assembling a Functional Clitoris and Vulva from a Pseudo-Penis: A Surgical Technique for an Adult Woman with Congenital Adrenal Hyperplasia.

    PubMed

    Tjalma, Wiebren A A

    2017-06-01

    Congenital adrenal hyperplasia (CAH) is associated with a genital deformation that might cause a negative body image. The genital ambiguity is generally "corrected" surgically during early infancy. The advantage is a psychological benefit. The disadvantages are multiple surgical procedures and the loss of orgasm. A 22-year-old woman with CAH consulted for genital reconstructive surgery. She had a pseudopenis of 4 cm and could achieve an orgasm by masturbating. During surgery, the penis was dismantled and with the preserved glans penis and the corpora cavernosa, a clitoris and vestibules were constructed, respectively. On the basis of the anamneses during the follow-up, she had a functional vagina and could still achieve orgasms. Genital correction surgery for CAH at an older age was easier, could be done in 1 step, and enabled the preservation of orgasm. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  8. Prenatal hormones and childhood sex-segregation: Playmate and play style preferences in girls with congenital adrenal hyperplasia

    PubMed Central

    Pasterski, Vickie; Geffner, Mitchell E.; Brain, Caroline; Hindmarsh, Peter; Brook, Charles; Hines, Melissa

    2011-01-01

    We investigated playmate and play style preference in children with congenital adrenal hyperplasia (CAH) (26 females, 31 males) and their unaffected siblings (26 females, 17 males) using the Playmate and Play Style Preferences Structured Interview (PPPSI). Both unaffected boys and girls preferred same-sex playmates and sex-typical play styles. In the conflict condition where children chose between a same-sex playmate engaged in an other-sex activity or an other-sex playmate engaged in a same-sex activity, boys (both CAH and unaffected brothers) almost exclusively chose playmates based on the preferred play style of the playmate as opposed to the preferred gender label of the playmate. By contrast, unaffected girls used play style and gender label about equally when choosing playmates. Girls with CAH showed a pattern similar to that of boys: their playmate selections were more masculine than unaffected girls, they preferred a boy-typical play style and, in the conflict condition, chose playmates engaged in a masculine activity. These findings suggest that prenatal androgen exposure contributes to sex differences in playmate selection observed in typically-developing children, and that, among boys and girls exposed to high levels of androgens prenatally, play style preferences drive sex segregation in play. PMID:21338606

  9. Prenatal hormones and childhood sex segregation: playmate and play style preferences in girls with congenital adrenal hyperplasia.

    PubMed

    Pasterski, Vickie; Geffner, Mitchell E; Brain, Caroline; Hindmarsh, Peter; Brook, Charles; Hines, Melissa

    2011-04-01

    We investigated playmate and play style preference in children with congenital adrenal hyperplasia (CAH) (26 females, 31 males) and their unaffected siblings (26 females, 17 males) using the Playmate and Play Style Preferences Structured Interview (PPPSI). Both unaffected boys and girls preferred same-sex playmates and sex-typical play styles. In the conflict condition where children chose between a same-sex playmate engaged in an other-sex activity or an other-sex playmate engaged in a same-sex activity, boys (both CAH and unaffected brothers) almost exclusively chose playmates based on the preferred play style of the playmate as opposed to the preferred gender label of the playmate. By contrast, unaffected girls used play style and gender label about equally when choosing playmates. Girls with CAH showed a pattern similar to that of boys: their playmate selections were more masculine than unaffected girls, they preferred a boy-typical play style and, in the conflict condition, chose playmates engaged in a masculine activity. These findings suggest that prenatal androgen exposure contributes to sex differences in playmate selection observed in typically developing children and that, among boys and girls exposed to high levels of androgens prenatally, play style preferences drive sex segregation in play. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Molecular defects of the CYP21A2 gene in Greek-Cypriot patients with congenital adrenal hyperplasia.

    PubMed

    Skordis, Nicos; Kyriakou, Andreas; Tardy, Véronique; Ioannou, Yiannis S; Varvaresou, Athanasia; Dracopoulou-Vabouli, Maria; Patsalis, Philippos C; Shammas, Christos; Neocleous, Vassos; Phylactou, Leonidas A

    2011-01-01

    To determine the mutations in the CYP21A2 gene in Greek-Cypriots with congenital adrenal hyperplasia (CAH) and attempt a genotype-phenotype correlation. Molecular analysis was performed by multiplex ligation-dependent probe amplification and direct sequencing of PCR products of the CYP21A2 gene in 32 CAH patients. The most frequent genetic defect in the classic salt-wasting and simple virilizing forms was the IVS2-13A/C>G (55%) mutation, followed by Large lesion (20%) and in the non-classical form, the p.V281L (79.5%). Genotypes were categorized in 4 mutation groups (null, A, B and C). All 3 patients in the null group manifested the salt-wasting form and all 6 patients in mutation group A presented with the classical form. One patient in group B had the simple virilizing form and 22 patients in group C exhibited the non-classical form. The spectrum of mutations of the CYP21A2 gene in our population is comparable to the most common reported in similar ethnic groups. The knowledge of the ethnic specificity of the CYP21A2 mutations represents a valuable diagnostic tool for all forms of CAH. Copyright © 2010 S. Karger AG, Basel.

  11. From Knowing Nothing to Knowing What, How and Now: Parents' Experiences of Caring for their Children With Congenital Adrenal Hyperplasia.

    PubMed

    Lundberg, Tove; Lindström, Anders; Roen, Katrina; Hegarty, Peter

    2017-06-01

    This study investigates various kinds of knowing that European parents use when caring for their children with congenital adrenal hyperplasia (CAH). Semi-structured qualitative interviews with 20 parents of 22 children with CAH. Parents emphasized the importance of knowing what CAH is and what support their child needs, but also knowing how to cope and make sense of the new situation, how to attend to their child's medical needs as well as how to talk to their child. Parents also reported challenges related to connecting with their social network, experiences of emergency care, and how to help their children become independent. These challenges require knowing now : being able to respond appropriately to unique circumstances. Parents experience diverse challenges that may moderate the effects of the diagnosis on children's well-being. Parenting children with CAH requires the development of knowing that goes beyond medical information. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  12. A patient with Alzheimer's disease complicated by elderly-onset Cushing's syndrome who had undergone surgical treatment for adrenocorticotropic hormone-independent macronodular adrenal hyperplasia.

    PubMed

    Haraguchi, Yoshinori; Mizoguchi, Yoshito; Noguchi, Tomoyuki; Arai, Takeo; Fukuyama, Junko; Kato, Takahiro A; Kawashima, Toshiro; Monji, Akira

    2016-07-01

    Cushing's syndrome (CS) is a rare disorder, especially in older people. Loss of brain volume and neurocognitive impairment of varying degrees has been demonstrated in patients with CS. However, there is a large difference between the median age of presentation of CS and that of Alzheimer's disease. We herein report a case of a patient with Alzheimer's disease complicated by elderly-onset CS who had undergone surgical treatment for adrenal hyperplasia. Surgical correction of hypercortisolism seems to have slowed the progression of brain volume loss and cognitive dysfunction and improved psychiatric symptoms such as visual hallucination, restlessness, and psychomotor excitement. These improvements have remarkably reduced the burden on the patient's caregivers. The present case suggests that subclinical CS may be present, particularly in rapidly progressive dementia, and that surgical treatment of CS for neuropsychiatric symptoms is useful. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

  13. Health Status of Adults with Congenital Adrenal Hyperplasia: A Cohort Study of 203 Patients

    PubMed Central

    Arlt, Wiebke; Willis, Debbie S.; Wild, Sarah H.; Krone, Nils; Doherty, Emma J.; Hahner, Stefanie; Han, Thang S.; Carroll, Paul V.; Conway, Gerry S.; Rees, D. Aled; Stimson, Roland H.; Walker, Brian R.; Connell, John M. C.; Ross, Richard J.

    2010-01-01

    Context: No consensus exists for management of adults with congenital adrenal hyperplasia (CAH) due to a paucity of data from cohorts of meaningful size. Objective: Our objective was to establish the health status of adults with CAH. Design and Setting: We conducted a prospective cross-sectional study of adults with CAH attending specialized endocrine centers across the United Kingdom. Patients: Participants included 203 CAH patients (199 with 21-hydroxylase deficiency): 138 women, 65 men, median age 34 (range 18–69) years. Main Outcome Measures: Anthropometric, metabolic, and subjective health status was evaluated. Anthropometric measurements were compared with Health Survey for England data, and psychometric data were compared with appropriate reference cohorts. Results: Glucocorticoid treatment consisted of hydrocortisone (26%), prednisolone (43%), dexamethasone (19%), or a combination (10%), with reverse circadian administration in 41% of patients. Control of androgens was highly variable with a normal serum androstenedione found in only 36% of patients, whereas 38% had suppressed levels suggesting glucocorticoid overtreatment. In comparison with Health Survey for England participants, CAH patients were significantly shorter and had a higher body mass index, and women with classic CAH had increased diastolic blood pressure. Metabolic abnormalities were common, including obesity (41%), hypercholesterolemia (46%), insulin resistance (29%), osteopenia (40%), and osteoporosis (7%). Subjective health status was significantly impaired and fertility compromised. Conclusions: Currently, a minority of adult United Kingdom CAH patients appear to be under endocrine specialist care. In the patients studied, glucocorticoid replacement was generally nonphysiological, and androgen levels were poorly controlled. This was associated with an adverse metabolic profile and impaired fertility and quality of life. Improvements in the clinical management of adults with CAH are

  14. The three subtypes of atrial natriuretic peptide (ANP) receptors are expressed in the rat adrenal gland.

    PubMed

    Grandclément, B; Ronsin, B; Morel, G

    1997-03-01

    Atrial natriuretic peptide (ANP) actions are mediated by highly selective and specific receptors. Three subtypes have been characterized and cloned: ANP receptor-A (or GC-A), -B (or GC-B) and -C (the so-called clearance receptor). In rat adrenal gland, the mRNA for each subtype was detected using 35S-dUTP or digoxigenin-11-dUTP specific labeled probes, and in situ hybridization at light and electron microscopic levels respectively. The three subtypes were expressed the most abundantly in the zona glomerulosa. The amount of GC-A mRNA expression, quantified using macro-autoradiography and densitometry, was higher than the amounts of GC-B mRNA and ANPR-C mRNA both in zona glomerulosa and medullary of adrenal gland. At electron microscopic level, the three subtypes of ANPR were revealed in glomerulosa cells. A noticeable signal was also present in the medullary area, especially for GC-A mRNA, in adrenaline-containing chromaffin cells. No signal was detected in noradrenaline-containing chromaffin cells. The subcellular localization of the three mRNAs is similar: in the cytoplasmic matrix and in the euchromatin of the nucleus in each cell of glomerulosa, and in the same compartments of the adrenaline-containing chromaffin cells. These data indicate that the adrenal gland is an important target tissue for ANP action both in glomerulosa cells and adrenaline-containing chromaffin cells. The mRNA expression levels were different for each ANPR subtype.

  15. Splicing mutation in CYP21 associated with delayed presentation of salt-wasting congenital adrenal hyperplasia

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

    Kohn, B.; Patel, S.V.; Pelczar, J.V.

    1995-07-03

    Patients with salt-wasting congenital adrenal hyperplasia (SW-CAH) most commonly carry an A-G transition at nucleotide 656 (nt 656 A{r_arrow}G), causing abnormal splicing of exons 2 and 3 in CYP21, the gene encoding active steroid 21-hydroxylase. Affected infants are severely deficient in cortisol and aldosterone, and usually come to medical attention during the neonatal period. We report on 2 affected boys, homozygous for the nt 656 mutation, who thrived in early infancy, but suffered salt-wasting crises unusually late in infancy, at 3.5 and 5.5 months, respectively. Laboratory studies at presentation showed hyponatremia, hyperkalemia, dehydration, and acidosis; serum aldosterone was low inmore » spite of markedly elevated plasma renin activity. Basal 17-hydroxyprogesterone levels were only moderately elevated, yet the stimulated levels were more typical of severe, classic CAH due to 21-hydroxylase deficiency. Genomic DNA from the patients was analyzed. Southern blot showed no major deletions or rearrangements. CYP21-specific amplification by polymerase chain reaction, coupled with allele-specific hybridization using wild-type and mutant probes at each of 9 sites for recognized disease-causing mutations, revealed a single, homozygous mutation in each patient: nt 656 A{r_arrow}G. These results were confirmed by sequence analysis. We conclude that the common nt 656 A{r_arrow}G mutation is sometimes associated with delayed phenotypic expression of SW-CAH. We speculate that variable splicing of the mutant CYP21 may modify the clinical manifestation of this disease. 22 refs., 1 fig., 1 tab.« less

  16. Catecholamine secretion by chemical hypoxia in guinea-pig, but not rat, adrenal medullary cells: differences in mitochondria.

    PubMed

    Harada, K; Endo, Y; Warashina, A; Inoue, M

    2015-08-20

    The effects of mitochondrial inhibitors (CN(-), a complex IV inhibitor and CCCP, protonophore) on catecholamine (CA) secretion and mitochondrial function were explored functionally and biochemically in rat and guinea-pig adrenal chromaffin cells. Guinea-pig chromaffin cells conspicuously secreted CA in response to CN(-) or CCCP, but rat cells showed a little, if any, secretory response to either of them. The resting metabolic rates in rat adrenal medullae did not differ from those in guinea-pig adrenal medullae. On the other hand, the time course of depolarization of the mitochondrial membrane potential (ΔΨm) in guinea-pig chromaffin cells in response to CN(-) was slower than that in rat chromaffin cells, and this difference was abolished by oligomycin, an F1F0-ATPase inhibitor. The extent of CCCP-induced decrease in cellular ATP in guinea-pig chromaffin cells, which was indirectly measured using a Mg(2+) indicator, was smaller than that in rat chromaffin cells. Relative expression levels of F1F0-ATPase inhibitor factor in guinea-pig adrenal medullae were smaller than in rat adrenal medullae, and the opposite was true for F1F0-ATPase α subunit. The present results indicate that guinea-pig chromaffin cells secrete more CA in response to a mitochondrial inhibitor than rat chromaffin cells and this higher susceptibility in the former is accounted for by a larger extent of reversed operation of F1F0-ATPase with the consequent decrease in ATP under conditions where ΔΨm is depolarized. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. A rare CYP21A2 mutation in a congenital adrenal hyperplasia kindred displaying genotype-phenotype nonconcordance.

    PubMed

    Khattab, Ahmed; Yuen, Tony; Al-Malki, Sultan; Yau, Mabel; Kazmi, Diya; Sun, Li; Harbison, Madeleine; Haider, Shozeb; Zaidi, Mone; New, Maria I

    2016-01-01

    Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is caused by the autosomal recessive inheritance of mutations in the gene CYP21A2. CYP21A2 mutations lead to variable impairment of the 21-hydroxylase enzyme, which, in turn, is associated with three clinical phenotypes, namely, salt wasting, simple virilizing, and nonclassical CAH. However, it is known that a given mutation can associate with different clinical phenotypes, resulting in a high rate of genotype-phenotype nonconcordance. We aimed to study the genotype-phenotype nonconcordance in a family with three siblings affected with nonclassical CAH. All had hormonal evidence of nonclassical CAH, but this phenotype could not be explained by the genotype obtained from commercial CYP21A2 genetic testing, which revealed heterozygosity for the maternal 30 kb deletion mutation. We performed Sanger sequencing of the entire CYP21A2 gene in this family to search for a rare mutation that was not covered by commercial testing and found in the three siblings a second, rare c.1097G>A (p.R366H) mutation in exon 8. Computational modeling confirmed that this was a mild mutation consistent with nonclassical CAH. We recommend that sequencing of entire genes for rare mutations should be carried out when genotype-phenotype nonconcordance is observed in patients with autosomal recessive monogenic disorders, including CAH. © 2015 New York Academy of Sciences.

  18. Linking Prenatal Androgens to Gender-Related Attitudes, Identity, and Activities: Evidence From Girls With Congenital Adrenal Hyperplasia.

    PubMed

    Endendijk, Joyce J; Beltz, Adriene M; McHale, Susan M; Bryk, Kristina; Berenbaum, Sheri A

    2016-10-01

    Key questions for developmentalists concern the origins of gender attitudes and their implications for behavior. We examined whether prenatal androgen exposure was related to gender attitudes, and whether and how the links between attitudes and gendered activity interest and participation were mediated by gender identity and moderated by hormones. Gender attitudes (i.e., gender-role attitudes and attitudes about being a girl), gender identity, and gender-typed activities were reported by 54 girls aged 10-13 years varying in degree of prenatal androgen exposure, including 40 girls with classical congenital adrenal hyperplasia (C-CAH) exposed to high prenatal androgens and 14 girls with non-classical (NC) CAH exposed to low, female-typical, prenatal androgens. Both girls with C-CAH and NC-CAH reported positive attitudes about being a girl and egalitarian gender attitudes, consistent with their female-typical gender identity. In contrast, girls with C-CAH had more male-typed activity interest and participation than girls with NC-CAH. Gender attitudes were linked to activities in both groups, with gender identity mediating the links. Specifically, gender-role attitudes and positive attitudes about being a girl were associated with feminine gender identity, which in turn was associated with decreased male-typed activity interests and participation, and increased female-typed activity interests. Our results are consistent with schema theories, with attitudes more closely associated with gender identity than with prenatal androgens.

  19. Utility of a precursor-to-product ratio in the evaluation of presumptive positives in newborn screening of congenital adrenal hyperplasia.

    PubMed

    Tieh, P Y; Yee, J K; Hicks, R A; Mao, C S; Lee, W-Np

    2017-03-01

    Screening for congenital adrenal hyperplasia (CAH) caused by 21-α-hydroxylase deficiency is challenging because factors such as prematurity and stress increase intermediate steroid metabolite levels in newborn infants. The objective of this study was to explore the use of the 17-α-hydroxyprogesterone (17-OHP)/11-deoxycortisol ratio as an adjunct measure in the follow-up evaluation of infants with presumptive positive newborn screens for CAH to distinguish between infants with no disorder and those with CAH. This was a retrospective cohort study of infants with presumptive positive newborn screens for CAH. The precursor-to-product ratio of 17-OHP/11-deoxycortisol was compared between infants with no disorder (n=47) and infants with CAH (n=5). The CAH infants had higher 17-OHP/11-deoxycortisol ratios than infants with no disorder: 26 (18 to 58) and 1.05 (0.69 to 1.46), respectively (P<0.05). Among infants with no disorder, higher levels of serum 17-OHP did not reflect higher ratios, indicating sufficient enzyme activity. The results suggest that a low 17-OHP/11-deoxycortisol ratio represents 21-α-hydroxylase sufficiency among presumptive positives in newborn screening of CAH.

  20. A case of hirsutism due to bilateral diffuse ovarian Leydig cell hyperplasia in a post-menopausal woman.

    PubMed

    Ali, F S.M.; Stanaway, S E.R.S.; Zakhour, H D.; Spearing, G; Bowen-Jones, D

    2003-11-01

    Hyperandrogenism in females usually results from ovarian or adrenal pathology. We present a case of virilizaton due to very rare bilateral ovarian diffuse interstitial proliferation of Leydig cells with no tumour or hilar cell hyperplasia identified. Interestingly, the case was further complicated by the finding of high levels of testosterone in one adrenal vein on selective venous sampling (SVS), resulting in an unnecessary unilateral adrenalectomy. Further sampling found high levels also in the ovarian veins, and the condition was finally cured by bilateral oophorectomy.

  1. Roux-en-Y gastric bypass in the treatment of non-classic congenital adrenal hyperplasia due to 11-hydroxylase deficiency.

    PubMed

    Kalani, Amir; Thomas, Nithin; Sacerdote, Alan; Bahtiyar, Gül

    2013-03-18

    Non-classic adrenal hyperplasia (NCAH) has been associated with insulin resistance (IR). Therapies such as metformin, thiazolidinediones and lifestyle alterations improve IR and also ameliorate the biochemical and clinical abnormalities of NCAH, much as they do in polycystic ovarian syndrome (PCOS). More recently, bariatric surgery, such as Roux-en-Y gastric bypass (RYGBP), has also been associated with improvement in IR and amelioration of PCOS and may, therefore, be beneficial in NCAH. We report a case of a 39-year-old, deaf-mute, obese woman with NCAH due to 11-hydroxylase deficiency who underwent RYGBP followed by improvement of NCAH manifestations. She was initially treated with metformin and pioglitazone, which lowered serum 11-deoxycortisol from 198 ng/dl (<51) to 26 ng/dl. Five weeks after undergoing RYGBP her body mass index fell from 44.18 kg/m(2) to 39.54 kg/m(2) and, despite not taking metformin or pioglitazone, serum 11-deoxycortisol remained normal at <40 ng/dl. Concurrently and subsequently, her NCAH symptoms, for example, alopecia, hirsutism and irregular menses normalised as well. We conclude that RYGBP, like other interventions that reduce IR, may be another way of treating non-classic 11-hydroxylase deficiency in selected patients.

  2. Complete virilization in congenital adrenal hyperplasia: clinical course, medical management and disease-related complications.

    PubMed

    Woelfle, J; Hoepffner, W; Sippell, W G; Brämswig, J H; Heidemann, P; Deiss, D; Bökenkamp, A; Roth, C; Irle, U; Wollmann, H A; Zachmann, M; Kubini, K; Albers, N

    2002-02-01

    In girls with congenital adrenal hyperplasia (CAH), genital ambiguity usually leads to a rapid neonatal diagnosis. Rarely, CAH causes complete virilization and male sex assignment with a delayed diagnosis. After being confronted with very specific problems in two of such patients, we collected data of patients with CAH and complete virilization in a nationwide study to delineate specific problems of these rare patients in order to improve their management. Through the German Working Group of Paediatric Endocrinology (Arbeitsgemeinschaft Pädiatrische Endokrinologie, APE), questionnaires were sent to all members caring for patients with CAH and complete virilization in their endocrine clinics. Data from 16 patients from 10 paediatric endocrine centres were assessed by questionnaire. The following problems have been encountered. (1) Sex assignment/gender identity: initially all patients had a male sex assignment. Six patients were diagnosed during the first month of life. Five were reassigned to female sex immediately, one at the age of 19 months. Except in one girl demonstrating some tomboyish behaviour, gender role behaviour in these patients did not differ from unaffected girls. Ten patients were diagnosed late at 3.4--7 years of age. In seven patients with a late diagnosis, male sex assignment was maintained; one of them expressed some concerns about living as a male. In three patients late sex reversal was performed, gender identity is very poor in one and new sex assignment is currently under consideration. (2) SURGERY: irrespective of the sex assigned, all patients had between one and three surgical procedures, including clitoris reduction and (repeated) vaginoplasties in patients with female sex assignment. Hysterectomy and ovarectomy were performed in patients with male sex assignment. (3) Short stature: patients with a late diagnosis of CAH had extremely advanced bone ages of +6.3 to +9.5 years, leading to severely reduced final height of 137 to 150 cm in

  3. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    ClinicalTrials.gov

    2017-09-26

    Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

  4. Are there parental socialization effects on the sex-typed behavior of individuals with congenital adrenal hyperplasia?

    PubMed

    Wong, Wang I; Pasterski, Vickie; Hindmarsh, Peter C; Geffner, Mitchell E; Hines, Melissa

    2013-04-01

    Influences of prenatal androgen exposure on human sex-typical behavior have been established largely through studies of individuals with congenital adrenal hyperplasia (CAH). However, evidence that addresses the potential confounding influence of parental socialization is limited. Parental socialization and its relationship to sex-typical toy play and spatial ability were investigated in two samples involving 137 individuals with CAH and 107 healthy controls. Females with CAH showed more boy-typical toy play and better targeting performance than control females, but did not differ in mental rotations performance. Males with CAH showed worse mental rotations performance than control males, but did not differ in sex-typical toy play or targeting. Reported parental encouragement of girl-typical toy play correlated with girl-typical toy play in all four groups. Moreover, parents reported encouraging less girl-typical, and more boy-typical, toy play in females with CAH than in control females and this reported encouragement partially mediated the relationship between CAH status and sex-typical toy play. Other evidence suggests that the reported parental encouragement of sex-atypical toy play in girls with CAH may be a response to the girls' preferences for boys' toys. Nevertheless, this encouragement could further increase boy-typical behavior in girls with CAH. In contrast to the results for toy play, we found no differential parental socialization for spatial activities and little evidence linking parental socialization to spatial ability. Overall, evidence suggests that prenatal androgen exposure and parental socialization both contribute to sex-typical toy play.

  5. Influence of hormonal control on LH pulsatility and secretion in women with classical congenital adrenal hyperplasia.

    PubMed

    Bachelot, Anne; Chakhtoura, Zeina; Plu-Bureau, Geneviève; Coudert, Mathieu; Coussieu, Christiane; Badachi, Yasmina; Dulon, Jérome; Charbit, Beny; Touraine, Philippe

    2012-10-01

    Women with classical congenital adrenal hyperplasia (CAH) exhibit reduced fertility due to several factors including anovulation. This has been attributed to a disturbed gonadotropic axis as in polycystic ovary syndrome (PCOS), but there is no precise evaluation. Our aim was to evaluate the gonadotropic axis and LH pulsatility patterns and to determine factor(s) that could account for the potential abnormality of LH pulsatility. Case/control study. Sixteen CAH women (11 with the salt-wasting form and five with the simple virilizing form), aged from 18 to 40 years, and 16 age-matched women, with regular menstrual cycles (28 ± 3 days), were included. LH pulse patterns over 6 h were determined in patients and controls. No differences were observed between patients and controls in terms of mean LH levels, LH pulse amplitude, or LH frequency. In CAH patients, LH pulsatility patterns were heterogeneous, leading us to perform a clustering analysis of LH data, resulting in a two-cluster partition. Patients in cluster 1 had similar LH pulsatility patterns to the controls. Patients in cluster 2 had: lower LH pulse amplitude and frequency and presented menstrual cycle disturbances more frequently; higher 17-OH progesterone, testosterone, progesterone, and androstenedione levels; and lower FSH levels. LH pulsatility may be normal in CAH women well controlled by hormonal treatment. Undertreatment is responsible for hypogonadotropic hypogonadism, with low LH pulse levels and frequency, but not PCOS. Suppression of progesterone and androgen concentrations during the follicular phase of the menstrual cycle should be a major objective in these patients.

  6. Results of early thyroidectomy for medullary thyroid carcinoma in children with multiple endocrine neoplasia type 2.

    PubMed

    Telander, R L; Zimmerman, D; van Heerden, J A; Sizemore, G W

    1986-12-01

    Children with multiple endocrine neoplasia type 2 (MEN2) often develop medullary carcinoma of the thyroid (MCT) or its precursor, C-cell hyperplasia. Survival results are improved if malignancy is diagnosed early from the results of plasma immunoreactive calcitonin (iCT) measurement. The effect of early detection and thyroidectomy in children with MEN2 syndrome was determined by reviewing the experience between 1975 and 1985. Seventeen children with MEN2 who were 12 years old or younger underwent a total thyroidectomy for MCT or C-cell hyperplasia. iCT was measured in all patients preoperatively and postoperatively. Of the 17 children, 14 (82%) had MEN2a and 3 (18%) had MEN2b. There were 14 (82%) female and three (18%) male patients; their mean age was 6.97 years (range 1.5 to 12 years). In all patients, the diagnosis of MCT was made from initial elevated levels of iCT after stimulation with pentagastrin. Three patients had clinical evidence of disease preoperatively. All patients underwent a total thyroidectomy and lymph nodes were removed from the central zone; a neck dissection was performed in the three with clinically obvious disease. MCT with C-cell hyperplasia was found in 11 children and C-cell hyperplasia alone in six. Of the 11 with carcinoma, eight had bilateral disease and three unilateral. Six children had bilateral C-cell hyperplasia. All 17 children were alive and feeling well at the time of this report; however, three had evidence of metastatic disease according to iCT measurements. None of the children had recurrent nerve injuries; one had evidence of hypoparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. GLI1+ progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic gonadal-like tissue.

    PubMed

    Dörner, Julia; Martinez Rodriguez, Verena; Ziegler, Ricarda; Röhrig, Theresa; Cochran, Rebecca S; Götz, Ronni M; Levin, Mark D; Pihlajoki, Marjut; Heikinheimo, Markku; Wilson, David B

    2017-02-05

    As certain strains of mice age, hyperplastic lesions resembling gonadal tissue accumulate beneath the adrenal capsule. Gonadectomy (GDX) accelerates this heterotopic differentiation, resulting in the formation of wedge-shaped adrenocortical neoplasms that produce sex steroids. Stem/progenitor cells that reside in the adrenal capsule and retain properties of the adrenogonadal primordium are thought to be the source of this heterotopic tissue. Here, we demonstrate that GLI1 + progenitors in the adrenal capsule give rise to gonadal-like cells that accumulate in the subcapsular region. A tamoxifen-inducible Cre driver (Gli1-creER T2 ) and two reporters (R26R-lacZ, R26R-confetti) were used to track the fate of GLI1 + cells in the adrenal glands of B6D2F2 mice, a strain that develops both GDX-induced adrenocortical neoplasms and age-dependent subcapsular cell hyperplasia. In gonadectomized B6D2F2 mice GLI1 + progenitors contributed to long-lived adrenal capsule cells and to adrenocortical neoplasms that expressed Gata4 and Foxl2, two prototypical gonadal markers. Pdgfra, a gene expressed in adrenocortical stromal cells, was upregulated in the GDX-induced neoplasms. In aged non-gonadectomized B6D2F2 mice GLI1 + progenitors gave rise to patches of subcapsular cell hyperplasia. Treatment with GANT61, a small-molecule GLI antagonist, attenuated the upregulation of gonadal-like markers (Gata4, Amhr2, Foxl2) in response to GDX. These findings support the premise that GLI1 + progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic tissue. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Genetic Disruption of 21-Hydroxylase in Zebrafish Causes Interrenal Hyperplasia.

    PubMed

    Eachus, Helen; Zaucker, Andreas; Oakes, James A; Griffin, Aliesha; Weger, Meltem; Güran, Tülay; Taylor, Angela; Harris, Abigail; Greenfield, Andy; Quanson, Jonathan L; Storbeck, Karl-Heinz; Cunliffe, Vincent T; Müller, Ferenc; Krone, Nils

    2017-12-01

    Congenital adrenal hyperplasia is a group of common inherited disorders leading to glucocorticoid deficiency. Most cases are caused by 21-hydroxylase deficiency (21OHD). The systemic consequences of imbalanced steroid hormone biosynthesis due to severe 21OHD remains poorly understood. Therefore, we developed a zebrafish model for 21OHD, which focuses on the impairment of glucocorticoid biosynthesis. A single 21-hydroxylase gene (cyp21a2) is annotated in the zebrafish genome based on sequence homology. Our in silico analysis of the 21-hydroxylase (Cyp21a2) protein sequence suggests a sufficient degree of similarity for the usage of zebrafish cyp21a2 to model aspects of human 21OHD in vivo. We determined the spatiotemporal expression patterns of cyp21a2 by whole-mount in situ hybridization and reverse transcription polymerase chain reaction throughout early development. Early cyp21a2 expression is restricted to the interrenal gland (zebrafish adrenal counterpart) and the brain. To further explore the in vivo consequences of 21OHD we created several cyp21a2 null-allele zebrafish lines by using a transcription activator-like effector nuclease genomic engineering strategy. Homozygous mutant zebrafish larvae showed an upregulation of the hypothalamic-pituitary-interrenal (HPI) axis and interrenal hyperplasia. Furthermore, Cyp21a2-deficient larvae had a typical steroid profile, with reduced concentrations of cortisol and increased concentrations of 17-hydroxyprogesterone and 21-deoxycortisol. Affected larvae showed an upregulation of the HPI axis and interrenal hyperplasia. Downregulation of the glucocorticoid-responsive genes pck1 and fkbp5 indicated systemic glucocorticoid deficiency. Our work demonstrates the crucial role of Cyp21a2 in glucocorticoid biosynthesis in zebrafish larvae and establishes an in vivo model allowing studies of systemic consequences of altered steroid hormone synthesis.

  9. Long term outcomes in 46, XX adult patients with congenital adrenal hyperplasia reared as males.

    PubMed

    Khattab, A; Yau, M; Qamar, A; Gangishetti, P; Barhen, A; Al-Malki, S; Mistry, H; Anthony, W; Toralles, M B; New, Maria I

    2017-01-01

    Patients with Congenital Adrenal Hyperplasia (CAH) owing to 21-hydroxylase deficiency and whose karyotype is 46, XX are usually assigned to the female gender. Reported herein are the long term outcomes in three patients with CAH whose karyotype is 46, XX and who were reared as males. A retrospective review of three CAH patients with a 46, XX karyotype who were reared as males was conducted. Gender assignment, clinical and biochemical data, pre and post-genitoplasty genital examinations were reviewed. Gender identity was tested by an extensive questionnaire. Gender role, sexual preference, marital status and sexual satisfaction were evaluated by interview. The three patients were genotyped for the CYP21A2 gene confirming the diagnosis of CAH. Owing to genital virilization, cultural preferences for male gender and the lack of newborn screening programs the three patients reported herein were assigned to the male gender at birth before the diagnosis of CAH was established. In adulthood the patients remained significantly virilized. Thorough psychosexual assessments in adulthood revealed well established male gender identities compatible with their male gender assignments at birth. In all three patients, gender role and behavior were consistent with male gender identity including sexual intercourse with female partners. The three patients reported herein revealed that male gender assignment to CAH patients with a 46, XX karyotype may have a successful outcome providing there is strong parental support and expert endocrine care. No standard guidelines have been published for the gender assignment of CAH patients with a 46, XX karyotype and genital ambiguity. More studies concerning gender assignment in CAH patients with a 46, XX karyotype reared as males are needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Noninvasive Prenatal Diagnosis of Congenital Adrenal Hyperplasia Using Cell-Free Fetal DNA in Maternal Plasma

    PubMed Central

    Tong, Yu K.; Yuen, Tony; Jiang, Peiyong; Pina, Christian; Chan, K. C. Allen; Khattab, Ahmed; Liao, Gary J. W.; Yau, Mabel; Kim, Se-Min; Chiu, Rossa W. K.; Sun, Li; Zaidi, Mone

    2014-01-01

    Context: Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition that arises from mutations in CYP21A2 gene, which encodes for the steroidogenic enzyme 21-hydroxylase. To prevent genital ambiguity in affected female fetuses, prenatal treatment with dexamethasone must begin on or before gestational week 9. Currently used chorionic villus sampling and amniocentesis provide genetic results at approximately 14 weeks of gestation at the earliest. This means that mothers who want to undergo prenatal dexamethasone treatment will be unnecessarily treating seven of eight fetuses (males and three of four unaffected females), emphasizing the desirability of earlier genetic diagnosis in utero. Objective: The objective of the study was to develop a noninvasive method for early prenatal diagnosis of fetuses at risk for CAH. Patients: Fourteen families, each with a proband affected by phenotypically classical CAH, were recruited. Design: Cell-free fetal DNA was obtained from 3.6 mL of maternal plasma. Using hybridization probes designed to capture a 6-Mb region flanking CYP21A2, targeted massively parallel sequencing (MPS) was performed to analyze genomic DNA samples from parents and proband to determine parental haplotypes. Plasma DNA from pregnant mothers also underwent targeted MPS to deduce fetal inheritance of parental haplotypes. Results: In all 14 families, the fetal CAH status was correctly deduced by targeted MPS of DNA in maternal plasma, as early as 5 weeks 6 days of gestation. Conclusions: MPS on 3.6 mL plasma from pregnant mothers could potentially provide the diagnosis of CAH, noninvasively, before the ninth week of gestation. Only affected female fetuses will thus be treated. Our strategy represents a generic approach for noninvasive prenatal testing for an array of autosomal recessive disorders. PMID:24606108

  11. Monitoring the Secretory Behavior of the Rat Adrenal Medulla by High-Performance Liquid Chromatography-Based Catecholamine Assay from Slice Supernatants

    PubMed Central

    De Nardi, Frédéric; Lefort, Claudie; Bréard, Dimitri; Richomme, Pascal; Legros, Christian; Guérineau, Nathalie C.

    2017-01-01

    Catecholamine (CA) secretion from the adrenal medullary tissue is a key step of the adaptive response triggered by an organism to cope with stress. Whereas molecular and cellular secretory processes have been extensively studied at the single chromaffin cell level, data available for the whole gland level are much scarcer. We tackled this issue in rat by developing an easy to implement experimental strategy combining the adrenal acute slice supernatant collection with a high-performance liquid chromatography-based epinephrine and norepinephrine (NE) assay. This technique affords a convenient method for measuring basal and stimulated CA release from single acute slices, allowing thus to individually address the secretory function of the left and right glands. Our data point that the two glands are equally competent to secrete epinephrine and NE, exhibiting an equivalent epinephrine:NE ratio, both at rest and in response to a cholinergic stimulation. Nicotine is, however, more efficient than acetylcholine to evoke NE release. A pharmacological challenge with hexamethonium, an α3-containing nicotinic acetylcholine receptor antagonist, disclosed that epinephrine- and NE-secreting chromaffin cells distinctly expressed α3 nicotinic receptors, with a dominant contribution in NE cells. As such, beyond the novelty of CA assays from acute slice supernatants, our study contributes at refining the secretory behavior of the rat adrenal medullary tissue, and opens new perspectives for monitoring the release of other hormones and transmitters, especially those involved in the stress response. PMID:28993760

  12. Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study.

    PubMed

    Castinetti, Frederic; Qi, Xiao-Ping; Walz, Martin K; Maia, Ana Luiza; Sansó, Gabriela; Peczkowska, Mariola; Hasse-Lazar, Kornelia; Links, Thera P; Dvorakova, Sarka; Toledo, Rodrigo A; Mian, Caterina; Bugalho, Maria Joao; Wohllk, Nelson; Kollyukh, Oleg; Canu, Letizia; Loli, Paola; Bergmann, Simona R; Biarnes Costa, Josefina; Makay, Ozer; Patocs, Attila; Pfeifer, Marija; Shah, Nalini S; Cuny, Thomas; Brauckhoff, Michael; Bausch, Birke; von Dobschuetz, Ernst; Letizia, Claudio; Barczynski, Marcin; Alevizaki, Maria K; Czetwertynska, Malgorzata; Ugurlu, M Umit; Valk, Gerlof; Plukker, John T M; Sartorato, Paola; Siqueira, Debora R; Barontini, Marta; Szperl, Malgorzata; Jarzab, Barbara; Verbeek, Hans H G; Zelinka, Tomas; Vlcek, Petr; Toledo, Sergio P A; Coutinho, Flavia L; Mannelli, Massimo; Recasens, Monica; Demarquet, Lea; Petramala, Luigi; Yaremchuk, Svetlana; Zabolotnyi, Dmitry; Schiavi, Francesca; Opocher, Giuseppe; Racz, Karoly; Januszewicz, Andrzej; Weryha, Georges; Henry, Jean-Francois; Brue, Thierry; Conte-Devolx, Bernard; Eng, Charis; Neumann, Hartmut P H

    2014-05-01

    The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2. This multinational observational retrospective population-based study compiled data on patients with multiple endocrine neoplasia type 2 from 30 academic medical centres across Europe, the Americas, and Asia. Patients were included if they were carriers of germline pathogenic mutations of the RET gene, or were first-degree relatives with histologically proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical information about patients'RET genotype, type of treatment for phaeochromocytoma (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic operations), and postoperative outcomes (adrenal function, malignancy, and death). The type of surgery was decided by each investigator and the timing of surgery was patient driven. The primary aim of our analysis was to compare disease-free survival after either adrenal-sparing surgery or adrenalectomy. 1210 patients with multiple endocrine neoplasia type 2 were included in our database, 563 of whom had phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery after 6-13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy (p=0.57). Postoperative adrenal insufficiency or steroid dependency developed in 292 (86%) of 339

  13. Glucocorticoid-suppressible hyperaldosteronism and adrenal tumors occurring in a single French pedigree.

    PubMed Central

    Pascoe, L; Jeunemaitre, X; Lebrethon, M C; Curnow, K M; Gomez-Sanchez, C E; Gasc, J M; Saez, J M; Corvol, P

    1995-01-01

    Glucocorticoid-suppressible hyperaldosteronism is a dominantly inherited form of hypertension believed to be caused by the presence of a hybrid CYP11B1/CYP11B2 gene which has arisen from an unequal crossing over between the two CYP11B genes in a previous meiosis. We have studied a French pedigree with seven affected individuals in which two affected individuals also have adrenal tumors and two others have micronodular adrenal hyperplasia. One of the adrenal tumors and the surrounding adrenal tissue has been removed, giving a rare opportunity to study the regulation and action of the hybrid gene causing the disease. The hybrid CYP11B gene was demonstrated to be expressed at higher levels than either CYP11B1 or CYP11B2 in the cortex of the adrenal by RT-PCR and Northern blot analysis. In situ hybridization showed that both CYP11B1 and the hybrid gene were expressed in all three zones of the cortex. In cell culture experiments hybrid gene expression was stimulated by ACTH leading to increased production of aldosterone and the hybrid steroids characteristic of glucocorticoid-suppressible hyperaldosteronism. The genetic basis of the adrenal pathologies in this family is not known but may be related to the duplication causing the hyperaldosteronism. Images PMID:7593610

  14. Male gender identity in children with 46,XX DSD with congenital adrenal hyperplasia after delayed presentation in mid-childhood.

    PubMed

    Chowdhury, Tanvir Kabir; Laila, Kamrun; Hutson, John M; Banu, Tahmina

    2015-12-01

    Girls with congenital adrenal hyperplasia (CAH) diagnosed at birth have some masculine behaviors but rarely convert to male gender. In developing countries, however, diagnosis and treatment (with secondary androgen suppression) are delayed. We aimed to assess effect of delayed treatment of CAH on gender identity. As part of a cross-sectional, case-control study of children with disorders of sex development (DSD), there were 11 patients with CAH. Patients and caregivers answered a questionnaire about gender identity, and behavior was assessed by observing toy play. Patients were examined for Prader score and gender identity. Of 11 CAH patients initially raised as girls, 3 (27%) had converted to male gender at presentation (5, 9, 9years) (Prader 3, 4, 4). Of the remaining 8 patients, one 4-year-old (Prader 2) had a male gender identity score. The remaining girls (2-13years, mean 8.1) (Prader 1-3) had gender identity scores in the female range. One third (4/11) of CAH patients presenting in mid-childhood had male gender identity scores, and ¾ had assumed male gender role. Although social and cultural factors are important in developing countries, this result suggests that delayed treatment may trigger male gender identity, and delayed female genital surgery may be unwise. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Prevalence of and markers for the attenuated form of congenital adrenal hyperplasia and hyperprolactinemia masquerading as polycystic ovarian disease.

    PubMed

    Benjamin, F; Deutsch, S; Saperstein, H; Seltzer, V L

    1986-08-01

    To determine the prevalence of the attenuated form of congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPPN) relative to polycystic ovarian disease (PCOD), 100 consecutive women presenting with the classic clinical features of PCOD were evaluated by basal hormonal profiles and subsequent adrenocorticotropic hormone (ACTH) stimulation tests. The study also sought biochemical markers for CAH other than ACTH stimulation. The prevalences were found to be as follows: PCOD, 65%; PCOD with HPPN, 9%; HPPN, 3%, end-organ hypersensitivity (EOH), 4%; homozygotic CAH, 4%; and heterozygotic CAH, 15%. Other than the differential response to ACTH, the only other biochemical markers observed for homozygotic CAH were significantly higher basal levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17-OHP). Luteinizing hormone/follicle-stimulating hormone ratio, androstenedione, and dehydroepiandrosterone sulfate all showed no significant differences between homozygotic CAH, heterozygotic CAH, HPPN, PCOD, and EOH. This study establishes the relative prevalences of the syndromes commonly mimicking PCOD. We also conclude that the observed low incidence of CAH does not justify routine ACTH testing on all patients presenting with features of PCOD--however, our data suggest that patients with basal serum levels of T and 17-OHP greater than 50% above the upper limit of normal should undergo this dynamic test, especially if there are also certain clinical features suggestive of CAH.

  16. A child with hypertension and ambiguous genitalia - an uncommon variant of congenital adrenal hyperplasia: a case report.

    PubMed

    Pant, Vivek; Baral, Suman; Shrestha, Bishal; Tumbapo, Arjun

    2017-06-23

    Deficiency in 11β-hydroxylase as a cause of congenital adrenal hyperplasia is uncommon. It should be considered in the differential diagnosis of hypertension with virilization in any prepubescent child. A 12-year-old Asian boy from eastern Nepal presented with pain in his abdomen and hypertension. He was raised as a male but had absent testicles since birth and had precocious puberty. Plasma testosterone, follicle-stimulating hormone, and luteinizing hormone were below baseline level. Basal 17-hydroxyprogesterone was elevated. Magnetic resonance imaging of his pelvis showed presence of Müllerian structures and karyotyping revealed 46,XX genotype. A clinical diagnosis of 11β-hydroxylase deficiency was made in view of hypertension with severe virilization in a 46,XX individual. Our patient's legal guardian was unwilling for our patient to change gender and because our patient is underage, the condition was well explained to his parents. He was managed with steroids and antihypertensive drugs. He was on regular follow-up; after 2 years there was no hypertension but he developed true puberty with functional ovaries. He was prescribed leuprolide (gonadotropin-releasing hormone analogue), letrozole (aromatase inhibitor), and a continuation of antihypertensive drugs. This case highlights the importance of a thorough physical examination of the external genitalia at birth and appropriate referral, and addresses issues in the management of such a disorder. Ethical issues pertaining to consent and who is entitled to give it should be clear so that the affected individual will have optimal psychological development and quality of life.

  17. Sexual orientation and medical history among Iranian people with Complete Androgen Insensitivity Syndrome and Congenital Adrenal Hyperplasia.

    PubMed

    Khorashad, Behzad S; Roshan, Ghasem M; Reid, Alistair G; Aghili, Zahra; Hiradfar, Mehran; Afkhamizadeh, Mozhgan; Talaei, Ali; Aarabi, Azadeh; Ghaemi, Nosrat; Taghehchian, Negin; Saberi, Hedieh; Farahi, Nazanin; Abbaszadegan, Mohammad Reza

    2017-01-01

    To report sexual orientation, relationship status and medical history of Iranian people with Differences of Sex Development (DSD) who were raised female. Our participants consisted of nineteen 46,XY individuals with Complete Androgen Insensitivity Syndrome (CAIS) and eighteen 46,XX individuals with Congenital Adrenal Hyperplasia (CAH) who were raised as females and older than 13years. As well as their relationship status and detailed medical history, an expert psychiatrist assessed their sexual orientation by a semi-structured psychiatric interview with them and, where applicable, their parents. Five percent of CAH participants and 42% of CAIS participants were in a relationship, which was significantly different. All CAH individuals had been diagnosed at birth; 89% of CAIS had been diagnosed after puberty and due to primary amenorrhea and 11% were diagnosed in childhood due to inguinal hernia. Genital reconstructive surgery had been performed in 100% of CAH participants and 37% of CAIS. Regarding sexual contact experiences and sexual fantasies (androphilic, gynephilic or both), no significant differences were found. However, CAH females had significantly more gynephilic dreams (P=0.045). This study, notable as one of the rare from a non-western culture, described sexual, medical and socioeconomic status of 46,XX CAH and 46,XY CAIS individuals living in Iran. Although broadly in line with previous findings from Western cultures, Iranian CAH individuals had fewer romantic relationships, but in contrast to previous studies their sexual orientation was only different from CAIS in the contents of sexual dreams. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Syndrome-Related Stigma in the General Social Environment as Reported by Women with Classical Congenital Adrenal Hyperplasia.

    PubMed

    Meyer-Bahlburg, Heino F L; Reyes-Portillo, Jazmin A; Khuri, Jananne; Ehrhardt, Anke A; New, Maria I

    2017-02-01

    Stigma defined as "undesired differentness" (Goffman, 1963) and subtyped as "experienced" or "enacted," "anticipated," and "internalized" has been documented for patients with diverse chronic diseases. However, no systematic data exist on the association of stigma with somatic intersexuality. The current report concerns women with classical congenital adrenal hyperplasia (CAH), the most prevalent intersex syndrome, and provides descriptive data on CAH-related stigma as experienced in the general social environment (excluding medical settings and romantic/sexual partners) during childhood, adolescence, and adulthood. A total of 62 adult women with classical CAH [41 with the salt-wasting (SW) variant and 21 with the simple-virilizing (SV) variant] underwent a qualitative retrospective interview, which focused on the impact of CAH and its medical treatment on many aspects of women's lives. Deductive content analysis was performed on the transcribed texts. The women's accounts of CAH-related stigma were identified and excerpted as vignettes, and the vignettes categorized according to social context, stigma type, and the associated features of the CAH condition. Nearly two-thirds of women with either variant of CAH provided stigma vignettes. The vignettes included all three stigma types, and most involved some somatic or behavioral feature related to sex or gender. Stigma situations were reported for all ages and all social contexts of everyday life: family, peers, colleagues at work, strangers, and the media. We conclude that there is a need for systematic documentation of stigma in intersexuality as a basis for the development of improved approaches to prevention and intervention.

  19. Case report: schwannoma arising from the unilateral adrenal area with bilateral hyperaldosteronism.

    PubMed

    Babaya, Naru; Makutani, Yukako; Noso, Shinsuke; Hiromine, Yoshihisa; Ito, Hiroyuki; Taketomo, Yasunori; Ueda, Kazuki; Ushijima, Hokuto; Komoike, Yoshifumi; Yamazaki, Yuto; Sasano, Hironobu; Kawabata, Yumiko; Ikegami, Hiroshi

    2017-12-06

    We report a rare case of a juxta-adrenal schwannoma that could not be discriminated from an adrenal tumor before surgical resection and was complicated by bilateral hyperaldosteronism. To the best of our knowledge, this is first case in which both a juxta-adrenal schwannoma and hyperaldosteronism co-existed. A 69-year-old male treated for hypertension was found to have a left supra-renal mass (5.8 × 5.2 cm) by abdominal computed tomography. His laboratory data showed that his plasma aldosterone concentration (PAC) was within the normal range, but his plasma renin activity (PRA) was reduced, resulting in an increased aldosterone/renin ratio (ARR). Load tests of captopril or furosemide in the standing position demonstrated autonomous aldosterone secretion and renin suppression. Adrenal venous sampling (AVS) with ACTH stimulation indicated bilateral hypersecretion of aldosterone. A left supra-renal tumor was resected because of the possibility of malignancy and was found to be a benign schwannoma arising from the juxta-adrenal region together with an adrenal gland. The dissected left adrenal gland was morphologically hyperplastic in the zona glomerulosa, but was immunohistochemically negative for CYP11B2 (aldosterone synthase). Multiple CYP11B2-positive adrenocortical micronodules were detected in the adrenal gland, indicating micronodular hyperplasia. Although bilateral aldosteronism was indicated by AVS before the operation, the PRA, PAC and ARR values were within their respective reference ranges after resection of the unilateral tumor, suggesting that the slight increase in hormone secretion from the remaining right-sided lesion could not be detected after resection. A clinical and morphologic diagnosis of juxta-adrenal schwannoma is difficult, particularly in a case of hyperaldosteronism, as shown in this case. These data suggest the complexity and difficulty diagnosing adrenal incidentaloma.

  20. Parathyroid hyperplasia

    MedlinePlus

    Enlarged parathyroid glands; Osteoporosis - parathyroid hyperplasia; Bone thinning - parathyroid hyperplasia; Osteopenia - parathyroid hyperplasia; High calcium level - parathyroid hyperplasia; Chronic kidney disease - parathyroid hyperplasia; ...

  1. How to learn from patients: Fuller Albright's exploration of adrenal function.

    PubMed

    Schwartz, T B

    1995-08-01

    Fuller Albright (1900-1969) was acknowledged as the preeminent clinical and investigative endocrinologist of his day by many of his contemporaries, but his many achievements are all but unknown to the present generation of physicians. This article describes how he used his clinical knowledge and a few tools--the measurement of urinary 17-ketosteroid excretion and the administration of methyltestosterone--to elucidate the major hormonal functions of the adrenal cortex and to clarify the pathophysiology of the Cushing syndrome. In addition, in a tour de force of clinical reasoning, he predicted, 5 years before the event, the discovery of a hormone that would reverse the endocrinologic abnormalities of congenital adrenal hyperplasia. Fittingly, he and pioneer pediatric endocrinologist Lawson Wilkins were the first to treat this disease successfully with cortisone.

  2. Dysphagia in a patient with bilateral medial medullary infarcts.

    PubMed

    Paliwal, Vimal K; Kalita, Jayanti; Misra, Usha K

    2009-09-01

    Bilateral medial medullary infarct is a rare stroke syndrome and only a handful of cases have been described. Dysphagia as a manifestation of medullary infarcts is well recognized but often associated with lateral medullary infarct. Bilateral medial medullary infarcts are commonly associated with severe dysphagia in addition to a number of other signs and symptoms. We describe a patient who had bilateral medial medullary infarct with severe dysphagia in addition to quadriplegia and respiratory difficulty, and analyze infarct topography with respect to dysphagia, risk factors, vascular territories involved, and prognosis in view of previously reported cases.

  3. Rapid steroid hormone quantification for congenital adrenal hyperplasia (CAH) in dried blood spots using UPLC liquid chromatography-tandem mass spectrometry.

    PubMed

    Janzen, Nils; Sander, Stefanie; Terhardt, Michael; Steuerwald, Ulrike; Peter, Michael; Das, Anibh M; Sander, Johannes

    2011-12-11

    Newborn screening for congenital adrenal hyperplasia (CAH) is usually done by quantifying 17α-hydroxyprogesterone using immunoassay. However, this test produces high rates of false positive results caused by cross reacting steroids. Therefore we have developed a selective and specific method with a short run time (1.25 min) for quantification of 17α-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, 11-deoxycorticosterone and cortisol from dried blood spots. The extraction procedure is very simple and steroid separation is ensured on a BEH C18 column and an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Analysis was done in positive ionization mode (ESI+) and recorded in multiple reaction monitoring mode (MRM). The method gave linear results for all steroids over a range of 5-200 (cortisol: 12.5-500)nmol/L with coefficients of regression >0.992. Absolute recovery was >64.1%. Across the analytical range the inter-assay coefficient of variation (CV) was <3%. Newborn blood samples of patients with confirmed 21-CAH and 11-CAH could clearly be distinguished from samples of unaffected newborns falsely positive on immunoassay. The method is not influenced by cross reactions as found on immunoassay. Analysis of dried blood spots shows that this method is sensitive and fast enough to allow rapid analysis and can therefore improve the newborn screening program. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. [Clinical management of adrenal incidentalomas: results of a survey].

    PubMed

    Moreno-Fernández, Jesús; García-Manzanares, Alvaro; Sánchez-Covisa, Miguel Aguirre; García, E Inés Rosa Gómez

    2009-12-01

    Incidentalomas are clinically silent adrenal masses that are discovered incidentally during diagnostic testing for clinical conditions unrelated to suspicion of adrenal disease. Several decision algorithms are used in the management of adrenal masses. We evaluated the routine use of these algorithms through a clinical activity questionnaire. The questionnaire included data on the work center, initial hormonal and radiological study, imaging and hormonal tests performed to complete the study, surgical indications and clinical follow-up. Thirty-three endocrinologists (79%) attending the annual congress of the Castilla-La Mancha Society of Endocrinology, Nutrition and Diabetes completed the questionnaire. Forty-six percent considered tumoral size to be the most important factor suggesting malignancy in the initial evaluation of adrenal incidentalomas, the limit being 4 cm for 78% of the endocrinologists. Imaging study was completed by magnetic resonance imaging by 39%. All the physicians always performed screening for hypercortisolism and pheochromocytoma. Other assessments always conducted in all incidentalomas included hyperaldosteronism (76%), sex hormone-producing tumor (51%) and congenital adrenal hyperplasia (30%). Seventy-nine percent of respondents began to refer incidentalomas larger than 4 cm for surgical treatment, and 46% referred all tumors larger than 6 cm for surgical treatment. With regard to hormonal function, patients with pheochromocytoma, Cushing's syndrome, hyperaldosteronism with poorly controlled blood pressure or sex hormoneproducing tumors were more frequently referred for surgery. Seventy-six percent of endocrinologists performed clinical follow-up in adrenal incidentalomas larger than 4 cm, preferably through computerized tomography (81%), and repeated studies for hormonal hypercortisolism (97%), primary hyperaldosteronism (42%) and pheochromocytoma (76%) over a 4-5 year period (67%). Clinical practice varied among the endocrinologists

  5. The role of the anterodorsal thalami nuclei in the regulation of adrenal medullary function, beta-adrenergic cardiac receptors and anxiety responses in maternally deprived rats under stressful conditions.

    PubMed

    Suárez, M M; Rivarola, M A; Molina, S M; Levin, G M; Enders, J; Paglini, P

    2004-09-01

    Maternal separation can interfere with growth and development of the brain and represents a significant risk factor for adult psychopathology. In rodents, prolonged separation from the mother affects the behavioral and endocrine responses to stress for the lifetime of the animal. Limbic structures such as the anterodorsal thalamic nuclei (ADTN) play an important role in the control of neuroendocrine and sympathetic-adrenal function. In view of these findings we hypothesized that the function of the ADTN may be affected in an animal model of maternal deprivation. To test this hypothesis female rats were isolated 4.5 h daily, during the first 3 weeks of life and tested as adults. We evaluated plasma epinephrine (E) and norepinephrine (NE), cardiac adrenoreceptors and anxiety responses after maternal deprivation and variable chronic stress (VCS) in ADTN-lesioned rats. Thirty days after ADTN lesion, in non-maternally deprived rats basal plasma NE concentration was greater and cardiac beta-adrenoreceptor density was lower than that in the sham-lesioned group. Maternal deprivation induced a significant increase in basal plasma NE concentration, which was greater in lesioned rats, and cardiac beta-adrenoreceptor density was decreased in lesioned rats. After VCS plasma catecholamine concentration was much greater in non-maternally deprived rats than in maternally-deprived rats; cardiac beta-adrenoreceptor density was decreased by VCS in both maternally-deprived and non-deprived rats, but more so in non-deprived rats, and further decreased by the ADTN lesion. In the plus maze test, the number of open arm entries was greater in the maternally deprived and in the stressed rats. Thus, sympathetic-adrenal medullary activation produced by VCS was much greater in non-deprived rats, and was linked to a down regulation of myocardial beta-adrenoceptors. The ADTN are not responsible for the reduced catecholamine responses to stress in maternally-deprived rats. Maternal deprivation or

  6. Clinical and Genetic Heterogeneity, Overlap with Other Tumor Syndromes, and Atypical Glucocorticoid Hormone Secretion in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Compared with Other Adrenocortical Tumors

    PubMed Central

    Hsiao, Hui-Pin; Kirschner, Lawrence S.; Bourdeau, Isabelle; Keil, Margaret F.; Boikos, Sosipatros A.; Verma, Somya; Robinson-White, Audrey J.; Nesterova, Maria; Lacroix, André; Stratakis, Constantine A.

    2009-01-01

    Objective: ACTH-independent macronodular adrenal hyperplasia (AIMAH) is often associated with subclinical cortisol secretion or atypical Cushing’s syndrome (CS). We characterized a large series of patients of AIMAH and compared them with patients with other adrenocortical tumors. Design and Patients: We recruited 82 subjects with: 1) AIMAH (n = 16); 2) adrenocortical cortisol-producing adenoma with CS (n = 15); 3) aldosterone-producing adenoma (n = 19); and 4) single adenomas with clinically nonsignificant cortisol secretion (n = 32). Methods: Urinary free cortisol (UFC) and 17-hydroxycorticosteroid (17OHS) were collected at baseline and during dexamethasone testing; aberrant receptor responses was also sought by clinical testing and confirmed molecularly. Peripheral and/or tumor DNA was sequenced for candidate genes. Results: AIMAH patients had the highest 17OHS excretion, even when UFCs were within or close to the normal range. Aberrant receptor expression was highly prevalent. Histology showed at least two subtypes of AIMAH. For three patients with AIMAH, there was family history of CS; germline mutations were identified in three other patients in the genes for menin (one), fumarate hydratase (one), and adenomatosis polyposis coli (APC) (one); a PDE11A gene variant was found in another. One patient had a GNAS mutation in adrenal nodules only. There were no mutations in any of the tested genes in the patients of the other groups. Conclusions: AIMAH is a clinically and genetically heterogeneous disorder that can be associated with various genetic defects and aberrant hormone receptors. It is frequently associated with atypical CS and increased 17OHS; UFCs and other measures of adrenocortical activity can be misleadingly normal. PMID:19509103

  7. Effects of Erythropoietin Administration on Adrenal Glands of Landrace/Large White Pigs after Ventricular Fibrillation.

    PubMed

    Faa, Armando; Faa, Gavino; Papalois, Apostolos; Obinu, Eleonora; Locci, Giorgia; Pais, Maria Elena; Lelovas, Pavlos; Barouxis, Dimitrios; Pantazopoulos, Charalampos; Vasileiou, Panagiotis V; Iacovidou, Nicoletta; Xanthos, Theodoros

    2016-01-01

    Aim. To evaluate the effects of erythropoietin administration on the adrenal glands in a swine model of ventricular fibrillation and resuscitation. Methods. Ventricular fibrillation was induced via pacing wire forwarded into the right ventricle in 20 female Landrace/Large White pigs, allocated into 2 groups: experimental group treated with bolus dose of erythropoietin (EPO) and control group which received normal saline. Cardiopulmonary resuscitation (CPR) was performed immediately after drug administration as per the 2010 European Resuscitation Council (ERC) guidelines for Advanced Life Support (ALS) until return of spontaneous circulation (ROSC) or death. Animals who achieved ROSC were monitored, mechanically ventilated, extubated, observed, and euthanized. At necroscopy, adrenal glands samples were formalin-fixed, paraffin-embedded, and routinely processed. Sections were stained with hematoxylin-eosin. Results. Oedema and apoptosis were the most frequent histological changes and were detected in all animals in the adrenal cortex and in the medulla. Mild and focal endothelial lesions were also detected. A marked interindividual variability in the degree of the intensity of apoptosis and oedema at cortical and medullary level was observed within groups. Comparing the two groups, higher levels of pathological changes were detected in the control group. No significant difference between the two groups was observed regarding the endothelial changes. Conclusions. In animals exposed to ventricular fibrillation, EPO treatment has protective effects on the adrenal gland.

  8. 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.

  9. Impact of food, alcohol and pH on modified-release hydrocortisone developed to treat congenital adrenal hyperplasia.

    PubMed

    Karunasena, Nayananjani; Margetson, Daniel N; Neal, Greg; Whitaker, Martin J; Ross, Richard Jm

    2017-04-01

    We developed a modified-release hydrocortisone, Chronocort, to replace the cortisol rhythm in patients with congenital adrenal hyperplasia. Food, alcohol and pH affect drug absorption, and it is important to assess their impact when replicating a physiological rhythm. In vitro dissolution to study impact of alcohol and pH on Chronocort. A phase 1, three-period, cross over study in 18 volunteers to assess the impact of food on Chronocort and to compare bioavailability to immediate-release hydrocortisone. In vitro dissolution of Chronocort was not affected by gastrointestinal pH up to 6.0 nor by an alcohol content up to 20% v/v. Food delayed and reduced the rate of absorption of Chronocort as reflected by a longer T max (fed vs fasted: 6.75 h vs 4.5 h, P  = 0005) and lower C max (549.49 nmol/L vs 708.46 nmol/L, ratio 77% with CI 71-85). Cortisol exposure was similar in fed and fasted state: Geo LSmean ratio (CI) AUC 0t for fed/fasted was 108.33% (102.30-114.72%). Cortisol exposure was higher for Chronocort compared to immediate-release hydrocortisone: Geo LSmean ratios (CI) 118.83% (111.58-126.54%); however, derived free cortisol showed cortisol exposure CIs were within 80.0-125.0%: Geo LSmean ratio (CI) for AUC 0t 112.73% (105.33-120.65%). Gastric pH ≤6.0 and alcohol do not affect hydrocortisone release from Chronocort. Food delays Chronocort absorption, but cortisol exposure is similar in the fasted and fed state and exposure as assessed by free cortisol is similar between Chronocort and immediate-release hydrocortisone. © 2017 The authors.

  10. Impact of food, alcohol and pH on modified-release hydrocortisone developed to treat congenital adrenal hyperplasia

    PubMed Central

    Karunasena, Nayananjani; Margetson, Daniel N; Neal, Greg; Whitaker, Martin J

    2017-01-01

    Background We developed a modified-release hydrocortisone, Chronocort, to replace the cortisol rhythm in patients with congenital adrenal hyperplasia. Food, alcohol and pH affect drug absorption, and it is important to assess their impact when replicating a physiological rhythm. Subjects and methods In vitro dissolution to study impact of alcohol and pH on Chronocort. A phase 1, three-period, cross over study in 18 volunteers to assess the impact of food on Chronocort and to compare bioavailability to immediate-release hydrocortisone. Results In vitro dissolution of Chronocort was not affected by gastrointestinal pH up to 6.0 nor by an alcohol content up to 20% v/v. Food delayed and reduced the rate of absorption of Chronocort as reflected by a longer Tmax (fed vs fasted: 6.75 h vs 4.5 h, P = 0005) and lower Cmax (549.49 nmol/L vs 708.46 nmol/L, ratio 77% with CI 71–85). Cortisol exposure was similar in fed and fasted state: Geo LSmean ratio (CI) AUC0t for fed/fasted was 108.33% (102.30–114.72%). Cortisol exposure was higher for Chronocort compared to immediate-release hydrocortisone: Geo LSmean ratios (CI) 118.83% (111.58–126.54%); however, derived free cortisol showed cortisol exposure CIs were within 80.0–125.0%: Geo LSmean ratio (CI) for AUC0t 112.73% (105.33–120.65%). Conclusions Gastric pH ≤6.0 and alcohol do not affect hydrocortisone release from Chronocort. Food delays Chronocort absorption, but cortisol exposure is similar in the fasted and fed state and exposure as assessed by free cortisol is similar between Chronocort and immediate-release hydrocortisone. PMID:28100629

  11. Functional studies of novel CYP21A2 mutations detected in Norwegian patients with congenital adrenal hyperplasia

    PubMed Central

    Brønstad, Ingeborg; Breivik, Lars; Methlie, Paal; Wolff, Anette S B; Bratland, Eirik; Nermoen, Ingrid; Løvås, Kristian; Husebye, Eystein S

    2014-01-01

    In about 95% of cases, congenital adrenal hyperplasia (CAH) is caused by mutations in CYP21A2 gene encoding steroid 21-hydroxylase (21OH). Recently, we have reported four novel CYP21A2 variants in the Norwegian population of patients with CAH, of which p.L388R and p.E140K were associated with salt wasting (SW), p.P45L with simple virilising (SV) and p.V211M+p.V281L with SV to non-classical (NC) phenotypes. We aimed to characterise the novel variants functionally utilising a newly designed in vitro assay of 21OH enzyme activity and structural simulations and compare the results with clinical phenotypes. CYP21A2 mutations and variants were expressed in vitro. Enzyme activity was assayed by assessing the conversion of 17-hydroxyprogesterone to 11-deoxycortisol by liquid chromatography tandem mass spectroscopy. PyMOL 1.3 was used for structural simulations, and PolyPhen2 and PROVEAN for predicting the severity of the mutants. The CYP21A2 mutants, p.L388R and p.E140K, exhibited 1.1 and 11.3% of wt 21OH enzyme activity, respectively, in vitro. We could not detect any functional deficiency of the p.P45L variant in vitro; although prediction tools suggest p.P45L to be pathogenic. p.V211M displayed enzyme activity equivalent to the wt in vitro, which was supported by in silico analyses. We found good correlations between phenotype and the in vitro enzyme activities of the SW mutants, but not for the SV p.P45L variant. p.V211M might have a synergistic effect together with p.V281L, explaining a phenotype between SV and NC CAH. PMID:24671123

  12. Interrelationships among cortisol, 17-hydroxyprogesterone, and androstenendione exposures in the management of children with congenital adrenal hyperplasia.

    PubMed

    Sarafoglou, Kyriakie; Zimmerman, Cheryl L; Gonzalez-Bolanos, Maria T; Willis, Brian A; Brundage, Richard

    2015-01-01

    Hydrocortisone is the standard replacement therapy for children with congenital adrenal hyperplasia (CAH). Relationships between cortisol exposures and pharmacodynamic responses of 17-hydroxyprogesterone and androstenedione exposures have not been systematically evaluated. (1) Assess individual oral hydrocortisone pharmacokinetics; (2) relate the observed cortisol exposure in each subject to the observed exposures of 17-hydroxyprogesterone and androstenedione; (3) determine potential individualized treatment regimens based on each subject's pharmacokinetic and pharmacodynamic parameters. Thirty-four patients (18 boys, 16 girls, aged 1.4 to 18.1 years) with CAH underwent 6-hour pharmacokinetic studies. Results were analyzed by noncompartmental methods to obtain the area under the curve (AUC) for cortisol, 17-hydroxyprogesterone, and androstenedione; maximum concentration and time-to-maximum concentration for cortisol; and minimum and time-to-minimum concentration for 17-hydroxyprogesterone and androstenedione. Mean (SD) cortisol half-life and Cmax were 1.01 (0.20) hours and 24.4 (5.4) μg/dL, respectively. The AUCs for cortisol, 17-hydroxyprogesterone and androstenedione were 40.8 (14.5) μg hour/dL, 29,490 (23,539) ng hour/dL, and 680 (795) ng hour/dL, respectively. No significant relationships existed between cortisol AUCs and the AUCs of either 17-hydroxyprogesterone (P=0.32) or androstenedione (P=0.99); nor were there differences between the change-from-baseline concentrations for cortisol with either 17-hydroxyprogesterone (P=0.80) or androstenedione (P=0.40). Cortisol simulations indicated that although four daily doses decreased 24-hour hypercortisolemia and hypocortisolemia, substantial periods of each remained. Concentration profiles of cortisol, 17-hydroxyprogesterone, and androstenedione are highly variable in children with CAH, and knowledge of them can assist in personalizing the therapy of CAH patients. Hydrocortisone's rapid half-life and the lack of

  13. Gendered Peer Involvement in Girls with Congenital Adrenal Hyperplasia: Effects of Prenatal Androgens, Gendered Activities, and Gender Cognitions.

    PubMed

    Berenbaum, Sheri A; Beltz, Adriene M; Bryk, Kristina; McHale, Susan

    2018-05-01

    A key question in understanding gender development concerns the origins of sex segregation. Children's tendencies to interact with same-sex others have been hypothesized to result from gender identity and cognitions, behavioral compatibility, and personal characteristics. We examined whether prenatal androgen exposure was related to time spent with boys and girls, and how that gendered peer involvement was related to sex-typed activities and gender identity and cognitions. We studied 54 girls with congenital adrenal hyperplasia (CAH) aged 10-13 years varying in degree of prenatal androgen exposure: 40 girls with classical CAH (C-CAH) exposed to high prenatal androgens and 14 girls with non-classical CAH (NC-CAH) exposed to low, female-typical, prenatal androgens. Home interviews and questionnaires provided assessments of gendered activity interests and participation, gender identity, and gender cognitions. Daily phone calls over 7 days assessed time spent in gendered activities and with peers. Girls with both C-CAH and NC-CAH interacted more with girls than with boys, with no significant group differences. The groups did not differ significantly in gender identity or gender cognitions, but girls with C-CAH spent more time in male-typed activities and less time in female-typed activities than did girls with NC-CAH. Time spent with girls reflected direct effects of gender identity/cognitions and gender-typed activities, and an indirect effect of prenatal androgens (CAH type) through gender-typed activities. Our results extend findings that prenatal androgens differentially affect gendered characteristics and that gendered peer interactions reflect combined effects of behavioral compatibility and feelings and cognitions about gender. The study also shows the value of natural experiments for testing hypotheses about gender development.

  14. Functional analysis of human cytochrome P450 21A2 variants involved in congenital adrenal hyperplasia

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

    Wang, Chunxue; Pallan, Pradeep S.; Zhang, Wei

    Cytochrome P450 (P450, CYP) 21A2 is the major steroid 21-hydroxylase, converting progesterone to 11-deoxycorticosterone and 17α-hydroxyprogesterone (17α-OH-progesterone) to 11-deoxycortisol. More than 100 CYP21A2 variants give rise to congenital adrenal hyperplasia (CAH). We previously reported a structure of WT human P450 21A2 with bound progesterone and now present a structure bound to the other substrate (17α-OH-progesterone). We found that the 17α-OH-progesterone- and progesterone-bound complex structures are highly similar, with only some minor differences in surface loop regions. Twelve P450 21A2 variants associated with either salt-wasting or nonclassical forms of CAH were expressed, purified, and analyzed. The catalytic activities of these 12more » variants ranged from 0.00009% to 30% of WT P450 21A2 and the extent of heme incorporation from 10% to 95% of the WT. Substrate dissociation constants (Ks) for four variants were 37–13,000-fold higher than for WT P450 21A2. Cytochrome b5, which augments several P450 activities, inhibited P450 21A2 activity. Similar to the WT enzyme, high noncompetitive intermolecular kinetic deuterium isotope effects (≥ 5.5) were observed for all six P450 21A2 variants examined for 21-hydroxylation of 21-d3-progesterone, indicating that C–H bond breaking is a rate-limiting step over a 104-fold range of catalytic efficiency. Using UV-visible and CD spectroscopy, we found that P450 21A2 thermal stability assessed in bacterial cells and with purified enzymes differed among salt-wasting- and nonclassical-associated variants, but these differences did not correlate with catalytic activity. Our in-depth investigation of CAH-associated P450 21A2 variants reveals critical insight into the effects of disease-causing mutations on this important enzyme.« less

  15. Medullary Thyroid Carcinoma Program | Center for Cancer Research

    Cancer.gov

    Medullary Thyroid Carcinoma Program Multiple endocrine neoplasia (MEN) types 2A and 2B are rare genetic diseases, which lead to the development of medullary thyroid cancer, usually in childhood. Surgery is the only standard treatment.

  16. Should we question early feminizing genitoplasty for patients with congenital adrenal hyperplasia and XX karyotype?

    PubMed

    Binet, A; Lardy, H; Geslin, D; Francois-Fiquet, C; Poli-Merol, M L

    2016-03-01

    There is a wide difference of opinion between the medical-surgical community and advocacy group regarding Disorders of Sexual Development (DSD) secondary to congenital adrenal hyperplasia (CAH) being ranked in the intersex category. This rupture is even more evident when the issue of genitoplasty is brought up. For physicians it is obvious and unequivocal that a person with CAH and an XX karyotype has a female gender identity, whereas associations tend to rank persons with CAH in the intersex category and advocate holding-off on surgical management. A retrospective case study vs. control group, spanning over 40years, included 21 patients who were treated in 3 different centers. Each patient and their parents were contacted independently and interviewed regarding interpersonal relationships, psychological impact of genitoplasty, gender identity and opinion on optimal care management for this disorder. Three couples controls (parent-child) per CAH patients were used and matched according to age, sex assigned at birth and ethnic origin. Sex assigned at birth seemed to concord with the gender identity perceived by the patients in 85.7% of cases. In fact, 89.7% of patients and 100% of parents felt that feminizing genitoplasty should be performed within the first year of life. There is however a significant difference compared to controls who felt that surgical management should occur later on in life. No difference was highlighted during childhood regarding parents-child relationships or social integration. However, during adolescence, the parents-child relationship tended to be significantly more painful for the CAH group. Integrating their parenting role was significantly harder for patients in the CAH-DSD group. In the population of CAH-DSD patients who had genitoplasty the level of sexual fulfillment was not lower to the one reported by the control group. Female sex assignment seems legitimate according to this study and the development of gender identity in these

  17. Comparison of different glucocorticoid regimens in the management of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

    PubMed

    Ajish, T P; Praveen, V P; Nisha, B; Kumar, Harish

    2014-11-01

    There are recommendations regarding the total dose of hydrocortisone to be administered in the treatment of classical congenital adrenal hyperplasia (CAH) to achieve the twin objectives of glucocorticoid replacement and control of hyperandrogenism. However, there is evidence gap regarding the breakup, timing and type of the steroid regimen. Efficacy of three different glucocorticoid regimens having the same total dose of steroid, differing in either the timing or type of evening steroid administered, in achieving biochemical control of the disease was assessed. The study was done in 13 prepubertal children with classical CAH over a 6-month period with 2 months devoted to each regimen. We used a prospective cross-over design using 10-15 mg/m(2) total dose of hydrocortisone. Two-fifths of the total dose of hydrocortisone was administered in the morning and one-fifth of the total dose was administered at noon in all the regimens. The regimens differed in the timing of the evening dose of hydrocortisone, 06.00-07.00 pm in regimen 1 and 09.00-10.00 pm in regimen 2. The third regimen had the evening dose of hydrocortisone replaced by an equivalent dose of prednisolone suspension which was administered at 10.00 pm. Serum 17-hydroxyprogesterone and testosterone levels were compared to assess the efficacy of treatment regimens. The three different regimens were found to be similar in their ability to control 17-hydroxyprogesterone and testosterone levels. The percentage of patients with predefined criteria for biochemically controlled disease was similar in all the three regimens. However, there was a trend toward better control of 17-hydroxyprogesterone levels in patients receiving evening dose of prednisolone. There is no significant advantage in administering the hydrocortisone dose late at night in patients with classical CAH.

  18. Is it useful to repeat an adrenal venous sampling in patients with primary hyperaldosteronism?

    PubMed

    Bouhanick, B; Delchier, M-C; Fauvel, J; Rousseau, H; Amar, J; Chamontin, B

    2014-02-01

    Adrenal venous sampling (AVS) is a challenging technical procedure and few patients had AVS procedure twice. To evaluate the reproducibility of the AVS, why AVS were repeated and the conclusions drawn from them. From 1997-2012, 12 patients underwent two AVS. A cortisol level in the adrenal vein greater than or equal to 1.1 to inferior vena cava defined a successful catheterization and a lateralization of secretion corresponded to an aldosterone-to-cortisol vein ratio greater than or equal to 2 between the one side to another. The same side of lateralization of secretion was found in 75% of them. The second AVS were due to technical failure (n=4), unproven lateralization (n=2), a lateralization opposite to the main nodule and ipsilateral to hyperplasia (n=4) on first AVS. For two patients, as the CT was normal, AVS was required again. The second AVS was successful in all patients, including those with an initial technical failure but only patient with technical failure underwent surgery, as BP and kaliemia were controlled. Lateralization on the side of hyperplasia or opposite to the biggest nodule was confirmed in two of four cases. When AVS is unsuccessful for technical reasons, it is worth doing it again but after being sure that surgery is still possibly indicated. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  19. Prenatal androgenization affects gender-related behavior but not gender identity in 5-12-year-old girls with congenital adrenal hyperplasia.

    PubMed

    Meyer-Bahlburg, Heino F L; Dolezal, Curtis; Baker, Susan W; Carlson, Ann D; Obeid, Jihad S; New, Maria I

    2004-04-01

    Gender assignment of children with intersexuality and related conditions has recently become highly controversial. On the basis of extensive animal research and a few human case reports, some authors have proposed the putative masculinization of the brain by prenatal hormones-indicated by the degree of genital masculinization-as the decisive criterion of gender assignment and have derived the recommendation that 46,XX newborns with congenital adrenal hyperplasia (CAH) and full genital masculinization should be assigned to the male gender. The purpose of this study was to test in CAH girls of middle childhood the assumption that prenatal androgens determine the development of gender identity. Fifteen girls with CAH (range of genital Prader stage, 2-4/5), 30 control girls, and 16 control boys (age range, 5-12 years) underwent 2 gender-play observation sessions, and a gender identity interview yielding scales of gender confusion/dysphoria. About half a year earlier, mothers had completed 2 questionnaires concerning their children's gender-related behavior. The results showed that, as expected, CAH girls scored more masculine than control girls on all scales measuring gender-related behavior, with robust effect sizes. By contrast, neither conventionally significant differences nor trends were found on the 3 scales of the gender identity interview. We conclude that prenatal androgenization of 46,XX fetuses leads to marked masculinization of later gender-related behavior, but the absence of any increased gender-identity confusion/dysphoria does not indicate a direct determination of gender identity by prenatal androgens and does not, therefore, support a male gender assignment at birth of the most markedly masculinized girls.

  20. Flow-injection analysis of catecholamine secretion from bovine adrenal medulla cells on microbeads.

    PubMed

    Herrera, M; Kao, L S; Curran, D J; Westhead, E W

    1985-01-01

    Bovine adrenal medullary cells have been cultured on microbeads which are placed in a low-volume flow system for measurements of stimulation-response parameters. Electronically controlled stream switching allows stimulation of cells with pulse lengths from 1 s to many minutes; pulses may be repeated indefinitely. Catecholamines secreted are detected by an electrochemical detector downstream from the cells. This flow-injection analysis technique provides a new level of sensitivity and precision for measurement of kinetic parameters of secretion. A manual injection valve allows stimulation by higher levels of stimulant in the presence of constant low levels of stimulant. Such experiments show interesting differences between the effects of K+ and acetylcholine on cells partially desensitized to acetylcholine.

  1. Reduced short term memory in congenital adrenal hyperplasia (CAH) and its relationship to spatial and quantitative performance.

    PubMed

    Collaer, Marcia L; Hindmarsh, Peter C; Pasterski, Vickie; Fane, Briony A; Hines, Melissa

    2016-02-01

    Girls and women with classical congenital adrenal hyperplasia (CAH) experience elevated androgens prenatally and show increased male-typical development for certain behaviors. Further, individuals with CAH receive glucocorticoid (GC) treatment postnatally, and this GC treatment could have negative cognitive consequences. We investigated two alternative hypotheses, that: (a) early androgen exposure in females with CAH masculinizes (improves) spatial perception and quantitative abilities at which males typically outperform females, or (b) CAH is associated with performance decrements in these domains, perhaps due to reduced short-term-memory (STM). Adolescent and adult individuals with CAH (40 female and 29 male) were compared with relative controls (29 female and 30 male) on spatial perception and quantitative abilities as well as on Digit Span (DS) to assess STM and on Vocabulary to assess general intelligence. Females with CAH did not perform better (more male-typical) on spatial perception or quantitative abilities than control females, failing to support the hypothesis of cognitive masculinization. Rather, in the sample as a whole individuals with CAH scored lower on spatial perception (p ≤ .009), a quantitative composite (p ≤ .036), and DS (p ≤ .001), despite no differences in general intelligence. Separate analyses of adolescent and adult participants suggested the spatial and quantitative effects might be present only in adult patients with CAH; however, reduced DS performance was found in patients with CAH regardless of age group. Separate regression analyses showed that DS predicted both spatial perception and quantitative performance (both p ≤ .001), when age, sex, and diagnosis status were controlled. Thus, reduced STM in CAH patients versus controls may have more general cognitive consequences, potentially reducing spatial perception and quantitative skills. Although hyponatremia or other aspects of salt-wasting crises or additional hormone

  2. Sodium Chloride Supplementation Is Not Routinely Performed in the Majority of German and Austrian Infants with Classic Salt-Wasting Congenital Adrenal Hyperplasia and Has No Effect on Linear Growth and Hydrocortisone or Fludrocortisone Dose.

    PubMed

    Bonfig, Walter; Roehl, Friedhelm; Riedl, Stefan; Brämswig, Jürgen; Richter-Unruh, Annette; Fricke-Otto, Susanne; Hübner, Angela; Bettendorf, Markus; Schönau, Eckhard; Dörr, Helmut; Holl, Reinhard W; Mohnike, Klaus

    2018-01-01

    Sodium chloride supplementation in salt-wasting congenital adrenal hyperplasia (CAH) is generally recommended in infants, but its implementation in routine care is very heterogeneous. To evaluate oral sodium chloride supplementation, growth, and hydrocortisone and fludrocortisone dose in infants with salt-wasting CAH due to 21-hydroxylase in 311 infants from the AQUAPE CAH database. Of 358 patients with classic CAH born between 1999 and 2015, 311 patients had salt-wasting CAH (133 females, 178 males). Of these, 86 patients (27.7%) received oral sodium chloride supplementation in a mean dose of 0.9 ± 1.4 mmol/kg/day (excluding nutritional sodium content) during the first year of life. 225 patients (72.3%) were not treated with sodium chloride. The percentage of sodium chloride-supplemented patients rose from 15.2% in children born 1999-2004 to 37.5% in children born 2011-2015. Sodium chloride-supplemented and -unsupplemented infants did not significantly differ in hydrocortisone and fludrocortisone dose, target height-corrected height-SDS, and BMI-SDS during the first 2 years of life. In the AQUAPE CAH database, approximately one-third of infants with salt-wasting CAH receive sodium chloride supplementation. Sodium chloride supplementation is performed more frequently in recent years. However, salt supplementation had no influence on growth, daily fludrocortisone and hydrocortisone dose, and frequency of adrenal crisis. © 2017 S. Karger AG, Basel.

  3. Diagnosing colorectal medullary carcinoma: interobserver variability and clinicopathological implications.

    PubMed

    Lee, Lik Hang; Yantiss, Rhonda K; Sadot, Eran; Ren, Bing; Calvacanti, Marcela Santos; Hechtman, Jaclyn F; Ivelja, Sinisa; Huynh, Be; Xue, Yue; Shitilbans, Tatiana; Guend, Hamza; Stadler, Zsofia K; Weiser, Martin R; Vakiani, Efsevia; Gönen, Mithat; Klimstra, David S; Shia, Jinru

    2017-04-01

    Colorectal medullary carcinoma, recognized by the World Health Organization as a distinct histologic subtype, is commonly regarded as a specific entity with an improved prognosis and unique molecular pathogenesis. A fundamental but as yet unaddressed question, however, is whether it can be diagnosed reproducibly. In this study, by analyzing 80 colorectal adenocarcinomas whose dominant growth pattern was solid (thus encompassing medullary carcinoma and its mimics), we provided a detailed description of the morphological spectrum from "classic medullary histology" to nonmedullary poorly differentiated histologies and demonstrated significant overlapping between categories. By assessing a selected subset (n=30) that represented the spectrum of histologies, we showed that the interobserver agreement for diagnosing medullary carcinoma by using 2010 World Health Organization criteria was poor; the κ value among 5 gastrointestinal pathologists was only 0.157 (95% confidence interval, 0.127-0.263; P=.001). When we arbitrarily classified the entire cohort into "classic" and "indeterminate" medullary tumors (group 1, n=19; group 2, n=26, respectively) and nonmedullary poorly differentiated tumors (group 3, n=35), groups 1 and 2 were more likely to exhibit mismatch repair protein deficiency than group 3 (P<.001); however, improved survival could not be detected in either group compared with group 3. Our findings suggest that the diagnosis of medullary carcinoma, as currently applied, may only serve as a morphological descriptor indicating an increased likelihood of mismatch-repair deficiency. Additional evidence including a more objective classification system is needed before medullary carcinoma can be regarded as a distinct entity with prognostic relevance. Until such evidence becomes available, caution should be exercised when making this diagnosis, as well as when comparing results across different studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Subtype Diagnosis of Primary Aldosteronism: Is Adrenal Vein Sampling Always Necessary?

    PubMed Central

    Buffolo, Fabrizio; Monticone, Silvia; Williams, Tracy A.; Rossato, Denis; Burrello, Jacopo; Tetti, Martina; Veglio, Franco; Mulatero, Paolo

    2017-01-01

    Aldosterone producing adenoma and bilateral adrenal hyperplasia are the two most common subtypes of primary aldosteronism (PA) that require targeted and distinct therapeutic approaches: unilateral adrenalectomy or lifelong medical therapy with mineralocorticoid receptor antagonists. According to the 2016 Endocrine Society Guideline, adrenal venous sampling (AVS) is the gold standard test to distinguish between unilateral and bilateral aldosterone overproduction and therefore, to safely refer patients with PA to surgery. Despite significant advances in the optimization of the AVS procedure and the interpretation of hormonal data, a standardized protocol across centers is still lacking. Alternative methods are sought to either localize an aldosterone producing adenoma or to predict the presence of unilateral disease and thereby substantially reduce the number of patients with PA who proceed to AVS. In this review, we summarize the recent advances in subtyping PA for the diagnosis of unilateral and bilateral disease. We focus on the developments in the AVS procedure, the interpretation criteria, and comparisons of the performance of AVS with the alternative methods that are currently available. PMID:28420172

  5. A marked proportional rise in IVC aldosterone following cosyntropin administration during AVS is a signal to the presence of adrenal hyperplasia in primary aldosteronism.

    PubMed

    Kline, G A; Pasieka, J L; Harvey, A; So, B; Dias, V C

    2014-05-01

    We hypothesized aldosteronoma responsiveness to cosyntropin may be a characterizing feature that could be determined in addition to standard adrenal vein sampling (AVS) data. We reviewed an AVS database from June 2005 to October 2011 including 65 patients with confirmed primary aldosteronism (PA) who underwent AVS and, if applicable, unilateral adrenalectomy. Patients were divided into confirmed lateralized and non-lateralized groups and subgrouped by histology. Plasma aldosterone in inferior vena cava (IVC) pre- and post-cosyntropin infusion during AVS was measured. Peak aldosterone and proportional change was compared between groups. Baseline and peak IVC aldosterone was higher in lateralized patients but incremental aldosterone rise was much greater in subjects with bilateral hyperplasia. From receiver operator characteristics (ROC) analysis, the optimized diagnostic cut point of peak IVC aldosterone of >649 pmol l(-1) would have a sensitivity of 94% for surgical disease although specificity of just 59%. A 250% increase in IVC aldosterone following cosyntropin would be specific enough to exclude 87% of surgical/lateralized disease. These diagnostic capabilities are similar to other results with non-AVS tests performed for diagnosis of lateralization. Although not specific enough to replace standard AVS interpretation, a marked IVC aldosterone increase after cosyntropin during AVS is a useful additional test to diagnose non-lateralizing forms of PA. Such a calculation requires no additional expense or tests.

  6. Recovery of Dysphagia in Lateral Medullary Stroke

    PubMed Central

    Gupta, Hitesh; Banerjee, Alakananda

    2014-01-01

    Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function. PMID:25045555

  7. Recovery of Dysphagia in lateral medullary stroke.

    PubMed

    Gupta, Hitesh; Banerjee, Alakananda

    2014-01-01

    Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function.

  8. Adrenal Fatigue

    MedlinePlus

    ... unlikely to cover the costs. What is the theory behind adrenal fatigue? Supporters of adrenal fatigue believe ... by producing hormones like cortisol. According to the theory of adrenal fatigue, when people are faced with ...

  9. [Role of adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes].

    PubMed

    Li, H Y; Li, P; Shen, S M; Zhang, X B; Feng, W H; Huang, H; Chen, W; Zhu, D L

    2017-11-14

    Objective: To investigate the role of adrenal vein sampling (AVS) in identifying the subtype of primary aldosteronism (PA). Methods: AVS was performed in 50 patients who were confirmed as PA between September 2010 and September 2016 in Nanjing Drum Tower Hospital. Clinical, biochemical and follow-up data were reviewed retrospectively. Bilaterally simultaneous catheterization without cosyntropin stimulation and contemporaneous cortisol measurement during AVS were used. Selectivity index (SI)≥1.5 suggested that the sample was from the adrenal vein.Lateralization index (LI) ≥2 suggested unilateral disease.Clinical data was further compared and the AVS findings were analyzed. Results: AVS was successful performed in 41 cases of 50 patients, and the success rate was 82%. According to the results of AVS and postoperative pathology, 41 cases were divided into aldosterone-producing adenoma (APA)/unilateral adrenal hyperplasia (UAH) group (24 cases) and idiopathic hyperaldosteronism (IHA) group (17 cases). Compared with IHA group, patients with APA/UAH showed longer duration of hypertension[10.0 (5.0, 13.0) y vs 4.0 (2.0, 8.0) y, P =0.046], higher proportion of hypokalemia (95.8% vs 64.7%, P =0.009). Furthermore, patients with APA/UAH demonstrated lower plasma renin activity ( P =0.089), higher plasma aldosterone concentration and aldosterone to renin ratio (ARR) (both P <0.05). The diagnostic concordance between CT and adrenal vein sampling was only 48.8%(20/41). Conclusions: The application of bilaterally simultaneous catheterization and contemporaneous cortisol measurement improves success rate and diagnostic accuracy of AVS. AVS is useful in subtype diagnosis of PA with equivocal imaging findings.

  10. A case of adrenal Cushing's syndrome with bilateral adrenal masses.

    PubMed

    Guo, Ya-Wun; Hwu, Chii-Min; Won, Justin Ging-Shing; Chu, Chia-Huei; Lin, Liang-Yu

    2016-01-01

    A functional lesion in corticotrophin (ACTH)-independent Cushing's syndrome is difficult to distinguish from lesions of bilateral adrenal masses. Methods for distinguishing these lesions include adrenal venous sampling and (131)I-6β-iodomethyl-19-norcholesterol ((131)I-NP-59) scintigraphy. We present a case of a 29-year-old Han Chinese female patient with a history of hypercholesterolaemia and polycystic ovary syndrome. She presented with a 6month history of an 8kg body weight gain and gradual rounding of the face. Serial examinations revealed loss of circadian rhythm of cortisol, elevated urinary free-cortisol level and undetectable ACTH level (<5pg/mL). No suppression was observed in both the low- and high-dose dexamethasone suppression tests. Adrenal computed tomography revealed bilateral adrenal masses. Adrenal venous sampling was performed, and the right-to-left lateralisation ratio was 14.29. The finding from adrenal scintigraphy with NP-59 was consistent with right adrenal adenoma. The patient underwent laparoscopic right adrenalectomy, and the pathology report showed adrenocortical adenoma. Her postoperative cortisol level was 3.2μg/dL, and her Cushingoid appearance improved. In sum, both adrenal venous sampling and (131)I-NP-59 scintigraphy are good diagnostic methods for Cushing's syndrome presenting with bilateral adrenal masses. The clinical presentation of Cushing' syndrome includes symptoms and signs of fat redistribution and protein-wasting features.The diagnosis of patients with ACTH-independent Cushing's syndrome with bilateral adrenal masses is challenging for localisation of the lesion.Both adrenal venous sampling and (131)I-NP-59 scintigraphy are good methods to use in these patients with Cushing's syndrome presenting with bilateral adrenal masses.

  11. Selective Ablation of Tumor Suppressors in Parafollicular C Cells Elicits Medullary Thyroid Carcinoma.

    PubMed

    Song, Hai; Lin, Chuwen; Yao, Erica; Zhang, Kuan; Li, Xiaoling; Wu, Qingzhe; Chuang, Pao-Tien

    2017-03-03

    Among the four different types of thyroid cancer, treatment of medullary thyroid carcinoma poses a major challenge because of its propensity of early metastasis. To further investigate the molecular mechanisms of medullary thyroid carcinoma and discover candidates for targeted therapies, we developed a new mouse model of medullary thyroid carcinoma based on our CGRP CreER mouse line. This system enables gene manipulation in parafollicular C cells in the thyroid, the purported cells of origin of medullary thyroid carcinoma. Selective inactivation of tumor suppressors, such as p53 , Rb , and Pten , in mature parafollicular C cells via an inducible Cre recombinase from CGRP CreER led to development of murine medullary thyroid carcinoma. Loss of Pten accelerated p53 / Rb -induced medullary thyroid carcinoma, indicating interactions between pathways controlled by tumor suppressors. Moreover, labeling differentiated parafollicular C cells by CGRP CreER allows us to follow their fate during malignant transformation to medullary thyroid tumor. Our findings support a model in which mutational events in differentiated parafollicular C cells result in medullary thyroid carcinoma. Through expression analysis including RNA-Seq, we uncovered major signaling pathways and networks that are perturbed following the removal of tumor suppressors. Taken together, these studies not only increase our molecular understanding of medullary thyroid carcinoma but also offer new candidates for designing targeted therapies or other treatment modalities. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Growth hormone therapy alone or in combination with gonadotropin-releasing hormone analog therapy to improve the height deficit in children with congenital adrenal hyperplasia.

    PubMed

    Quintos, J B; Vogiatzi, M G; Harbison, M D; New, M I

    2001-04-01

    Short stature in the adult patient with congenital adrenal hyperplasia (CAH) is commonly seen, even among patients in excellent adrenal control during childhood and puberty. In this study we examine the effect of GH therapy on height prediction in children with both CAH and compromised height prediction. Leuprolide acetate, a GnRH analog (GnRHa), was given to patients with evidence of early puberty. GH (n = 12) or the combination of GH and GnRHa (n = 8) was administered to 20 patients with CAH while they continued therapy with glucocorticoids. Each patient in the treatment group was matched according to age, sex, bone age, puberty, and type of CAH with another CAH patient treated only with glucocorticoid replacement. The match was made at the start of GH treatment. Of the 20 patients, 12 have completed 2 yr of therapy. After 1 yr of GH or combination GH and GnRHa therapy, the mean growth rate increased from 5 +/- 1.9 to 7.8 +/- 1.6 cm/yr vs. 5.4 +/- 1.7 to 5 +/- 2 cm/yr in the group not receiving GH (P < 0.0001). During the second year of treatment, the mean growth rate was 6 +/- 1.6 vs. 4.2 +/- 2.1 cm/yr in the group not receiving GH (P < 0.001). The height SD score for chronological age in the treatment group at the end of 1 and 2 yr of treatment improved significantly more than the nontreatment group (P < 0.01). A similar improvement in the height SD score for bone age was found in the treatment group after 1 (-1.4 +/- 0.9 vs. -1.7 +/- 0.9; P < 0.0001) and 2 yr of therapy (-0.67 +/- 0.68 vs. -1.7 +/- 1.2; P < 0.0004). The mean predicted adult height improved from 159 +/- 11 (baseline) to 170 +/- 7.5 cm (after 2 yr of therapy) closely approximating target height (173 +/- 8 cm). All patients continued the hydrocortisone treatment. In patients with CAH and compromised height prediction, treatment with GH or the combination of GH and GnRHa results in an improvement of growth rate and height prediction and a reduction in height deficit for bone age.

  13. Intrinsic factors, adrenal gland morphology, and disease burden in captive cheetahs (Acinonyx jubatus) in South Africa.

    PubMed

    Gillis-Germitsch, Nina; Vybiral, Pamela-Rose; Codron, Daryl; Clauss, Marcus; Kotze, Antoinette; Mitchell, Emily P

    2017-01-01

    Adrenal gland weight (AW) and corticomedullary ratio (ACMR) are used as indicators of stress in animals. Captive cheetahs (Acinonyx jubatus) have higher ACMRs than free-ranging ones and stress has been linked to gastritis, amyloidosis, glomerulosclerosis, and myocardial fibrosis. We reviewed age, sex, body weight (BW), kidney weight (KW), and left AW and ACMR with necropsy findings in 51 South African captive cheetahs. Eleven common histopathologic lesions were counted for each animal as measure of its disease burden. Adrenal corticomedullary hyperplasia was significantly correlated with left AW and ACMR. Males had significantly higher AWs than females; other parameters showed no difference between the sexes. Disease burden, gastritis, and myocardial fibrosis were moderately correlated with adrenal morphology supporting prior evidence that gastritis and myocardial fibrosis are linked to stress. Glomerulosclerosis was not correlated with adrenal morphology and neither kidney nor liver amyloidosis contributed significantly to variation in AW or ACMR on multivariate analyses. Interstitial nephritis showed much stronger correlations with kidney and liver amyloidosis than gastritis. All three adrenal parameters were correlated with age; age was the only significant variable affecting ACMR on the multivariate analyses; and disease burden as well as systemic amyloidosis and kidney disease (except for fibrosis) showed moderate correlations with age. Age may, therefore, be important in the pathogenesis of disease in captive cheetahs, particularly of amyloidosis and kidney disease. None of the intrinsic measurements or adrenal parameters were sufficiently closely linked to disease to be used as ante-mortem proxies for disease burden or specific diseases. Zoo Biol. 36:40-49, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Clinical, hormonal, ovarian, and genetic aspects of 46,XX patients with congenital adrenal hyperplasia due to CYP17A1 defects.

    PubMed

    Carvalho, Luciane Carneiro de; Brito, Vinicius Nahime; Martin, Regina Matsunaga; Zamboni, Aline Machado; Gomes, Larissa Garcia; Inácio, Marlene; Mermejo, Livia Mara; Coeli-Lacchini, Fernanda; Teixeira, Virginia Ribeiro; Gonçalves, Fabrícia Torres; Carrilho, Alexandre José Faria; Del Toro Camargo, Kenny Yelena; Finkielstain, Gabriela Paula; Taboada, Giselle Fernandes; Frade Costa, Elaine Maria; Domenice, Sorahia; Mendonca, Berenice Bilharinho

    2016-06-01

    To perform a clinical, biochemical, and molecular evaluation of patients with CYP17A1 defects, including ovarian imaging. Retrospective study. Tertiary care center. Sixteen patients with congenital adrenal hyperplasia due to CYP17A1 defects with a median chronological age of 20 years and belonging to 10 unrelated families. None. Clinical and biochemical parameters, molecular diagnosis, ovarian imaging, and therapeutic management. Seventy-one percent of patients presented with primary amenorrhea, 50% had no breast development, and pubic hair was absent or sparse in all patients; 88% had high blood pressure at diagnosis. Basal LH and P levels were high, and androgen levels were low in all patients. Ultrasound revealed ovarian enlargement in 68.7% and ovarian macrocysts in 62.5% of patients before treatment; three patients had a previous surgical correction of ovarian torsion or rupture. Molecular analysis revealed inactivating CYP17A1 mutations in all patients. The most prevalent mutation was p.W406R, and one patient bore a novel p.G478S/p.I223Nfs*10 compound heterozygous mutation. Treatment with dexamethasone, estrogen, and P resulted in reduction of ovarian volume. Amenorrhea, absent/sparse pubic hair, hypertension, and ovarian macrocysts, whichincrease the risk of ovarian torsion, are important elements in the diagnosis of 46,XX patients with CYP17A1 defects. High basal P levels in patients with hypergonadotropic hypogonadism point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  15. Gender role behavior, sexuality, and psychosocial adaptation in women with congenital adrenal hyperplasia due to CYP21A2 deficiency.

    PubMed

    Frisén, Louise; Nordenström, Anna; Falhammar, Henrik; Filipsson, Helena; Holmdahl, Gundela; Janson, Per Olof; Thorén, Marja; Hagenfeldt, Kerstin; Möller, Anders; Nordenskjöld, Agneta

    2009-09-01

    Gender-atypical behavior has been described in young girls as well as in women with congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency. The aim of the study was to assess health-related, psychosexual, and psychosocial parameters and correlate the results to CYP21A2 genotype. Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire and a validated quality of life instrument [psychological general well-being (PGWB) formula] to identify psychosexual and psychosocial parameters. The patients were divided into four CYP21A2 genotype groups. The women with CAH held more male-dominant occupations (30%) compared to controls (13%) (P = 0.04), especially those in the null genotype group (55%) (P = 0.006). They also reported a greater interest in rough sports (74%) compared to controls (50%) (P = 0.007). Eight women with CAH (14%) reported a prime interest in motor vehicles, compared to none of the controls (P = 0.002). Non-heterosexual orientation was reported by 19% of women with CAH (P = 0.005), 50% in the null genotype group (P = 0.0001), 30% in I2 splice (NS), and 5% in I172N (NS). PGWB total score did not differ between patients and controls. We identified increased gender-atypical behavior in women with CAH that could be correlated to the CYP21A2 genotype. This speaks in favor of dose-dependent effects of prenatal androgens on the development of higher brain functions. The impact of the disease on upbringing and interpersonal relationships did not correlate with disease severity, indicating that other factors, such as coping strategies, are important for psychosocial adaptation. This illustrates the need for psychological support to parents and patients.

  16. Obesity in children with congenital adrenal hyperplasia in the Minnesota cohort: importance of adjusting body mass index for height-age.

    PubMed

    Sarafoglou, Kyriakie; Forlenza, Gregory P; Yaw Addo, O; Kyllo, Jennifer; Lteif, Aida; Hindmarsh, P C; Petryk, Anna; Gonzalez-Bolanos, Maria Teresa; Miller, Bradley S; Thomas, William

    2017-05-01

    To evaluate obesity and overweight in children with congenital adrenal hyperplasia (CAH) and associations with glucocorticoids, fludrocortisone and disease control. Adjusting body mass index-for-height-age (BMI HA ) percentile is proposed to correct misclassification of obese/overweight status in CAH children with advanced bone age and tall-for-age stature. Longitudinal. One hundred and ninety-four children with CAH seen from 1970 to 2013: 124 salt wasting (SW); 70 simple virilizing (SV); 102 females. Body mass index (BMI) end-points were overweight (85-94 percentile) and obese (≥95 percentile). Approximately 50% of the children had at least one BMI measurement ≥95 percentile and about 70% had at least one ≥85 percentile. Using BMI HA percentiles, obesity incidence decreased slightly in SW children (47-43%) and markedly in SV children (50-33%); however, overweight status was not reduced. Only 6% of SW and 1% of SV children were persistently obese (≥3 clinic visits) when BMI HA was applied, whereas overweight status persisted in 35% of SW and 33% of SV children. Most obesity or overweight when using BMI HA occurred before age 10 and there was no association with hydrocortisone (HC) or fludrocortisone dosing. Adiposity rebound for SW children occurred by 3·3 years and in SV females by age 3·8 years, over a year earlier than the adiposity rebound for healthy children. Children with CAH are at higher risk for early onset obesity and overweight with or without using BMI HA but rates of persistent obesity were lower than previously reported. Careful HC dosing during early childhood is needed to prevent increased weight gain and an early adiposity rebound. © 2017 John Wiley & Sons Ltd.

  17. Aldosterone hypersecretion in “non-salt-losing” congenital adrenal hyperplasia

    PubMed Central

    Bartter, Frederic C.; Henkin, Robert I.; Bryan, George T.

    1968-01-01

    Patients with the “non-salt-losing” form of the adrenogenital syndrome were studied before and after suppression of adrenal cortical activity with carbohydrate-active steroids. The response of aldosterone secretion to sodium deprivation was measured; in some patients response to adrenocorticotropic hormone (ACTH) was measured as well. The aldosterone secretion was normal and responded normally to sodium deprivation in all patients studied during suppression with carbohydrate-active steroids. This finding suggests that 21-hydroxylation of progesterone is normal in this syndrome. The sole abnormality in the production of aldosterone in these patients was found to be excessive secretion of aldosterone while they were not receiving suppressive doses of carbohydrate-active steroids. This finding strongly supports the view that the biogenetic pathways through which aldosterone is produced from progesterone are intact in this syndrome. No patient showed hypertension or hypokalemic alkalosis despite very high aldosterone secretion rates. This observation suggests that the hyper-aldosteronism is secondary to a tendency to sodium loss in the patient whose ACTH production is not suppressed. These studies provide additional evidence in support of the hypothesis that the salt-losing and “non-salt-losing” forms of adrenogenital syndrome are genetically and biochemically distinct. PMID:4299011

  18. Renal Medullary and Urinary Oxygen Tension during Cardiopulmonary Bypass in the Rat

    PubMed Central

    Sgouralis, Ioannis; Evans, Roger G.; Layton, Anita T.

    2017-01-01

    Renal hypoxia could result from a mismatch in renal oxygen supply and demand, particularly in the renal medulla. Medullary hypoxic damage is believed to give rise to acute kidney injury, which is a prevalent complication of cardiac surgery performed on cardiopulmonary bypass (CPB). To determine the mechanisms that could lead to medullary hypoxia during CPB in the rat kidney, we developed a mathematical model which incorporates (i) autoregulation of renal blood flow and glomerular filtration rate, (ii) detailed oxygen transport and utilization in the renal medulla, and (iii) oxygen transport along the ureter. Within the outer medulla, the lowest interstitial tissue PO2, which is an indicator of renal hypoxia, is predicted near the thick ascending limbs. Interstitial tissue PO2 exhibits a general decrease along the inner medullary axis, but urine PO2 increases significantly along the ureter. Thus, bladder urinary PO2 is predicted to be substantially higher than medullary PO2. The model is used to identify the phase of cardiac surgery performed on CPB that is associated with the highest risk for hypoxic kidney injury. Simulation results indicate that the outer medulla’s vulnerability to hypoxic injury depends, in part, on the extent to which medullary blood flow is autoregulated. With imperfect medullary blood flow autoregulation, the model predicts that the rewarming phase of CPB, in which medullary blood flow is low but medullary oxygen consumption remains high, is the phase in which the kidney is most likely to suffer hypoxic injury. PMID:27281792

  19. Polyphenols of Rubus coreanum Inhibit Catecholamine Secretion from the Perfused Adrenal Medulla of SHRs

    PubMed Central

    Yu, Byung-Sik; Na, Duck-Mi; Kang, Mi-Young

    2009-01-01

    The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC (20~180 µg/ml) perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high K+ (56 mM), DMPP (100 µM) and McN-A-343 (100 µM). PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC (60 µg/ml), the CA secretory responses to veratridine (a selective Na+ channel activator (10 µM), Bay-K-8644 (a L-type dihydropyridine Ca2+ channel activator, 10 µM), and cyclopiazonic acid (a cytoplasmic Ca2+ -ATPase inhibitor, 10 µM) were significantly reduced, respectively. In the simultaneous presence of PCRC (60 µg/ml) and L-NAME (an inhibitor of NO synthase, 30 µM), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high K+, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC (60 µg/ml) was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of Ca2+ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase. PMID:20054501

  20. Characteristics of stroke mechanisms in patients with medullary infarction.

    PubMed

    Lee, M J; Park, Y G; Kim, S J; Lee, J J; Bang, O Y; Kim, J S

    2012-11-01

    Few studies have focused on the mechanisms underlying medullary infarctions. Our aim in this study was to investigate stroke mechanisms in patients with medullary infarctions and to determine the clinical, radiological and laboratory characteristics of these patients with different underlying stroke etiologies. Consecutive patients with medullary infarction were analysed. Stroke mechanisms were classified as large artery disease (LAD), cardiogenic embolism (CE), small vessel disease (SVD), arterial dissection or undetermined etiology. Clinical, radiological and laboratory factors were analysed according to the location of the lesion and stroke mechanisms. A total of 77 patients were enrolled in this study. Amongst them, 53 (68.8%) patients had lateral medullary infarction (LMI), 22 (28.6%) had medial medullary infarction (MMI), and the remaining 2 (2.6%) had hemimedullary infarction. In both LMI and MMI patients, LAD was the most frequently encountered stroke mechanism. Arterial dissection was the second most common cause followed by SVD and CE in patients with LMI, whereas SVD was more frequently observed (P < 0.001) and dissection and CE were less prevalent (P < 0.001 and P = 0.024, respectively) in MMI than in LMI. Regarding differences amongst stroke etiologies, patients with dissection were younger and had a significantly lower incidence of metabolic syndrome (P = 0.002 and P = 0.009, respectively) than patients with LAD and SVD. Patients in the LAD (19/34, 60%) and dissection groups (12/14, 75%) had abnormal perfusion-weighted MRI (PWI) findings, whereas all patients with SVD (9/9) had normal PWI findings (P < 0.001). Stroke mechanisms in medullary infarction differ between LMI and MMI. Clinical and radiological characteristics, especially PWI features, are helpful in discriminating the etiologies of stroke in these patients. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

  1. Do egg-laying crocodilian (Alligator mississippiensis) archosaurs form medullary bone?

    PubMed

    Schweitzer, M H; Elsey, R M; Dacke, C G; Horner, J R; Lamm, E-T

    2007-04-01

    It is beyond question that Mesozoic dinosaurs, like Aves and Crocodylia, are archosaurs. However, within the archosaurian clade, the origin and distribution of some major features are less clear, particularly with respect to reproductive physiology. Medullary bone, a highly mineralized, bony reproductive tissue present in the endosteal cavities of all extant egg-laying birds thus far examined, has recently been reported in Tyrannosaurus rex. Its presence or absence in extant crocodilians, therefore, may shed light on the timing of its evolutionary appearance. If medullary bone is present in all three taxa, it arose before the three lineages diverged. However, if medullary bone arose after this divergence, it may be present in both extinct dinosaurs and birds, or in birds only. If present in extinct dinosaurs and birds, but not crocodilians, it would indicate that it arose in the common ancestor of this clade, thus adding support to the closer phylogenetic relationship of dinosaurs and birds relative to crocodilians. Thus, the question of whether the crocodilian Alligator mississippiensis forms medullary bone during the production of eggs has important evolutionary significance. Our examination of long bones from several alligators (two alligators with eggs in the oviducts, one that had produced eggs in the past but was not currently in reproductive phase, an immature female and an adult male) shows no differences on the endosteal surfaces of the long bones, and no evidence of medullary bone, supporting the hypothesis that medullary bone first evolved in the dinosaur-bird line, after the divergence of crocodilians from this lineage.

  2. Lateral medullary infarction with ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy.

    PubMed

    Li, Xiaodi; Wang, Yuzhou

    2014-04-01

    Here, we present a rare case of a lateral medullary infarction with ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy. In this case, we proved Opalski's hypothesis by diffusion tensor tractography that ipsilateral hemiparesis in a medullary infarction is due to the involvement of the decussated corticospinal tract. We found that the clinical triad of ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy, which had been regarded as a variant of medial medullary syndrome, turned out to be caused by lateral lower medullary infarction. Therefore, this clinical triad does not imply the involvement of the anteromedial part of medulla oblongata, when it is hard to distinguish a massive lateral medullary infarction from a hemimedullary infarction merely from MR images. At last, we suggest that hyperreflexia and Babinski's sign may not be indispensable to the diagnosis of Opalski's syndrome and we propose that "hemimedullary infarction with ipsilateral hemiparesis" is intrinsically a variant of lateral medullary infarction.

  3. Acute encephalopathy with unilateral cortical-subcortical lesions in two unrelated kindreds treated with glucocorticoids prenatally for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: established facts and novel insight.

    PubMed

    Grunt, Sebastian; Steinlin, Maja; Weisstanner, Christian; Schöning, Martin; Mullis, Primus E; Flück, Christa E

    2013-01-01

    Prenatal glucocorticoid (GC) treatment of the female fetus with 21-hydroxylase deficiency (21-OHD) may prevent genital virilization and androgen effects on the brain, but prenatal GC therapy is controversial because of possible adverse effects on fetal programming, the cardiovascular system and the brain. We report 2 patients with congenital adrenal hyperplasia (CAH) due to 21-OHD who were treated prenatally with dexamethasone, suffered from an acute encephalopathy and showed focal and multifocal cortical and subcortical diffusion restrictions in early MRI and signs of permanent alterations in the follow-up neuroimaging studies. Both patients recovered from the acute episode. Whereas the first patient recovered without neurological sequelae the second patient showed hemianopsia and spastic hemiplegia in the neurological follow-up examination. These are 2 children with CAH, both treated prenatally with high doses of dexamethasone to prevent virilization. The question arises whether prenatal high-dose GC treatment in patients with CAH might represent a risk factor for brain lesions in later life. Adverse effects/events should be reported systematically in patients undergoing prenatal GC treatment and long-term follow-up studies involving risk factors for cerebrovascular disease should be performed. Copyright © 2013 S. Karger AG, Basel.

  4. Coexistence and gene expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase, and neuropeptide tyrosine in the rat and bovine adrenal gland: effects of reserpine.

    PubMed

    Schalling, M; Dagerlind, A; Brené, S; Hallman, H; Djurfeldt, M; Persson, H; Terenius, L; Goldstein, M; Schlesinger, D; Hökfelt, T

    1988-11-01

    Expression and regulation of the catecholamine-synthesizing enzymes phenylethanolamine N-methyltransferase (PNMTase; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28) and tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the coexisting neuropeptide tyrosine (NPY) were studied in rat and bovine adrenal medulla. By using both immunohistochemistry and in situ hybridization, PNMTase- and NPY-positive cells exhibited a close overlap in bovine medulla and were preferentially localized in the outer two-thirds of the medulla. Although TyrOHase and its mRNA were observed in virtually all medullary gland cells, TyrOHase mRNA levels were much higher in the PNMTase- and NPY-positive cells. After administration of the catecholamine-depleting drug reserpine to rats, a brief increase, followed by a dramatic decrease, in the level of PNMTase mRNA was observed in the adrenal medulla. In contrast, mRNA for both TyrOHase and NPY only exhibited an increase, whereby the TyrOHase mRNA peak preceded that of NPY mRNA. Different regulatory mechanisms may thus operate for these three compounds coexisting in the adrenal medulla.

  5. Coexistence and gene expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase, and neuropeptide tyrosine in the rat and bovine adrenal gland: effects of reserpine.

    PubMed Central

    Schalling, M; Dagerlind, A; Brené, S; Hallman, H; Djurfeldt, M; Persson, H; Terenius, L; Goldstein, M; Schlesinger, D; Hökfelt, T

    1988-01-01

    Expression and regulation of the catecholamine-synthesizing enzymes phenylethanolamine N-methyltransferase (PNMTase; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28) and tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the coexisting neuropeptide tyrosine (NPY) were studied in rat and bovine adrenal medulla. By using both immunohistochemistry and in situ hybridization, PNMTase- and NPY-positive cells exhibited a close overlap in bovine medulla and were preferentially localized in the outer two-thirds of the medulla. Although TyrOHase and its mRNA were observed in virtually all medullary gland cells, TyrOHase mRNA levels were much higher in the PNMTase- and NPY-positive cells. After administration of the catecholamine-depleting drug reserpine to rats, a brief increase, followed by a dramatic decrease, in the level of PNMTase mRNA was observed in the adrenal medulla. In contrast, mRNA for both TyrOHase and NPY only exhibited an increase, whereby the TyrOHase mRNA peak preceded that of NPY mRNA. Different regulatory mechanisms may thus operate for these three compounds coexisting in the adrenal medulla. Images PMID:2903502

  6. Renal, hepatic, pulmonary and adrenal tumors induced by prenatal inorganic arsenic followed by dimethylarsinic acid in adulthood in CD1 mice

    PubMed Central

    Tokar, Erik J.; Diwan, Bhalchandra A.; Waalkes, Michael P.

    2012-01-01

    Inorganic arsenic, an early life carcinogen in humans and mice, can initiate lesions promotable by other agents in later life. The biomethylation product of arsenic, dimethylarsinic acid (DMA), is a multi-site tumor promoter. Thus, pregnant CD1 mice were given drinking water (0 or 85 ppm arsenic) from gestation day 8 to 18 and after weaning male offspring received DMA (0 or 200 ppm; drinking water) for up to 2 years. No renal tumors occurred in controls or DMA alone treated mice while gestational arsenic exposure plus later DMA induced a significant renal tumor incidence of 17% (primarily renal cell carcinoma). Arsenic plus DMA or arsenic alone also increased renal hyperplasia over control but DMA alone did not. Arsenic alone, DMA alone and arsenic plus DMA all induced urinary bladder hyperplasia (33–35%) versus control (2%). Compared to control (6%), arsenic alone tripled hepatocellular carcinoma (20%), and arsenic plus DMA doubled this rate again (43%), but DMA alone had no effect. DMA alone, arsenic alone, and arsenic plus DMA increased lung adenocarcinomas and adrenal adenomas versus control. Overall, DMA in adulthood promoted tumors/lesions initiated by prenatal arsenic in the kidney and liver, but acted independently in the urinary bladder, lung and adrenal. PMID:22230260

  7. Genetics Home Reference: 21-hydroxylase deficiency

    MedlinePlus

    ... Urinary Tract Defects Orphanet: Congenital adrenal hyperplasia Screening, Technology, and Research in Genetics (PDF) Vanderbilt Childrens Hospital: Congenital Adrenal Hyperplasia (PDF) Virginia Department of ...

  8. A review of 17 cases of carcinoma of the thyroid and phaeochromocytoma

    PubMed Central

    Williams, E. D.

    1965-01-01

    The salient features of 15 cases of carcinoma of the thyroid and phaeochromocytoma taken from the literature and two personal cases are reviewed. The significant points noted are the frequency with which the adrenal tumours were bilateral, the frequency with which a family history of phaeochromocytoma (six cases) and thyroid carcinoma (four cases) was present, and the frequency with which the type of thyroid tumour was medullary carcinoma. In four of the 15 published cases the thyroid tumour was described as being medullary. Two personal cases both had medullary carcinoma of the thyroid, and this was also the type of thyroid carcinoma present in five of the published cases in which the thyroid histology was personally reviewed, making a total of 11 medullary carcinomas out of 17 cases. At least one other tumour was probably medullary, judging by the histological description. It is suggested that the association between phaeochromocytoma and thyroid carcinoma is specifically with medullary carcinoma of the thyroid. Both personal cases showed multiple neural tumours; and because of this and the association with phaeochromocytoma the possible neural origin of medullary carcinoma of the thyroid is briefly discussed. The occurrence in a few cases of parathyroid tumours has raised the possibility that these cases are related to the multiple endocrine adenoma syndrome. The dissimilarity between the cases with medullary carcinoma of the thyroid and phaeochromocytoma and those cases with ademonas involving pituitary, parathyroid, adrenal cortex and pancreatic islets is stressed. The term `medullary tumour syndrome' is suggested as a convenient non-committal name for this association of medullary carcinoma of the thyroid with tumours of the adrenal medulla. Images PMID:14304238

  9. Bilateral medial medullary infarction due to bilateral vertebral artery dissection.

    PubMed

    Fukuda, Masafumi; Aiba, Toyotaka; Takahashi, Sho

    2004-03-01

    We describe a 52-year-old woman who experienced transient motor weakness and numbness of the left extremities and presented 2 days later with severe hemiparesis and sensory impairment of the right extremities and right lingual palsy. Magnetic resonance imaging (MRI) revealed bilateral upper medial medullary infarction, primarily in the left ventral portion. The findings of both three-dimensional (3D) computed tomographic and conventional angiography suggested dissection of both intracranial vertebral arteries (VAs). Medial medullary infarction is generally caused by atherosclerosis within a VA or anterior spinal artery. This is the first report of bilateral medial medullary infarction due to dissection of both intracranial VAs.

  10. Role of medullary progenitor cells in epithelial cell migration and proliferation

    PubMed Central

    Chen, Dong; Chen, Zhiyong; Zhang, Yuning; Park, Chanyoung; Al-Omari, Ahmed

    2014-01-01

    This study is aimed at characterizing medullary interstitial progenitor cells and to examine their capacity to induce tubular epithelial cell migration and proliferation. We have isolated a progenitor cell side population from a primary medullary interstitial cell line. We show that the medullary progenitor cells (MPCs) express CD24, CD44, CXCR7, CXCR4, nestin, and PAX7. MPCs are CD34 negative, which indicates that they are not bone marrow-derived stem cells. MPCs survive >50 passages, and when grown in epithelial differentiation medium develop phenotypic characteristics of epithelial cells. Inner medulla collecting duct (IMCD3) cells treated with conditioned medium from MPCs show significantly accelerated cell proliferation and migration. Conditioned medium from PGE2-treated MPCs induce tubule formation in IMCD3 cells grown in 3D Matrigel. Moreover, most of the MPCs express the pericyte marker PDGFR-b. Our study shows that the medullary interstitium harbors a side population of progenitor cells that can differentiate to epithelial cells and can stimulate tubular epithelial cell migration and proliferation. The findings of this study suggest that medullary pericyte/progenitor cells may play a critical role in collecting duct cell injury repair. PMID:24808539

  11. A phase 2 study of Chronocort, a modified-release formulation of hydrocortisone, in the treatment of adults with classic congenital adrenal hyperplasia.

    PubMed

    Mallappa, Ashwini; Sinaii, Ninet; Kumar, Parag; Whitaker, Martin J; Daley, Lori-Ann; Digweed, Dena; Eckland, David J A; Van Ryzin, Carol; Nieman, Lynnette K; Arlt, Wiebke; Ross, Richard J; Merke, Deborah P

    2015-03-01

    Treatment of congenital adrenal hyperplasia (CAH) is suboptimal. Inadequate suppression of androgens and glucocorticoid excess are common and current glucocorticoid formulations cannot replace the cortisol circadian rhythm. The primary objective was to characterize the pharmacokinetic profile of Chronocort, a modified-release hydrocortisone formulation, in adults with CAH. Secondary objectives included examining disease control following 6 months of Chronocort with dose titration. Sixteen adults (eight females) with classic CAH participated in an open-label, nonrandomized, Phase 2 study at the National Institutes of Health Clinical Center. Twenty-four-hour blood sampling was performed on conventional glucocorticoids and following 6 months of Chronocort. Chronocort was initiated at 10 mg (0700 h) and 20 mg (2300 h). Dose titration was performed based on androstenedione and 17-hydroxyprogresterone (17-OHP) levels and clinical symptomatology. The primary outcome was cortisol pharmacokinetics of Chronocort and secondary outcomes included biomarkers of CAH control (androstenedione and 17-OHP). In patients with CAH, Chronocort cortisol profiles were similar to physiologic cortisol secretion. Compared with conventional therapy, 6 months of Chronocort resulted in a decrease in hydrocortisone dose equivalent (28 ± 11.8 vs 25.9 ± 7.1 mg/d), with lower 24-hour (P = .004), morning (0700-1500 h; P = .002), and afternoon (1500-2300 h; P = .011) androstenedione area under the curve (AUC) and lower 24-hour (P = .023) and morning (0700-1500 h; P = .02) 17-OHP AUC. Twice-daily Chronocort approximates physiologic cortisol secretion, and was well tolerated and effective in controlling androgen excess in adults with CAH. This novel hydrocortisone formulation represents a new treatment approach for patients with CAH.

  12. Two-year pilot study of newborn screening for congenital adrenal hyperplasia in New South Wales compared with nationwide case surveillance in Australia.

    PubMed

    Gleeson, Helena K; Wiley, Veronica; Wilcken, Bridget; Elliott, Elizabeth; Cowell, Christopher; Thonsett, Michael; Byrne, Geoffrey; Ambler, Geoffrey

    2008-10-01

    To assess the benefits and practicalities of setting up a newborn screening (NBS) program in Australia for congenital adrenal hyperplasia (CAH) through a 2 year pilot screening in ACT/NSW and comparing with case surveillance in other states. The pilot newborn screening occurred between 1/10/95 and 30/9/97 in NSW/ACT. Concurrently, case reporting for all new CAH cases occurred through the Australian Paediatric Surveillance Unit (APSU) across Australia. Details of clinical presentation, re-sampling and laboratory performance were assessed. 185,854 newborn infants were screened for CAH in NSW/ACT. Concurrently, 30 cases of CAH were reported to APSU, twelve of which were from NSW/ACT. CAH incidence was 1 in 15 488 (screened population) vs 1 in 18,034 births (unscreened) (difference not significant). Median age of initial notification was day 8 with confirmed diagnosis at 13(5-23) days in the screened population vs 16(7-37) days in the unscreened population (not significant). Of the 5 clinically unsuspected males in the screened population, one had mild salt-wasting by the time of notification, compared with salt-wasting crisis in all 6 males from the unscreened population. 96% of results were reported by day 10. Resampling was requested in 637 (0.4%) and median re-sampling delay was 11(0-28) days with higher resample rates in males (p < 0.0001). The within-laboratory cost per case of clinically unsuspected cases was A$42 717. There seems good justification for NBS for CAH based on clear prevention of salt-wasting crises and their potential long-term consequences. Also, prospects exist for enhancing screening performance.

  13. Diagnosis of adrenal insufficiency.

    PubMed

    Dorin, Richard I; Qualls, Clifford R; Crapo, Lawrence M

    2003-08-05

    The cosyntropin stimulation test is the initial endocrine evaluation of suspected primary or secondary adrenal insufficiency. To critically review the utility of the cosyntropin stimulation test for evaluating adrenal insufficiency. The MEDLINE database was searched from 1966 to 2002 for all English-language papers related to the diagnosis of adrenal insufficiency. Studies with fewer than 5 persons with primary or secondary adrenal insufficiency or with fewer than 10 persons as normal controls were excluded. For secondary adrenal insufficiency, only studies that stratified participants by integrated tests of adrenal function were included. Summary receiver-operating characteristic (ROC) curves were generated from all studies that provided sensitivity and specificity data for 250-microg and 1-microg cosyntropin tests; these curves were then compared by using area under the curve (AUC) methods. All estimated values are given with 95% CIs. At a specificity of 95%, sensitivities were 97%, 57%, and 61% for summary ROC curves in tests for primary adrenal insufficiency (250-microg cosyntropin test), secondary adrenal insufficiency (250-microg cosyntropin test), and secondary adrenal insufficiency (1-microg cosyntropin test), respectively. The area under the curve for primary adrenal insufficiency was significantly greater than the AUC for secondary adrenal insufficiency for the high-dose cosyntropin test (P < 0.001), but AUCs for the 250-microg and 1-microg cosyntropin tests did not differ significantly (P > 0.5) for secondary adrenal insufficiency. At a specificity of 95%, summary ROC analysis for the 250-microg cosyntropin test yielded a positive likelihood ratio of 11.5 (95% CI, 8.7 to 14.2) and a negative likelihood ratio of 0.45 (CI, 0.30 to 0.60) for the diagnosis of secondary adrenal insufficiency. Cortisol response to cosyntropin varies considerably among healthy persons. The cosyntropin test performs well in patients with primary adrenal insufficiency, but the

  14. Osteopontin expression is correlated with differentiation and good prognosis in medullary thyroid carcinoma.

    PubMed

    Ferreira, Luciana Bueno; Eloy, Catarina; Pestana, Ana; Lyra, Joana; Moura, Margarida; Prazeres, Hugo; Tavares, Catarina; Sobrinho-Simões, Manuel; Gimba, Etel; Soares, Paula

    2016-04-01

    Osteopontin (OPN) or secreted phosphoprotein 1 (SPP1) is a matricellular glycoprotein whose expression is elevated in various types of cancer and has been shown to be involved in tumourigenesis and metastasis in many malignancies, including follicular cell-derived thyroid carcinomas. Its role in C-cell-derived thyroid lesions and tumours remains to be established. The objective of this study is to clarify the role of OPN expression in the development of medullary thyroid carcinoma (MTC). OPN expression was analysed in a series of 116 MTCs by immunohistochemistry and by qPCR mRNA quantification of the 3 OPN isoforms (OPNa, OPNb and OPNc) in six cases from which fresh frozen tissue was available. Statistical tests were used to evaluate the relationship of OPN expression and the clinicopathological and molecular characteristics of patients and tumours. OPN expression was detected in 91 of 116 (78.4%) of the MTC. We also observed high OPN expression in C-cell hyperplasia as well as in C-cells scattered in the thyroid parenchyma adjacent to the tumours. OPN expression was significantly associated with smaller tumour size, PTEN nuclear expression and RAS status, and suggestively associated with non-invasive tumours. OPNa isoform was expressed significantly at higher levels in tumours than in non-tumour samples. OPNb and OPNc presented similar levels of expression in all samples. Furthermore, OPNa isoform overexpression was significantly associated with reduced growth and viability in the MTC-derived cell line (TT). The expression of OPN in normal C-cells and C-cell hyperplasia suggests that OPN is a differentiation marker of C-cells, rather than a marker of biological aggressiveness in this setting. At variance with other cancers, OPN expression is associated with good prognostic features in MTC. © 2016 European Society of Endocrinology.

  15. Isolated medial medullary infarction due to vertebral artery dissection.

    PubMed

    Wakita, M; Matsuoka, H; Hamada, R; Kasuya, J; Osame, M

    2003-12-01

    A 54-year-old man developed left hemiparesis and tactile and deep sensory disturbance following onset of rightside cervical pain. These symptoms resulted from an isolated infarct in the right medial area of the upper medulla oblongata and intracranial vertebral artery (VA) dissection. Atherosclerotic disease of the VA is the most common cause of medial medullary infarction. In past reports of isolated medial medullary infarction, only a few cases involved VA dissection.

  16. Imaging Characteristics of Pathologically Proven Thymic Hyperplasia: Identifying Features That Can Differentiate True From Lymphoid Hyperplasia

    PubMed Central

    Araki, Tetsuro; Sholl, Lynette M.; Gerbaudo, Victor H.; Hatabu, Hiroto; Nishino, Mizuki

    2014-01-01

    OBJECTIVE The purpose of this article is to investigate the imaging characteristics of pathologically proven thymic hyperplasia and to identify features that can differentiate true hyperplasia from lymphoid hyperplasia. MATERIALS AND METHODS Thirty-one patients (nine men and 22 women; age range, 20–68 years) with pathologically confirmed thymic hyperplasia (18 true and 13 lymphoid) who underwent preoperative CT (n = 27), PET/CT (n = 5), or MRI (n = 6) were studied. The length and thickness of each thymic lobe and the transverse and anterior-posterior diameters and attenuation of the thymus were measured on CT. Thymic morphologic features and heterogeneity on CT and chemical shift on MRI were evaluated. Maximum standardized uptake values were measured on PET. Imaging features between true and lymphoid hyperplasia were compared. RESULTS No significant differences were observed between true and lymphoid hyperplasia in terms of thymic length, thickness, diameters, morphologic features, and other qualitative features (p > 0.16). The length, thickness, and diameters of thymic hyperplasia were significantly larger than the mean values of normal glands in the corresponding age group (p < 0.001). CT attenuation of lymphoid hyperplasia was significantly higher than that of true hyperplasia among 15 patients with contrast-enhanced CT (median, 47.9 vs 31.4 HU; Wilcoxon p = 0.03). The receiver operating characteristic analysis yielded greater than 41.2 HU as the optimal threshold for differentiating lymphoid hyperplasia from true hyperplasia, with 83% sensitivity and 89% specificity. A decrease of signal intensity on opposed-phase images was present in all four cases with in- and opposed-phase imaging. The mean maximum standardized uptake value was 2.66. CONCLUSION CT attenuation of the thymus was significantly higher in lymphoid hyperplasia than in true hyperplasia, with an optimal threshold of greater than 41.2 HU in this cohort of patients with pathologically confirmed

  17. Spontaneous nystagmus in dorsolateral medullary infarction indicates vestibular semicircular canal imbalance.

    PubMed

    Rambold, H; Helmchen, C

    2005-01-01

    Spontaneous nystagmus caused by dorsolateral medullary infarction may be of vestibular origin. To test if imbalance of the central pathways of the semicircular canals contributes to spontaneous nystagmus in dorsolateral medullary syndrome. We examined four patients with dorsolateral medullary syndrome and recorded spontaneous nystagmus binocularly at gaze straight ahead with the three-dimensional search coil technique. The median slow phase velocity of the nystagmus was analysed in the light and in the dark, and the normalised velocity axes were compared with the rotation axes as predicted from anatomical data of the semicircular canal. The slow phase rotation axes of all patients aligned best with the rotation axes resulting from stimulation of the contralesional posterior and horizontal semicircular canals. This alignment cannot be explained by pure otolith imbalance. We propose that vestibular imbalance caused by an ipsilesional lesion of the central semicircular canal pathways of the horizontal and anterior semicircular canals largely accounts for spontaneous nystagmus in dorsolateral medullary syndrome.

  18. Experience with long-term glucocorticoid treatment in congenital adrenal hyperplasia: growth pattern compared with genetic height potential.

    PubMed

    Aycan, Zehra; Ocal, Gonul; Berberoglu, Merih; Cetinkaya, Ergun; Adiyaman, Pelin; Evliyaoglu, Olcay

    2006-03-01

    Long-term replacement treatment with high doses of steroids in congenital adrenal hyperplasia (CAH) is known to have a negative influence on growth. We evaluated the effects of long-term steroid treatment in patients with classical CAH on height development in relation to genetic height potential. Twenty-three patients with CAH (16 females, 7 males, mean age: 9.8 +/- 3.5 years) were included in this longitudinal study. The effect of steroid treatment on growth was determined by monitoring patients for 8.61 +/- 3.46 years (2-17 years) while they were treated with hydrocortisone at a mean dosage of 17.64 +/- 3.60 mg/m2/day. The height standard deviation scores (Ht-SDS), target Ht-SDS, and corrected Ht-SDS for target height was calculated for all patients. Predicted adult height according to bone age was calculated and it was determined whether height was developing according to the genetic height potential. In addition, patients were grouped as 'tight control' or 'poor control' according to their mean serum 17OH-progesterone or ACTH levels while on treatment. We evaluated whether height development was different for the tight and poor control groups. The mean chronological age of our patients at the time of the study was 9.89 +/- 3.53 years, Ht-SDS -0.77 +/- 1.57, target height (TH) 161.03 +/- 6.54 cm, TH-SDS -0.60 +/- 0.90, predicted height (PH) 157.2 +/- 11.16 cm, PH-SDS -1.1 +/- 1.69, and corrected Ht-SDS -0.75 +/- 1.14. There was no significant difference between the actual Ht-SDS and TH-SDS of our patients (p >0.05) but the corrected Ht-SDS was less than zero. Only 28.5% of our patients had normal height according to their genetic potential while 71.5% were shorter than their genetic height potential. While the Ht-SDS and corrected Ht-SDS were similar in the tight and poor metabolic control groups, the predicted height was significantly greater in the tight control group. We demonstrated that a hydrocortisone dose of 17.64 +/- 3.60 mg/m2/day in classical CAH had

  19. [Addison's disease : Primary adrenal insufficiency].

    PubMed

    Pulzer, A; Burger-Stritt, S; Hahner, S

    2016-05-01

    Adrenal insufficiency, a rare disorder which is characterized by the inadequate production or absence of adrenal hormones, may be classified as primary adrenal insufficiency in case of direct affection of the adrenal glands or secondary adrenal insufficiency, which is mostly due to pituitary or hypothalamic disease. Primary adrenal insufficiency affects 11 of 100,000 individuals. Clinical symptoms are mainly nonspecific and include fatigue, weight loss, and hypotension. The diagnostic test of choice is dynamic testing with synthetic ACTH. Patients suffering from chronic adrenal insufficiency require lifelong hormone supplementation. Education in dose adaption during physical and mental stress or emergency situations is essential to prevent life-threatening adrenal crises. Patients with adrenal insufficiency should carry an emergency card and emergency kit with them.

  20. Inhibitory effect of strychnine on acetylcholine receptor activation in bovine adrenal medullary chromaffin cells.

    PubMed Central

    Kuijpers, G A; Vergara, L A; Calvo, S; Yadid, G

    1994-01-01

    1. Strychnine, which is known as a potent and selective antagonist of the inhibitory glycine receptor in the central nervous system, inhibits the nicotinic stimulation of catecholamine release from bovine cultured adrenal chromaffin cells in a concentration-dependent (1-100 microM) manner. At 10 microM nicotine, the IC50 value for strychnine is approximately 30 microM. Strychnine also inhibits the nicotine-induced membrane depolarization and increase in intracellular Ca2+ concentration. 2. The inhibitory action of strychnine is reversible and is selective for nicotinic stimulation, with no effect observed on secretion elicited by a high external K+ concentration, histamine or angiotensin II. 3. Strychnine competes with nicotine in its effect, but not modify the apparent positive cooperatively of the nicotine binding sites. In the absence of nicotine, strychnine has no effect on catecholamine release. Glycine does not affect catecholamine release nor the inhibitory action of strychnine on this release. 4. These results suggest that strychnine interacts with the agonist binding site of the nicotinic acetylcholine receptor in chromaffin cells, thus exerting a pharmacological effect independently of the glycine receptor. PMID:7834198

  1. Renal cell carcinoma, unclassified with medullary phenotype: poorly differentiated adenocarcinomas overlapping with renal medullary carcinoma.

    PubMed

    Sirohi, Deepika; Smith, Steven C; Ohe, Chisato; Colombo, Piergiuseppe; Divatia, Mukul; Dragoescu, Ema; Rao, Priya; Hirsch, Michelle S; Chen, Ying-Bei; Mehra, Rohit; Amin, Mahul B

    2017-09-01

    Renal medullary carcinoma (RMC) is a highly aggressive renal cell carcinoma arising in the collecting system and requiring careful correlation with status of sickle cell trait. A panel of international experts has recently proposed provisional diagnostic terminology, renal cell carcinoma, unclassified, with medullary phenotype, based on encountering an extraordinarily rare tumor with RMC morphology and immunophenotype in an individual proven not to have a hemoglobinopathy. Herein, we extend this observation to a cohort of 5 such tumors, morphologically similar to RMC, lacking SMARCB1 expression by immunohistochemistry, but each without evidence of a hemoglobinopathy. The tumors arose in 4 men and 1 woman with a mean age of 44 years, occurring in 3 left and 2 right kidneys. Clinically, aggression was apparent with involvement of perinephric adipose tissue in all 5 cases, nodal metastasis in 4 of 5 cases, and death of disease in 4 of 5 cases within 3-27 months. Histologic sections showed poorly differentiated adenocarcinoma, often with solid and nested growth patterns, as well as infiltrative glandular, tubulopapillary, cribriform, or reticular growth. Rhabdoid and sarcomatoid cytomorphology was seen in a subset. All tumors showed PAX8 nuclear positivity and SMARCB1 loss, with OCT3/4 expression in 4 of 5 cases. In summary, this first series of renal cell carcinoma, unclassified, with medullary phenotype documents tumors with morphologic, immunophenotypic, and prognostic features of RMC occurring in individuals without sickle cell trait. Although greater biologic and molecular understanding is needed, the available evidence points to these cases representing a sporadic counterpart to sickle cell trait-associated RMC. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Physical and radiological findings specific for medullary carcinoma of the thyroid gland.

    PubMed

    Fujimoto, Y; Oka, A; Fukumitsu, M; Obara, T; Akisada, M

    1975-06-01

    Preoperative physical and radiological findings, if specific to a certain extent, are important for detecting patients with sporadic form of medullary thyroid carcinoma and especially for the first patient in the family having a hereditary form of medullary thyroid carcinoma and pheochromocytoma syndrome. To delineate clinical features of medullary thyroid carcinoma, a total of 9 patients with this tumor were reviewed retrospectively. In most patients, the thyroid lesions were located in the upper two thirds of the lobe, which was determined by careful palpation or 131I scintiscanning of the thyroid. The primary lesion in the thyroid could be felt more or less as a round, sharply demarcated nodule with fairly good mobility. These findings suggested rather a benign thyroid nodule when there was no lymph node involvement. However, it could be considered a sign suggesting medullary thyroid carcinoma when accompanied by marked lymph node metastasis. In our recent 2 cases, the diagnosis of medullary thyroid carcinoma was strongly suspected on these clinical bases, one of the cases being presented in detail. In 4 patients, lymph node metastasis in the central neck extended to either submandibular or upper mediastinal regions or both. In about one third of the patients, calcified deposits were shown in the cervical roentgenograms. With the use of soft tissue roentgenography, grossly punctate calcific deposits associated with psammoma-like shadows were recognized and the pattern was a criterion for definitive diagnosis of medullary thyroid carcinoma.

  3. A Phase 2 Study of Chronocort, a Modified-Release Formulation of Hydrocortisone, in the Treatment of Adults With Classic Congenital Adrenal Hyperplasia

    PubMed Central

    Sinaii, Ninet; Kumar, Parag; Whitaker, Martin J.; Daley, Lori-Ann; Digweed, Dena; Eckland, David J. A.; Van Ryzin, Carol; Nieman, Lynnette K.; Arlt, Wiebke; Merke, Deborah P.

    2015-01-01

    Context: Treatment of congenital adrenal hyperplasia (CAH) is suboptimal. Inadequate suppression of androgens and glucocorticoid excess are common and current glucocorticoid formulations cannot replace the cortisol circadian rhythm. Objectives: The primary objective was to characterize the pharmacokinetic profile of Chronocort, a modified-release hydrocortisone formulation, in adults with CAH. Secondary objectives included examining disease control following 6 months of Chronocort with dose titration. Design, Setting, and Patients: Sixteen adults (eight females) with classic CAH participated in an open-label, nonrandomized, Phase 2 study at the National Institutes of Health Clinical Center. Twenty-four-hour blood sampling was performed on conventional glucocorticoids and following 6 months of Chronocort. Chronocort was initiated at 10 mg (0700 h) and 20 mg (2300 h). Dose titration was performed based on androstenedione and 17-hydroxyprogresterone (17-OHP) levels and clinical symptomatology. Main Outcome Measures: The primary outcome was cortisol pharmacokinetics of Chronocort and secondary outcomes included biomarkers of CAH control (androstenedione and 17-OHP). Results: In patients with CAH, Chronocort cortisol profiles were similar to physiologic cortisol secretion. Compared with conventional therapy, 6 months of Chronocort resulted in a decrease in hydrocortisone dose equivalent (28 ± 11.8 vs 25.9 ± 7.1 mg/d), with lower 24-hour (P = .004), morning (0700–1500 h; P = .002), and afternoon (1500–2300 h; P = .011) androstenedione area under the curve (AUC) and lower 24-hour (P = .023) and morning (0700–1500 h; P = .02) 17-OHP AUC. Conclusions: Twice-daily Chronocort approximates physiologic cortisol secretion, and was well tolerated and effective in controlling androgen excess in adults with CAH. This novel hydrocortisone formulation represents a new treatment approach for patients with CAH. PMID:25494662

  4. Surgical management of medullary thyroid cancer.

    PubMed

    Mazeh, H; Sippel, R S

    2012-12-01

    Although thyroid cancer accounts for only 1.5% of all malignancies in the US it is the most rapidly increasing cancer in incidence and it is the most common endocrine malignancy that accounts for over 95% of the endocrine malignancies. Medullary thyroid cancer (MTC) originates from the parafollicular C cells and it represents 6-8% of all thyroid cancer cases. As many as 25% of the MTCs are familial and carry a specific germline mutation as compared to only than 10% familial inheritance in non-medullary thyroid cancers. While well-differentiated thyroid malignancies carry a very good prognosis, recurrence and survival rates of patients with MTC are significantly worse. The difference in cell origin and differentiation also results in different available adjunct therapy. The aim of this study is to review in detail the surgical management of patients with MTC.

  5. Adrenal Insufficiency

    MedlinePlus

    ... three types of steroid hormones. In adrenal insufficiency (AI), the cortex does not make enough steroid hormones. ... unlike “adrenal fatigue.” There are two kinds of AI: • Primary AI, also called Addison’s disease. In this ...

  6. CD14 Deficiency Impacts Glucose Homeostasis in Mice through Altered Adrenal Tone

    PubMed Central

    Young, James L.; Mora, Alfonso; Cerny, Anna; Czech, Michael P.; Woda, Bruce; Kurt-Jones, Evelyn A.; Finberg, Robert W.; Corvera, Silvia

    2012-01-01

    The toll-like receptors comprise one of the most conserved components of the innate immune system, signaling the presence of molecules of microbial origin. It has been proposed that signaling through TLR4, which requires CD14 to recognize bacterial lipopolysaccharide (LPS), may generate low-grade inflammation and thereby affect insulin sensitivity and glucose metabolism. To examine the long-term influence of partial innate immune signaling disruption on glucose homeostasis, we analyzed knockout mice deficient in CD14 backcrossed into the diabetes-prone C57BL6 background at 6 or 12 months of age. CD14-ko mice, fed either normal or high-fat diets, displayed significant glucose intolerance compared to wild type controls. They also displayed elevated norepinephrine urinary excretion and increased adrenal medullary volume, as well as an enhanced norepinephrine secretory response to insulin-induced hypoglycemia. These results point out a previously unappreciated crosstalk between innate immune- and sympathoadrenal- systems, which exerts a major long-term effect on glucose homeostasis. PMID:22253759

  7. Effect of medullary cavity in cancellous bone on two-wave phenomenon

    NASA Astrophysics Data System (ADS)

    Hachiken, Takuma; Nakanishi, Shoko; Matsukawa, Mami

    2016-07-01

    Osteoporotic patients have a larger medullary cavity in their cancellous bone than healthy people. In this study, the effect of the medullary cavity on the two-wave phenomenon was experimentally investigated using a cancellous bone model and a radius bone model. In the cancellous bone model, with the increase in hole (medullary cavity) diameter, the amplitudes of the fast waves became smaller, whereas the amplitudes of the slow waves became larger. In the radius bone model, the fast wave overlapped with the circumferential wave. The slow wave became larger with increasing hole diameter. The analysis of the slow wave thus seems to be useful for the in vivo diagnosis of the degree of osteoporosis.

  8. Persistent Primary Aldosteronism Despite Iatrogenic Adrenal Hemorrhage After Adrenal Vein Sampling.

    PubMed

    Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Abe, Ichiro; Kobayashi, Kunihisa; Ishii, Tatsu; Haraoka, Seiji; Urata, Hidenori

    2018-01-01

    Before surgery for primary aldosteronism (PA), localization is evaluated with adrenal vein sampling (AVS). A 56-year-old Japanese woman had a right adrenal mass, hypokalemia, and a high aldosterone/renin ratio. Stress tests confirmed the diagnosis of PA. Subsequently, preoperative AVS was performed and right adrenal hemorrhage (AH) occurred unexpectedly. Because hypertension persisted, laparoscopic right adrenalectomy was performed. Postoperatively, the blood pressure was normalized. Pathological examination revealed an adrenal cortical adenoma largely unaffected by necrosis and hemorrhage. Previous reports have also indicated that AH may not ameliorate PA. We discussed the clinical progress of AH and the measures to prevent causing AH.

  9. Traumatic and non-traumatic adrenal emergencies.

    PubMed

    Chernyak, Victoria; Patlas, Michael N; Menias, Christine O; Soto, Jorge A; Kielar, Ania Z; Rozenblit, Alla M; Romano, Luigia; Katz, Douglas S

    2015-12-01

    Multiple traumatic and non-traumatic adrenal emergencies are occasionally encountered during the cross-sectional imaging of emergency department patients. Traumatic adrenal hematomas are markers of severe polytrauma, and can be easily overlooked due to multiple concomitant injuries. Patients with non-traumatic adrenal emergencies usually present to an emergency department with a non-specific clinical picture. The detection and management of adrenal emergencies is based on cross-sectional imaging. Adrenal hemorrhage, adrenal infection, or rupture of adrenal neoplasm require immediate detection to avoid dire consequences. More often however, adrenal emergencies are detected incidentally in patients being investigated for non-specific acute abdominal pain. A high index of suspicion is required for the establishment of timely diagnosis and to avert potentially life-threatening complications. We describe cross-sectional imaging findings in patients with traumatic and non-traumatic adrenal hemorrhage, adrenal infarctions, adrenal infections, and complications of adrenal masses.

  10. Congenital Adrenal Hyperplasia

    MedlinePlus

    ... YouTube follow us on Flickr follow us on Instagram Español NICHD Theme Browse AZTopics Browse A-Z ... Publications Sitemap Español facebook twitter pinterest youtube flickr Instagram NEWSROOM NICHD News Videos OUTREACH Safe to Sleep® ...

  11. Persistent Primary Aldosteronism Despite Iatrogenic Adrenal Hemorrhage After Adrenal Vein Sampling

    PubMed Central

    Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Abe, Ichiro; Kobayashi, Kunihisa; Ishii, Tatsu; Haraoka, Seiji; Urata, Hidenori

    2018-01-01

    Before surgery for primary aldosteronism (PA), localization is evaluated with adrenal vein sampling (AVS). A 56-year-old Japanese woman had a right adrenal mass, hypokalemia, and a high aldosterone/renin ratio. Stress tests confirmed the diagnosis of PA. Subsequently, preoperative AVS was performed and right adrenal hemorrhage (AH) occurred unexpectedly. Because hypertension persisted, laparoscopic right adrenalectomy was performed. Postoperatively, the blood pressure was normalized. Pathological examination revealed an adrenal cortical adenoma largely unaffected by necrosis and hemorrhage. Previous reports have also indicated that AH may not ameliorate PA. We discussed the clinical progress of AH and the measures to prevent causing AH. PMID:29238437

  12. Androgen and psychosexual development: core gender identity, sexual orientation and recalled childhood gender role behavior in women and men with congenital adrenal hyperplasia (CAH).

    PubMed

    Hines, Melissa; Brook, Charles; Conway, Gerard S

    2004-02-01

    We assessed core gender identity, sexual orientation, and recalled childhood gender role behavior in 16 women and 9 men with CAH and in 15 unaffected female and 10 unaffected male relatives, all between the ages of 18 and 44 years. Women with congenital adrenal hyperplasia (CAH) recalled significantly more male-typical play behavior as children than did unaffected women, whereas men with and without CAH did not differ. Women with CAH also reported significantly less satisfaction with the female sex of assignment and less heterosexual interest than did unaffected women. Again, men with CAH did not differ significantly from unaffected men in these respects. Our results for women with CAH are consistent with numerous prior reports indicating that girls with CAH show increased male-typical play behavior. They also support the hypotheses that these women show reduced heterosexual interest and reduced satisfaction with the female sex of assignment. Our results for males are consistent with most prior reports that boys with CAH do not show a general alteration in childhood play behavior. In addition, they provide initial evidence that core gender identity and sexual orientation are unaffected in men with CAH. Finally, among women with CAH, we found that recalled male-typical play in childhood correlated with reduced satisfaction with the female gender and reduced heterosexual interest in adulthood. Although prospective studies are needed, these results suggest that those girls with CAH who show the greatest alterations in childhood play behavior may be the most likely to develop a bisexual or homosexual orientation as adults and to be dissatisfied with the female sex of assignment.

  13. Complement component 4 copy number variation and CYP21A2 genotype associations in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

    PubMed

    Chen, Wuyan; Xu, Zhi; Nishitani, Miki; Van Ryzin, Carol; McDonnell, Nazli B; Merke, Deborah P

    2012-12-01

    Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of cortisol biosynthesis caused by CYP21A2 mutations. An increase in gene copy number variation (CNV) exists at the CYP21A2 locus. CNV of C4, a neighboring gene that encodes complement component 4, is associated with autoimmune disease susceptibility. In this study, we performed comprehensive genetic analysis of the RP-C4-CYP21-TNX (RCCX) region in 127 unrelated 21-OHD patients (100 classic, 27 nonclassic). C4 copy number was determined by Southern blot. C4 CNV and serum C4 levels were evaluated in relation to CYP21A2 mutations and relevant phenotypes. We found that the most common CYP21A2 mutation associated with the nonclassic form of CAH, V281L, was associated with high C4 copy number (p = 7.13 × 10(-16)). Large CYP21A2 deletion, a common mutation associated with the classic form of CAH, was associated with low C4 copy number (p = 1.61 × 10(-14)). Monomodular RCCX with a short C4 gene, a risk factor for autoimmune disease, was significantly less frequent in CAH patients compared to population estimates (2.8 vs. 10.6 %; p = 1.08 × 10(-4)). In conclusion, CAH patients have increased C4 CNV, with mutation-specific associations that may be protective for autoimmune disease. The study of CYP21A2 in relation to neighboring genes provides insight into the genetics of CNV hotspots, an important determinant of human health.

  14. Glucagon Like Peptide-1 Receptor Expression in the Human Thyroid Gland

    PubMed Central

    Gier, Belinda; Butler, Peter C.; Lai, Chi K.; Kirakossian, David; DeNicola, Matthew M.

    2012-01-01

    Background: Glucagon like peptide-1 (GLP-1) mimetic therapy induces medullary thyroid neoplasia in rodents. We sought to establish whether C cells in human medullary thyroid carcinoma, C cell hyperplasia, and normal human thyroid express the GLP-1 receptor. Methods: Thyroid tissue samples with medullary thyroid carcinoma (n = 12), C cell hyperplasia (n = 9), papillary thyroid carcinoma (n = 17), and normal human thyroid (n = 15) were evaluated by immunofluorescence for expression of calcitonin and GLP-1 receptors. Results: Coincident immunoreactivity for calcitonin and GLP-1 receptor was consistently observed in both medullary thyroid carcinoma and C cell hyperplasia. GLP-1 receptor immunoreactivity was also detected in 18% of papillary thyroid carcinoma (three of 17 cases). Within normal human thyroid tissue, GLP-1 receptor immunoreactivity was found in five of 15 of the examined cases in about 35% of the total C cells assessed. Conclusions: In humans, neoplastic and hyperplastic lesions of thyroid C cells express the GLP-1 receptor. GLP-1 receptor expression is detected in 18% papillary thyroid carcinomas and in C cells in 33% of control thyroid lobes. The consequence of long-term pharmacologically increased GLP-1 signaling on these GLP-1 receptor-expressing cells in the thyroid gland in humans remains unknown, but appropriately powered prospective studies to exclude an increase in medullary or papillary carcinomas of the thyroid are warranted. PMID:22031513

  15. Congenital adrenal hyperplasia and risk for psychiatric disorders in girls and women born between 1915 and 2010: A total population study.

    PubMed

    Engberg, Hedvig; Butwicka, Agnieszka; Nordenström, Anna; Hirschberg, Angelica Lindén; Falhammar, Henrik; Lichtenstein, Paul; Nordenskjöld, Agneta; Frisén, Louise; Landén, Mikael

    2015-10-01

    Congenital adrenal hyperplasia (CAH) is a chronic condition and individuals are exposed to elevated androgen levels in utero as a result of the endogenous cortisol deficiency. Prenatal androgen exposure has been suggested to influence mental health, but population based studies on psychiatric morbidity among girls and women with CAH are lacking. Therefore, we performed a cohort study based on Swedish nationwide registers linked with the national CAH register. Girls and women with CAH due to 21-hydroxylase deficiency (n = 335) born between January 1915 and January 2010 were compared with aged-matched female (n = 33500) and male controls (n = 33500). Analyses were stratified by phenotype [salt wasting (SW), simple virilizing (SV), and non-classical type (NC)] and by CYP21A2 genotype subgroups (null, I2splice, I172N, and P30L). Results are presented as estimated risks (OR, 95%CI) of psychiatric disorders among girls and women with CAH compared with age-matched controls. Any psychiatric diagnoses were more common in CAH females compared with female and male population controls [1.9 (1.4-2.5), and 2.2 (1.7-2.9)]. In particular, the risk of alcohol misuse was increased compared with female and male population controls [2.8 (1.7-4.7) and 2.1 (1.2-3.5)], and appeared most common among the girls and women with the most severe null genotype [6.7 (2.6-17.8)]. The risk of stress and adjustment disorders was doubled compared with female population controls [2.1 (1.3-3.6)]. Girls and women with CAH have an increased risk of psychiatric disorders in general and substance use disorders in particular compared with unexposed females, with the highest risk among those with the most severe genotype. Prenatal androgen exposure and deficient endogenous cortisol and/or adrenaline production may provide explanations for these findings, but other factors related to CAH cannot be excluded. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Recurrent intramedullary epidermoid cyst of conus medullaris

    PubMed Central

    Fleming, Christina; Kaliaperumal, Chandrasekaran; O’Sullivan, Michael

    2011-01-01

    Spinal intramedullary epidermoid cyst is a rare condition. Recurrent epidermoid cyst in the spine cord is known to occur. The authors describe a case of recurrent conus medullaris epidermoid cyst in a 24-year-old female. She initially presented at 7 years of age with bladder disturbance in the form of diurnal enuresis and recurrent urinary tract infection. MRI lumbar spine revealed a 4 cm conus medullaris epidermoid cyst. Since the initial presentation, the cyst had recurred seven times in the same location and she underwent surgical intervention in the form of exploration and debulking. This benign condition, owing to its anatomical location, has posed a surgical and overall management challenge. This occurrence is better managed in a tertiary-care centre requiring multi-disciplinary treatment approach. PMID:22669964

  17. Variable expressivity of familial medullary thyroid carcinoma (FMTC) due to a RET V804M (GTG-->ATG) mutation.

    PubMed

    Feldman, G L; Edmonds, M W; Ainsworth, P J; Schuffenecker, I; Lenoir, G M; Saxe, A W; Talpos, G B; Roberson, J; Petrucelli, N; Jackson, C E

    2000-07-01

    Multiple endocrine neoplasia type 2 (MEN 2) and familial medullary thyroid carcinoma (FMTC) are autosomal dominantly inherited cancer syndromes that predispose to C-cell hyperplasia and MTC. MEN 2A and FMTC are caused by mutations in the RET proto-oncogene. We used a multiplex polymerase chain reaction-based assay to screen exons 10, 11, 13, and 14 of RET for mutations in 2 families with FMTC. We correlated mutation status with calcitonin and pathologic studies to determine genotype-phenotype correlations. We identified a mutation in codon 804 in exon 14 (GTG-->ATG; V804M) in both families. An 86-year-old person who was a gene carrier and other individuals over age 70 who were suspected by pedigree analysis to be gene carriers had no overt clinical evidence of MTC. Four of 21 patients who underwent a thyroidectomy also had papillary thyroid cancer. One individual in each family had metastatic MTC at age 30 and 32 years, and all 26 people having thyroidectomies had either MTC or C-cell hyperplasia, leading us to continue to recommend prophylactic thyroidectomy for all identified patients who were gene carriers. Because of active MTC in younger members of these families, including metastases, we have continued to advocate thyroid surgery in mutation-positive individuals. While DNA diagnosis of gene carriers and subsequent genetic counseling was relatively straightforward, the acceptance of surgical recommendations was more difficult for some individuals. These families demonstrate that the search for RET mutations should include exons 13, 14, 15, and 16 in patients whose studies in exons 10 and 11 are negative.

  18. Intra-adrenal Aldosterone Secretion: Segmental Adrenal Venous Sampling for Localization.

    PubMed

    Satani, Nozomi; Ota, Hideki; Seiji, Kazumasa; Morimoto, Ryo; Kudo, Masataka; Iwakura, Yoshitsugu; Ono, Yoshikiyo; Nezu, Masahiro; Omata, Kei; Ito, Sadayoshi; Satoh, Fumitoshi; Takase, Kei

    2016-01-01

    To use segmental adrenal venous sampling (AVS) (S-AVS) of effluent tributaries (a version of AVS that, in addition to helping identify aldosterone hypersecretion, also enables the evaluation of intra-adrenal hormone distribution) to detect and localize intra-adrenal aldosterone secretion. The institutional review board approved this study, and all patients provided informed consent. S-AVS was performed in 65 patients with primary aldosteronism (34 men; mean age, 50.9 years ± 11 [standard deviation]). A microcatheter was inserted in first-degree tributary veins. Unilateral aldosterone hypersecretion at the adrenal central vein was determined according to the lateralization index after cosyntropin stimulation. Excess aldosterone secretion at the adrenal tributary vein was considered to be present when the aldosterone/cortisol ratio from this vein exceeded that from the external iliac vein; suppressed secretion was indicated by the opposite pattern. Categoric variables were expressed as numbers and percentages; continuous variables were expressed as means ± standard errors of the mean. The AVS success rate, indicated by a selectivity index of 5 or greater, was 98% (64 of 65). The mean numbers of sampled tributaries on the left and right sides were 2.11 and 1.02, respectively. The following diagnoses were made on the basis of S-AVS results: unilateral aldosterone hypersecretion in 30 patients, bilateral hypersecretion without suppressed segments in 22 patients, and bilateral hypersecretion with at least one suppressed segment in 12 patients. None of the patients experienced severe complications. S-AVS could be used to identify heterogeneous intra-adrenal aldosterone secretion. Patients who have bilateral aldosterone-producing adenomas can be treated with adrenal-sparing surgery or other minimally invasive local therapies if any suppressed segment is identified at S-AVS. © RSNA, 2015.

  19. [A Case of Hereditary Medullary Thyroid Cancer (MEN2A/FMTC) Diagnosed at the Time of Recurrence].

    PubMed

    Enomoto, Keisuke; Shimizu, Kotaro; Hirose, Masayuki; Miyabe, Haruka; Morizane, Natsue; Takenaka, Yukinori; Shimazu, Kohki; Fushimi, Hiroaki; Uno, Atsuhiko

    2015-03-01

    We report a 42-year-old man with hereditary medullary thyroid cancer (multiple endocrine neoplasia, MEN2A/familial medullary thyroid carcinoma, FMTC), which was diagnosed at the time of tumor recurrence. He had a past history of a left thyroidectomy with neck dissection 7 years previously. A RET gene analysis revealed a point mutation (codon 618), and we diagnosed him as having hereditary medullary thyroid cancer. We resected the recurrent tumor in the right thyroid lobe together with performing a right lateral and central neck dissection. A RET gene analysis should be performed for patients with medullary thyroid cancer. When a RET gene mutation is present, a total thyroidectomy must be performed for the medullary thyroid cancer.

  20. Steroid Profiling by Gas Chromatography–Mass Spectrometry and High Performance Liquid Chromatography–Mass Spectrometry for Adrenal Diseases

    PubMed Central

    McDonald, Jeffrey G.; Matthew, Susan

    2012-01-01

    The ability to measure steroid hormone concentrations in blood and urine specimens is central to the diagnosis and proper treatment of adrenal diseases. The traditional approach has been to assay each steroid hormone, precursor, or metabolite using individual aliquots of serum, each with a separate immunoassay. For complex diseases, such as congenital adrenal hyperplasia and adrenocortical cancer, in which the assay of several steroids is essential for management, this approach is time consuming and costly, in addition to using large amounts of serum. Gas chromatography/mass spectrometry profiling of steroid metabolites in urine has been employed for many years but only in a small number of specialized laboratories and suffers from slow throughput. The advent of commercial high-performance liquid chromatography instruments coupled to tandem mass spectrometers offers the potential for medium- to high-throughput profiling of serum steroids using small quantities of sample. Here, we review the physical principles of mass spectrometry, the instrumentation used for these techniques, the terminology used in this field and applications to steroid analysis. PMID:22170384

  1. Adrenal Gland Cancer

    MedlinePlus

    ... either benign or malignant. Benign tumors aren't cancer. Malignant ones are. Most adrenal gland tumors are ... and may not require treatment. Malignant adrenal gland cancers are uncommon. Types of tumors include Adrenocortical carcinoma - ...

  2. Increased Dietary Sodium Induces COX2 Expression by activating NFκB in Renal Medullary Interstitial Cells

    PubMed Central

    Zhao, Min; Davis, Linda S.; Blackwell, Timothy S.; Yull, Fiona; Breyer, Matthew D.; Hao, Chuan-Ming

    2013-01-01

    High salt diet induces renal medullary COX2 expression. Selective blockade of renal medullary COX2 activity in rats causes salt sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NFκB in mediating this COX2 induction in response to increased dietary salt. High salt diet (8% NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6J mice. Co-immunofluorescence using a COX2 antibody and antibodies against AQP2, ClC-K, AQP1 and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NFκB reporter transgenic mice, we observed a 7 fold increase of luciferase activity in the renal medulla of the NFκB-luciferase reporter mice following high salt diet, and a robust induction of EGFP expression mainly in renal medullary interstitial cells of the NFκB-EGFP reporter mice following high salt diet. Treating high salt diet fed C57Bl/6J mice with selective IκB kinase inhibitor IMD-0354 (8mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary PGE2. These data therefore suggest that renal medullary interstitial cell NFκB plays an important role in mediating renal medullary COX2 expression and promoting renal PGE2 synthesis in response to increased dietary sodium. PMID:23900806

  3. Immunohistochemical Localization of AT1a, AT1b, and AT2 Angiotensin II Receptor Subtypes in the Rat Adrenal, Pituitary, and Brain with a Perspective Commentary

    PubMed Central

    Premer, Courtney; Lamondin, Courtney; Mitzey, Ann; Speth, Robert C.; Brownfield, Mark S.

    2013-01-01

    Angiotensin II increases blood pressure and stimulates thirst and sodium appetite in the brain. It also stimulates secretion of aldosterone from the adrenal zona glomerulosa and epinephrine from the adrenal medulla. The rat has 3 subtypes of angiotensin II receptors: AT1a, AT1b, and AT2. mRNAs for all three subtypes occur in the adrenal and brain. To immunohistochemically differentiate these receptor subtypes, rabbits were immunized with C-terminal fragments of these subtypes to generate receptor subtype-specific antibodies. Immunofluorescence revealed AT1a and AT2 receptors in adrenal zona glomerulosa and medulla. AT1b immunofluorescence was present in the zona glomerulosa, but not the medulla. Ultrastructural immunogold labeling for the AT1a receptor in glomerulosa and medullary cells localized it to plasma membrane, endocytic vesicles, multivesicular bodies, and the nucleus. AT1b and AT2, but not AT1a, immunofluorescence was observed in the anterior pituitary. Stellate cells were AT1b positive while ovoid cells were AT2 positive. In the brain, neurons were AT1a, AT1b, and AT2 positive, but glia was only AT1b positive. Highest levels of AT1a, AT1b, and AT2 receptor immunofluorescence were in the subfornical organ, median eminence, area postrema, paraventricular nucleus, and solitary tract nucleus. These studies complement those employing different techniques to characterize Ang II receptors. PMID:23573410

  4. MEDULLARY THICK ASCENDING LIMB BUFFER VASOCONSTRICTION OF RENAL OUTER-MEDULLARY VASA RECTA IN SALT-RESISTANT BUT NOT SALT-SENSITIVE RATS

    PubMed Central

    O’Connor, Paul M.; Cowley, Allen W.

    2013-01-01

    We have previously demonstrated that paracrine signaling occurs between medullary thick ascending limb (mTAL) and the contractile pericytes of outer-medullary vasa recta (VR) termed ‘tubular-vascular cross talk’. The aim of the current study was to determine whether tubular-vascular cross talk has a functional effect on vasoconstrictor responses to angiotensin II, and to determine whether this is altered in the Dahl salt-sensitive (SS) rat. Studies were performed on salt-resistant consomic SS.13BN and SS rats using a novel outer medullary tissue strip preparation in which freshly isolated VR within VR bundles were perfused either alone or in combination with nearby mTAL. In VR from SS.13BN rats, angiotensin II (1μM) increased VR bundle intracellular Ca2+ concentration ([Ca2+]VR) 19±9nM (n=8) and reduced focal diameter in perfused VR by (−20±7%;n=5). In the presence of nearby mTAL however, [Ca2+]VR (−9±8nM; n=8) and VR diameter (−1±4%, n=7) in SS.13BN rats was unchanged by angiotensin II. In contrast, in Dahl SS rats, angiotensin II resulted in rapid and sustained increase in [Ca2+]VR (89±48 n=7;50±24% n=8) and a reduction in VR diameter of (−17±7;n=7 and −11±4%;n=5) in both isolated VR and VR with nearby mTAL, respectively. In VR with mTAL from SS13BN rats, inhibiton of purinergic receptors resulted in an increase in [Ca2+]VR, indicating purinergic signaling buffers vasoconstriction. Importantly, our in vitro data were able to predict medullary blood flow responses to angiotensin II in SS and SS.13BN rats in vivo. We conclude that paracrine signaling from mTAL buffers angiotensin II vasoconstriction in Dahl salt-resistant SS.13BN rats but not SS rats. PMID:22926950

  5. Adrenal cortical oncocytoma mimicking pheochromocytoma.

    PubMed

    Kiriakopoulos, Andreas; Papaioannou, Dimitrios; Linos, Dimitrios

    2011-01-01

    Adrenal tumors present with clinical features and signs unique to their specific hormonal hypersecretion. However, there have been cases in which the clinical expression has been in conflict with the histologic features of the tumor. In this communication we report an unusual clinical presentation of an adrenal cortical tumor with histologic features of an oncocytoma that clinically mimicked a pheochromocytoma. A 49-year old man was referred to our Unit due to type B aortic dissection and a mass of the left adrenal gland. Computed tomography and magnetic resonance imaging confirmed the presence of aortic dissection extending from the left subclavian artery to both iliac arteries and also revealed a 6 cm tumor on the left adrenal gland. Preoperative endocrine evaluation showed a near tenfold increase of urinary vanillylmandelic acid (VMA) and metanephrine values. Transperitoneal laparoscopic adrenalectomy was successfully performed. The adrenal tumor proved to be an adrenal cortical neoplasm with histologic features of oncocytoma. Although the case of an adrenal cortical adenoma clinically mimicking a pheochromocytoma has been described in the literature, to the best of our knowledge, there has been no previous report of an adrenal cortical neoplasm with predominant features of oncocytoma.

  6. A 9 years boy with MEN-2B variant of medullary thyroid carcinoma.

    PubMed

    Sattar, M A; Hadi, H I; Ekramuddoula, F M; Hasanuzzaman, S M

    2013-04-01

    To highlight a rare disease like multiple endocrine neoplasia (MEN)-2B variant of medullary thyroid carcinoma and to optimize the management option in such cases, we present a nine year old boy with thyroid swelling, cervical lymphadenopathy and thick lips. His calcitonin level was raised. Investigation's results of the boy were as following fine needle aspiration cytology (FNAC) was medullary carcinoma of thyroid, preoperative calcitonin was >2000pg/ml, post operative histopathological report was medullary carcinoma. Total thyroidectomy with aggressive initial neck surgery may reduce the recurrence and increase better prognosis and survival rate. Calcitonin is used as diagnostic and follow-up marker.

  7. Increased dietary sodium induces COX2 expression by activating NFκB in renal medullary interstitial cells.

    PubMed

    He, Wenjuan; Zhang, Min; Zhao, Min; Davis, Linda S; Blackwell, Timothy S; Yull, Fiona; Breyer, Matthew D; Hao, Chuan-Ming

    2014-02-01

    High salt diet induces renal medullary cyclooxygenase 2 (COX2) expression. Selective blockade of renal medullary COX2 activity in rats causes salt-sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NFκB in mediating this COX2 induction in response to increased dietary salt. High salt diet (8 % NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6 J mice. Co-immunofluorescence using a COX2 antibody and antibodies against aquaporin-2, ClC-K, aquaporin-1, and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NFκB reporter transgenic mice, we observed a sevenfold increase of luciferase activity in the renal medulla of the NFκB-luciferase reporter mice following high salt diet, and a robust induction of enhanced green fluorescent protein (EGFP) expression mainly in renal medullary interstitial cells of the NFκB-EGFP reporter mice following high salt diet. Treating high salt diet-fed C57Bl/6 J mice with selective IκB kinase inhibitor IMD-0354 (8 mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary prostaglandin E2 (PGE2). These data therefore suggest that renal medullary interstitial cell NFκB plays an important role in mediating renal medullary COX2 expression and promoting renal PGE2 synthesis in response to increased dietary sodium.

  8. Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues.

    PubMed

    Morimoto, Ryo; Satoh, Fumitoshi; Murakami, Osamu; Hirose, Takuo; Totsune, Kazuhito; Imai, Yutaka; Arai, Yoichi; Suzuki, Takashi; Sasano, Hironobu; Ito, Sadayoshi; Takahashi, Kazuhiro

    2008-07-01

    Adrenomedullin 2/intermedin (AM2/IMD) is a new member of calcitonin/calcitonin gene-related peptide family. AM is expressed in various tumors including adrenocortical tumors and modulates tumor growth. The AM2/IMD expression has not been studied, however, in adrenal tumors. The expression of AM2/IMD and AM was therefore studied in human adrenal tumors and attached non-neoplastic adrenal tissues by immunocytochemistry (ICC). Immunoreactive (IR)-AM2/IMD was measured by RIA. Furthermore, the expression of AM2/IMD and its receptor components, calcitonin receptor-like receptor (CRLR), and receptor activity-modifying proteins (RAMPs) 1, 2, and 3 mRNA in these tissues was studied by reverse transcription PCR (RT-PCR). ICC showed that AM2/IMD and AM immunoreactivities were localized in adrenocortical tumors and pheochromocytomas. AM2/IMD and AM immunoreactivities were detected in medulla of attached non-neoplastic tissues, while the degree of immunoreactivity for AM2/IMD and AM in cortices of attached adrenals was relatively weak or undetectable. RIA detected IR-AM2/IMD in adrenal tumors (0.414+/-0.12 to 0.786+/-0.27 pmol/g wet weight, mean+/-S.E.M.) and attached adrenal tissues (0.397+/-0.052 pmol/g wet weight). Reverse-phase high-performance liquid chromatography showed one broad peak eluted in the similar position to synthetic AM2/IMD with several minor peaks. RT-PCR showed expression of AM2/IMD, CRLR, and RAMP1, RAMP2, and RAMP3 mRNA in tissues of adrenal tumors and attached adrenal glands. In conclusion, AM2/IMD is expressed in human adrenal tumors and attached non-neoplastic adrenal tissues and may play (patho-)physiological roles in normal and neoplastic adrenals as an autocrine/paracrine regulator.

  9. Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome

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

    Sarma, Asha, E-mail: ashasarma@gmail.com; Shyn, Paul B., E-mail: pshyn@partners.org; Vivian, Mark A.

    Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: One was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements.

  10. Benign prostate hyperplasia (BPH) - resources

    MedlinePlus

    Resources - benign prostatic hyperplasia (BPH); Prostate enlargement resources; BPH resources ... organizations provide information on benign prostatic hyperplasia ( prostate enlargement ): National Institute of Diabetes and Digestive and Kidney ...

  11. Bittersweet: Real-Time, Dynamic Changes in Blood Glucose Levels during an Acute Ozone Exposure in Rats

    EPA Science Inventory

    In humans and rats, acute exposures to ozone have been shown to activate the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal axes to induce multi-organ metabolic alterations including impaired glucose homeostasis. These findings have largely been gleaned from on...

  12. Bladder urine oxygen tension for assessing renal medullary oxygenation in rabbits: experimental and modeling studies

    PubMed Central

    Sgouralis, Ioannis; Kett, Michelle M.; Ow, Connie P. C.; Abdelkader, Amany; Layton, Anita T.; Gardiner, Bruce S.; Smith, David W.; Lankadeva, Yugeesh R.

    2016-01-01

    Oxygen tension (Po2) of urine in the bladder could be used to monitor risk of acute kidney injury if it varies with medullary Po2. Therefore, we examined this relationship and characterized oxygen diffusion across walls of the ureter and bladder in anesthetized rabbits. A computational model was then developed to predict medullary Po2 from bladder urine Po2. Both intravenous infusion of [Phe2,Ile3,Orn8]-vasopressin and infusion of NG-nitro-l-arginine reduced urinary Po2 and medullary Po2 (8–17%), yet had opposite effects on renal blood flow and urine flow. Changes in bladder urine Po2 during these stimuli correlated strongly with changes in medullary Po2 (within-rabbit r2 = 0.87–0.90). Differences in the Po2 of saline infused into the ureter close to the kidney could be detected in the bladder, although this was diminished at lesser ureteric flow. Diffusion of oxygen across the wall of the bladder was very slow, so it was not considered in the computational model. The model predicts Po2 in the pelvic ureter (presumed to reflect medullary Po2) from known values of bladder urine Po2, urine flow, and arterial Po2. Simulations suggest that, across a physiological range of urine flow in anesthetized rabbits (0.1–0.5 ml/min for a single kidney), a change in bladder urine Po2 explains 10–50% of the change in pelvic urine/medullary Po2. Thus, it is possible to infer changes in medullary Po2 from changes in urinary Po2, so urinary Po2 may have utility as a real-time biomarker of risk of acute kidney injury. PMID:27385734

  13. Notch3 as a novel therapeutic target in metastatic medullary thyroid cancer.

    PubMed

    Lou, Irene; Odorico, Scott; Yu, Xiao-Min; Harrison, April; Jaskula-Sztul, Renata; Chen, Herbert

    2018-01-01

    Medullary thyroid cancer portends poor survival once liver metastasis occurs. We hypothesize that Notch3 overexpression in medullary thyroid cancer liver metastasis will decrease proliferation and growth of the tumor. TT cells were modified genetically to overexpress Notch3 in the presence of doxycycline, creating the TT-Notch3 cell line. Mice were injected intrasplenically with either TT-Notch3 or control vector TT-TRE cells. Each cell line had 3 treatment groups: control with 12 weeks of standard chow, early DOX with doxycycline chow at day 0 and for 70 days thereafter, and late DOX with doxycycline chow at 8 weeks. Each animal underwent micro-computed tomography to evaluate for tumor formation and tumor quantification was performed. Animals were killed at 12 weeks, and the harvested liver was stained with Ki-67, hematoxylin and eosin, and Notch3. Induction of Notch3 did not prevent formation of medullary thyroid cancer liver metastases as all mice in the early DOX group developed tumors. However, induction of Notch after medullary thyroid cancer liver tumor formation decreased tumor size, as seen on micro-computed tomography scans (late DOX group). This translated to a 37-fold decrease in tumor volume (P = .001). Notch3 overexpression also resulted in decreased Ki-67 index (P = .038). Moreover, Notch3 induction led to increased areas of neutrophil infiltration and necrosis on hematoxylin and eosin staining of the tumors CONCLUSION: Notch3 overexpression demonstrates an antiproliferative effect on established metastatic medullary thyroid cancer liver tumors and is a potential therapeutic target in treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Animal models of medullary thyroid cancer: state of the art and view to the future.

    PubMed

    Vitale, Giovanni; Gaudenzi, Germano; Circelli, Luisa; Manzoni, Marco F; Bassi, Andrea; Fioritti, Niccolò; Faggiano, Antongiulio; Colao, Annamaria

    2017-01-01

    Medullary thyroid carcinoma is a neuroendocrine tumour originating from parafollicular C cells accounting for 5-10% of thyroid cancers. Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid carcinoma. These drugs increase progression-free survival; however, they are often poorly tolerated and most treatment responses are transient. Animal models are indispensable tools for investigating the pathogenesis, mechanisms for tumour invasion and metastasis and new therapeutic approaches for cancer. Unfortunately, only few models are available for medullary thyroid carcinoma. This review provides an overview of the state of the art of animal models in medullary thyroid carcinoma and highlights future developments in this field, with the aim of addressing salient features and clinical relevance. © 2017 Society for Endocrinology.

  15. Subareolar Sclerosing Ductal Hyperplasia.

    PubMed

    Cheng, Esther; D'Alfonso, Timothy M; Arafah, Maria; Marrero Rolon, Rebecca; Ginter, Paula S; Hoda, Syed A

    2017-02-01

    Subareolar sclerosing duct hyperplasia (SSDH) remains to be fully characterized nearly 20 years after initial description. Thirty-five SSDH cases diagnosed over a 16-year period (January 2000 to December 2015) were reviewed. All patients were female (mean age = 59 years, range = 18-80) who had presented with a unilateral solitary lesion (left 22, right 13) with a mean size of 1.3 cm (range = 0.4-3.0 cm), and showed florid and papillary epithelial hyperplasia with dense sclerosis without involvement of nipple or areolar epidermis. Significant lesions concurrent within SSDH included low-grade adenosquamous carcinoma (n = 1), ductal carcinoma in situ (DCIS; n = 1), lobular carcinoma in situ (LCIS; n = 1), and atypical ductal hyperplasia (ADH; n = 13). No case of SSDH recurred in a mean follow-up of 44 months (range = 6-189). Subsequent significant lesions occurred in 6 patients: DCIS (n = 3; ipsilateral 2, contralateral 1), ipsilateral ADH (n = 2), and ipsilateral atypical lobular hyperplasia (n = 1). Long-term follow-up for patients with SSDH is indicated as DCIS can occur subsequently in either breast.

  16. Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing disease and nonmalignant primary adrenal Cushing syndrome.

    PubMed

    Prete, Alessandro; Paragliola, Rosa Maria; Bottiglieri, Filomena; Rota, Carlo Antonio; Pontecorvi, Alfredo; Salvatori, Roberto; Corsello, Salvatore Maria

    2017-03-01

    Successful treatment of Cushing syndrome causes transient or permanent adrenal insufficiency deriving from endogenous hypercortisolism-induced hypothalamus-pituitary-adrenal-axis suppression. We analyzed pre-treatment factors potentially affecting the duration of adrenal insufficiency. We conducted a retrospective analysis on patients successfully treated for Cushing disease (15 patients) who underwent transsphenoidal surgery, and nonmalignant primary adrenal Cushing syndrome (31 patients) who underwent unilateral adrenalectomy, divided into patients with overt primary adrenal Cushing syndrome (14 patients) and subclinical primary adrenal Cushing syndrome (17 patients). Epidemiological data, medical history, and hormonal parameters depending on the etiology of hypercortisolism were collected and compared to the duration of adrenal insufficiency. The median duration of follow-up after surgery for Cushing disease and primary adrenal Cushing syndrome was 70 and 48 months, respectively. In the Cushing disease group, the median duration of adrenal insufficiency after transsphenoidal surgery was 15 months: younger age at diagnosis and longer duration of signs and symptoms of hypercortisolism before diagnosis and surgery were associated with longer duration of adrenal insufficiency. The median duration of adrenal insufficiency was 6 months for subclinical primary adrenal Cushing syndrome and 18.5 months for overt primary adrenal Cushing syndrome. The biochemical severity of hypercortisolism, the grade of hypothalamus-pituitary-adrenal-axis suppression, and treatment with ketoconazole before surgery accounted for longer duration of adrenal insufficiency. In patients with Cushing disease, younger age and delayed diagnosis and treatment predict longer need for glucocorticoid replacement therapy after successful transsphenoidal surgery. In patients with primary adrenal Cushing syndrome, the severity of hypercortisolism plays a primary role in influencing the duration of

  17. [Endometrial hyperplasia, diagnosis. Clinical, paraclinical exam and management].

    PubMed

    Pangal, Alexandra; Costăchescu, Gh; Aldea, Marie Jeanne

    2010-01-01

    Factors associated with unopposed estrogenic stimulation such as obesity, exogenous hormone use endometrial hyperplasia are related to the development of the most common form of endometrial carcinoma, that is, the endometroid subtype. We selected a group of patients diagnosed with endometrial hyperplasia by endometrial biopsy and histopathological examination. The main complaint in all cases was abnormal uterine bleeding. All patients had gynecological examination, vaginal ultrasound, hysteroscopy endometrial biopsy or D&C. 32 patients had also immunohistochemical staining for Ki67, EGF, ER, PGR. Cases with ages between 24-67 years were classified as: 100 simple hyperplasia, 10 complex hyperplasia, 43 atypical simple hyperplasia, 7 atypical complex hyperplasia. PR were 40-60% at all forms of hyperplasia, E2R were 30-40% in simple hyperplasia without atypia and 50-70% in complex hyperplasia without atypia. Correlation between immunohistochemical expression of E2R, PGR, Ki-67, EGF and body mass revealed an high immunohistochemical expression of E2R and Ki-67 in patients with hyperplasia without atypia and a low expression and high reactivity of EGF in cases with high body mass. Vaginal ultrasound and hysteroscopy are efficacious completion for histopathological diagnosis. We recommend an age/risk appropriate screening to detect risk factors and early disease in the asymptomatic patients.

  18. European Adrenal Insufficiency Registry (EU-AIR): a comparative observational study of glucocorticoid replacement therapy.

    PubMed

    Ekman, Bertil; Fitts, David; Marelli, Claudio; Murray, Robert D; Quinkler, Marcus; Zelissen, Pierre M J

    2014-05-09

    Increased morbidity and mortality associated with conventional glucocorticoid replacement therapy for primary adrenal insufficiency (primary AI; estimated prevalence 93-140/million), secondary AI (estimated prevalence, 150-280/million, respectively) or congenital adrenal hyperplasia (estimated prevalence, approximately 65/million) may be due to the inability of typical glucocorticoid treatment regimens to reproduce the normal circadian profile of plasma cortisol. A once-daily modified-release formulation of hydrocortisone has been developed to provide a plasma cortisol profile that better mimics the daytime endogenous profile of cortisol. Here, we describe the protocol for the European Adrenal Insufficiency Registry (EU-AIR), an observational study to assess the long-term safety of modified-release hydrocortisone compared with conventional glucocorticoid replacement therapies in routine clinical practice (ClinicalTrials.gov identifier: NCT01661387). Patients enrolled in EU-AIR have primary or secondary AI and are receiving either modified-release or conventional glucocorticoid replacement therapy. The primary endpoints of EU-AIR are the incidence of intercurrent illness, adrenal crisis and serious adverse events (SAEs), as well as the duration of SAEs and dose changes related to SAEs. Data relating to morbidity, mortality, adverse drug reactions, dosing and concomitant therapies will be collected. Patient diaries will record illness-related dose changes between visits. All decisions concerning medical care are made by the registry physician and patient. Enrolment is targeted at achieving 3600 patient-years of treatment (1800 patient-years per group) for the primary analysis, which is focused on determining the non-inferiority of once-daily modified-release replacement therapy compared with conventional glucocorticoid therapy. Recruitment began in August 2012 and, as of March 2014, 801 patients have been enrolled. Fifteen centres are participating in Germany, the UK

  19. The diagnosis of nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, based on serum basal or post-ACTH stimulation 17-hydroxyprogesterone, can lead to false-positive diagnosis.

    PubMed

    Ambroziak, Urszula; Kępczyńska-Nyk, Anna; Kuryłowicz, Alina; Małunowicz, Ewa Maria; Wójcicka, Anna; Miśkiewicz, Piotr; Macech, Magdalena

    2016-01-01

    As nonclassic congenital adrenal hyperplasia (NCCAH) needs to be taken into account in women with hyperandrogenism, we aimed to assess whether the recommended level of poststimulated 17OHP ≥30 nmol/l confirms NCCAH. Forty, consecutive women with biochemical and/or clinical hyperandrogenism (aged 25·4, 18-38) suspected of having NCCAH were recruited to the study. In patients with 17OHP level between 5·1 and 29·9 nmol/l an ACTH stimulation test was performed. In patients with basal or poststimulated 17OHP ≥30 nmol/l, twenty-four-hour urinary steroid profile (USP) analysis was performed and CYP21A2 mutation was assessed. In selected patients with poststimulated 17OHP <30 nmol/l USP was also performed. The group was divided into two subgroups with basal or poststimulated 17OHP ≥30 nmol/l (group A) and with poststimulated 17OHP <30 nmol/l (group B). Among 40 patients, basal or poststimulated 17OHP ≥30 nmol/l was found in 21, but NCCAH was confirmed by USP followed by genetic testing only in 5 (24%). Four patients were diagnosed as heterozygotes, and in twelve, no CYP21A2 mutation was detected. The diagnosis of NCCAH based only on serum 17OHP measurements (basal or poststimulated) may lead to false-positive diagnosis when performed by immunoassay with a cut-off value of ≥30 nmol/l. The definitive diagnosis can be established based on USP and/or genetic testing. © 2015 John Wiley & Sons Ltd.

  20. Adrenal Gland Tumors: Statistics

    MedlinePlus

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  1. Review analysis of medullary carcinoma thyroid--15-year Indian experience.

    PubMed

    Dorairajan, N; Saravanakumar, P; Karthikeyan, S; Siddharth, D; Kanna, Srinivasulu

    2005-08-01

    To emphasize the importance of adequate primary surgery in cases of medullary carcinoma of the thyroid, 44 cases of treated medullary carcinoma of thyroid were retrospectively reviewed in Government General Hospital, Chennai between 1987 and 2002. Patients who underwent total thyroidectomy with only central compartment dissection were compared with those who had undergone total thyroidectomy with meticulous triple compartment (bilateral lateral and central groups) nodal dissection. The group of total thyroidectomy with only central compartment dissection had high rate of lymph nodal recurrence and persistent hypercalcitoninaemia when compared with the group of total thyroidectomy with meticulous triple compartment nodal dissection. (Chi square value 4.503 with p<0.05).

  2. Florid reactive lymphoid hyperplasia of terminal ileum.

    PubMed

    Kanakala, Venkatesh; Birch, Peter; Kasaraneni, Ramesh

    2010-01-01

    Florid lymphoid hyperplasia in the terminal ileum can present to surgeons as an acute abdominal pain. Only few cases were reported in the literature. Our case illustrates that a rare case of florid lymphoid hyperplasia can present to surgeons as acute appendicitis. During the operation the gross appearance may mimic Crohn's disease. A limited resection is sufficient to clinch the diagnosis of florid lymphoid hyperplasia / Crohn's disease. In florid lymphoid hyperplasia limited resection may be curative.

  3. Florid reactive lymphoid hyperplasia of terminal ileum

    PubMed Central

    Kanakala, Venkatesh; Birch, Peter; Kasaraneni, Ramesh

    2010-01-01

    Florid lymphoid hyperplasia in the terminal ileum can present to surgeons as an acute abdominal pain. Only few cases were reported in the literature. Our case illustrates that a rare case of florid lymphoid hyperplasia can present to surgeons as acute appendicitis. During the operation the gross appearance may mimic Crohn’s disease. A limited resection is sufficient to clinch the diagnosis of florid lymphoid hyperplasia / Crohn’s disease. In florid lymphoid hyperplasia limited resection may be curative. PMID:22242075

  4. Gastric inhibitory polypeptide-dependent cortisol hypersecretion--a new cause of Cushing's syndrome.

    PubMed

    Lacroix, A; Bolté, E; Tremblay, J; Dupré, J; Poitras, P; Fournier, H; Garon, J; Garrel, D; Bayard, F; Taillefer, R

    1992-10-01

    Corticotropin-independent nodular adrenal hyperplasia is a rare cause of Cushing's syndrome, and the factors responsible for the adrenal hyperplasia are not known. We studied a 48-year-old woman with Cushing's syndrome, nodular adrenal hyperplasia, and undetectable plasma corticotropin concentrations in whom food stimulated cortisol secretion. Cortisol secretion had an inverse diurnal rhythm in this patient, with low-to-normal fasting plasma cortisol concentrations and elevated postprandial cortisol concentrations that could not be suppressed with dexamethasone. The cortisol concentrations increased in response to oral glucose (4-fold increase) and a lipid-rich meal (4.8-fold increase) or a protein-rich meal (2.6-fold increase), but not intravenous glucose. The infusion of somatostatin blunted the plasma cortisol response to oral glucose. Intravenous infusion of gastric inhibitory polypeptide (GIP) for one hour increased the plasma cortisol concentration in the patient but not in four normal subjects. Fasting plasma GIP concentrations in the patient were similar to those in the normal subjects; feeding the patient test meals induced increases in plasma GIP concentrations that paralleled those in plasma cortisol concentrations. Cell suspensions of adrenal tissue from the patient produced more cortisol when stimulated by GIP than when stimulated by corticotropin. In contrast, adrenal cells from normal adults and fetuses or patients with cortisol-producting or aldosterone-producing adenomas responded to corticotropin but not to GIP. Nodular adrenal hyperplasia and Cushing's syndrome may be food-dependent as a result of abnormal responsiveness of adrenal cells to physiologic secretion of GIP. "Illicit" (ectopic) expression of GIP receptors on adrenal cells presumably underlies this disorder.

  5. [Adrenal tumours in childhood].

    PubMed

    Martos-Moreno, G A; Pozo-Román, J; Argente, J

    2013-09-01

    This special article aims to summarise the current knowledge regarding the two groups of tumours with their origin in the adrenal gland: 1) adrenocortical tumours, derived from the cortex of the adrenal gland and 2) phaeochromocytomas and paragangliomas, neuroendocrine tumours derived from nodes of neural crest derived cells symmetrically distributed at both sides of the entire spine (paragangliomas [PG]). These PGs can be functioning tumors that secrete catecholamines, which confers their typical dark colour after staining with chromium salts (chromaffin tumors). Among these, the term phaeochromocytoma (PC) is restricted to those PGs derived from the chromaffin cells in the adrenal medulla (intra-adrenal PGs), whereas the term PG is used for those sympathetic or parasympathetic ones in an extra-adrenal location. We analyse the state of the art of their pathogenic and genetic bases, as well as their clinical signs and symptoms, the tests currently available for performing their diagnosis (biochemical, hormonal, imaging and molecular studies) and management (surgery, pre- and post-surgical medical treatment), considering the current and developing strategies in chemo- and radiotherapy. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  6. Adrenal hormones before and after venography during adrenal venous sampling: a self-controlled study.

    PubMed

    Koike, Yuya; Matsui, Seishi; Omura, Masao; Makita, Kohzoh; Obara, Alfonso W D; Moriya, Nobukazu; Nishikawa, Tetsuo

    2017-03-01

    A stress reaction involving increased adrenal hormone release occurs when starting adrenal venous sampling (AVS). The purpose of the present study was to investigate the effect of single shot venography on adrenal hormone production during AVS. This was a prospective self-controlled study. We enrolled 54 consecutive patients (21 men, 33 women; mean age 52 ± 11 years) with primary aldosteronism who underwent AVS from May 2014 to February 2015. Under non-stimulated conditions, blood samples were obtained from a common trunk of the left adrenal vein before and after single shot venography. The initial plasma aldosterone and cortisol concentration (PAC and PCC) were compared with those measured after venography for each patient. PAC and PCC were slightly but significantly decreased between before and after venography (after log transformation 2.12 ± 0.73 vs 2.07 ± 0.72, P = 0.00066, 1.89 ± 0.52 vs 1.83 ± 0.53, P = 0.00031, respectively). During non-stimulated left AVS, adrenal hormone secretion was slightly but significantly decreased after venography, similar to the normal time-related stress reaction. Venography did not increase the adrenal hormone secretion.

  7. Bone sialoprotein keratan sulfate proteoglycan (BSP-KSPG) and FGF-23 are important physiological components of medullary bone.

    PubMed

    Hadley, Jill A; Horvat-Gordon, Maria; Kim, Woo-Kyun; Praul, Craig A; Burns, Dennis; Leach, Roland M

    2016-04-01

    Medullary bone is a specialized bone found in the marrow cavity of laying birds. It provides a significant contribution to the calcium supply for egg shell formation. Medullary bone is distinguished from cortical bone by the presence of large amounts of a keratan sulfate proteoglycan (KSPG). The aims of the present experiment are to confirm the identity of the core protein of KSPG, identify a marker of medullary bone metabolism, and determine whether changes in keratan sulfate (KS) concentration in blood are associated with the egg-laying cycle. Using two different isolation techniques- one specific for bone and another for blood- we have identified bone sialoprotein (BSP) to be the core protein of this KSPG. We also determined that the amount of keratan sulfate (KS) in laying hen blood fluctuates in synchrony with the egg-laying cycle, and thus can serve as a specific marker for medullary bone metabolism. During the course of this investigation, we also found FGF-23 (phosphatonin) to be expressed in medullary bone, in synchrony with the egg-laying cycle. Western blotting was used to demonstrate the presence of this peptide in both laying hen blood and medullary bone extracts. The importance of FGF-23 (phosphatonin) and parathyroid hormone in normalizing the dramatic changes in plasma calcium and phosphorus during the 24h egg-laying cycle is discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Prognostic significance of atypical papillary urothelial hyperplasia.

    PubMed

    Swierczynski, Sharon L; Epstein, Jonathan I

    2002-05-01

    Typical papillary hyperplasia, a recently recognized precursor lesion to low-grade papillary urothelial neoplasms, consists of undulating folds of cytologically benign urothelium. Well-developed, branching fibrovascular cores of a papillary neoplasm are not evident. We have noted lesions with the architectural pattern of papillary hyperplasia; however, the overlying urothelium demonstrated varying degrees of cytologic atypia. We identified 15 cases of atypical papillary hyperplasia (13 males, 2 females, age 55 to 92) with overlying urothelium showing cytologic atypia. Of these cases, 8 (53%) were received in consultation. Of the 15 cases, 8 exhibited overlying flat carcinoma in situ (CIS), 4 had overlying dysplasia, and 3 were transitional between papillary hyperplasia with atypia and the earliest lesions of papillary neoplasia. Of these cases, 5 patients had multiple specimens with atypical papillary hyperplasia (range, 2 to 8) over time. Concurrent to the diagnosis of atypical papillary hyperplasia, there were 25 different urothelial lesions: CIS (n = 11), papilloma (n = 1), papillary neoplasm of low malignant potential with CIS (n = 1), high-grade papillary urothelial carcinoma (n = 10; 3 with CIS), small-cell carcinoma (n = 1), and infiltrating urothelial carcinoma (n = 1). Of 11 patients with known prior history, 2 had 12 prior urothelial neoplasms (9 low-grade papillary neoplasms, 2 papillary urothelial neoplasms of low malignant potential, and 1 high-grade papillary cancer). Of 10 patients with atypical papillary hyperplasia and a minimum of 1 year of follow-up, 9 had 19 recurrences: CIS (n = 4), papilloma (n = 1), papillary neoplasm of low malignant potential (n = 1), infiltrating urothelial carcinoma (n = 3; 1 with CIS), and high-grade papillary urothelial carcinoma (n = 10; 5 with invasion and 2 with CIS). Whether the papillary hyperplasia had overlying CIS or dysplasia did not affect the correlation with urothelial neoplasms. Immunohistochemical analysis

  9. Autonomic control of adrenal function.

    PubMed Central

    Edwards, A V; Jones, C T

    1993-01-01

    Recent studies of adrenal function in conscious calves are reviewed. These have involved collecting the whole of the adrenal effluent blood from the right adrenal gland at intervals and, where necessary, prior functional hypophysectomy by destruction of the pituitary stalk under general halothane anaesthesia 3 d previously. The adrenal medulla was found to release numerous neuropeptides, in addition to catecholamines, in response to stimulation of the peripheral end of the right splanchnic nerve, which was carried out below behavioural threshold. Many of these responses were enhanced by stimulating intermittently at a relatively high frequency. Intra-aortic infusions of a relatively low dose of acetylcholine (4.5 nmol min-1 kg-1) elicited similar responses. In the adrenal cortex, agonists which either potentiated the steroidogenic response to ACTH or exerted a direct steroidogenic action included VIP, CGRP, CRF and ACh acting via muscarinic receptors. Stimulation of the peripheral end of the right splanchnic nerve strongly potentiated the steroidogenic response to ACTH and there is compelling evidence that the innervation normally plays an important part in cortisol secretion. PMID:8300417

  10. A novel pipeline for adrenal tumour segmentation.

    PubMed

    Koyuncu, Hasan; Ceylan, Rahime; Erdogan, Hasan; Sivri, Mesut

    2018-06-01

    Adrenal tumours occur on adrenal glands surrounded by organs and osteoid. These tumours can be categorized as either functional, non-functional, malign, or benign. Depending on their appearance in the abdomen, adrenal tumours can arise from one adrenal gland (unilateral) or from both adrenal glands (bilateral) and can connect with other organs, including the liver, spleen, pancreas, etc. This connection phenomenon constitutes the most important handicap against adrenal tumour segmentation. Size change, variety of shape, diverse location, and low contrast (similar grey values between the various tissues) are other disadvantages compounding segmentation difficulty. Few studies have considered adrenal tumour segmentation, and no significant improvement has been achieved for unilateral, bilateral, adherent, or noncohesive tumour segmentation. There is also no recognised segmentation pipeline or method for adrenal tumours including different shape, size, or location information. This study proposes an adrenal tumour segmentation (ATUS) pipeline designed to eliminate the above disadvantages for adrenal tumour segmentation. ATUS incorporates a number of image methods, including contrast limited adaptive histogram equalization, split and merge based on quadtree decomposition, mean shift segmentation, large grey level eliminator, and region growing. Performance assessment of ATUS was realised on 32 arterial and portal phase computed tomography images using six metrics: dice, jaccard, sensitivity, specificity, accuracy, and structural similarity index. ATUS achieved remarkable segmentation performance, and was not affected by the discussed handicaps, on particularly adherence to other organs, with success rates of 83.06%, 71.44%, 86.44%, 99.66%, 99.43%, and 98.51% for the metrics, respectively, for images including sufficient contrast uptake. The proposed ATUS system realises detailed adrenal tumour segmentation, and avoids known disadvantages preventing accurate

  11. Pharmacotherapy for benign prostatic hyperplasia.

    PubMed Central

    Narayan, P; Indudhara, R

    1994-01-01

    Benign prostatic hyperplasia is a benign neoplasm of the prostate seen in men of advancing age. Microscopic evidence of the disorder is seen in about 70% of men by 70 years of age, whereas symptoms requiring some form of surgical intervention occur in 30% of men during their lifetime. Although the exact cause of benign prostatic hyperplasia is not clear, it is well recognized that high levels of intraprostatic androgens are required for the maintenance of prostatic growth. In recent years, extensive surveys of patients undergoing transurethral resection of the prostate reveal an 18% incidence of morbidity that has essentially not changed in the past 30 years. This procedure is also the second highest reimbursed surgical therapy under Medicare. These findings have resulted in an intensive search for alternative therapies for prostatic hyperplasia. An alternative that has now been well defined is the use of alpha-adrenergic blockers to relax the prostatic urethra. This is based on findings that a major component of benign prostatic hyperplasia symptoms is spasm of the prostatic urethra and bladder neck, which is mediated by the alpha-adrenergic nerves. A second approach is to block androgens involved in maintaining prostate growth. Several such drugs are now available for clinical use, and we discuss their side effects and use. We also include the newer recommendations on evaluating benign prostatic hyperplasia that are cost-effective yet comprehensive. Images PMID:7528957

  12. Monogenic Disorders of Adrenal Steroidogenesis.

    PubMed

    Baranowski, Elizabeth S; Arlt, Wiebke; Idkowiak, Jan

    2018-06-06

    Disorders of adrenal steroidogenesis comprise autosomal recessive conditions affecting steroidogenic enzymes of the adrenal cortex. Those are located within the 3 major branches of the steroidogenic machinery involved in the production of mineralocorticoids, glucocorticoids, and androgens. This mini review describes the principles of adrenal steroidogenesis, including the newly appreciated 11-oxygenated androgen pathway. This is followed by a description of pathophysiology, biochemistry, and clinical implications of steroidogenic disorders, including mutations affecting cholesterol import and steroid synthesis, the latter comprising both mutations affecting steroidogenic enzymes and co-factors required for efficient catalysis. A good understanding of adrenal steroidogenic pathways and their regulation is crucial as the basis for sound management of these disorders, which in the majority present in early childhood. © 2018 The Author(s) Published by S. Karger AG, Basel.

  13. Regulation of IL-17 Family Members by Adrenal Hormones During Experimental Sepsis in Mice

    PubMed Central

    Bosmann, Markus; Meta, Fabien; Ruemmler, Robert; Haggadone, Mikel D.; Sarma, J. Vidya; Zetoune, Firas S.; Ward, Peter A.

    2014-01-01

    Severe sepsis is a life-threatening disease that causes major morbidity and mortality. Catecholamines and glucocorticoids often have been used for the treatment of sepsis. Several recent studies have suggested a potential role of IL-17 during the development and progression of sepsis in small animal models. In this study, the cross-talk of catecholamines and glucocorticoids with members of the IL-17 family was investigated during sepsis in C57BL/6 mice. The concentrations in plasma of IL-17A, IL-17F, and the IL-17AF heterodimer all were increased greatly in mice after endotoxemia or cecal ligation and puncture as compared with sham mice. Surprisingly, when compared with IL-17A (487 pg/mL), the concentrations of IL-17F (2361 pg/mL) and the heterodimer, IL-17AF (5116 pg/mL), were much higher 12 hours after endotoxemia. After surgical removal of the adrenal glands, mice had much higher mortality after endotoxemia or cecal ligation and puncture. The absence of endogenous adrenal gland hormones (cortical and medullary) was associated with 3- to 10-fold higher concentrations of IL-17A, IL-17F, IL-17AF, and IL-23. The addition of adrenaline, noradrenaline, hydrocortisone, or dexamethasone to lipopolysaccharide-activated peritoneal macrophages dose-dependently suppressed the expression and release of IL-17s. The production of IL-17s required activation of c-Jun-N-terminal kinase, which was antagonized by both catecholamines and glucocorticoids. These data provide novel insights into the molecular mechanisms of immune modulation by catecholamines and glucocorticoids during acute inflammation. PMID:23499051

  14. Regulation of IL-17 family members by adrenal hormones during experimental sepsis in mice.

    PubMed

    Bosmann, Markus; Meta, Fabien; Ruemmler, Robert; Haggadone, Mikel D; Sarma, J Vidya; Zetoune, Firas S; Ward, Peter A

    2013-04-01

    Severe sepsis is a life-threatening disease that causes major morbidity and mortality. Catecholamines and glucocorticoids often have been used for the treatment of sepsis. Several recent studies have suggested a potential role of IL-17 during the development and progression of sepsis in small animal models. In this study, the cross-talk of catecholamines and glucocorticoids with members of the IL-17 family was investigated during sepsis in C57BL/6 mice. The concentrations in plasma of IL-17A, IL-17F, and the IL-17AF heterodimer all were increased greatly in mice after endotoxemia or cecal ligation and puncture as compared with sham mice. Surprisingly, when compared with IL-17A (487 pg/mL), the concentrations of IL-17F (2361 pg/mL) and the heterodimer, IL-17AF (5116 pg/mL), were much higher 12 hours after endotoxemia. After surgical removal of the adrenal glands, mice had much higher mortality after endotoxemia or cecal ligation and puncture. The absence of endogenous adrenal gland hormones (cortical and medullary) was associated with 3- to 10-fold higher concentrations of IL-17A, IL-17F, IL-17AF, and IL-23. The addition of adrenaline, noradrenaline, hydrocortisone, or dexamethasone to lipopolysaccharide-activated peritoneal macrophages dose-dependently suppressed the expression and release of IL-17s. The production of IL-17s required activation of c-Jun-N-terminal kinase, which was antagonized by both catecholamines and glucocorticoids. These data provide novel insights into the molecular mechanisms of immune modulation by catecholamines and glucocorticoids during acute inflammation. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. Impact of renal medullary three-dimensional architecture on oxygen transport.

    PubMed

    Fry, Brendan C; Edwards, Aurélie; Sgouralis, Ioannis; Layton, Anita T

    2014-08-01

    We have developed a highly detailed mathematical model of solute transport in the renal medulla of the rat kidney to study the impact of the structured organization of nephrons and vessels revealed in anatomic studies. The model represents the arrangement of tubules around a vascular bundle in the outer medulla and around a collecting duct cluster in the upper inner medulla. Model simulations yield marked gradients in intrabundle and interbundle interstitial fluid oxygen tension (PO2), NaCl concentration, and osmolality in the outer medulla, owing to the vigorous active reabsorption of NaCl by the thick ascending limbs. In the inner medulla, where the thin ascending limbs do not mediate significant active NaCl transport, interstitial fluid composition becomes much more homogeneous with respect to NaCl, urea, and osmolality. Nonetheless, a substantial PO2 gradient remains, owing to the relatively high oxygen demand of the inner medullary collecting ducts. Perhaps more importantly, the model predicts that in the absence of the three-dimensional medullary architecture, oxygen delivery to the inner medulla would drastically decrease, with the terminal inner medulla nearly completely deprived of oxygen. Thus model results suggest that the functional role of the three-dimensional medullary architecture may be to preserve oxygen delivery to the papilla. Additionally, a simulation that represents low medullary blood flow suggests that the separation of thick limbs from the vascular bundles substantially increases the risk of the segments to hypoxic injury. When nephrons and vessels are more homogeneously distributed, luminal PO2 in the thick ascending limb of superficial nephrons increases by 66% in the inner stripe. Furthermore, simulations predict that owing to the Bohr effect, the presumed greater acidity of blood in the interbundle regions, where thick ascending limbs are located, relative to that in the vascular bundles, facilitates the delivery of O2 to support the

  16. A new CYP21A1P/CYP21A2 chimeric gene identified in an Italian woman suffering from classical congenital adrenal hyperplasia form

    PubMed Central

    Concolino, Paola; Mello, Enrica; Minucci, Angelo; Giardina, Emiliano; Zuppi, Cecilia; Toscano, Vincenzo; Capoluongo, Ettore

    2009-01-01

    Background More than 90% of Congenital Adrenal Hyperplasia (CAH) cases are associated with mutations in the 21-hydroxylase gene (CYP21A2) in the HLA class III area on the short arm of chromosome 6p21.3. In this region, a 30 kb deletion produces a non functional chimeric gene with its 5' and 3' ends corresponding to CYP21A1P pseudogene and CYP21A2, respectively. To date, five different CYP21A1P/CYP21A2 chimeric genes have been found and characterized in recent studies. In this paper, we describe a new CYP21A1P/CYP21A2 chimera (CH-6) found in an Italian CAH patient. Methods Southern blot analysis and CYP21A2 sequencing were performed on the patient. In addition, in order to isolate the new CH-6 chimeric gene, two different strategies were used. Results The CYP21A2 sequencing analysis showed that the patient was homozygote for the g.655C/A>G mutation and heterozygote for the p.P30L missense mutation. In addition, the promoter sequence revealed the presence, in heterozygosis, of 13 SNPs generally produced by microconversion events between gene and pseudogene. Southern blot analysis showed that the woman was heterozygote for the classic 30-kb deletion producing a new CYP21A1P/CYP21A2 chimeric gene (CH-6). The hybrid junction site was located between the end of intron 2 pseudogene, after the g.656C/A>G mutation, and the beginning of exon 3, before the 8 bp deletion. Consequently, CH-6 carries three mutations: the weak pseudogene promoter region, the p.P30L and the g.655C/A>G splice mutation. Conclusion We describe a new CYP21A1P/CYP21A2 chimera (CH-6), associated with the HLA-B15, DR13 haplotype, in a young Italian CAH patient. PMID:19624807

  17. Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis in vitro and adrenal gene expression

    PubMed Central

    Gehrand, Ashley; Bruder, Eric D.; Hoffman, Matthew J.; Engeland, William C.; Moreno, Carol

    2014-01-01

    The classic renin-angiotensin system is partly responsible for controlling aldosterone secretion from the adrenal cortex via the peptide angiotensin II (ANG II). In addition, there is a local adrenocortical renin-angiotensin system that may be involved in the control of aldosterone synthesis in the zona glomerulosa (ZG). To characterize the long-term control of adrenal steroidogenesis, we utilized adrenal glands from renin knockout (KO) rats and compared steroidogenesis in vitro and steroidogenic enzyme expression to wild-type (WT) controls (Dahl S rat). Adrenal capsules (ZG; aldosterone production) and subcapsules [zona reticularis/fasciculata (ZFR); corticosterone production] were separately dispersed and studied in vitro. Plasma renin activity and ANG II concentrations were extremely low in the KO rats. Basal and cAMP-stimulated aldosterone production was significantly reduced in renin KO ZG cells, whereas corticosterone production was not different between WT and KO ZFR cells. As expected, adrenal renin mRNA expression was lower in the renin KO compared with the WT rat. Real-time PCR and immunohistochemical analysis showed a significant decrease in P450aldo (Cyp11b2) mRNA and protein expression in the ZG from the renin KO rat. The reduction in aldosterone synthesis in the ZG of the renin KO adrenal seems to be accounted for by a specific decrease in P450aldo and may be due to the absence of chronic stimulation of the ZG by circulating ANG II or to a reduction in locally released ANG II within the adrenal gland. PMID:25394830

  18. Steroid profiling for congenital adrenal hyperplasia by tandem mass spectrometry as a second-tier test reduces follow-up burdens in a tertiary care hospital: a retrospective and prospective evaluation.

    PubMed

    Seo, Ja Young; Park, Hyung-Doo; Kim, Jong Won; Oh, Hyeon Ju; Yang, Jeong Soo; Chang, Yun Sil; Park, Won Soon; Lee, Soo-Youn

    2014-01-01

    Newborn screening for congenital adrenal hyperplasia (CAH) based on measuring 17-hydroxyprogesterone (17-OHP) by immunoassay generates a number of false-positive results, especially in preterm neonates. We applied steroid profiling by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a second-tier test in newborns with positive CAH screening and evaluated its clinical utility in a tertiary care hospital setting. By performing a 4-year retrospective data review, we were able to test 121 dried blood spots from newborns with positive CAH screening for 17-OHP, androstenedione and cortisol levels by LC-MS/MS. We prospectively evaluated the clinical utility of steroid profiling after the implementation of steroid profiling as a second-tier test in our routine clinical practice. During the 2-year prospective study period, 104 cases with positive initial screening by FIA were tested by LC-MS/MS. Clinical and laboratory follow-up were performed for at least 6 months. The preterm neonates accounted for 50.7% (76/150) and 70.4% (88/125) of screening-positive cases in retrospective and prospective cohorts, respectively. By applying steroid profiling as a second-tier test for positive CAH screening, we eliminated all false-positive results and decreased the median follow-up time from 75 to 8 days. Our data showed that steroid profiling reduced the burden of follow-up exams by improving the positive predictive value of the CAH screening program. The use of steroid profiling as a second-tier test for positive CAH screening will improve clinical practice particularly in a tertiary care hospital setting where positive CAH screening from preterm neonates is frequently encountered.

  19. Equine fetal adrenal, gonadal and placental steroidogenesis.

    PubMed

    Legacki, Erin L; Ball, Barry A; Corbin, C Jo; Loux, Shavahn C; Scoggin, Kirsten E; Stanley, Scott D; Conley, Alan J

    2017-10-01

    Equine fetuses have substantial circulating pregnenolone concentrations and thus have been postulated to provide significant substrate for placental 5α-reduced pregnane production, but the fetal site of pregnenolone synthesis remains unclear. The current studies investigated steroid concentrations in blood, adrenal glands, gonads and placenta from fetuses (4, 6, 9 and 10 months of gestational age (GA)), as well as tissue steroidogenic enzyme transcript levels. Pregnenolone and dehydroepiandrosterone (DHEA) were the most abundant steroids in fetal blood, pregnenolone was consistently higher but decreased progressively with GA. Tissue steroid concentrations generally paralleled those in serum with time. Adrenal and gonadal tissue pregnenolone concentrations were similar and 100-fold higher than those in allantochorion. DHEA was far higher in gonads than adrenals and progesterone was higher in adrenals than gonads. Androstenedione decreased with GA in adrenals but not in gonads. Transcript analysis generally supported these data. CYP17A1 was higher in fetal gonads than adrenals or allantochorion, and HSD3B1 was higher in fetal adrenals and allantochorion than gonads. CYP11A1 transcript was also significantly higher in adrenals and gonads than allantochorion and CYP19 and SRD5A1 transcripts were higher in allantochorion than either fetal adrenals or gonads. Given these data, and their much greater size, the fetal gonads are the source of DHEA and likely contribute more than fetal adrenal glands to circulating fetal pregnenolone concentrations. Low CYP11A1 but high HSD3B1 and SRD5A1 transcript abundance in allantochorion, and low tissue pregnenolone, suggests that endogenous placental pregnenolone synthesis is low and likely contributes little to equine placental 5α-reduced pregnane secretion. © 2017 Society for Reproduction and Fertility.

  20. Clinical associations of hepatic stellate cell (HSC) hyperplasia.

    PubMed

    Mounajjed, Taofic; Graham, Rondell P; Sanderson, Schuyler O; Smyrk, Thomas C

    2014-07-01

    Hepatic stellate cell (HSC) hyperplasia has been principally attributed to hypervitaminosis A. There are sporadic reports of HSC hyperplasia in other conditions such as chronic biliary disease and hepatitis C, but clinical associations of this entity have not been studied in detail. We aimed to investigate the clinical associations of HSC hyperplasia aside from hypervitaminosis A. We identified 34 patients whose liver histology showed HSC hyperplasia. We reviewed the liver samples; additional histologic findings in addition to HSC hyperplasia were consolidated into a histologic diagnosis. We collected clinical, laboratory, and radiologic data; the histologic diagnosis was combined with this data to reach an "overall diagnosis." Four patients had hypervitaminosis A (all native livers). In native livers (n = 24), HSC hyperplasia also occurred in association with drug-induced hepatitis [n = 6, niacin was the most common inducing agent (n = 3)], reactive hepatitis (n = 4), chronic hepatitis C (n = 4), autoimmune hepatitis (n = 3), steatohepatitis (n = 1), chronic biliary disease (n = 1), and portal venopathy (n = 1). In liver allografts (n = 10), HSC hyperplasia was seen in protocol biopsies without other significant abnormalities (n = 5), chronic biliary disease (n = 4), and acute cellular rejection (n = 1). All patients used medications (total of 99) and 82 % were on multiple medications. HSC hyperplasia is an uncommon and relatively nonspecific finding that most commonly occurs in multimedicated patients, often in the absence of hypervitaminosis A. Associated conditions include drug toxicity (such as niacin), post-liver transplant setting, reactive hepatitis (due to systemic illness or inflammatory disorders of the gastrointestinal tract), and chronic liver disease.

  1. Treatment of medullary thyroid carcinoma with apatinib

    PubMed Central

    Cai, Sina; Deng, Huan; Chen, Yinkui; Wu, Xing; Guan, Xiaoqian

    2017-01-01

    Abstract Rationale: Medullary thyroid carcinoma (MTC) is a rare type thyroid carcinoma originating from the thyroid parafollicular cells (C cells). Chemotherapy has a limited efficacy for treating persistent or recurrent MTC. Patient concerns: A 46-year-old woman who underwent thyroidectomy for MTC in December 2007. She began experience recurring diarrhea in January 2015 and started to cough and feel shortness of breath in March 2016. Diagnoses: A chestcomputed tomography (CT) scan showed metastases in the bilateral lungs, pulmonary hilum, and mediastinal lymph nodes. Percutaneous biopsy of the pulmonary occupying lesions performed on March 21, 2016 indicated medullary carcinoma metastases at the right pulmonary hilum. Interventions: This patient was treated with oral apatinib (500 mg daily). Outcomes: The patient's symptoms of diarrhea, coughing, and shortness of breath disappeared. CT reexaminations for efficacy assessment at 1, 2, and 3 months after the treatment indicated partial remission. Systemic migrating bone and joint pains occurred during the treatment, which were considered to be adverse events of apatinib. Lessons: Treatment of MTC with apatinib has been shown to be effective in our case. Tyrosine kinase inhibitors (TKIs) that suppress rearranged during transfection (RET) and vascular endothelial growth factor receptor (VEGFR) should be considered as a effective therapeutic approaches. PMID:29390263

  2. Variant adrenal venous anatomy in 546 laparoscopic adrenalectomies.

    PubMed

    Scholten, Anouk; Cisco, Robin M; Vriens, Menno R; Shen, Wen T; Duh, Quan-Yang

    2013-04-01

    Knowing the types and frequency of adrenal vein variants would help surgeons identify and control the adrenal vein during laparoscopic adrenalectomy. To establish the surgical anatomy of the main vein and its variants for laparoscopic adrenalectomy and to analyze the relationship between variant adrenal venous anatomy and tumor size, pathologic diagnosis, and operative outcomes. In a retrospective review of patients at a tertiary referral hospital, 506 patients underwent 546 consecutive laparoscopic adrenalectomies between April 22, 1993, and October 21, 2011. Patients with variant adrenal venous anatomy were compared with patients with normal adrenal venous anatomy regarding preoperative variables (patient and tumor characteristics [size and location] and clinical diagnosis), intraoperative variables (details on the main adrenal venous drainage, any variant venous anatomy, duration of operation, rate of conversion to hand-assisted or open procedure, and estimated blood loss), and postoperative variables (transfusion requirement, reoperation for bleeding, duration of hospital stay, and histologic diagnosis). Laparoscopic adrenalectomy. Prevalence of variant adrenal venous anatomy and its relationship to tumor characteristics, pathologic diagnosis, and operative outcomes. Variant venous anatomy was encountered in 70 of 546 adrenalectomies (13%). Variants included no main adrenal vein identifiable (n = 18), 1 main adrenal vein with additional small veins (n = 11), 2 adrenal veins (n = 20), more than 2 adrenal veins (n = 14), and variants of the adrenal vein drainage to the inferior vena cava and hepatic vein or of the inferior phrenic vein (n = 7). Variants occurred more often on the right side than on the left side (42 of 250 glands [17%] vs. 28 of 296 glands [9%], respectively; P = .02). Patients with variant anatomy compared with those with normal anatomy had larger tumors (mean, 5.1 vs 3.3 cm, respectively; P < .001), more pheochromocytomas (24 of 70 [35%] vs

  3. Double NF1 Inactivation Affects Adrenocortical Function in NF1Prx1 Mice and a Human Patient

    PubMed Central

    Kobus, Karolina; Hartl, Daniela; Ott, Claus Eric; Osswald, Monika; Huebner, Angela; von der Hagen, Maja; Emmerich, Denise; Kühnisch, Jirko; Morreau, Hans; Hes, Frederik J.; Mautner, Victor F.; Harder, Anja; Tinschert, Sigrid; Mundlos, Stefan; Kolanczyk, Mateusz

    2015-01-01

    Background Neurofibromatosis type I (NF1, MIM#162200) is a relatively frequent genetic condition, which predisposes to tumor formation. Apart from tumors, individuals with NF1 often exhibit endocrine abnormalities such as precocious puberty (2,5–5% of NF1 patients) and some cases of hypertension (16% of NF1 patients). Several cases of adrenal cortex adenomas have been described in NF1 individuals supporting the notion that neurofibromin might play a role in adrenal cortex homeostasis. However, no experimental data were available to prove this hypothesis. Materials and Methods We analysed Nf1Prx1 mice and one case of adrenal cortical hyperplasia in a NF1patient. Results In Nf1Prx1 mice Nf1 is inactivated in the developing limbs, head mesenchyme as well as in the adrenal gland cortex, but not the adrenal medulla or brain. We show that adrenal gland size is increased in NF1Prx1 mice. Nf1Prx1 female mice showed corticosterone and aldosterone overproduction. Molecular analysis of Nf1 deficient adrenals revealed deregulation of multiple proteins, including steroidogenic acute regulatory protein (StAR), a vital mitochondrial factor promoting transfer of cholesterol into steroid making mitochondria. This was associated with a marked upregulation of MAPK pathway and a female specific increase of cAMP concentration in murine adrenal lysates. Complementarily, we characterized a patient with neurofibromatosis type I with macronodular adrenal hyperplasia with ACTH-independent cortisol overproduction. Comparison of normal control tissue- and adrenal hyperplasia- derived genomic DNA revealed loss of heterozygosity (LOH) of the wild type NF1 allele, showing that biallelic NF1 gene inactivation occurred in the hyperplastic adrenal gland. Conclusions Our data suggest that biallelic loss of Nf1 induces autonomous adrenal hyper-activity. We conclude that Nf1 is involved in the regulation of adrenal cortex function in mice and humans. PMID:25775093

  4. Experimental selective elevation of renal medullary blood flow in hypertensive rats: evidence against short-term hypotensive effect.

    PubMed

    Bądzyńska, B; Sadowski, J

    2012-08-01

    Renal medullary blood flow (MBF) can be selectively increased by intrarenal or systemic infusion of bradykinin (Bk) in anaesthetized normotensive rats. We reproduced this effect in a number of rat models of arterial hypertension and examined whether increased perfusion of the renal medulla can cause a short-term decrease in blood pressure (BP) that is not mediated by increased renal excretion and depletion of body fluids. In uninephrectomized Sprague-Dawley rats, BP was elevated to approx. 145 mmHg by acute i.v. infusion of noradrenaline (NA) or angiotensin II (Ang II) (groups 1, 2), 2-week exposure to high-salt diet (3), high-salt diet + chronic low-dose infusion of Ang II using osmotic minipumps (4) or chronic high-dose Ang II infusion on normal diet (5). Uninephrectomized spontaneous hypertensive rats (SHR) were also examined (6,7). To selectively increase medullary perfusion, in anaesthetized rats, bradykinin was infused during 30-75 min into the renal medullary interstitium or intravenously. Bradykinin increased outer- and inner-medullary blood flow (laser-Doppler fluxes) by 10-20% in groups (1, 2), by 30-50% in groups (3, 4, 5) and approx. 20% in SHR (6, 7). The concurrent increase in total renal blood flow (Transonic probe) was < 3%. A minor (<3%) decrease in BP was seen only in rats acutely rendered hypertensive by NA or Ang II infusions; however, the decreases in BP and increases in medullary perfusion were not correlated. Thus, there was no evidence that in hypertensive rats, substantial selective increases in medullary perfusion can cause a short-term decrease in BP. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

  5. Papillary endothelial hyperplasia in angiokeratoma.

    PubMed

    Mehta, Anurag; Sayal, Satish Kumar; Raman, Deep Kumar; Sood, Aradhana

    2003-01-01

    Papillary endothelial hyperplasia (Masson's tumour) is a reactive proliferation of endothelium producing papillary structures with fibrovascular cores. Dilatation, stasis and accompanying inflammation have been incriminated as the inciting events, evident by the presence of this lesion in haemorrhoids, urethral caruncles and laryngeal polyps. We present here a case of papillary endothelial hyperplasia in angiokeratoma hitherto undescribed despite sharing common etiopathogenetic features of dilatation and stasis with other aforementioned lesions.

  6. Flat epithelial atypia and atypical ductal hyperplasia: carcinoma underestimation rate.

    PubMed

    Ingegnoli, Anna; d'Aloia, Cecilia; Frattaruolo, Antonia; Pallavera, Lara; Martella, Eugenia; Crisi, Girolamo; Zompatori, Maurizio

    2010-01-01

    This study was carried out to determine the underestimation rate of carcinoma upon surgical biopsy after a diagnosis of flat epithelial atypia and atypical ductal hyperplasia and 11-gauge vacuum-assisted breast biopsy. A retrospective review was conducted of 476 vacuum-assisted breast biopsy performed from May 2005 to January 2007 and a total of 70 cases of atypia were identified. Fifty cases (71%) were categorized as pure atypical ductal hyperplasia, 18 (26%) as pure flat epithelial atypia and two (3%) as concomitant flat epithelial atypia and atypical ductal hyperplasia. Each group were compared with the subsequent open surgical specimens. Surgical biopsy was performed in 44 patients with atypical ductal hyperplasia, 15 patients with flat epithelial atypia, and two patients with flat epithelial atypia and atypical ductal hyperplasia. Five cases of atypical ductal hyperplasia were upgraded to ductal carcinoma in situ, three cases of flat epithelial atypia yielded one ductal carcinoma in situ and two cases of invasive ductal carcinoma, and one case of flat epithelial atypia/atypical ductal hyperplasia had invasive ductal carcinoma. The overall rate of malignancy was 16% for atypical ductal hyperplasia (including flat epithelial atypia/atypical ductal hyperplasia patients) and 20% for flat epithelial atypia. The presence of flat epithelial atypia and atypical ductal hyperplasia at biopsy requires careful consideration, and surgical excision should be suggested.

  7. Proteus syndrome: association with gingival hyperplasia.

    PubMed

    Arendorf, T M; Hanslo, B

    1995-09-01

    A 9-year old Black boy with gigantism of the hands and feet, and recurrent gingival hyperplasia, diagnosed as Proteus syndrome is presented. The oral manifestations of this syndrome are described. To the best of our knowledge, this is the first reported case of gingival hyperplasia associated with Proteus syndrome.

  8. [Hemorrhagic adrenal pseudocyst: case report].

    PubMed

    Basile, G; Buffone, A; Cicciarella, G; di Mari, P; Cirino, E

    2004-01-01

    Adrenal cysts are usually asymptomatic; they are usually identified occasionally during ultrasound or C.T. scans (incidentaloma). Among adrenal cysts the most common types are epithelial cysts and pseudocysts. Intracystic haemorrhage is one of the possible complications of adrenal pseudocysts. We report a case of a young woman with right superior abdominal pain, fever and acute anemia. A C.T. scan showed a 10 cm. mass between the liver and the right kidney. To be sure of the nature of this mass also M.R., urography and C.T.-guided biopsy were carried out. This latter only let us make the final diagnosis of hemorrhagic adrenal pseudocyst. Thereafter, a laparotomic right adrenalectomy was performed, with full recovery of the patient. Adrenal cysts may cause differential diagnostic problems with masses of contiguous organs like kidney, liver and gallbladder. For this reason, ultrasound and C.T. scans may not be sufficient and must be completed by M.R., urography and/or C.T.-guided biopsy. Intracystic hamorrhage, spontaneous or post-traumatic, may cause to the patient acute anemia which, as soon as the diagnosis is confirmed, indicates surgery. The operation usually is a laparotomic adrenalectomy, since the laparoscopic approach is not sufficient to control large masses with active bleeding inside.

  9. [Progress in diagnosis and treatment of adrenal metastases tumor].

    PubMed

    Wu, Chu-jun; Qiu, Min; Ma, Lu-lin

    2015-08-18

    The adrenal gland is a common site of metastases, only second to pulmonary, liver and bone. The prevalence of adrenal metastases in patients with a history of cancer is between 10%-25%.The most common sites of origin are cancers of the lung, kidney, breast, gastrointestinal tract, and skin (melanoma).The mainstays of adrenal metastases diagnosis are computerized tomogramphy (CT), magnetic resonance imaging (MRI), and positron emission tomogramphy (PET). All patients should undergo complete hormonal evaluation to rule out functional adrenal tumors. Adrenal biopsy should be reserved for cases in which the results of non-invasive techniques are equivocal. In patients with isolated adrenal metastases, adrenalectomy is recommended, because of improved overall survival. For the patient with unresectable adrenal metastases tumor, radiotherapy and ablative therapy are feasible and useful methods for controlling adrenal metastases and offer patients opportunities for improved survival.

  10. Adrenal clocks and the role of adrenal hormones in the regulation of circadian physiology.

    PubMed

    Leliavski, Alexei; Dumbell, Rebecca; Ott, Volker; Oster, Henrik

    2015-02-01

    The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) and subordinate clocks that disseminate time information to various central and peripheral tissues. While the function of the SCN in circadian rhythm regulation has been extensively studied, we still have limited understanding of how peripheral tissue clock function contributes to the regulation of physiological processes. The adrenal gland plays a special role in this context as adrenal hormones show strong circadian secretion rhythms affecting downstream physiological processes. At the same time, they have been shown to affect clock gene expression in various other tissues, thus mediating systemic entrainment to external zeitgebers and promoting internal circadian alignment. In this review, we discuss the function of circadian clocks in the adrenal gland, how they are reset by the SCN and may further relay time-of-day information to other tissues. Focusing on glucocorticoids, we conclude by outlining the impact of adrenal rhythm disruption on neuropsychiatric, metabolic, immune, and malignant disorders. © 2014 The Author(s).

  11. Image-Guided Ablation of Adrenal Lesions

    PubMed Central

    Yamakado, Koichiro

    2014-01-01

    Although laparoscopic adrenalectomy has remained the standard of care for the treatment for adrenal tumors, percutaneous image-guided ablation therapy, such as chemical ablation, radiofrequency ablation, cryoablation, and microwave ablation, has been shown to be clinically useful in many nonsurgical candidates. Ablation therapy has been used to treat both functioning adenomas and malignant tumors, including primary adrenal carcinoma and metastasis. For patients with functioning adenomas, biochemical and symptomatic improvement is achieved in 96 to 100% after ablation; for patients with malignant adrenal neoplasms, however, the survival benefit from ablation therapy remains unclear, though good initial results have been reported. This article outlines the current role of ablation therapy for adrenal lesions, as well as identifying some of the technical considerations for this procedure. PMID:25049444

  12. Diagnosis and classification of Addison's disease (autoimmune adrenalitis).

    PubMed

    Brandão Neto, Rodrigo Antonio; de Carvalho, Jozélio Freire

    2014-01-01

    Autoimmune adrenalitis, or autoimmune Addison disease (AAD), is the most prevalent cause of primary adrenal insufficiency in the developed world. AAD is rare and can easily be misdiagnosed as other conditions. The diagnosis depends on demonstrating inappropriately low cortisol production and the presence of high titers of adrenal cortex autoantibodies (ACAs), along with excluding other causes of adrenal failure using other tests as necessary. The treatment corticosteroid replacement, and the prognosis following the treatment is the same as the normal population. Spontaneous recovery of adrenal function has been described but is rare. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Genetics Home Reference: X-linked adrenal hypoplasia congenita

    MedlinePlus

    ... Home Health Conditions X-linked adrenal hypoplasia congenita X-linked adrenal hypoplasia congenita Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked adrenal hypoplasia congenita is a disorder that ...

  14. Giant fibroadenomatoid hyperplasia of the breast: a case report.

    PubMed

    Zhang, Hao; Wang, Xin-Lu; Ren, Wei-Dong; Shi, Tie-Mei

    2014-01-01

    Fibroadenomatoid hyperplasia of the breast (FAHB) is a rare benign breast lesion and its clinical features are similar to fibroadenoma and fibrocystic changes. FAHB has been previously termed sclerosing lobular hyperplasia, fibroadenomatosis, fibroadenomatoid change, or fibroadenomatoid mastopathy. Typically, FAHB is derived from stroma and epithelia. The pathologic characteristics of FAHB are microfocal lobulocentric proliferation of stroma accompanied by epithelial and myoepithelial components resembling similar histological changes, as found in fibroadenoma, apocrine hyperplasia, intraductal hyperplasia, and lobular hyperplasia. FAHB could be present as a localized or diffused pattern in pathology. Most cases show no well-circumscribed mass lesions and no apparent capsules; it is usually identified as an incidental finding in other benign lesions or in random sampling in cancerous breast tissues. FAHB is categorized as a benign proliferative breast disease and it has previously been reported; however, the authors believe this study may be the first case with two giant masses reported. Fiber adenoma hyperplasia is a rare cystic hyperplasia of breast pathology and its ultrasonographic manifestations are easily confused with breast cancer. Comparative MRI ultrasound analysis will help make the differential diagnosis. © 2014 S. Karger AG, Basel.

  15. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial.

    PubMed

    Dekkers, Tanja; Prejbisz, Aleksander; Kool, Leo J Schultze; Groenewoud, Hans J M M; Velema, Marieke; Spiering, Wilko; Kołodziejczyk-Kruk, Sylwia; Arntz, Mark; Kądziela, Jacek; Langenhuijsen, Johannes F; Kerstens, Michiel N; van den Meiracker, Anton H; van den Born, Bert-Jan; Sweep, Fred C G J; Hermus, Ad R M M; Januszewicz, Andrzej; Ligthart-Naber, Alike F; Makai, Peter; van der Wilt, Gert-Jan; Lenders, Jacques W M; Deinum, Jaap

    2016-09-01

    The distinction between unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia as causes of primary aldosteronism is usually made by adrenal CT or by adrenal vein sampling (AVS). Whether CT or AVS represents the best test for diagnosis remains unknown. We aimed to compare the outcome of CT-based management with AVS-based management for patients with primary aldosteronism. In a randomised controlled trial, we randomly assigned patients with aldosteronism to undergo either adrenal CT or AVS to determine the presence of aldosterone-producing adenoma (with subsequent treatment consisting of adrenalectomy) or bilateral adrenal hyperplasia (subsequent treatment with mineralocorticoid receptor antagonists). The primary endpoint was the intensity of drug treatment for obtaining target blood pressure after 1 year of follow-up, in the intention-to-diagnose population. Intensity of drug treatment was expressed as daily defined doses. Key secondary endpoints included biochemical outcome in patients who received adrenalectomy, health-related quality of life, cost-effectiveness, and adverse events. This trial is registered with ClinicalTrials.gov, number NCT01096654. We recruited 200 patients between July 6, 2010, and May 30, 2013. Of the 184 patients that completed follow-up, 92 received CT-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist) and 92 received AVS-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist). We found no differences in the intensity of antihypertensive medication required to control blood pressure between patients with CT-based treatment and those with AVS-based treatment (median daily defined doses 3·0 [IQR 1·0-5·0] vs 3·0 [1·1-5·9], p=0·52; median number of drugs 2 [IQR 1-3] vs 2 [1-3], p=0·87). Target blood pressure was reached in 39 (42%) patients and 41 (45%) patients, respectively (p=0·82). On secondary endpoints we found no differences in health-related quality of

  16. Impacts of nitric oxide and superoxide on renal medullary oxygen transport and urine concentration.

    PubMed

    Fry, Brendan C; Edwards, Aurélie; Layton, Anita T

    2015-05-01

    The goal of this study was to investigate the reciprocal interactions among oxygen (O2), nitric oxide (NO), and superoxide (O2 (-)) and their effects on medullary oxygenation and urinary output. To accomplish that goal, we developed a detailed mathematical model of solute transport in the renal medulla of the rat kidney. The model represents the radial organization of the renal tubules and vessels, which centers around the vascular bundles in the outer medulla and around clusters of collecting ducts in the inner medulla. Model simulations yield significant radial gradients in interstitial fluid oxygen tension (Po2) and NO and O2 (-) concentration in the OM and upper IM. In the deep inner medulla, interstitial fluid concentrations become much more homogeneous, as the radial organization of tubules and vessels is not distinguishable. The model further predicts that due to the nonlinear interactions among O2, NO, and O2 (-), the effects of NO and O2 (-) on sodium transport, osmolality, and medullary oxygenation cannot be gleaned by considering each solute's effect in isolation. An additional simulation suggests that a sufficiently large reduction in tubular transport efficiency may be the key contributing factor, more so than oxidative stress alone, to hypertension-induced medullary hypoxia. Moreover, model predictions suggest that urine Po2 could serve as a biomarker for medullary hypoxia and a predictor of the risk for hospital-acquired acute kidney injury. Copyright © 2015 the American Physiological Society.

  17. Impacts of nitric oxide and superoxide on renal medullary oxygen transport and urine concentration

    PubMed Central

    Edwards, Aurélie; Layton, Anita T.

    2015-01-01

    The goal of this study was to investigate the reciprocal interactions among oxygen (O2), nitric oxide (NO), and superoxide (O2−) and their effects on medullary oxygenation and urinary output. To accomplish that goal, we developed a detailed mathematical model of solute transport in the renal medulla of the rat kidney. The model represents the radial organization of the renal tubules and vessels, which centers around the vascular bundles in the outer medulla and around clusters of collecting ducts in the inner medulla. Model simulations yield significant radial gradients in interstitial fluid oxygen tension (Po2) and NO and O2− concentration in the OM and upper IM. In the deep inner medulla, interstitial fluid concentrations become much more homogeneous, as the radial organization of tubules and vessels is not distinguishable. The model further predicts that due to the nonlinear interactions among O2, NO, and O2−, the effects of NO and O2− on sodium transport, osmolality, and medullary oxygenation cannot be gleaned by considering each solute's effect in isolation. An additional simulation suggests that a sufficiently large reduction in tubular transport efficiency may be the key contributing factor, more so than oxidative stress alone, to hypertension-induced medullary hypoxia. Moreover, model predictions suggest that urine Po2 could serve as a biomarker for medullary hypoxia and a predictor of the risk for hospital-acquired acute kidney injury. PMID:25651567

  18. MIBG scintiscan

    MedlinePlus

    Adrenal medullary imaging; Meta-iodobenzylguanidine scintiscan; Pheochromocytoma - MIBG; Neuroblastoma - MIBG; Carcinoid MIBG ... answer. It is also used to help diagnose neuroblastoma and can be used for carcinoid tumors.

  19. Comparison of cortisol exposures and pharmacodynamic adrenal steroid responses to hydrocortisone suspension vs. commercial tablets.

    PubMed

    Sarafoglou, Kyriakie; Gonzalez-Bolanos, Maria T; Zimmerman, Cheryl L; Boonstra, Timothy; Yaw Addo, O; Brundage, Richard

    2015-04-01

    The Endocrine Society Clinical Practice Guidelines on congenital adrenal hyperplasia (CAH) recommend against using hydrocortisone suspension based on a study that examined a commercial suspension. Our objective was to examine the absorption of an extemporaneously prepared hydrocortisone suspension and compare it to tablets. Secondary objectives were to evaluate the 17-hydroxyprogesterone and androstenedione adrenal steroid responses. Using a parallel design, 34 children diagnosed with CAH received either suspension (n = 9; median age 1.8 years) or tablets (n = 25; median age 7.5 years). Patients were given their usual morning hydrocortisone formulation and dose; 12 serial blood samples were obtained and the area under the curve (AUC) was calculated. The mg/m(2) dose-normalized cortisol AUCs were no different in the suspension and tablet groups (P = ·06), nor was there a significant difference in the C(max) or T(max) (P = .08 and P = .41, respectively). Although there were no differences in the 17-hydroxyprogesterone change-from-baseline AUCs, baseline concentrations, or the nadir concentrations when comparing suspension and tablet formulations, the androstenedione values were significantly lower as expected in the younger aged suspension group. Our results offer compelling evidence that an extemporaneously prepared hydrocortisone suspension provides comparable cortisol exposures to commercially available tablet formulations in children and can be used to safely and effectively treat CAH. © 2014, The American College of Clinical Pharmacology.

  20. ADC histogram analysis for adrenal tumor histogram analysis of apparent diffusion coefficient in differentiating adrenal adenoma from pheochromocytoma.

    PubMed

    Umanodan, Tomokazu; Fukukura, Yoshihiko; Kumagae, Yuichi; Shindo, Toshikazu; Nakajo, Masatoyo; Takumi, Koji; Nakajo, Masanori; Hakamada, Hiroto; Umanodan, Aya; Yoshiura, Takashi

    2017-04-01

    To determine the diagnostic performance of apparent diffusion coefficient (ADC) histogram analysis in diffusion-weighted (DW) magnetic resonance imaging (MRI) for differentiating adrenal adenoma from pheochromocytoma. We retrospectively evaluated 52 adrenal tumors (39 adenomas and 13 pheochromocytomas) in 47 patients (21 men, 26 women; mean age, 59.3 years; range, 16-86 years) who underwent DW 3.0T MRI. Histogram parameters of ADC (b-values of 0 and 200 [ADC 200 ], 0 and 400 [ADC 400 ], and 0 and 800 s/mm 2 [ADC 800 ])-mean, variance, coefficient of variation (CV), kurtosis, skewness, and entropy-were compared between adrenal adenomas and pheochromocytomas, using the Mann-Whitney U-test. Receiver operating characteristic (ROC) curves for the histogram parameters were generated to differentiate adrenal adenomas from pheochromocytomas. Sensitivity and specificity were calculated by using a threshold criterion that would maximize the average of sensitivity and specificity. Variance and CV of ADC 800 were significantly higher in pheochromocytomas than in adrenal adenomas (P < 0.001 and P = 0.001, respectively). With all b-value combinations, the entropy of ADC was significantly higher in pheochromocytomas than in adrenal adenomas (all P ≤ 0.001), and showed the highest area under the ROC curve among the ADC histogram parameters for diagnosing adrenal adenomas (ADC 200 , 0.82; ADC 400 , 0.87; and ADC 800 , 0.92), with sensitivity of 84.6% and specificity of 84.6% (cutoff, ≤2.82) with ADC 200 ; sensitivity of 89.7% and specificity of 84.6% (cutoff, ≤2.77) with ADC 400 ; and sensitivity of 94.9% and specificity of 92.3% (cutoff, ≤2.67) with ADC 800 . ADC histogram analysis of DW MRI can help differentiate adrenal adenoma from pheochromocytoma. 3 J. Magn. Reson. Imaging 2017;45:1195-1203. © 2016 International Society for Magnetic Resonance in Medicine.

  1. Posterior retroperitoneoscopic adrenal surgery for clinical and subclinical Cushing's syndrome in patients with bilateral adrenal disease.

    PubMed

    Lowery, Aoife J; Seeliger, Barbara; Alesina, Pier F; Walz, Martin K

    2017-08-01

    The treatment of hypercortisolism for patients with bilateral adrenal disease (BAD) is controversial. Bilateral total adrenalectomy results in permanent hypocortisolaemia requiring lifelong steroid replacement. A more conservative surgical approach, with less than bilateral total adrenalectomy (leaving functional adrenal tissue either unilaterally or bilaterally), represents an alternative option; however, long-term outcome or recurrence data are limited. We report our experience with the surgical management of hypercortisolism caused by BAD. Between 2004 and 2016, 42 patients (12 male, 30 female; mean age 58 ± 10 years) with clinical or subclinical Cushing's syndrome (CS/sCS) caused by BAD underwent adrenal surgery via the posterior retroperitoneoscopic approach. Adrenal surgery was defined as "adrenalectomy" when total gland excision was performed or "resection" when a partial or subtotal adrenal resection was performed. Clinical, radiological and biochemical parameters were evaluated preoperatively and postoperatively. Seventy adrenal operations performed in total included unilateral resection (n = 3), unilateral adrenalectomy (n = 15), bilateral resection (n = 9), adrenalectomy and contralateral resection (n = 14) and bilateral total adrenalectomy (n = 3). Median operating time was 47.5 min (30-150) with no difference between unilateral and bilateral (synchronous included) procedures (p = 0.15). Mortality was zero. Clavien-Dindo grade of postoperative complications was I (n = 5) and IV (n = 3). All but one patient with CS and 17/31 patients with sCS received postoperative steroid supplementation for a median duration of 20 (1.5-129) months. After median follow-up of 40 months (3-129), the remission rate was 92%; 11 patients required ongoing steroid supplementation. There were three biochemical recurrences (two underwent contralateral resection); two patients with new/progressive radiological nodularity are biochemically eucortisolaemic. A

  2. Adrenal Incidentaloma

    MedlinePlus

    ... or subclinical hypercortisolism: conditions caused by too much cortisol Hyperaldosteronism : too much aldosterone A pheochromocytoma: a rare ... in which the adrenal glands make too little cortisol and aldosterone, and too much androgen Cancer of ...

  3. Laparoscopic Adrenalectomy for Adrenal Tumors

    PubMed Central

    Chuan-yu, Sun; Yat-faat, Ho; Wei-hong, Ding; Yuan-cheng, Gou; Qing-feng, Hu; Ke, Xu; Bin, Gu; Guo-wei, Xia

    2014-01-01

    Objective. To evaluate the indication and the clinical value of laparoscopic adrenalectomy of different types of adrenal tumor. Methods. From 2009 to 2014, a total of 110 patients were diagnosed with adrenal benign tumor by CT scan and we performed laparoscopic adrenalectomy. The laparoscopic approach has been the procedure of choice for surgery of benign adrenal tumors, and the upper limit of tumor size was thought to be 6 cm. Results. 109 of 110 cases were successful; only one was converted to open surgery due to bleeding. The average operating time and intraoperative blood loss of pheochromocytoma were significantly more than the benign tumors (P < 0.05). After 3 months of follow-up, the preoperative symptoms were relieved and there was no recurrence. Conclusions. Laparoscopic adrenalectomy has the advantages of minimal invasion, less blood loss, fewer complications, quicker recovery, and shorter hospital stay. The full preparation before operation can decrease the average operating time and intraoperative blood loss of pheochromocytomas. Laparoscopic adrenalectomy should be considered as the first choice treatment for the resection of adrenal benign tumor. PMID:25132851

  4. Diagnosis and management of pediatric adrenal insufficiency.

    PubMed

    Uçar, Ahmet; Baş, Firdevs; Saka, Nurçin

    2016-08-01

    Adrenal insufficiency (AI) is a wellknown cause of potentially life-threatening disorders. Defects at each level of the hypothalamic-pituitary-adrenal axis can impair adrenal function, leading to varying degrees of glucocorticoid (GC) deficiency. Iatrogenic AI induced by exogenous GCs is the most common cause of AI. The criteria for the diagnosis and management of iatrogenic AI, neonatal AI, and critical illness-related corticosteroid insufficiency (CIRCI) are not clear. We reviewed the recent original publications and classical data from the literature, as well as the clinical, diagnostic and management strategies of pediatric AI. Practical points in the diagnosis and management of AI with an emphasis on iatrogenic AI, neonatal AI, and CIRCI are provided. Given the lack of sensitive and practical biochemical tests for diagnosis of subtle AI, GC treatment has to be tailored to highly suggestive clinical symptoms and signs. Treatment of adrenal crisis is well standardized and patients almost invariably respond well to therapy. It is mainly the delay in treatment that is responsible for mortality in adrenal crisis. Education of patients and health care professionals is mandatory for timely interventions for patients with adrenal crisis.

  5. Acute lymphoblastic leukemia terminating as histiocytic medullary reticulosis.

    PubMed

    Shreiner, D P

    1975-02-24

    A young man with acute lymphoblastic leukemia was treated with vincristine sulfate, prednisone, and intrathecally injected methotrexate sodium for central nervous system involvement. A good remission was induced, but three months later he had hepatosplenomegaly, an enlarging mediastinal mass, and progressive anemia. Histiocytic medullary reticulosis was confirmed by a bone marrow biopsy specimen. The patient died of respiratory failure because of infiltration of the lungs by malignant histiocytes.

  6. [Adrenal tumors. Principles of diagnostics and operative treatment].

    PubMed

    Gonsior, A; Pfeiffer, H; Führer, D; Liatsikos, E; Schwalenberg, T; Stolzenburg, J-U

    2010-05-01

    Adrenal masses are very heterogeneous and comprise benign or malignant tumors, unilateral or bilateral masses and variable endocrine activity. Because of these attributes adrenal gland masses are a clinical challenge. This article gives a summary of diagnostic steps and indications for adrenal surgery including perioperative management.

  7. Study of adrenal function in patients with tuberculosis.

    PubMed

    Sarin, Bipan Chander; Sibia, Keerat; Kukreja, Sahiba

    2018-07-01

    Although subclinical adrenal insufficiency has been documented in tuberculosis but it has been neglected in mainstream management of TB due to inconclusive data on its prevalence in TB. The fact that adrenal insufficiency may result not only in poor general condition of the patient but also sudden death due to adrenal crisis, makes it all the more important to address this issue seriously. In this non-randomized interventional study comprising of 100 cases of TB, our aim was to assess the adreno-cortical functions in patients with pulmonary TB (50 cases) and extra-pulmonary TB (50 cases) in an attempt to determine if there is any compromise of adrenal function. In this study, 100 cases of active TB were investigated for adrenal insufficiency by measuring morning fasting basal serum cortisol levels, followed by low dose ACTH stimulation test using 1μg synacthen (synthetic ACTH analog). The post-stimulation serum cortisol levels were estimated. Basal serum cortisol levels<220nmol/L or post-stimulation test serum cortisol level increment<200nmol/L or post-stimulation serum cortisol levels<500nmol/L were suggestive of adrenal insufficiency. Basal serum cortisol level was low in 16% cases and after low dose ACTH stimulation test, cortisol response was subnormal in 76% cases. Incidence of adrenal insufficiency in pulmonary TB (74%) and extra-pulmonary TB (78%) were comparable. The number of females having adrenal insufficiency in both the groups was higher than the males (67.3% males and 83.3% females) but the difference was statistically significant only in extra-pulmonary TB group (p=0.011). On analysing the data, the sensitivity of basal serum cortisol level estimation in diagnosing adrenal insufficiency was observed to be 21.05% and its specificity was 100%. Positive predictive value was 100% and negative predictive value was 28.57%. Diagnostic accuracy of basal serum cortisol level estimation was observed to be 40%. The incidence of subclinical adrenal

  8. Increased Cross-Gender Identification Independent of Gender Role Behavior in Girls with Congenital Adrenal Hyperplasia: Results from a Standardized Assessment of 4- to 11-Year-Old Children.

    PubMed

    Pasterski, Vickie; Zucker, Kenneth J; Hindmarsh, Peter C; Hughes, Ieuan A; Acerini, Carlo; Spencer, Debra; Neufeld, Sharon; Hines, Melissa

    2015-07-01

    While reports showing a link between prenatal androgen exposure and human gender role behavior are consistent and the effects are robust, associations to gender identity or cross-gender identification are less clear. The aim of the current study was to investigate potential cross-gender identification in girls exposed prenatally to high concentrations of androgens due to classical congenital adrenal hyperplasia (CAH). Assessment included two standardized measures and a short parent interview assessing frequency of behavioral features of cross-gender identification as conceptualized in Part A of the diagnostic criteria for gender identity disorder (GID) in the DSM-IV-TR. Next, because existing measures may have conflated gender role behavior with gender identity and because the distinction is potentially informative, we factor analyzed items from the measures which included both gender identity and gender role items to establish the independence of the two constructs. Participants were 43 girls and 38 boys with CAH and 41 unaffected female and 31 unaffected male relatives, aged 4- to 11-years. Girls with CAH had more cross-gender responses than female controls on all three measures of cross-gender identification as well as on a composite measure of gender identity independent of gender role behavior. Furthermore, parent report indicated that 5/39 (12.8 %) of the girls with CAH exhibited cross-gender behavior in all five behavioral domains which comprise the cross-gender identification component of GID compared to 0/105 (0.0 %) of the children in the other three groups combined. These data suggest that girls exposed to high concentrations of androgens prenatally are more likely to show cross-gender identification than girls without CAH or boys with and without CAH. Our findings suggest that prenatal androgen exposure could play a role in gender identity development in healthy children, and may be relevant to gender assignment in cases of prenatal hormone disruption

  9. Nodular Graves' disease with medullary thyroid cancer.

    PubMed

    Khan, Shoukat Hussain; Rather, Tanveer Ahmed; Makhdoomi, Rumana; Malik, Dharmender

    2015-01-01

    Co-existence of thyroid nodules with Graves' disease has been reported in various studies. 10-15% of such nodules harbor thyroid cancer with papillary thyroid cancer being the commonest. Medullary thyroid cancer (MTC) in nodules associated with Graves' disease is rare. On literature survey, we came across 11 such cases reported so far. We report a 62-year-old female with Graves' disease who also had a thyroid nodule that on fine-needle aspiration cytology and the subsequent postthyroidectomy histopathological examination was reported to be MTC.

  10. Therapeutic patient education in adrenal insufficiency.

    PubMed

    Guignat, Laurence

    2018-06-01

    It is essential to encourage patient autonomy in the management of their illness, and notably their participation in treatment education programs; specific programs target avoidance or early preventive treatment of acute adrenal insufficiency, which is a life-threatening complication. Therapeutic patient education is recommended by the two international consensus statements on the management of primary adrenal insufficiency and the French consensus on adrenal insufficiency. Although there is no common international reference framework to date, the objective of the French consensus was to provide a frame of reference to facilitate the development of therapeutic education for patients with adrenal insufficiency. The principal educational objectives were: for the patient to always carry the necessary emergency equipment; be able to identify situations of increased risk and the early signs of adrenal crisis; know how to adjust oral glucocorticoid treatment; be capable of administering hydrocortisone by subcutaneous injection; be able to adjust treatment to different situations (heat, physical exercise, travel); and be able to appropriately use the resources of the healthcare services. Other programs could also be developed to respond to patients' needs and expectations, notably concerning hydrocortisone dose adjustment to avoid overdose in the context of chronic fatigue syndrome. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. 17-OH progesterone

    MedlinePlus

    17-hydroxyprogesterone; Progesterone - 17-OH ... A high level of 17-OH progesterone may be due to: Tumors of the adrenal gland Congenital adrenal hyperplasia (CAH) In infants with CAH, the 17-OHP level ranges ...

  12. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors.

    PubMed

    Fassnacht, Martin; Arlt, Wiebke; Bancos, Irina; Dralle, Henning; Newell-Price, John; Sahdev, Anju; Tabarin, Antoine; Terzolo, Massimo; Tsagarakis, Stylianos; Dekkers, Olaf M

    2016-08-01

    : By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called 'subclinical' Cushing's syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? SELECTED RECOMMENDATIONS: (i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow-up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50nmol/L (1.8µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1mg dexamethasone >138nmol/L (>5µg/dL), we propose the term 'autonomous cortisol secretion'. (iv) All patients with '(possible) autonomous cortisol' secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with

  13. [Modern tendencies in treatment of atypical glandular hyperplasia--our and foreign experience].

    PubMed

    Ivanov, S; Kovachev, E; Tsonev, A; Abbud, A

    2010-01-01

    Our aim was to summarize our and foreign experience in the field of diagnosis, progression and modern treatment of precancer of the endometrium-the atypical glandular hyperplasia. We researched 750 cases with glandular and atypical glandular hyperplasia for 10 years period (2000-2010). The hyperplasia were followed up for progression from glandular hyperplasia into atypical glandular hyperplasia and early endometrial cancer. The hyperplasias were evaluated with or without progestagen hormonal therapy. All patients were treated by D&C before and after the hormonal treatment. The main symptom in all patients was the postmenopausal bleeding (72% from the cases). In 90% of the patients (675) there was obesity. Exogenous use of estrogens was found in 30% (225) of the patients. The cases with complex hyperplasia in 12% (65/525) progressed into atypical glandular hyperplasia and in 4% (21/525) progressed into endometrial cancer. The patients with atypical glandular hyperplasia in 60% (90/150) progressed into endometrial cancer. Remission was observed in 70% of the patients (194/278) with glandular hyperplasia and progestagen treatment. The remission was detected by the golden standart (D&C). The patients without hormonal treatment and with complex glandular hyperplasia have in 15% (37/247) remission. Except with progestagen therapy, we have also 15 patients treated with GnRh-analogs (Zoladex a 3.6 mg) for 3-6 months. For them we have 80% (12/15) remission. The glandular hyperplasia without atypical cells can be influenced by the hormonal treatment with progestagens and GnRh-analogs. Nevertheless this hormonal treatment--before and after we have to perform D&C and to follow up patients by ultrasound measuring the endometrial thickness. If the fertility plans of the patients are over and if they are in postmenopause with histological result from D&C-atypical glandular hyperplasia--we have to treat them more radically with simple total hysterectomy.

  14. Nodular Graves’ disease with medullary thyroid cancer

    PubMed Central

    Khan, Shoukat Hussain; Rather, Tanveer Ahmed; Makhdoomi, Rumana; Malik, Dharmender

    2015-01-01

    Co-existence of thyroid nodules with Graves’ disease has been reported in various studies. 10–15% of such nodules harbor thyroid cancer with papillary thyroid cancer being the commonest. Medullary thyroid cancer (MTC) in nodules associated with Graves’ disease is rare. On literature survey, we came across 11 such cases reported so far. We report a 62-year-old female with Graves’ disease who also had a thyroid nodule that on fine-needle aspiration cytology and the subsequent postthyroidectomy histopathological examination was reported to be MTC. PMID:26430321

  15. Risk Factors, Etiological Classification, Topographical Location, and Outcome in Medullary Infarctions.

    PubMed

    Gökçal, Elif; Baran, Gözde; Niftaliyev, Elvin; Güzel, Vildan; Asil, Talip

    2017-07-01

    An understanding of the etiological mechanisms is important for therapeutic decisions and prognostic evaluation of patients with ischemic stroke. The object of this study was to evaluate the risk factors, etiological subtypes, and topography of lesion in patients with medullary infarctions (MIs). Besides, we also investigated early neurological deterioration, new vascular events, and functional outcome of all patients at 3-month follow-up. We analyzed our database consisting of patients who were diagnosed with acute MI and who were admitted within 24 hours of onset. Etiological classification of stroke was made on the basis of the Trial of Org 1972 in Acute Stroke Treatment criteria. All of the infarctions were grouped into anteromedial, anterolateral, lateral, and posterior arterial territories and also categorized into those involving the upper, middle, or lower medulla oblongata. Early neurological deterioration, major vascular events within the first 3 months of follow-up and modified Rankin Score at 3 months were reviewed. A total of 65 patients with medullary infarctions were reviewed. Involved arterial territories differed according to the etiological classification. Large artery atherosclerosis was the most common etiological subtype; however, small vessel disease was the most common subtype in medial MIs. The lesions involving the anteromedial territory were common in the upper medullary region, whereas the lesions involving the posterior and lateral territories were common in the lower medulla oblangata. Recurrent stroke was seen in the posterior and lateral territories; however, early progression and poor functional outcome were mostly seen in lesions involving the anteromedial territories.

  16. Cellular transport of l-arginine determines renal medullary blood flow in control rats, but not in diabetic rats despite enhanced cellular uptake capacity.

    PubMed

    Persson, Patrik; Fasching, Angelica; Teerlink, Tom; Hansell, Peter; Palm, Fredrik

    2017-02-01

    Diabetes mellitus is associated with decreased nitric oxide bioavailability thereby affecting renal blood flow regulation. Previous reports have demonstrated that cellular uptake of l-arginine is rate limiting for nitric oxide production and that plasma l-arginine concentration is decreased in diabetes. We therefore investigated whether regional renal blood flow regulation is affected by cellular l-arginine uptake in streptozotocin-induced diabetic rats. Rats were anesthetized with thiobutabarbital, and the left kidney was exposed. Total, cortical, and medullary renal blood flow was investigated before and after renal artery infusion of increasing doses of either l-homoarginine to inhibit cellular uptake of l-arginine or N ω -nitro- l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase. l-Homoarginine infusion did not affect total or cortical blood flow in any of the groups, but caused a dose-dependent reduction in medullary blood flow. l-NAME decreased total, cortical and medullary blood flow in both groups. However, the reductions in medullary blood flow in response to both l-homoarginine and l-NAME were more pronounced in the control groups compared with the diabetic groups. Isolated cortical tubular cells displayed similar l-arginine uptake capacity whereas medullary tubular cells isolated from diabetic rats had increased l-arginine uptake capacity. Diabetics had reduced l-arginine concentrations in plasma and medullary tissue but increased l-arginine concentration in cortical tissue. In conclusion, the reduced l-arginine availability in plasma and medullary tissue in diabetes results in reduced nitric oxide-mediated regulation of renal medullary hemodynamics. Cortical blood flow regulation displays less dependency on extracellular l-arginine and the upregulated cortical tissue l-arginine may protect cortical hemodynamics in diabetes. Copyright © 2017 the American Physiological Society.

  17. Nephrotoxicity of Hydrocarbon Propellants to Male, Fischer-344 Rats

    DTIC Science & Technology

    1983-08-01

    debris in medullary tubules and mild to moderate, multifocal, papillary hyperplasia of pelvic urothelium along the surface of the renal papillus...con- trast, etiologic factors leading to papillary hyperplasia of the pelvic urothelium can only be theorized. Hyperplastic pelvic lin- ing cells are...results in the loss of inhibitory chalones (i.e. N factors related to contact inhibition) and the subsequent "release" of nearby surface urothelium to

  18. Denture hyperplasia with areas simulating oral inverted ductal papilloma.

    PubMed

    Vargas, Pablo Agustin; Perez, Danyel Elias da Cruz; Jorge, Jacks; Rangel, Ana Lúcia Carrinho Ayrosa; León, Jorge Esquiche; Almeida, Oslei Paes de

    2005-07-01

    Denture hyperplasia is a reactive lesion of the oral mucosa, usually associated to an ill-fitting denture. This lesion is easily diagnosed and in some cases distinct microscopic variations such as osseous, oncocytic and squamous metaplasia may be found. These metaplastic alterations probably are associated with the lymphocytic infiltrate usually present in denture hyperplasia. We present a case of denture hyperplasia containing salivary gland tissue with ductal alterations mimicking an oral inverted ductal papilloma.

  19. C-Arm Computed Tomography-Assisted Adrenal Venous Sampling Improved Right Adrenal Vein Cannulation and Sampling Quality in Primary Aldosteronism.

    PubMed

    Park, Chung Hyun; Hong, Namki; Han, Kichang; Kang, Sang Wook; Lee, Cho Rok; Park, Sungha; Rhee, Yumie

    2018-05-04

    Adrenal venous sampling (AVS) is a gold standard for subtype classification of primary aldosteronism (PA). However, this procedure has a high failure rate because of the anatomical difficulties in accessing the right adrenal vein. We investigated whether C-arm computed tomography-assisted AVS (C-AVS) could improve the success rate of adrenal sampling. A total of 156 patients, diagnosed with PA who underwent AVS from May 2004 through April 2017, were included. Based on the medical records, we retrospectively compared the overall, left, and right catheterization success rates of adrenal veins during the periods without C-AVS (2004 to 2010, n=32) and with C-AVS (2011 to 2016, n=134). The primary outcome was adequate bilateral sampling defined as a selectivity index (SI) >5. With C-AVS, the rates of adequate bilateral AVS increased from 40.6% to 88.7% (P<0.001), with substantial decreases in failure rates (43.7% to 0.8%, P<0.001). There were significant increases in adequate sampling rates from right (43.7% to 91.9%, P<0.001) and left adrenal veins (53.1% to 95.9%, P<0.001) as well as decreases in catheterization failure from right adrenal vein (9.3% to 0.0%, P<0.001). Net improvement of SI on right side remained significant after adjustment for left side (adjusted SI, 1.1 to 9.0; P=0.038). C-AVS was an independent predictor of adequate bilateral sampling in the multivariate model (odds ratio, 9.01; P<0.001). C-AVS improved the overall success rate of AVS, possibly as a result of better catheterization of right adrenal vein. Copyright © 2018 Korean Endocrine Society.

  20. 60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH.

    PubMed

    Gallo-Payet, Nicole

    2016-05-01

    The pituitary adrenocorticotropic hormone (ACTH) plays a pivotal role in homeostasis and stress response and is thus the major component of the hypothalamo-pituitary-adrenal axis. After a brief summary of ACTH production from proopiomelanocortin (POMC) and on ACTH receptor properties, the first part of the review covers the role of ACTH in steroidogenesis and steroid secretion. We highlight the mechanisms explaining the differential acute vs chronic effects of ACTH on aldosterone and glucocorticoid secretion. The second part summarizes the effects of ACTH on adrenal growth, addressing its role as either a mitogenic or a differentiating factor. We then review the mechanisms involved in steroid secretion, from the classical Cyclic adenosine monophosphate second messenger system to various signaling cascades. We also consider how the interaction between the extracellular matrix and the cytoskeleton may trigger activation of signaling platforms potentially stimulating or repressing the steroidogenic potency of ACTH. Finally, we consider the extra-adrenal actions of ACTH, in particular its role in differentiation in a variety of cell types, in addition to its known lipolytic effects on adipocytes. In each section, we endeavor to correlate basic mechanisms of ACTH function with the pathological consequences of ACTH signaling deficiency and of overproduction of ACTH. © 2016 Society for Endocrinology.

  1. Percutaneous interstitial brachytherapy for adrenal metastasis: technical report.

    PubMed

    Kishi, Kazushi; Tamura, Shinji; Mabuchi, Yasushi; Sonomura, Tetsuo; Noda, Yasutaka; Nakai, Motoki; Sato, Morio; Ino, Kazuhiko; Yamanaka, Noboru

    2012-09-01

    We developed and evaluated the feasibility of a brachytherapy technique as a safe and effective treatment for adrenal metastasis. Adapting a paravertebral insertion technique in radiofrequency ablation of adrenal tumors, we developed an interstitial brachytherapy for adrenal metastasis achievable on an outpatient basis. Under local anesthesia and under X-ray CT guidance, brachytherapy applicator needles were percutaneously inserted into the target. A treatment plan was created to eradicate the tumor while preserving normal organs including the spinal cord and kidney. We applied this interstitial brachytherapy technique to two patients: one who developed adrenal metastasis as the third recurrence of uterine cervical cancer after reirradiation, and one who developed metachronous multiple metastases from malignant melanoma. The whole procedure was completed in 2.5 hours. There were no procedure-related or radiation-related early/late complications. FDG PET-CT images at two and three months after treatment showed absence of FDG uptake, and no recurrence of the adrenal tumor was observed for over seven months until expiration, and for six months until the present, respectively. This interventional interstitial brachytherapy procedure may be useful as a safe and eradicative treatment for adrenal metastasis.

  2. Maxillary sinus marrow hyperplasia in sickle cell anemia.

    PubMed

    Fernandez, M; Slovis, T L; Whitten-Shurney, W

    1995-11-01

    Marrow hyperplasia is a sequela of sickle cell anemia (SCA) and may be seen in the skull in children after 5 years of age [1]. The facial bones, except for the mandible and orbits, are usually not involved [1-3]. We report an unusual case of a 28-month-old black boy with SCA who presented with extensive marrow hyperplasia of the maxillary sinuses in addition to severe calvarial and mandibular changes. The imaging characteristics on CT (similar to other sites of marrow hyperplasia) and MR (low signal on both T1 and T2 sequences) should aid in making the correct diagnosis.

  3. Direct effects of recurrent hypoglycaemia on adrenal catecholamine release.

    PubMed

    Orban, Branly O; Routh, Vanessa H; Levin, Barry E; Berlin, Joshua R

    2015-01-01

    In Type 1 and advanced Type 2 diabetes mellitus, elevation of plasma epinephrine plays a key role in normalizing plasma glucose during hypoglycaemia. However, recurrent hypoglycaemia blunts this elevation of plasma epinephrine. To determine whether recurrent hypoglycaemia affects peripheral components of the sympatho-adrenal system responsible for epinephrine release, male rats were administered subcutaneous insulin daily for 3 days. These recurrent hypoglycaemic animals showed a smaller elevation of plasma epinephrine than saline-injected controls when subjected to insulin-induced hypoglycaemia. Electrical stimulation of an adrenal branch of the splanchnic nerve in recurrent hypoglycaemic animals elicited less release of epinephrine and norepinephrine than in controls, without a change in adrenal catecholamine content. Responsiveness of isolated, perfused adrenal glands to acetylcholine and other acetylcholine receptor agonists was also unchanged. These results indicate that recurrent hypoglycaemia compromised the efficacy with which peripheral neuronal activity stimulates adrenal catecholamine release and demonstrate that peripheral components of the sympatho-adrenal system were directly affected by recurrent hypoglycaemia. © The Author(s) 2014.

  4. Ultrasonographic adrenal gland findings in healthy semi-captive cheetahs (Acinonyx jubatus).

    PubMed

    Kirberger, Robert M; Tordiffe, Adrian S W

    2016-05-01

    Cheetahs in captivity are believed to suffer from stress predisposing them to poor health. To date fecal glucocorticoids have been used as a non-invasive indicator of chronic stress. This study examines, the feasibility of transabdominal adrenal gland ultrasonography in cheetahs and determined normal adrenal measurements that can potentially be used as a more reliable indicator of chronic stress and/or adrenal function. Thirty-three adult cheetahs, aged between 2 and 13 years, accommodated in large off-display camps were examined over 9 days under general anesthesia. The adrenals were readily identified, with the right adrenal being more difficult to find and measure than the left, and were smaller than those expected in similar sized dogs. The left adrenal was shorter and slightly more oval shaped than the right with a length and cranial pole width at a 95% prediction interval of 16.3-22.4 and 4.1-8.7 mm. The same measurements for the right adrenal were 16.8-26.2 and 3.4-10.8 mm, respectively. Corticomedullary ratios were larger for the left adrenal. When corrected for body size, females had significantly longer and greater left adrenal corticomedullary ratios than males. Adrenal measurements did not correlate with left renal length, body size measurements, or enclosure size. Measurements that increased with age included the cortical and total adrenal widths. Adrenal ultrasonography offers potential benefits in assessment of individual cheetah adrenal pathology or the evaluation of stress induced adrenomegally especially in combination with other evaluations such as non-invasive fecal glucocorticoid analyses. Zoo Biol. 35:260-268, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice.

    PubMed

    Huang, Ya; Chen, Huaguo; Zhou, Xin; Wu, Xingdong; Hu, Enming; Jiang, Zhengmeng

    2017-08-15

    This study aimed to evaluate the inhibitory effects and explore mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice. Benign prostatic hyperplasia model was induced in experimental groups by daily subcutaneous injections of testosterone propionate (7.5mg/kg/d) consecutively for 14 d. A total of 60 mice were randomly divided into six groups: (Group 1) normal control group, (Group 2) benign prostatic hyperplasia model control group, (Group 3) benign prostatic hyperplasia mice treated with finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group 5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group). Animals were sacrificed on the scheduled termination, pick out the eyeball to get blood, then prostates were weighed and prostatic index were determined. Then the serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeⅡ5-alpha-reductase (SRD5A2) levels were measured and observed morphological changes of the prostate. Comparing with benign prostatic hyperplasia model group, the high and medium dose of chlorogenic acid could significantly reduce prostate index and levels of acid phosphatase, prostatic acid phosphatase and typeⅡ5-alpha-reductase (P<0.05 or P<0.01). These findings were supported by histopathological observations of prostate tissues. Histopathological examination also indicated that chlorogenic acid treatment at the high and medium doses inhibited testosterone-induced prostatic hyperplasia. The results indicated that chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia model animals, and its mechanism might be related to inhibit typeⅡ5-alpha reductase activity. Copyright © 2017

  6. Downstream anastomotic hyperplasia. A mechanism of failure in Dacron arterial grafts.

    PubMed Central

    LoGerfo, F W; Quist, W C; Nowak, M D; Crawshaw, H M; Haudenschild, C C

    1983-01-01

    The precise location and progression of anastomotic hyperplasia and its possible relationship to flow disturbances was investigated in femoro-femoral Dacron grafts in 28 dogs. In 13 grafts, the outflow from the end-to-side downstream anastomosis was bidirectional (BDO), and in 15 it was unidirectional (UDO) (distally). Grafts were electively removed at intervals of two to 196 days or at the time of thrombosis. Each anastomosis and adjacent artery was perfusion-fixed and sectioned sagittally. The mean sagittal section was projected onto a digitized pad, and the total area of hyperplasia internal to the arterial internal elastic lamina and within the adjacent graft was integrated by computer. The location of the hyperplasia was compared with previously established sites of flow separation and stagnation. The observation was made that hyperplasia is significantly greater at the downstream, as compared with the upstream, anastomosis in both groups (BDO = p less than 0.001 and UDO = p less than 0.001) (analysis of variance for independent groups). Furthermore, this downstream hyperplasia was progressive with time (BDO p less than 0.01) (UDO p less than 0.01); Spearman Rank Correlation. There was no significant increase in the extent of downstream hyperplasia where flow separation was known to be greater (BDO). Five grafts failed (three BDO, two UDO), as a result of complete occlusion of the downstream anastomosis by fibrous hyperplasia. Transmission electron microscopy showed the hyperplasia to consist of collagen-producing smooth muscle cells. Anastomotic hyperplasia is significantly greater at the downstream anastomosis, is progressive with time, and is the primary cause of failure of Dacron arterial grafts in this model. Quantitative analysis of downstream anastomotic hyperplasia may be a valuable measure of the biocompatibility of Dacron grafts. Images Fig. 2. Fig. 3. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:6219641

  7. Adrenal Ewing's Sarcoma in an Elderly Man.

    PubMed

    Toda, Kazuyoshi; Ishii, Sumiyasu; Yasuoka, Hidetoshi; Nishioka, Masaki; Kobayashi, Takayuki; Horiguchi, Kazuhiko; Tomaru, Takuya; Ozawa, Atsushi; Shibusawa, Nobuyuki; Satoh, Tetsurou; Koshi, Hiromi; Segawa, Atsuki; Shimizu, Shin-Ichi; Oyama, Tetsunari; Yamada, Masanobu

    2018-02-15

    Ewing's sarcoma usually arises in the bones of children and adolescents. We herein report a 74-year-old man with Ewing's sarcoma in the adrenal gland. The diagnosis was confirmed by a genetic test, pathological studies, and several imaging studies. He already had multiple liver metastases when he was transferred to our hospital and died on the 37th day. The diagnosis was further confirmed by autopsy studies. Adrenal Ewing's sarcoma is very rare, and our patient was older than other reported cases. Ewing's sarcoma should be considered even in elderly patients with adrenal tumors.

  8. Adrenal tuberculosis after a pheochromocytoma: a misleading tumoral presentation.

    PubMed

    Hiéronimus, S; Bernard, J-L; Chevallier, P; Chevallier, A; Chyderiotis, G; Fenichel, P; Landraud, L

    2007-06-01

    Adrenal gland involvement could account for 6% of active tuberculosis. The diagnosis of this extrapulmonary form of tuberculosis is difficult, especially when presenting as unilateral adrenal tumor. This report describes an unusual case of adrenal tuberculosis presenting as a tumor occurring shortly after surgical removal of an adrenal pheochromocytoma located in the opposite gland, in a 63-year-old woman with a previous history of breast cancer. At initial presentation, the patient suffered from symptomatic paroxysmal hypertension. A pheochromocytoma in the left adrenal was diagnosed and resected. One year later, while physical examination and biological parameters were unremarkable, an enhanced adrenal computed tomography (CT) scan showed a right adrenal mass mimicking the CT features of the resected pheochromocytoma. A peripheral tissular rim delineating a central hypodensity characterized this tumor. Magnetic resonance imaging (MRI) showed the same findings on gadolinium-enhanced T1-weighted slices, while the mass was not seen on T2-weighted images. No tumoral signal loss was observed on out of phase images when using the in phase-out of phase T1-weighted sequence. Because of the tumoral evolution and the uncertainty of the nature of that lesion, the patient underwent a second adrenalectomy. Definitive diagnosis was provided by culture of tissue sample, which resulted in the identification of Mycobacterium tuberculosis. In an era of tuberculosis resurgence, this unusual case underscores the necessity of keeping in mind adrenal tuberculosis as a possible differential diagnosis in adrenal tumors of uncertainty nature. It stresses the importance of culture of biopsy tumor, whenever feasible, to avoid unnecessary operations. In the near future, interferon-gamma assay could be a valuable means to recognize extrapulmonary forms of tuberculosis.

  9. Incidence and Cause of Hypertension During Adrenal Radiofrequency Ablation

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

    Yamakado, Koichiro, E-mail: yama@clin.medic.mie-u.ac.jp; Takaki, Haruyuki; Yamada, Tomomi

    Purpose: To evaluate the incidence and cause of hypertension prospectively during adrenal radiofrequency ablation (RFA). Methods: For this study, approved by our institutional review board, written informed consent was obtained from all patients. Patients who received RFA for adrenal tumors (adrenal ablation) and other abdominal tumors (nonadrenal ablation) were included in this prospective study. Blood pressure was monitored during RFA. Serum adrenal hormone levels including epinephrine, norepinephrine, dopamine, and cortisol levels were measured before and during RFA. The respective incidences of procedural hypertension (systolic blood pressure >200 mmHg) of the two patient groups were compared. Factors correlating with procedural systolicmore » blood pressure were evaluated by regression analysis.ResultsNine patients underwent adrenal RFA and another 9 patients liver (n = 5) and renal (n = 4) RFA. Asymptomatic procedural hypertension that returned to the baseline by injecting calcium blocker was found in 7 (38.9%) of 18 patients. The incidence of procedural hypertension was significantly higher in the adrenal ablation group (66.7%, 6/9) than in the nonadrenal ablation group (11.1%, 1/9, P < 0.0498). Procedural systolic blood pressure was significantly correlated with serum epinephrine (R{sup 2} = 0.68, P < 0.0001) and norepinephrine (R{sup 2} = 0.72, P < 0.0001) levels during RFA. The other adrenal hormones did not show correlation with procedural systolic blood pressure. Conclusion: Hypertension occurs frequently during adrenal RFA because of the release of catecholamine.« less

  10. [Toxoplasmosis in patients with lymphoid hyperplasia of the head and neck].

    PubMed

    Yariktaş, Murat; Demirci, Mustafa; Döner, Fehmi; Kaya, Selçuk; Doğru, Harun

    2004-01-01

    To investigate the incidence of toxoplasmosis in patients with lymphoid hyperplasia of the head and neck. In this study, 53 patients (32 males, 21 females; mean age 11.2+/-4.3 years, range 5 to 22) were investigated. There were hypertrophic tonsillitis in 13 patients, hypertrophic tonsillitis and adenoid hyperplasia in 22 patients, adenoid hyperplasia in 10 patients, and lymphadenopathy of the neck in eight patients. In venous blood samples, IgM and IgG antibodies for Toxoplasma gondii were investigated with the enzyme-linked immunoabsorbent assay (Axsym, Abbott). Positive IgG was determined in 23 patients (48%) with hypertrophic tonsillitis (n=6), hypertrophic tonsillitis and adenoid hyperplasia (n=10), adenoid hyperplasia (n=3), and lymphadenopathy of the neck (n=4). Positive IgM was determined in 5 patients (9.4%) with hypertrophic tonsillitis (n=1), hypertrophic tonsillitis and adenoid hyperplasia (n=1), and lymphadenopathy of the neck (n=3). Toxoplasmosis, which is known to cause lymphadenopathy, may be a reason for lymphadenopathy of the neck. Toxoplasmosis should be considered in the differential diagnosis of untreated patients with tonsillitis, adenoid hyperplasia, and chronic neck lymphadenopathy.

  11. Blood Test: 17-Hydroxyprogesterone (For Parents)

    MedlinePlus

    ... congenital adrenal hyperplasia (CAH). CAH can affect both boys and girls. It causes the adrenal glands to make excess ... symptoms may be hard to spot in infant boys. In baby girls, the most common sign is ambiguous genitalia (a ...

  12. Naloxone inhibits and morphine potentiates. The adrenal steroidogenic response to ACTH

    NASA Technical Reports Server (NTRS)

    Heybach, J. P.; Vernikos, J.

    1980-01-01

    The adrenal actions were stereospecific since neither the positve stereoisomer of morphine, nor that of naloxone, had any effect on the adrenal response to exogenous adrenocorticotrophic hormone (ACTH). The administration of human beta endorphin to phyophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone secreting cells of the adrenal cortex.

  13. ACTH-independent macronodular adrenocortical hyperplasia reveals prevalent aberrant in vivo and in vitro responses to hormonal stimuli and coupling of arginine-vasopressin type 1a receptor to 11β-hydroxylase

    PubMed Central

    2013-01-01

    Background Adrenal Cushing’s syndrome caused by ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) can be accompanied by aberrant responses to hormonal stimuli. We investigated the prevalence of adrenocortical reactions to these stimuli in a large cohort of AIMAH patients, both in vivo and in vitro. Methods In vivo cortisol responses to hormonal stimuli were studied in 35 patients with ACTH-independent bilateral adrenal enlargement and (sub-)clinical hypercortisolism. In vitro, the effects of these stimuli on cortisol secretion and steroidogenic enzyme mRNA expression were evaluated in cultured AIMAH and other adrenocortical cells. Arginine-vasopressin (AVP) receptor mRNA levels were determined in the adrenal tissues. Results Positive serum cortisol responses to stimuli were detected in 27/35 AIMAH patients tested, with multiple responses within individual patients occurring for up to four stimuli. AVP and metoclopramide were the most prevalent hormonal stimuli triggering positive responses in vivo. Catecholamines induced short-term cortisol production more often in AIMAH cultures compared to other adrenal cells. Short- and long-term incubation with AVP increased cortisol secretion in cultures of AIMAH cells. AVP also increased steroidogenic enzyme mRNA expression, among which an aberrant induction of CYP11B1. AVP type 1a receptor was the only AVPR expressed and levels were high in the AIMAH tissues. AVPR1A expression was related to the AVP-induced stimulation of CYP11B1. Conclusions Multiple hormonal signals can simultaneously induce hypercortisolism in AIMAH. AVP is the most prevalent eutopic signal and expression of its type 1a receptor was aberrantly linked to CYP11B1 expression. PMID:24034279

  14. Standards of ultrasound imaging of the adrenal glands

    PubMed Central

    Jakubowski, Wiesław S.; Dobruch-Sobczak, Katarzyna; Kasperlik-Załuska, Anna A.

    2015-01-01

    Adrenal glands are paired endocrine glands located over the upper renal poles. Adrenal pathologies have various clinical presentations. They can coexist with the hyperfunction of individual cortical zones or the medulla, insufficiency of the adrenal cortex or retained normal hormonal function. The most common adrenal masses are tumors incidentally detected in imaging examinations (ultrasound, tomography, magnetic resonance imaging), referred to as incidentalomas. They include a range of histopathological entities but cortical adenomas without hormonal hyperfunction are the most common. Each abdominal ultrasound scan of a child or adult should include the assessment of the suprarenal areas. If a previously non-reported, incidental solid focal lesion exceeding 1 cm (incidentaloma) is detected in the suprarenal area, computed tomography or magnetic resonance imaging should be conducted to confirm its presence and for differentiation and the tumor functional status should be determined. Ultrasound imaging is also used to monitor adrenal incidentaloma that is not eligible for a surgery. The paper presents recommendations concerning the performance and assessment of ultrasound examinations of the adrenal glands and their pathological lesions. The article includes new ultrasound techniques, such as tissue harmonic imaging, spatial compound imaging, three-dimensional ultrasound, elastography, contrast-enhanced ultrasound and parametric imaging. The guidelines presented above are consistent with the recommendations of the Polish Ultrasound Society. PMID:26807295

  15. Acute adrenal crisis

    MedlinePlus

    ... condition that occurs when there is not enough cortisol. This is a hormone produced by the adrenal ... parts. The outer portion, called the cortex, produces cortisol. This is an important hormone for controlling blood ...

  16. A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery

    PubMed Central

    Morimoto, R; Satani, N; Iwakura, Y; Ono, Y; Kudo, M; Nezu, M; Omata, K; Tezuka, Y; Seiji, K; Ota, H; Kawasaki, Y; Ishidoya, S; Nakamura, Y; Arai, Y; Takase, K; Sasano, H; Ito, S; Satoh, F

    2016-01-01

    Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl−1 and aldosterone renin activity ratio of 90.2 (ng dl−1 per ng ml−1 h−1), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl−1 confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production. PMID:26538381

  17. Unusual Metastasis of Medullary Thyroid Carcinoma to the Breast: A Cytological and Histopathological Correlation

    PubMed Central

    Tanwar, Parul; Gandhi, Jatin S; Sharma, Anila; Gupta, Manoj; Choudhary, Partha S

    2018-01-01

    Breast metastases are a relatively rare condition and account for approximately 0.5–2% of all breast tumors. Recognition of metastatic tumors in the breast is important because it would prevent unnecessary mutilating surgery and would lead to appropriate treatment of the primary tumor. Breast metastases from medullary thyroid cancer (MTC) are very rare with only 21 reported cases in the literature. Some MTCs mimic primary invasive lobular carcinoma of the breast histopathologically and radiologically, making the distinction between the two diagnostically challenging. We present the case of a 45-year-old female presenting with a lump breast, which was later found out to be metastasis from medullary carcinoma thyroid. PMID:29643661

  18. Benign Prostatic Hyperplasia (BPH)

    MedlinePlus

    ... Benign prostatic hyperplasia (BPH) — also called prostate gland enlargement — is a common condition as men get older. ... There are several effective treatments for prostate gland enlargement, including medications, minimally invasive therapies and surgery. To ...

  19. Pituitary Tumors: Condition Information

    MedlinePlus

    ... Congenital Adrenal Hyperplasia (CAH) Cushing Syndrome Infertility and Fertility NICHD News and Features NIH researchers find potential genetic cause of Cushing syndrome Getting to Know the New NICHD Director Little Glands, Big Effects: Understanding and Treating Adrenal Gland Disorders All related ...

  20. Principles and management of adrenal cancer

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

    Javadpour, N.

    1987-01-01

    This book provides information on adrenal diseases of latest developments and guides the clinicians in the care of their patients. The book is divided into two parts. The first section gives an overview of the embryology, anatomy, physiology, markers, pathology, imaging and the current progress in the field. The second edition covers specific diseases of the adrenal cortex and medulla. The increasingly significant roles played by steroids, catecholamines, blockers, computed tomography and magnetic resonance are elucidated and discussed. The contents include: Overview of progress; current problems, and perspectives - embryology anatomy, physiology, and biologic markers; pathology; advances in diagnosis; imagingmore » techniques; adrenal disorders in childhood; primary aldosteronism; Cushing's syndrome; carcinoma; pheochromocytoma; neuroblastoma; metastatic disease; surgical management; and subject index.« less

  1. Hereditary pituitary hyperplasia with infantile gigantism.

    PubMed

    Gläsker, Sven; Vortmeyer, Alexander O; Lafferty, Antony R A; Hofman, Paul L; Li, Jie; Weil, Robert J; Zhuang, Zhengping; Oldfield, Edward H

    2011-12-01

    We report hereditary pituitary hyperplasia. The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. The study is a retrospective analysis of three cases from one family. The study was conducted at the National Institutes of Health, a tertiary referral center. A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. The condition was treated by total hypophysectomy. We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development.

  2. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma.

    PubMed

    Wells, Samuel A; Asa, Sylvia L; Dralle, Henning; Elisei, Rossella; Evans, Douglas B; Gagel, Robert F; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G

    2015-06-01

    The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice.

  3. Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma

    PubMed Central

    Asa, Sylvia L.; Dralle, Henning; Elisei, Rossella; Evans, Douglas B.; Gagel, Robert F.; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F.; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M. Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G.

    2015-01-01

    Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice. PMID:25810047

  4. Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia.

    PubMed

    Matsuo, Koji; Ramzan, Amin A; Gualtieri, Marc R; Mhawech-Fauceglia, Paulette; Machida, Hiroko; Moeini, Aida; Dancz, Christina E; Ueda, Yutaka; Roman, Lynda D

    2015-11-01

    Although a fraction of endometrial hyperplasia cases have concurrent endometrial carcinoma, patient characteristics associated with concurrent malignancy are not well described. The aim of our study was to identify predictive clinico-pathologic factors for concurrent endometrial carcinoma among patients with endometrial hyperplasia. A case-control study was conducted to compare endometrial hyperplasia in both preoperative endometrial biopsy and hysterectomy specimens (n=168) and endometrial carcinoma in hysterectomy specimen but endometrial hyperplasia in preoperative endometrial biopsy (n=43). Clinico-pathologic factors were examined to identify independent risk factors of concurrent endometrial carcinoma in a multivariate logistic regression model. The most common histologic subtype in preoperative endometrial biopsy was complex hyperplasia with atypia [CAH] (n=129) followed by complex hyperplasia without atypia (n=58) and simple hyperplasia with or without atypia (n=24). The majority of endometrial carcinomas were grade 1 (86.0%) and stage I (83.7%). In multivariate analysis, age 40-59 (odds ratio [OR] 3.07, p=0.021), age≥60 (OR 6.65, p=0.005), BMI≥35kg/m(2) (OR 2.32, p=0.029), diabetes mellitus (OR 2.51, p=0.019), and CAH (OR 9.01, p=0.042) were independent predictors of concurrent endometrial carcinoma. The risk of concurrent endometrial carcinoma rose dramatically with increasing number of risk factors identified in multivariate model (none 0%, 1 risk factor 7.0%, 2 risk factors 17.6%, 3 risk factors 35.8%, and 4 risk factors 45.5%, p<0.001). Hormonal treatment was associated with decreased risk of concurrent endometrial cancer in those with ≥3 risk factors. Older age, obesity, diabetes mellitus, and CAH are predictive of concurrent endometrial carcinoma in endometrial hyperplasia patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Blockade of renal medullary bradykinin B2 receptors increases tubular sodium reabsorption in rats fed a normal-salt diet

    PubMed Central

    Sivritas, Sema-Hayriye; Ploth, David W.; Fitzgibbon, Wayne R.

    2008-01-01

    The present study was performed to test the hypothesis that under normal physiological conditions and/or during augmentation of kinin levels, intrarenal kinins act on medullary bradykinin B2 (BKB2) receptors to acutely increase papillary blood flow (PBF) and therefore Na+ excretion. We determined the effect of acute inner medullary interstitial (IMI) BKB2 receptor blockade on renal hemodynamics and excretory function in rats fed either a normal (0.23%)- or a low (0.08%)-NaCl diet. For each NaCl diet, two groups of rats were studied. Baseline renal hemodynamic and excretory function were determined during IMI infusion of 0.9% NaCl into the left kidney. The infusion was then either changed to HOE-140 (100 μg·kg−1·h−1, treated group) or maintained with 0.9% NaCl (time control group), and the parameters were again determined. In rats fed a normal-salt diet, HOE-140 infusion decreased left kidney Na+ excretion (urinary Na+ extraction rate) and fractional Na+ excretion by 40 ± 5% and 40 ± 4%, respectively (P < 0.01), but did not alter glomerular filtration rate, inner medullary blood flow (PBF), or cortical blood flow. In rats fed a low-salt diet, HOE-140 infusion did not alter renal regional hemodynamics or excretory function. We conclude that in rats fed a normal-salt diet, kinins act tonically via medullary BKB2 receptors to increase Na+ excretion independent of changes in inner medullary blood flow. PMID:18632797

  6. Eliminating medullary 5-HT neurons delays arousal and decreases the respiratory response to repeated episodes of hypoxia in neonatal rat pups

    PubMed Central

    Schneider, Robert W.; Tobia, Christine M.; Commons, Kathryn G.

    2015-01-01

    Arousal from sleep is a critical defense mechanism when infants are exposed to hypoxia, and an arousal deficit has been postulated as contributing to the etiology of the sudden infant death syndrome (SIDS). The brainstems of SIDS infants are deficient in serotonin (5-HT) and tryptophan hydroxylase (TPH) and have decreased binding to 5-HT receptors. This study explores a possible connection between medullary 5-HT neuronal activity and arousal from sleep in response to hypoxia. Medullary raphe 5-HT neurons were eliminated from neonatal rat pups with intracisterna magna (CM) injections of 5,7-dihydroxytryptamine (DHT) at P2-P3. Each pup was then exposed to four episodes of hypoxia during sleep at three developmental ages (P5, P15, and P25) to produce an arousal response. Arousal, heart rate, and respiratory rate responses of DHT-injected pups were compared with pups that received CM artificial cerebrospinal fluid (aCSF) and those that received DHT but did not have a significant reduction in medullary 5-HT neurons. During each hypoxia exposure, the time to arousal from the onset of hypoxia (latency) was measured together with continuous measurements of heart and respiratory rates, oxyhemoglobin saturation, and chamber oxygen concentration. DHT-injected pups with significant losses of medullary 5-HT neurons exhibited significantly longer arousal latencies and decreased respiratory rate responses to hypoxia compared with controls. These results support the hypothesis that in newborn and young rat pups, 5-HT neurons located in the medullary raphe contribute to the arousal response to hypoxia. Thus alterations medullary 5-HT mechanisms might contribute to an arousal deficit and contribute to death in SIDS infants. PMID:26702023

  7. The clinical manifestations, diagnosis, and treatment of adrenal emergencies.

    PubMed

    Tucci, Veronica; Sokari, Telematé

    2014-05-01

    Emergency medicine physicians should be able to identify and treat patients whose clinical presentations, including key historical, physical examination, and laboratory findings are consistent with diagnoses of primary, secondary, and tertiary adrenal insufficiency, adrenal crisis, and pheochromocytoma. Failure to make a timely diagnosis leads to increased morbidity and mortality. As great mimickers, adrenal emergencies often present with a constellation of nonspecific signs and symptoms that can lead even the most diligent emergency physician astray. The emergency physician must include adrenal emergencies in the differential diagnosis when encountering such clinical pictures. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Peptide Receptor Radionuclide Therapy (PRRT) of Medullary and Nonmedullary Thyroid Cancer Using Radiolabeled Somatostatin Analogues.

    PubMed

    Salavati, Ali; Puranik, Ameya; Kulkarni, Harshad R; Budiawan, Hendra; Baum, Richard P

    2016-05-01

    As therapeutic options in advanced medullary and non-iodine avid differentiated (nonmedullary) thyroid cancers are limited and associated with significant toxicity, targeting of somatostatin receptors (SSTRs) for internal radiation therapy provides a promising option. Theranostics (therapy and diagnosis) using radiolabeled somatostatin analogues has proved to be a milestone in the management of SSTR-expressing tumors. Peptide receptor radionuclide therapy using (177)Lu-labeled or (90)Y-labeled somatostatin analogues may have a significant role in the management of medullary and nonmedullary thyroid cancers in those patients where PET/CT with (68)Ga-labeled somatostatin analogues demonstrates significant SSTR expression. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Staged Bilateral Laparoscopic Adrenalectomy for Infantile ACTH-independent Cushing's Syndrome (Bilateral Micronodular Non-pigmented Adrenal Hyperplasia): A Case Report.

    PubMed

    Simforoosh, Nasser; Razzaghy Azar, Maryam; Soltani, Mohmmad Hossein; Nourbakhsh, Mona; Shemshaki, Hamidreza

    2017-08-29

    ACTH-independent Cushing's syndrome is an uncommon disorder in children. While laparoscopic adrenalectomy is well-established in adults, it is rarely used in infants and is associated with some concerns. A seven-month infant was referred to our hospital due to progressive signs and symptoms of Cushing's syndrome. Laboratory data confirmed ACTH-independent hypercortisolism. No history of exogenous corticosteroid contact was observed. The patient underwent left transperitoneal laparoscopic adrenalectomy when she was 7 months old, nevertheless,complete response was not seen. The patient underwent right laparoscopic adrenalectomy (contra-lateral adrenal gland) when she was 20 months old. The signs and symptoms of Cushing's syndrome began to resolve and serum and urine cortisol levels became normal 3 months after the second surgery. laparoscopic adrenalectomy is safe and feasible in infants, and in this case, relieved patient of the symptoms and saved her life.

  10. Mortality of Septic Mice Strongly Correlates With Adrenal Gland Inflammation.

    PubMed

    Jennewein, Carla; Tran, Nguyen; Kanczkowski, Waldemar; Heerdegen, Lars; Kantharajah, Ajith; Dröse, Stefan; Bornstein, Stefan; Scheller, Bertram; Zacharowski, Kai

    2016-04-01

    Sepsis and septic shock are commonly present in the ICU and accompanied by significant morbidity, mortality, and cost. The frequency of secondary adrenal insufficiency in sepsis remains open to debate and a challenge to identify and treat appropriately. Animal models of sepsis using genetic or surgical initiation of adrenal insufficiency resulted in increased mortality, but the mechanisms are still unclear. The present study investigates the impact of adrenal inflammation in septic mice challenged with cecal ligation and puncture. Prospective experimental study. University laboratory. C57BL/6N wild-type mice. Sepsis, induced by cecal ligation and puncture for 24 and 48 hours. Both septic and control mice were carefully monitored (every 30 min) for up to 48 hours and divided into survivors and nonsurvivors. We observed a significant and massive increase of interleukin-6, interleukin-1β, and tumor necrosis factor-α in adrenal protein extracts of nonsurvivors compared with sham animals and survivors. This pattern was partly reflected in liver and lung but not in plasma samples. Notably, a significant increase in nonsurvivors compared with survivors was only found for lung interleukin-6. In line with these findings, we detected a higher degree of leukocyte infiltration and hemorrhage in the adrenal glands of deceased mice. Evaluation of the hypothalamic-pituitary-adrenal axis response in these animals revealed an increase of adrenocorticotropic hormone, which was only partly reflected in the corticosterone level. Notably, using the adrenocorticotropic hormone stimulation test, we found an impaired adrenocorticotropic hormone response, particularly in nonsurvivors, which significantly correlated with the number of infiltrated leukocytes. Cecal ligation and puncture-induced murine sepsis induces a strong inflammatory response in the adrenal glands, which is accompanied by cell death and hemorrhage. Our data suggest that mortality and adrenal incapacitation are

  11. A review of the anatomy and clinical significance of adrenal veins.

    PubMed

    Cesmebasi, Alper; Du Plessis, Maira; Iannatuono, Mark; Shah, Sameer; Tubbs, R Shane; Loukas, Marios

    2014-11-01

    The adrenal veins may present with a multitude of anatomical variants, which surgeons must be aware of when performing adrenalectomies. The adrenal veins originate during the formation of the prerenal inferior vena cava (IVC) and are remnants of the caudal portion of the subcardinal veins, cranial to the subcardinal sinus in the embryo. The many communications between the posterior cardinal, supracardinal, and subcardinal veins of the primordial venous system provide an explanation for the variable anatomy. Most commonly, one central vein drains each adrenal gland. The long left adrenal vein joins the inferior phrenic vein and drains into the left renal vein, while the short right adrenal vein drains immediately into the IVC. Multiple variations exist bilaterally and may pose the risk of surgical complications. Due to the potential for collaterals and accessory adrenal vessels, great caution must be taken during an adrenalectomy. Adrenal venous sampling, the gold standard in diagnosing primary hyperaldosteronism, also requires the clinician to have a thorough knowledge of the adrenal vein anatomy to avoid iatrogenic injury. The adrenal vein acts as an important conduit in portosystemic shunts, thus the nature of the anatomy and hypercoagulable states pose the risk of thrombosis. © 2014 Wiley Periodicals, Inc.

  12. Laser autofluorescent spectroscopy in adrenal tumor surgery

    NASA Astrophysics Data System (ADS)

    Vetshev, Petr S.; Ippolitov, Leonid I.; Loschenov, Victor B.; Kazaryan, Airazat M.; Minnibaev, Marat T.; Vetshev, Sergei P.

    1999-12-01

    Determination of a histological type of adrenal lesion at the preoperative or intraoperative stage allows to choose the optimal volume of surgery and in the short time effectively correct the postoperative hormonal therapy. 12 patients with different adrenal tumours (3 - lightcellular adenoma, 3 - mixedcellular adenoma, 1 - darkcellular adenoma, 1 - trabecular adenoma, 1 - malignant lymphoma, 3 - aldosteroma, 1 - pheochromocytoma, including the chance of combination of mixedcellular adenoma and aldosteroma of left adrenal) were operated on. The patients' aged varied from 33 to 62 years. For the first time we made intraoperative laser autofluorescent spectroscopy (IOLAS). The laser ve1ength was 632.8 nm. We defined a autofluorescent intensity. Portable equipment was used. The duration of the procedure did not exceed 2mm. The autofluorescent peak of adrenal tissue was 1.33+/-0.05 relativistic unit (RU) at 685 nm. The autofiurescent peaks of adrenal adenomas were 1 .07 RU, 0.9-1 .15 RU, 1.7-1 .9 RU, 3.4 RU accordingly for trabecular adenoma, lightcellular adenoma, mixedcellular adenoma, darkcellular adenoma Besides greater contribution of longwave component to auflurescence is characteristic for mixecellular adenoma and especially for darkcellular adenoma. The autofiurescent peaks of aldosteroma and pheochromocytoma were accordingly 1.2-1.4 RU and 2.2 RU. Spectral distribution of intensity was like mixedcellular adenoma's one. In the case of malignant lymphoma the autofiurescence peak was 2,3 RU and we also noted displacement of maximum of autoflurescence (-15 nm, from 685 nm to 670 nm).The results of IOLAS application as a adjuvant diagnosticmethod point to promise for intraoperative rapid diagnostics of adrenal tumours.

  13. Bilateral medial medullary infarction: a systematic review.

    PubMed

    Pongmoragot, Jitphapa; Parthasarathy, Sujatha; Selchen, Daniel; Saposnik, Gustavo

    2013-08-01

    Bilateral infarction of the medial medulla (MMI) is rare. Limited information is available on clinical characteristics, etiology, and prognosis. High-resolution neuroimaging has a major role in elucidating the underlying stroke mechanism. The aim of this systematic review was to analyze the clinical presentations, stroke mechanisms, and outcomes in patients with bilateral MMI. We performed a systematic review of the literature from 1992-2011 that reported on clinical presentations, stroke mechanism, and/or outcomes in patients with magnetic resonance imaging-proven bilateral MMI. Medline, EMBASE, and Web of Science Scholars Portal were searched without language restriction. Two reviewers independently assessed identified studies to determine eligibility, validity, and quality. The primary outcome was inpatient mortality; a secondary outcome was case fatality at 12 months. We identified 138 articles from Medline, EMBASE, and Scholars Portal including the MeSH terms "brainstem infarction," "medulla," and "bilateral." Twenty-nine articles met our inclusion criteria, including a total of 38 cases with bilateral MMI, and included in our study. These 38 patients had a mean age of 62.2 years and were predominately male (74.2%). The most common clinical presentations were motor weakness in 78.4%, dysarthria in 48.6%, and hypoglossal palsy in 40.5%. The most common vascular pathology was vertebral artery atherosclerosis, in 38.5%. The clinical outcome was poor (mortality, 23.8%; dependency, 61.9%). Bilateral medial medullary infarction is a rare stroke syndrome. Clinical presentations were mostly rostral medullary lesions. Large-artery atherosclerosis and branch disease were the most common stroke mechanisms. The clinical outcome was usually poor. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Adrenal Function Status in Patients with Paracoccidioidomycosis after Prolonged Post-Therapy Follow-Up

    PubMed Central

    Tobón, Angela M.; Agudelo, Carlos A.; Restrepo, Carlos A.; Villa, Carlos A.; Quiceno, William; Estrada, Santiago; Restrepo, Angela

    2010-01-01

    This study assessed adrenal function in patients with paracoccididioidomycosis who had been treated to determine a possible connection between high antibody titers and adrenal dysfunction attributable to persistence of the fungus in adrenal gland. Adrenal gland function was studied in 28 previously treated patients, 2 (7.1%) of whom were shown to have adrenal insufficiency and 7 (259%) who showed a below normal response to stimuli by adrenocorticotropic hormone. Paracoccidioides brasiliensis was detected in the adrenal gland from one of the patients with adrenal insufficiency. Although the study failed to demonstrate a significant difference between high antibody titers and low cortisol levels, the proportion of adrenal insufficiency detected and the subnormal response to adrenocorticotropic hormone confirmed that adrenal damage is an important sequela of paracoccidioidomycosis. Studies with a larger number of patients should be conducted to confirm the hypothesis of persistence of P. brasiliensis in adrenal gland after therapy. PMID:20595488

  15. Characterization of Adrenal Adenoma by Gaussian Model-Based Algorithm.

    PubMed

    Hsu, Larson D; Wang, Carolyn L; Clark, Toshimasa J

    2016-01-01

    We confirmed that computed tomography (CT) attenuation values of pixels in an adrenal nodule approximate a Gaussian distribution. Building on this and the previously described histogram analysis method, we created an algorithm that uses mean and standard deviation to estimate the percentage of negative attenuation pixels in an adrenal nodule, thereby allowing differentiation of adenomas and nonadenomas. The institutional review board approved both components of this study in which we developed and then validated our criteria. In the first, we retrospectively assessed CT attenuation values of adrenal nodules for normality using a 2-sample Kolmogorov-Smirnov test. In the second, we evaluated a separate cohort of patients with adrenal nodules using both the conventional 10HU unit mean attenuation method and our Gaussian model-based algorithm. We compared the sensitivities of the 2 methods using McNemar's test. A total of 183 of 185 observations (98.9%) demonstrated a Gaussian distribution in adrenal nodule pixel attenuation values. The sensitivity and specificity of our Gaussian model-based algorithm for identifying adrenal adenoma were 86.1% and 83.3%, respectively. The sensitivity and specificity of the mean attenuation method were 53.2% and 94.4%, respectively. The sensitivities of the 2 methods were significantly different (P value < 0.001). In conclusion, the CT attenuation values within an adrenal nodule follow a Gaussian distribution. Our Gaussian model-based algorithm can characterize adrenal adenomas with higher sensitivity than the conventional mean attenuation method. The use of our algorithm, which does not require additional postprocessing, may increase workflow efficiency and reduce unnecessary workup of benign nodules. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Bilateral medial medullary syndrome secondary to Takayasu arteritis.

    PubMed

    Deshpande, Anirudda; Chandran, Vijay; Pai, Aparna; Rao, Suryanarayana; Shetty, Ranjan

    2013-08-13

    Medial medullary syndrome (MMS) is a rare type of stroke which results due to occlusion of the anterior spinal artery or vertebral artery or its branches. In this case report we present a patient who developed MMS secondary to Takayasu arteritis (TA). TA is a chronic inflammatory arteritis primarily involving the arch of aorta and its branches, which in our patient resulted in occlusion of subclavian arteries as well as infarction of the medial medulla bilaterally. To our knowledge this is the first time that MMS has been found to occur secondary to TA.

  17. Farnesoid X receptor is essential for the survival of renal medullary collecting duct cells under hypertonic stress.

    PubMed

    Xu, Sujuan; Huang, Shizheng; Luan, Zhilin; Chen, Tingyue; Wei, Yuanyi; Xing, Miaomiao; Li, Yaqing; Du, Chunxiu; Wang, Bing; Zheng, Feng; Wang, Nanping; Guan, Youfei; Gustafsson, Jan-Åke; Zhang, Xiaoyan

    2018-05-22

    Hypertonicity in renal medulla is critical for the kidney to produce concentrated urine. Renal medullary cells have to survive high medullary osmolarity during antidiuresis. Previous study reported that farnesoid X receptor (FXR), a nuclear receptor transcription factor activated by endogenous bile acids, increases urine concentrating ability by up-regulating aquaporin 2 expression in medullary collecting duct cells (MCDs). However, whether FXR is also involved in the maintenance of cell survival of MCDs under dehydration condition and hypertonic stress remains largely unknown. In the present study, we demonstrate that 24-hours water restriction selectively up-regulated renal medullary expression of FXR with little MCD apoptosis in wild-type mice. In contrast, water deprivation caused a massive apoptosis of MCDs in both global FXR gene-deficient mice and collecting duct-specific FXR knockout mice. In vitro studies showed that hypertonicity significantly increased FXR and tonicity response enhancer binding protein (TonEBP) expression in mIMCD3 cell line and primary cultured MCDs. Activation and overexpression of FXR markedly increased cell viability and decreased cell apoptosis under hyperosmotic conditions. In addition, FXR can increase gene expression and nuclear translocation of TonEBP. We conclude that FXR protects MCDs from hypertonicity-induced cell injury very likely via increasing TonEBP expression and nuclear translocation. This study provides insights into the molecular mechanism by which FXR enhances urine concentration via maintaining cell viability of MCDs under hyperosmotic condition.

  18. Thyroid epithelial cell hyperplasia in IFN-gamma deficient NOD.H-2h4 mice.

    PubMed

    Yu, Shiguang; Sharp, Gordon C; Braley-Mullen, Helen

    2006-01-01

    The role of inflammatory cells in thyroid epithelial cell (thyrocyte) hyperplasia is unknown. Here, we demonstrate that thyrocyte hyperplasia in IFN-gamma-/- NOD.H-2h4 mice has an autoimmune basis. After chronic exposure to increased dietary iodine, 60% of IFN-gamma-/- mice had severe thyrocyte hyperplasia with minimal or moderate lymphocyte infiltration, and thyroid dysfunction with reduced serum T4. All mice produced anti-thyroglobulin autoantibody. Some wild-type NOD.H-2h4 mice had isolated areas of thyrocyte hyperplasia with predominantly lymphocytic infiltration, whereas IL-4-/- and 50% of wild-type NOD.H-2h4 mice developed lymphocytic thyroiditis but no thyrocyte hyperplasia. Both thyroid infiltrating inflammatory cells and environmental factors (iodine) were required to induce thyrocyte hyperplasia. Splenocytes from IFN-gamma-/- mice with thyrocyte hyperplasia, but not splenocytes from naïve IFN-gamma-/- mice, induced hyperplasia in IFN-gamma-/- NOD.H-2h4.SCID mice. These results may provide clues for understanding the mechanisms underlying development of epithelial cell hyperplasia not only in thyroids but also in other tissues and organs.

  19. Hereditary Pituitary Hyperplasia with Infantile Gigantism

    PubMed Central

    Gläsker, Sven; Vortmeyer, Alexander O.; Lafferty, Antony R. A.; Hofman, Paul L.; Li, Jie; Weil, Robert J.; Zhuang, Zhengping

    2011-01-01

    Context: We report hereditary pituitary hyperplasia. Objective: The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. Design: The study is a retrospective analysis of three cases from one family. Setting: The study was conducted at the National Institutes of Health, a tertiary referral center. Patients: A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. Interventions: The condition was treated by total hypophysectomy. Main Outcome Measure(s): We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. Results: All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. Conclusions: This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development. PMID:21976722

  20. [A case of bilateral medial medullary infarction caused by unilateral vertebral artery dissection].

    PubMed

    Akimoto, Takayoshi; Hara, Makoto; Saito, Mari; Takahashi, Keiko; Kamei, Satoshi

    2015-01-01

    A 34-year-old man developed right neck pain. Several hours later, he felt numbness of his extremities and presented at our hospital. He developed right hemiparesis and hypoesthesia of the right extremities. A few hours later, upbeat nystagmus and dysarthria appeared along with a sensory disturbance that spread to all extremities, and right hemiparesis progressed to tetraplegia. Brain MR diffusion-weighted images revealed a high-intensity lesion in the bilateral medial medulla oblongata and we diagnosed this bilateral medial medullary infarction. Three dimentional CT angiography revealed dissection of the right VA. We administered intravenous argatroban, edaravone, glycerin and oral clopidogrel. He was assessed as having modified Rankin scale 4 and was transferred to another hospital for rehabilitation on day 30. When the medial medulla oblongata is supplied by the unilateral VA, a unilateral VA dissection can cause bilateral medial medullary infarction.

  1. Case report of a bilateral adrenal myelolipoma associated with Cushing disease.

    PubMed

    Park, Se Yoon; Kwak, Mi Kyung; Kim, Hye Jeong; Park, Hyeong Kyu; Suh, Kyo-Il; Yoo, Myung Hi; Jin, So Young; Yun, Sumi; Byun, Dong Won

    2017-12-01

    Adrenal myelolipomas are rare benign tumors, composed of a variable mixture of mature adipose tissue and hematopoietic tissue. These tumors are frequently detected incidentally and are usually asymptomatic, and hormonally inactive. During a routine health checkup, a 52-year-old man was found to have a tumor on the bilateral adrenal glands. Abdominal computed tomography revealed a well-defined, heterogeneously enhanced bilateral adrenal mass, suggesting a myelolipoma. The hormonal evaluation revealed adrenocorticotropic hormone (ACTH) dependent Cushing syndrome. The patient underwent left adrenalectomy, and transsphenoidal resection of a pituitary mass. The final diagnosis was adrenal myelolipoma associated with Cushing disease. Growth of right adrenal myelolipoma was detected during the 7-year follow-up. There were enhancing pituitary lesions in repeat magnetic resonance imaging of the sellar region, which implies persistent or recurrent pituitary adenoma. This case reinforces relationship between Cushing disease and adrenal myelolipoma. To the best of our knowledge, this is the first reported pathologically confirmed bilateral adrenal myelolipoma associated with Cushing disease. This report supports the idea that ACTH is associated with the development of adrenal myelolipoma. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  2. Adrenal incidentaloma caused by extramedullary haematopoiesis: conservative management is optimal.

    PubMed

    Sekar, Suganya; Burad, Deepak; Abraham, Aby; Paul, Mazhuvanchary Jacob

    2015-09-21

    We present a thalassaemic patient with extramedullary haematopoiesis in the adrenal gland, which is one of the rare sites of involvement. A 29-year-old man presented with a history of anaemia since childhood which required blood transfusion recently. On examination, he had pallor, icterus and splenomegaly with no other palpable abdominal mass. He was diagnosed to have β-thalassaemia. Ultrasonography of the abdomen showed an incidental right adrenal mass with splenomegaly; CT revealed a large right adrenal mass with heterogeneous density. Adrenal adenoma, carcinoma and extramedullary haematopoiesis were considered in the differential diagnosis. After excluding a functioning tumour, the diagnosis was confirmed by ultrasound-guided biopsy. Since the patient was asymptomatic, the adrenal lesion was managed conservatively. 2015 BMJ Publishing Group Ltd.

  3. Progression to Adrenocortical Tumorigenesis in Mice and Humans through Insulin-Like Growth Factor 2 and β-Catenin

    PubMed Central

    Heaton, Joanne H.; Wood, Michelle A.; Kim, Alex C.; Lima, Lorena O.; Barlaskar, Ferdous M.; Almeida, Madson Q.; Fragoso, Maria C.B.V.; Kuick, Rork; Lerario, Antonio M.; Simon, Derek P.; Soares, Ibere C.; Starnes, Elisabeth; Thomas, Dafydd G.; Latronico, Ana C.; Giordano, Thomas J.; Hammer, Gary D.

    2013-01-01

    Dysregulation of the WNT and insulin-like growth factor 2 (IGF2) signaling pathways has been implicated in sporadic and syndromic forms of adrenocortical carcinoma (ACC). Abnormal β-catenin staining and CTNNB1 mutations are reported to be common in both adrenocortical adenoma and ACC, whereas elevated IGF2 expression is associated primarily with ACC. To better understand the contribution of these pathways in the tumorigenesis of ACC, we examined clinicopathological and molecular data and used mouse models. Evaluation of adrenal tumors from 118 adult patients demonstrated an increase in CTNNB1 mutations and abnormal β-catenin accumulation in both adrenocortical adenoma and ACC. In ACC, these features were adversely associated with survival. Mice with stabilized β-catenin exhibited a temporal progression of increased adrenocortical hyperplasia, with subsequent microscopic and macroscopic adenoma formation. Elevated Igf2 expression alone did not cause hyperplasia. With the combination of stabilized β-catenin and elevated Igf2 expression, adrenal glands were larger, displayed earlier onset of hyperplasia, and developed more frequent macroscopic adenomas (as well as one carcinoma). Our results are consistent with a model in which dysregulation of one pathway may result in adrenal hyperplasia, but accumulation of a second or multiple alterations is necessary for tumorigenesis. PMID:22800756

  4. Over-the-Counter "Adrenal Support" Supplements Contain Thyroid and Steroid-Based Adrenal Hormones.

    PubMed

    Akturk, Halis Kaan; Chindris, Ana Maria; Hines, Jolaine M; Singh, Ravinder J; Bernet, Victor J

    2018-03-01

    To assess whether dietary supplements that are herbal and/or animal-derived products, marketed for enhancing metabolism or promoting energy, "adrenal fatigue," or "adrenal support," contain thyroid or steroid hormones. Twelve dietary adrenal support supplements were purchased. Pregnenolone, androstenedione, 17-hydroxyprogesterone, cortisol, cortisone, dehydroepiandrosterone sulfate, synthetic glucocorticoids (betamethasone, dexamethasone, fludrocortisone, megestrol acetate, methylprednisolone, prednisolone, prednisone, budesonide, and triamcinolone acetonide) levels were measured twice in samples in a blinded fashion. This study was conducted between February 1, 2016, and November 1, 2016. Among steroids, pregnenolone was the most common hormone in the samples. Budesonide, 17-hydroxyprogesterone, androstenedione, cortisol, and cortisone were the others in order of prevalence. All the supplements revealed a detectable amount of triiodothyronine (T3) (63-394.9 ng/tablet), 42% contained pregnenolone (66.12-205.2 ng/tablet), 25% contained budesonide (119.5-610 ng/tablet), 17% contained androstenedione (1.27-7.25 ng/tablet), 8% contained 17-OH progesterone (30.09 ng/tablet), 8% contained cortisone (79.66 ng/tablet), and 8% contained cortisol (138.5 ng/tablet). Per label recommended doses daily exposure was up to 1322 ng for T3, 1231.2 ng for pregnenolone, 1276.4 ng for budesonide, 29 ng for androstenedione, 60.18 ng for 17-OH progesterone, 277 ng for cortisol, and 159.32 ng for cortisone. All the supplements studied contained a small amount of thyroid hormone and most contained at least 1 steroid hormone. This is the first study that measured thyroid and steroid hormones in over-the-counter dietary "adrenal support" supplements in the United States. These results may highlight potential risks of hidden ingredients in unregulated supplements. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  5. Medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome.

    PubMed

    Karunarathne, Suneth; Udayakumara, Yapa; Govindapala, Dumitha; Fernando, Harshini

    2012-07-26

    Medullary nephrocalcinosis and distal renal tubular acidosis are closely associated and each can lead to the other. These clinical entities are rare in patients with nephrotic syndrome and polycythaemia is an unusual finding in such patients. We describe the presence of medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome due to minimal change disease. Proposed mechanisms of polycythaemia in patients with nephrotic syndrome and distal renal tubular acidosis include, increased erythropoietin production and secretion of interleukin 8 which in turn stimulate erythropoiesis. A 22 year old Sri Lankan Sinhala male with nephrotic syndrome due to minimal change disease was investigated for incidentally detected polycythaemia. Investigations revealed the presence of renal tubular acidosis type I and medullary nephrocalcinosis. Despite extensive investigation, a definite cause for polycythaemia was not found in this patient. Treatment with potassium and bicarbonate supplementation with potassium citrate led to correction of acidosis thereby avoiding the progression of nephrocalcinosis and harmful effects of chronic acidosis. The constellation of clinical and biochemical findings in this patient is unique but the pathogenesis of erythrocytosis is not clearly explained. The proposed mechanisms for erythrocytosis in other patients with proteinuria include increased erythropoietin secretion due to renal hypoxia and increased secretion of interleukin 8 from the kidney. This case illustrates that there may exist hitherto unknown connections between tubular and glomerular dysfunction in patients with nephrotic syndrome.

  6. Adrenal suppression in bronchiectasis and the impact of inhaled corticosteroids.

    PubMed

    Holme, J; Tomlinson, J W; Stockley, R A; Stewart, P M; Barlow, N; Sullivan, A L

    2008-10-01

    The present study identified three patients with bronchiectasis receiving inhaled corticosteroids (ICSs) who had symptomatic adrenal suppression secondary to ICS. The prevalence of adrenal suppression is unknown in bronchiectasis. The frequency of adrenal suppression and the impact of ICS use in bronchiectasis patients were examined. In total, 50 outpatients (33 receiving ICSs) underwent a short Synacthen test and completed a St George's Respiratory Questionnaire (SGRQ). Symptoms of adrenal suppression, steroid use and lung function were compared between subjects who were suppressed and those who were not. Adrenal suppression was evident in 23.5% of subjects who did not receive ICSs and 48.5% of those who did. Basal cortisol and the increments by which cortisol increased 30 min after Synacthen were lower in suppressed than in nonsuppressed subjects. The incremental cortisol rise was negatively correlated with SGRQ impacts and total score, suggesting a worse quality of life in those who had an impaired adrenal response. The greatest frequency of generalised symptoms was seen in the suppressed group. A significant proportion of subjects with bronchiectasis have evidence of adrenal suppression, and this is increased when inhaled corticosteroids are also used. Impairment of the cortisol response to stimulation is associated with poorer health status.

  7. The contributions of adrenal hormones, hemodynamic factors, and the endotoxin-related stress reaction to stable prostaglandin analog-induced peripheral lymphopenia and neutrophilia.

    PubMed

    Ulich, T R; Keys, M; Ni, R X; del Castillo, J; Dakay, E B

    1988-01-01

    Stable prostaglandin analogs are known to induce lymphopenia and neutrophilia in a dose-dependent fashion after subcutaneous injection in rats. The purpose of the present investigation is to determine whether the prostaglandin-induced changes in circulating leukocytes might be secondary to hypotension with the ensuing release of adrenal hormones. The adrenal medullary catecholamine epinephrine was found to induce neutrophilia in both intact and adrenalectomized rats, and the glucocorticosteroid analog dexamethasone induced a profound lymphopenia in rats as reported by previous investigators. A stable analog of PGF2 alpha (15-S-15-methyl PGF2 alpha; M-PGF2 alpha) at the dose of 1 mg/kg induced marked systemic hypotension 1 h after injection, with lymphopenia and neutrophilia 6 h after injection. The non-prostanoid hypotensive agent captopril, at a dose of 63 mg/kg, induced a hypotension of similar magnitude and kinetics to that induced by prostaglandin. Captopril also induced lymphopenia and neutrophilia at 6 h, although the neutrophilia was of lesser magnitude than that induced by prostaglandins. The prostaglandin-induced lymphopenia was found to be mediated, at least in part, by the hypotension-induced release of adrenal hormones, as evidenced by the abrogation of lymphopenia in prostaglandin-treated adrenalectomized rats. Captopril-treated adrenalectomized rats, however, did develop a significant lymphopenia, suggesting that hypotension can result in lymphopenia even in adrenalectomized rats. The M-PGF2 alpha-induced neutrophilia in adrenalectomized rats, by comparison to captopril-induced neutrophilia in adrenalectomized rats, was greater than the neutrophilia expected as the result of hypotension alone. Indeed, the M-PGF2 alpha-induced neutrophilia in adrenalectomized rats was greater than the captopril-induced neutrophilia in sham-adrenalectomized rats. Thus, a portion of the neutrophilia induced by M-PGF2 alpha in intact rats may be mediated through adrenal

  8. The influence of age on positions of the conus medullaris, Tuffier's line, dural sac, and sacrococcygeal membrane in infants, children, adolescents, and young adults.

    PubMed

    Jung, Ji-Yun; Kim, Eun-Hee; Song, In-Kyung; Lee, Ji-Hyun; Kim, Hee-Soo; Kim, Jin-Tae

    2016-12-01

    The purpose of this study was to analyze the distances between the conus medullaris and the Tuffier's line, and between the dural sac and the sacrococcygeal membrane (SCM) in the same pediatric population. Spinal magnetic resonance images and simple X-ray images of 350 patients aged from 1 month to 20 years were reviewed. Positions of the conus medullaris, Tuffier's line, the dural sac, and the SCM were identified. Each position was recorded in relation to the corresponding vertebral body segments. The distances between the conus medullaris and Tuffier's line, and between the dural sac and the SCM, were measured and then assessed according to age using an analysis of variance and a linear regression analysis. The median levels of the conus medullaris and Tuffier's line were in the lower third of L1 [the first lumbar vertebral body] and the middle third of L5, respectively. The levels of the conus medullaris and Tuffier's line were lower in younger populations. The distance between the conus medullaris and Tuffier's line ranged from 1.5 to 4.75 vertebral body height. However, a narrow range of 1.5-2.5 vertebral height was observed only in children younger than 2 years. The level of the dural sac did not differ greatly by age, but the upper limit of the SCM was lower in older populations. The distance between the dural sac and the upper limit of the SCM increased with age. In children, there is a distance of 1.5-4.75 vertebral body height between the conus medullaris and the Tuffier's line. However, these distances were narrower among younger populations. The distance between the dural sac and the upper limit of the SCM increased with age. © 2016 John Wiley & Sons Ltd.

  9. Hidradenitis suppurativa/acne inversa: bilocated epithelial hyperplasia with very different sequelae.

    PubMed

    von Laffert, M; Stadie, V; Wohlrab, J; Marsch, W C

    2011-02-01

    Hidradenitis suppurativa/acne inversa is a chronic, inflammatory, scarring disease in the terminal hair follicle and apocrine gland-bearing areas (skin folds). There is considerable histological evidence that perifolliculitis and follicular hyperkeratosis precede the rupture of the follicle. The timing of the epithelial hyperplasia at the infundibula of inflamed terminal follicles has not yet been clarified. To clarify the early histopathological life of lesions ('chronology') in hidradenitis suppurativa/acne inversa, focusing on the terminal follicle structure and its surrounding tissue (hyperkeratosis, hyperplasia of follicular epithelium, perifolliculitis and rupture). In total, 485 operative specimens obtained from 128 patients with diagnosed hidradenitis suppurativa/acne inversa (all surgically treated by wide excision) were examined histologically. Two to five histological preparations (total 485) per operation area (total 196) were prepared by multiple slicing. Hidradenitis suppurativa/acne inversa showed a heterogeneous histological pattern: hyperkeratosis of the terminal follicles (89%), hyperplasia of follicular epithelium (80%), pronounced perifolliculitis (68%) and follicle rupture (24%). Perifolliculitis, follicular hyperkeratosis and hyperplasia occurred prior to the rupture of the follicle. Other histological criteria were: subepidermal cellular inflammatory infiltrate (82%), epidermal psoriasiform hyperplasia (56%), pronounced acute dermal inflammation (28%), pronounced chronic dermal inflammation (49%), and involvement of apocrine glands (52%) and subcutis (31%). Infundibular hyperkeratosis, hyperplasia of the follicular epithelium and perifolliculitis are major histopathological characteristics of hidradenitis suppurativa/acne inversa. These apparently precede rupture of the follicle. In particular, hyperplasia of the follicular epithelium probably marks the beginning of sinus formation, which usually spreads horizontally. Psoriasiform hyperplasia

  10. Adrenal trauma: Elvis Presley Memorial Trauma Center experience.

    PubMed

    Mehrazin, Reza; Derweesh, Ithaar H; Kincade, Matthew C; Thomas, Adam C; Gold, Robert; Wake, Robert W

    2007-11-01

    Adrenal gland injury is a potentially devastating event if unrecognized in the treatment course of a trauma patient. We reviewed our single-center experience and outcomes in patients with adrenal gland trauma. We performed a retrospective review of all patients presenting with trauma to the Regional Medical Center at Memphis who had adrenal gland injuries from January 1991 through March 2006. Each chart was reviewed with attention to the demographics, associated injuries, complications, and outcomes. Patients were stratified into two subgroups according to age (35 years or younger and older than 35 years) to allow for an age-based comparison between the two groups. Of 58,000 patients presenting with trauma, 130 (0.22%) were identified with adrenal injuries, of which 8 (6.2%) were isolated and 122 (93.8%) were not. Of these 130 patients, 125 (96.2%) had their injury diagnosed by computed tomography and 5 (3.8%) had their injury diagnosed during exploratory laparotomy. Right-sided injuries predominated (78.5%), with six (4.6%) bilateral. Four patients (3.1%) underwent adrenalectomy. Seven patients (5.4%) with adrenal injuries died. One patient (0.77%) required chronic steroid therapy. Patients older than 35 years were more likely to have complications such as deep venous thrombosis, pneumonia, and urinary tract infections. Patient age of 35 years or younger was associated with a significantly increased incidence of liver lacerations. Adrenal gland injury is uncommon, although mostly associated with greater injury severity. Although adding to morbidity, most are self-limited and do not require intervention.

  11. Adrenal collision tumor (parachordoma and ganglioneuroma): A case report.

    PubMed

    Lai, Yulin; Zhou, Liang; Hu, Jia; Li, Wenhua; Cui, Lin; Lai, Yongqing; Ni, Liangchao

    2018-06-01

    Adrenal collision tumors (ACTs) are distinct tumors that occur simultaneously in the same adrenal gland and are very rare. We herein report the case of a 56-year-old woman who was admitted to the hospital for medical imaging. The findings of the physical and laboratory examinations, including endocrine function, were unremarkable. Contrast-enhanced computed tomography of the abdomen revealed a 28×20×33-mm mass in the left adrenal medial limb, for which a laparoscopic surgery was performed. Postoperative pathological examination revealed two distinct tumors, namely a parachordoma and a ganglioneuroma. To the best of our knowledge, and following a thorough literature search, this is the first report of coexisting parachordoma and ganglioneuroma in the same adrenal gland.

  12. Multifocal Epithelial Hyperplasia.

    PubMed

    Agnew, Caitlin; Alexander, Sherene; Prabhu, Neeta

    2017-01-15

    Multifocal epithelial hyperplasia is a rare disease associated with human papilloma virus types 13 and 32. Diagnosis is based on clinical and histopathological findings, and most lesions are asymptomatic and regress spontaneously with time. The purpose of this paper is to describe a five-year-old girl who presented with multiple intraoral lesions on the buccal mucosa and tongue, which regressed spontaneously in 15 months.

  13. Intestinal nodular lymphoid hyperplasia and extraintestinal lymphoma--a rare association.

    PubMed

    Monsanto, P; Lérias, C; Almeida, N; Lopes, S; Cabral, J E; Figueiredo, P; Silva, M; Julião, M; Gouveia, H; Sofia, C

    2012-06-01

    Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of innumerable small discrete nodules involving a variable segment of the gastrointestinal tract. The association between nodular lymphoid hyperplasia and other benign and malignant diseases has been clearly described, with an increased risk of gastrointestinal tumours, namely gastrointestinal lymphoma. However, the association with extraintestinal lymphoma seems extremely rare. The authors present a clinical case of a patient with nodular lymphoid hyperplasia of the small and large intestine that subsequently developed an extraintestinal lymphoma (diffuse large B-cell lymphoma).

  14. Imaging of adrenal masses with emphasis on adrenocortical tumors.

    PubMed

    Sundin, Anders

    2012-01-01

    Because of the more widespread and frequent use of cross-sectional techniques, mainly computed tomography (CT), an increasing number of adrenal tumors are detected as incidental findings ("incidentalomas"). These incidentaloma patients are much more frequent than those undergoing imaging because of symptoms related to adrenal disease. CT and magnetic resonance imaging (MRI) are in most patients sufficient for characterization and follow-up of the incidentaloma. In a minor portion of patients, biochemical screening reveals a functional tumor and further diagnostic work-up and therapy need to be performed according to the type of hormonal overproduction. In oncological patients, especially when the morphological imaging criteria indicate an adrenal metastasis, biopsy of the lesion should be considered after pheochromocytoma is ruled out biochemically. In the minority of patients in whom CT and MRI fail to characterize the tumor and when time is of essence, functional imaging mainly by positron emission tomography (PET) is available using various tracers. The most used PET tracer, [(18)F]fluoro-deoxy-glucose ((18)FDG), is able to differentiate benign from malignant adrenal tumors in many patients. (11)C-metomidate ((11)C-MTO) is a more specialized PET tracer that binds to the 11-beta-hydroxylase enzyme in the adrenal cortex and thus makes it possible to differ adrenal tumors (benign adrenocortical adenoma and adrenocortical cancer) from those of non-adrenocortical origin.

  15. Focal fibrous hyperplasia: A review of 193 cases.

    PubMed

    de Santana Santos, Thiago; Martins-Filho, Paulo Ricardo Saquete; Piva, Marta Rabello; de Souza Andrade, Emanuel Sávio

    2014-09-01

    Focal fibrous hyperplasia, also known as irritation or traumatic fibroma, is a reactive, inflammatory hyperplastic lesion of the connective tissue. The aim of this study is to perform a retrospective study of a focal fibrous hyperplasia of 18 years. We retrospectively reviewed 193 cases of focal fibrous hyperplasia of the oral cavity from the medical and histological reports of the Department of Oral Pathology, Pernambuco University, Brazil, during the period between January 1992 and December 2009. Data with regard to age, gender, location, size of the lesion (equal to or less than 1 cm, between 1 and 2 cm and greater than 2 cm), pain, history of trauma, treatment, length of follow-up (from diagnosis to release or last review) and recurrence, were collected. The most commonly affected site was the buccal mucosa (n = 119, 61.7%). Almost two-thirds of the cases were concentrated from the second to the fifth decade of life. Females were more affected than men and a history of trauma was related by 90.7% of the patients. Two recurrences were notified (1.0%). Further studies are needed on the distribution of the lesion in different ethnic and geographical populations. The influence of sex hormones on the development of focal fibrous hyperplasia must be clarified.

  16. News about the genetics of congenital primary adrenal insufficiency.

    PubMed

    Roucher-Boulez, Florence; Mallet-Motak, Delphine; Tardy-Guidollet, Véronique; Menassa, Rita; Goursaud, Claire; Plotton, Ingrid; Morel, Yves

    2018-04-13

    Primary adrenal insufficiency (PAI) is characterized by impaired production of steroid hormones due to an adrenal cortex defect. This condition incurs a risk of acute insufficiency which may be life-threatening. Today, 80% of pediatric forms of PAI have a genetic origin but 5% have no clear genetic support. Recently discovered mutations in genes relating to oxidative stress have opened the way to research on genes unrelated to the adrenal gland. Identification of causal mutations in a gene responsible for PAI allows genetic counseling, guidance of follow-up and prevention of complications. This is particularly true for stress oxidative anomalies, as extra-adrenal manifestations may occur due to the sensitivity to oxidative stress of other organs such as the heart, thyroid, liver, kidney and pancreas. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  17. Quality of compounded hydrocortisone capsules used in the treatment of children.

    PubMed

    Neumann, Uta; Burau, Daniela; Spielmann, Sarah; Whitaker, Martin J; Ross, Richard J; Kloft, Charlotte; Blankenstein, Oliver

    2017-08-01

    Due to the lack of paediatric-licensed formulations, children are often treated with individualized pharmacy-compounded adult medication. An international web-based survey about the types of medication in children with adrenal insufficiency (AI) revealed that the majority of paediatric physicians are using pharmacy-compounded medication to treat children with AI. Observations of loss of therapy control in children with congenital adrenal hyperplasia with compounded hydrocortisone capsules and regained control after prescribing a new hydrocortisone batch led to this 'real world' evaluation of pharmacy-compounded paediatric hydrocortisone capsules. Capsule samples were collected randomly from volunteering parents of treated children suffering from congenital adrenal hyperplasia from all over Germany. Analysis of net mass and hydrocortisone content by high-performance liquid chromatography with ultraviolet (HPLC-UV) detection method was performed based on the European Pharmacopeia. In a total of 61 batches that were sent, 5 batches could not be analysed because of missing dose information, insufficient number of capsules or were not possible to be evaluated. Fifty-six batches containing 1125 capsules were evaluated. 21.4% of the batches revealed insufficiency in uniformity of net mass or drug content and additional 3.6% failed because they did not contain the labelled drug. Compounded medication is a possible cause of variation of steroid doses in children with adrenal insufficiency or congenital adrenal hyperplasia, putting these vulnerable patients at risk of poor disease control and adrenal crisis. These data may apply to other individualized compounded oral medication as well, emphasizing the need for development of licensed paediatric formulations approved by regulatory authorities. © 2017 European Society of Endocrinology.

  18. Expression of CTLA-4 (CD152) on human medullary CD4+ thymocytes.

    PubMed

    Castan, J; Klauenberg, U; Kalmár, P; Fleischer, B; Bröker, B M

    1998-06-01

    CTLA-4 (CD152) is a T cell surface receptor with sequence homology to the co-stimulatory molecule CD28. The molecule, which is essential for the inhibitory regulation of the immune response, becomes transiently expressed on mature T cells after stimulation in vitro. In situ, CTLA-4+ T cells are enriched in the light zones of the germinal centers in human peripheral lymphoid organs. In this study we have studied expression of CTLA-4 in human thymus in situ. CTLA-4 was expressed on about one third of CD4+/CD8-/CD1- medullary thymocytes. CTLA-4 was acquired by a subset of immature (CD1+) thymocytes and lost from the mature (CD1-) subpopulation within 48 h of cell culture, suggesting that the expression on medullary thymocytes is transient. The demonstration of CTLA-4 on a substantial subpopulation of mature CD4+ thymocytes adds a new dimension to the understanding of this important molecule. When contemplating application of anti-CTLA-4 for therapy its potential influence on T cell maturation has to be taken into account.

  19. Successful Adrenal Venous Sampling by Non-experts with Reference to CT Images

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

    Morita, Satoru, E-mail: i@imodey.com; Yamazaki, Hiroshi; Sonoyama, Yasuyuki

    PurposeTo establish technical success rates and safety of adrenal venous sampling (AVS) performed by non-experts with reference to CT images.Materials and Methods104 AVS procedures with adrenocorticotropic hormone stimulation were performed for patients with suspected primary aldosteronism. One of three radiology residents with 2nd, 5th, and 5th grade experience undertook the procedure under the guidance of an experienced, board-certified interventional radiologist with reference to contrast-enhanced CT images obtained in 102 cases. Successful catheterization of the adrenal veins was assessed using three criteria: an adrenal venous cortisol concentration of more than 200 μg/dL (criterion A); an adrenal vein/inferior vena cava cortisol ratio ofmore » more than 5:1 (criterion B); and an adrenal vein/inferior vena cava cortisol ratio of more than 10:1 (criterion C).ResultsThe operators were aware of the anatomy of the left adrenal veins in 102 cases (98 %) and of the right adrenal veins in 99 cases (95 %) prior to the procedure. CT identified the correct position of the right adrenal vein orifice in 82 of 99 cases (83 %). The overall technical success rates for AVS from the right adrenal vein according to criteria A, B, and C, were 96, 96, and 94 %, respectively. Those for the left adrenal vein were 97, 98, and 94 %, respectively. No significant differences in success rates were observed between the operators (p = 0.922–0.984). No major complications, including adrenal vein rupture, were observed.ConclusionsWhen CT images are used to guide AVS, the procedure can be performed successfully and safely even by non-experts.« less

  20. Review analysis of medullary carcinoma of the thyroid: a 15-year Indian experience.

    PubMed

    Dorairajan, N; Siddharth, D; Kanna, Srinivasulu

    2006-01-01

    The aim of this study was to emphasize the importance of adequate primary surgery in cases of medullary carcinoma of the thyroid. We retrospectively reviewed 44 cases of medullary carcinoma of the thyroid treated in Government General Hospital, Chennai between 1987 and 2002. Patients who underwent total thyroidectomy with only central compartment dissection were compared with those who had undergone total thyroidectomy with meticulous triple compartment (bilateral lateral and central groups) nodal dissection. The group of total thyroidectomy with only central compartment dissection had a high rate of lymph nodal recurrence and persistent hypercalcitoninemia compared with the group with total thyroidectomy with meticulous triple compartment nodal dissection. (chi square, 4.503; P > 0.05). Primary surgery with total thyroidectomy with meticulous triple compartment dissection is superior to total thyroidectomy with central compartment dissection alone in terms of preventing nodal and local recurrences and achieving normal (basal and stimulated) serum calcitonin levels postoperatively.

  1. Ewing's Sarcoma of the Adrenal Gland.

    PubMed

    Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

    2016-01-01

    Ewing's sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing's sarcoma is very rare. Here we report a case of Ewing's sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery.

  2. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study.

    PubMed

    Hahner, Stefanie; Spinnler, Christina; Fassnacht, Martin; Burger-Stritt, Stephanie; Lang, Katharina; Milovanovic, Danijela; Beuschlein, Felix; Willenberg, Holger S; Quinkler, Marcus; Allolio, Bruno

    2015-02-01

    Adrenal crisis (AC) is a life-threatening complication of adrenal insufficiency (AI), which according to retrospective data represents a significant clinical complication. Here we aimed to prospectively assess incidence of AC and mortality associated with AC in patients with chronic AI. A total of 423 patients with AI (primary AI, n = 221; secondary AI, n = 202) were prospectively followed up for 2 years. Baseline assessment included a general questionnaire and detailed written instructions on glucocorticoid dose adaptation during stress. Patients received follow-up questionnaires every 6 months and were contacted by phone in case of reported adrenal crisis. A total of 423 data sets were available for baseline analysis, and 364 patients (86%) completed the whole study. Sixy-four AC in 767.5 patient-years were documented (8.3 crises per 100 patient-years). Precipitating causes were mainly gastrointestinal infection, fever, and emotional stress (20%, respectively) but also other stressful events (eg, major pain, surgery, strenuous physical activity, heat, pregnancy) or unexplained sudden onset of AC (7%) were documented. Patients with a previous AC were at higher risk of crisis (odds ratio 2.85, 95% confidence interval 1.5-5.5, P < .01). However, no further risk factors could be identified. Ten patients died during follow-up; in four cases death was associated with AC (0.5 AC related deaths per 100 patient-years). Even in educated patients with chronic adrenal insufficiency, AC occurs in a substantial proportion of cases. Furthermore, we identified AC-associated mortality in approximately 6% of AC. Our findings further emphasize the need for improved management of AC in patients with chronic AI.

  3. Lymphangioma circumscriptum, angiokeratoma, or superficial vascular ectasia with epithelial hyperplasia?

    PubMed

    Katsoulas, Nikolaos; Tosios, Konstantinos I; Argyris, Prokopios; Koutlas, Ioannis G; Sklavounou, Alexandra

    2014-08-01

    We report a case of lymphangioma circumscriptum (cavernous lymphangioma with epithelial hyperplasia) in a 12-year-old girl, presenting as a papillary tumor on the right dorsal side of her tongue. Microscopic examination found cavernous vascular channels lined by a single layer of CD31(+), podoplanin-positive, CD34(-) endothelial cells that occupied the papillary lamina propria and were accompanied by epithelial hyperplasia. A review of the literature on oral vascular tumors with epithelial hyperplasia, namely, lymphangioma circumscriptum and angiokeratoma, provided information that draws into question the use of these terms. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Adrenal maturation, nutritional status, and mucosal immunity in Bolivian youth.

    PubMed

    Hodges-Simeon, Carolyn R; Prall, Sean P; Blackwell, Aaron D; Gurven, Michael; Gaulin, Steven J C

    2017-09-10

    Humans-and several other apes-exhibit a unique pattern of post-natal adrenal maturation; however, the causes and consequences of variation in adrenal development are not well understood. In this study, we examine developmental and age-related maturation of the adrenal gland (measured via dehydroepiandrosterone-sulfate [DHEA-S]) for potential life-history associations with growth and mucosal immunity in a rural population of immune-challenged Bolivian juveniles and adolescents. Salivary DHEA-S, anthropometrics, and salivary mucosal immunity (secretory IgA [sIgA]) were measured in 171 males and females, aged 8-23. Males with greater energy (i.e. fat) stores showed higher DHEA-S levels. Controlling for age and energetic condition (to control for phenotypic correlation), higher DHEA-S was associated with higher mucosal immunity (sIgA) among both males and females. Higher DHEA-S levels were positively associated with growth (i.e. height and strength) in males. In accordance with predictions derived from life-history theory, males with higher energy stores secrete more adrenal androgens. This suggests that adrenal maturation is costly and subject to constraints; that is, only males with sufficient reserves will invest in accelerated adrenal maturation. Further, DHEA-S appears to have a measureable influence on immunocompetence in adolescent males and females; therefore, deficits in DHEA-S may have important consequences for health and maturation during this period. Adrenal maturation is an important, but understudied component of human growth and development. © 2017 Wiley Periodicals, Inc.

  5. Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency.

    PubMed

    Hershkovitz, Eli; Arafat, Maram; Loewenthal, Neta; Haim, Alon; Parvari, Ruti

    2015-09-01

    The nicotinamide nucleotide transhydrogenase (NNT) enzyme is the main generator of nicotinamide adenine dinucleotide phosphate-oxidase in the mitochondrion. Mutations of the NNT gene have been recently implicated in familial glucocorticoid deficiency. We describe the long-term clinical course of a NNT-deficient 20-year-old patient with combined adrenal failure who had developed a testicular adrenal rest tumor and precocious puberty. The patient's medical records were reviewed. Whole-exome sequencing was performed on DNA obtained from the patient and family members. The patient experienced Addisonian crisis at 10 months of age. Enlarged testicular volume and precocious puberty, accompanied by increased testosterone levels, were noted at 6 years. Testicular biopsy revealed a adrenal rest tumor, which regressed after intensification of glucocorticoid treatment. Genetic studies disclosed a c.1163A>C, p.Tyr388Ser substitution on the NNT gene. This mutation is predicted to be damaging to NNT function. We demonstrated for the first time that the clinical spectrum of NNT deficiency may consist of mineralocorticoid deficiency and testicular involvement as well.

  6. Allium sativum Compared to Cilostazol as an Inhibitor of Myointimal Hyperplasia.

    PubMed

    Lima, Paulo Roberto da Silva; Bandeira, Francisco Chavier Vieira; Rolim, Janio Cipriano; Nogueira, Manuel Ricardo Sena; Pordeus, Mizael Armando Abrantes; de Oliveira, Andressa Feitosa Bezerra; Pitta, Guilherme Benjamin Brandão

    2016-01-01

    Intimal hyperplasia is associated with graft failure and vascular sutures in the first year after surgery and in postangioplasty restenosis. Allium sativum (common garlic) lowers cholesterol and has antioxidant effects; it also has antiplatelet and antitumor properties and, therefore, has great potential to reduce or inhibit intimal hyperplasia of the arteries. Our objective is to determine if the garlic has an efficacy to inhibit myointimal hyperplasia compared to cilostazol. Female New Zealand rabbits were divided into the following groups (n=10 each) according to treatment: group A, garlic, 800 µg×kg-1×day-1, orally; group C, cilostazol, 50 mg.day-1, orally; group PS, 10 ml of 0.9% physiological saline solution, orally. Our primary is the difference of the mean of myointimal hyperplasia. Statistical analysis was performed by using ANOVA and Tukey tests, as well as the Chi-square test. We calculated the 95% confidence interval for each point estimate, and the P value was set as < 0.05. Group PS had a mean hyperplasia rate of 35.74% (95% CI, 31.76-39.71%); group C, 16.21% (95% CI, 13.36-19.05%); and group A, 21.12% (95% CI, 17.26-25.01%); P < 0.0001. We conclude that Allium sativum had the same efficacy in inhibiting myointimal hyperplasia when compared to the positive control, cilostazol.

  7. Altered Exocytosis in Chromaffin Cells from Mouse Models of Neurodegenerative Diseases.

    PubMed

    de Diego, Antonio M G; García, Antonio G

    2018-05-09

    Chromaffin cells from the adrenal gland (CCs) have extensively been used to explore the molecular structure and function of the exocytotic machinery, neurotransmitter release and synaptic transmission. The CC is integrated in the sympathoadrenal axis that helps the body maintain homeostasis during both routine life and in acute stress conditions. This function is exquisitely controlled by the cerebral cortex and the hypothalamus. We propose the hypothesis that damage undergone by the brain during neurodegenerative diseases is also affecting the neurosecretory function of adrenal medullary CCs. In this context we review here the following themes: (i) how the discharge of catecholamines is centrally and peripherally regulated at the sympatho-adrenal axis; (ii) which are the intricacies of the amperometric techniques used to study the quantal release of single-vesicle exocytotic events; (iii) which are the alterations of the exocytotic fusion pore so far reported, in CCs of mouse models of neurodegenerative diseases; (iv) how some proteins linked to neurodegenerative pathologies affects the kinetics of exocytotic events; (v) finally we try to integrate available data into a hypothesis to explain how the centrally originated neurodegenerative diseases may alter the kinetics of single-vesicle exocytotic events in peripheral adrenal medullary CCs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Bilateral Medial Medullary Infarction with Nondominant Vertebral Artery Occlusion.

    PubMed

    Zhang, Lei; Zhang, Gui-lian; Du, Ju-mei; Ma, Zhu-lin

    2015-09-01

    Bilateral medial medullary infarction (MMI) is a rare stroke subtype. Here, we report a case with bilateral MMI caused by nondominant vertebral artery occlusion confirmed by brain digital subtraction angiography and magnetic resonance imaging basi-parallel-anatomical-scanning. We highlight that anterior spinal arteries could originate from a unilateral vertebral artery (VA). Radiologists and neurologists should pay attention to the nondominant VA as bilateral MMI may be induced by occlusion of nondominant VA that supplies the bilateral anteromedial territories of the medulla. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  9. Robotic Radiosurgery for Adrenal Gland Metastases

    PubMed Central

    Heidorn, Sarah-Charlotta; Kremer, Nikolaus; Muacevic, Alexander; Fürweger, Christoph

    2017-01-01

    Introduction The purpose of this study was to investigate the safety and efficacy of CyberKnife (CK) robotic radiosurgery for treatment of adrenal metastases. Methods We performed a retrospective analysis of 23 patients with adrenal metastases who had been treated with CK between October 2006 and December 2015. Fifteen patients received chemotherapy prior to radiosurgery, all patients underwent computer tomography (CT) fluoroscopically guided percutaneous placement of one to three gold fiducials into the adrenal gland. Nineteen patients were selected for single-fraction radiosurgery with a median dose of 22 Gy, four patients were treated in three fractions with a median dose of 13.5 Gy. Results Median follow-up time was 23.6 months. Four patients (17%) experienced local relapse during the evaluation period with a mean time of 19 months to tumor progression. The actuarial local tumor control rate was 95% after one year and 81% after two years. Three of the four patients with local recurrence were retreated with CK radiosurgery. Dynamic tumor tracking enabled accurate treatment with correlation errors less than 2 mm, despite extensive respiration-induced target motion up to 22 mm. Apart from nausea directly after treatment in five patients, we observed no early or late treatment-related side effects. Conclusions Single fraction robotic radiosurgery for adrenal gland metastases is a safe and effective treatment option for patients who are not eligible for surgical resection. PMID:28451479

  10. Renal and adrenal tumors: Pathology, radiology, ultrasonography, therapy, immunology

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

    Lohr, E.; Leder, L.D.

    1987-01-01

    Aspects as diverse as radiology, pathology, urology, pediatrics and immunology have been brought together in one book. The most up-do-date methods of tumor diagnosis by CT, NMR, and ultrasound are covered, as are methods of catheter embolization and radiation techniques in case of primarily inoperable tumors. Contents: Pathology of Renal and Adrenal Neoplasms; Ultrasound Diagnosis of Renal and Pararenal Tumors; Computed-Body-Tomography of Renal Carcinoma and Perirenal Masses; Magnetic Resonance Imaging of Renal Mass Lesions; I-125 Embolotherapy of Renal Tumors; Adrenal Mass Lesions in Infants and Children; Computed Tomography of the Adrenal Glands; Scintigraphic Studies of Renal and Adrenal Function; Surgicalmore » Management of Renal Cell Carcinoma; Operative Therapy of Nephroblastoma; Nonoperative Treatment of Renal Cell Carcinoma; Prenatal Wilms' Tumor; Congenital Neuroblastoma; Nonsurgical Management of Wilms' Tumor; Immunologic Aspects of Malignant Renal Disease.« less

  11. AgNOR histochemical expression in benign prostatic hyperplasia and prostatic adenocarcinoma

    NASA Astrophysics Data System (ADS)

    Rita, R.; Delyuzar; Laksmi, L. I.

    2018-03-01

    Benign prostatic hyperplasia and prostatic adenocarcinoma were common diseases and usually occurred after the 5th decade of life. The problem in diagnosing using Hematoxylin and Eosin staining was how to differentiate whether it is benign or malignant zone. Therefore, proliferating markers, such as AgNOR, could be helping to over this difficulty. A descriptive study using consecutive sampling as the method of sample recruiting was conducted to describe AgNOR histochemical expression in benign prostatic hyperplasia and prostatic adenocarcinoma. AgNOR staining was done in 13 benign prostatic hyperplasia samples and 7 prostatic adenocarcinoma samples, which have been confirmed using p63 immunohistochemical staining before. Benign prostatic hyperplasia usually showed lower AgNOR proliferating activity while all of theprostatic adenocarcinoma (100%) had high AgNOR proliferating activity.

  12. Differential Activation of Medullary Vagal Nuclei Caused by Stimulation of Different Esophageal Mechanoreceptors

    PubMed Central

    Lang, Ivan M.; Medda, Bidyut K.; Shaker, Reza

    2010-01-01

    Esophageal mechanorecptors, i.e. muscular slowly adapting tension receptors and mucosal rapidly adapting touch receptors, mediate different sets of reflexes. The aim of this study was to determine the medullary vagal nuclei involved in the reflex responses to activation of these receptors. Thirty-three cats were anesthetized with alpha-chloralose and the esophagus was stimulated by slow balloon or rapid air distension. The physiological effects of the stimuli (N=4) were identified by recording responses from the pharyngeal, laryngeal, and hyoid muscles, esophagus, and the lower esophageal sphincter (LES). The effects on the medullary vagal nuclei of the stimuli: slow distension (N=10), rapid distension (N=9), and in control animals (N=10) were identified using the immunohistochemical analysis of c-fos. The experimental groups were stimulated 3 times per minute for 3 hours. After the experiment, the brains were removed and processed for c-fos immunoreactivity or thioinin. We found that slow balloon distension activated the esophago-UES contractile reflex and esophago LES relaxation response, and rapid air injection activated the belch and its component reflexes. Slow balloon distension activated the NTSce, NTSdl, NTSvl, DMNc, DMNr and NAr; and rapid air injection primarily activated AP, NTScd, NTSim, NTSis, NTSdm, NTSvl, NAc and NAr. We concluded that different sets of medullary vagal nuclei mediate different reflexes of the esophagus activated from different sets of mechanoreceptors. The NTScd is the primary NTS subnucleus mediating reflexes from the mucosal rapidly adapting touch receptors, and the NTSce is the primary NTS subnucleus mediating reflexes from the muscular slowly adapting tension receptors. The AP may be involved in mediation of belching. PMID:20971087

  13. Neglected issues concerning teaching human adrenal steroidogenesis in popular biochemistry textbooks.

    PubMed

    Han, Zhiyong; Elliott, Mark S

    2017-11-01

    In the human body, the adrenal steroids collectively regulate a plethora of fundamental functions, including electrolyte and water balance, blood pressure, stress response, intermediary metabolism, inflammation, and immunity. Therefore, adrenal steroidogenesis is an important biochemistry topic for students to learn in order for them to understand health consequences caused by deficiencies of enzymes in the adrenal steroidogenic pathways. However, popular biochemistry textbooks contain insufficient information and may sometimes give students a misimpression about certain aspects of human adrenal steroidogenesis. This article highlights two neglected issues in teaching human adrenal steroidogenesis in popular biochemistry textbooks. The purpose of this article is to draw attention to these issues. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(6):469-474, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

  14. A Novel Method of Adrenal Venous Sampling via an Antecubital Approach

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

    Jiang, Xiongjing, E-mail: jxj103@hotmail.com; Dong, Hui; Peng, Meng

    PurposeCurrently, almost all adrenal venous sampling (AVS) procedures are performed by femoral vein access. The purpose of this study was to establish the technique of AVS via an antecubital approach and evaluate its safety and feasibility.Materials and MethodsFrom January 2012 to June 2015, 194 consecutive patients diagnosed as primary aldosteronism underwent AVS via an antecubital approach without ACTH simulation. Catheters used for bilateral adrenal cannulations were recorded. The success rate of bilateral adrenal sampling, operation time, fluoroscopy time, dosage of contrast, and incidence of complications were calculated.ResultsA 5F MPA1 catheter was first used to attempt right adrenal cannulation in all patients.more » Cannulation of the right adrenal vein was successfully performed in 164 (84.5%) patients. The 5F JR5, Cobra2, and TIG catheters were the ultimate catheters for right adrenal cannulation in 16 (8.2%), 5 (2.6%), and 9 (4.6%) patients, respectively. For left adrenal cannulation, JR5 and Cobra2 catheters were used in 19 (9.8%) and 10 (5.2%) patients, respectively, while only TIG catheters were used in the remaining 165 (85.1%) patients. The rate of successful adrenal sampling on the right, left, and bilateral sides was 91.8%, 93.3%, and 87.6%, respectively. The mean time of operation was (16.3 ± 4.3) minutes, mean fluoroscopy time was (4.7 ± 1.3) minutes, and the mean use of contrast was (14.3 ± 4.7) ml. The incidence of adrenal hematoma was 1.0%.ConclusionsThis study showed that AVS via an antecubital approach was safe and feasible, with a high rate of successful sampling.« less

  15. Focal fibrous hyperplasia: A review of 193 cases

    PubMed Central

    de Santana Santos, Thiago; Martins-Filho, Paulo Ricardo Saquete; Piva, Marta Rabello; de Souza Andrade, Emanuel Sávio

    2014-01-01

    Context: Focal fibrous hyperplasia, also known as irritation or traumatic fibroma, is a reactive, inflammatory hyperplastic lesion of the connective tissue. Aim: The aim of this study is to perform a retrospective study of a focal fibrous hyperplasia of 18 years. Materials and Methods: We retrospectively reviewed 193 cases of focal fibrous hyperplasia of the oral cavity from the medical and histological reports of the Department of Oral Pathology, Pernambuco University, Brazil, during the period between January 1992 and December 2009. Settings and Design: Data with regard to age, gender, location, size of the lesion (equal to or less than 1 cm, between 1 and 2 cm and greater than 2 cm), pain, history of trauma, treatment, length of follow-up (from diagnosis to release or last review) and recurrence, were collected. Results: The most commonly affected site was the buccal mucosa (n = 119, 61.7%). Almost two-thirds of the cases were concentrated from the second to the fifth decade of life. Females were more affected than men and a history of trauma was related by 90.7% of the patients. Two recurrences were notified (1.0%). Conclusion: Further studies are needed on the distribution of the lesion in different ethnic and geographical populations. The influence of sex hormones on the development of focal fibrous hyperplasia must be clarified. PMID:25364187

  16. SIRT1 Limits Adipocyte Hyperplasia through c-Myc Inhibition*

    PubMed Central

    Abdesselem, Houari; Madani, Aisha; Hani, Ahmad; Al-Noubi, Muna; Goswami, Neha; Ben Hamidane, Hisham; Billing, Anja M.; Pasquier, Jennifer; Bonkowski, Michael S.; Halabi, Najeeb; Dalloul, Rajaa; Sheriff, Mohamed Z.; Mesaeli, Nasrin; ElRayess, Mohamed; Sinclair, David A.; Graumann, Johannes; Mazloum, Nayef A.

    2016-01-01

    The expansion of fat mass in the obese state is due to increased adipocyte hypertrophy and hyperplasia. The molecular mechanism that drives adipocyte hyperplasia remains unknown. The NAD+-dependent protein deacetylase sirtuin 1 (SIRT1), a key regulator of mammalian metabolism, maintains proper metabolic functions in many tissues, counteracting obesity. Here we report that differentiated adipocytes are hyperplastic when SIRT1 is knocked down stably in mouse 3T3-L1 preadipocytes. This phenotype is associated with dysregulated adipocyte metabolism and enhanced inflammation. We also demonstrate that SIRT1 is a key regulator of proliferation in preadipocytes. Quantitative proteomics reveal that the c-Myc pathway is altered to drive enhanced proliferation in SIRT1-silenced 3T3-L1 cells. Moreover, c-Myc is hyperacetylated, levels of p27 are reduced, and cyclin-dependent kinase 2 (CDK2) is activated upon SIRT1 reduction. Remarkably, differentiating SIRT1-silenced preadipocytes exhibit enhanced mitotic clonal expansion accompanied by reduced levels of p27 as well as elevated levels of CCAAT/enhancer-binding protein β (C/EBPβ) and c-Myc, which is also hyperacetylated. c-Myc activation and enhanced proliferation phenotype are also found to be SIRT1-dependent in proliferating mouse embryonic fibroblasts and differentiating human SW872 preadipocytes. Reducing both SIRT1 and c-Myc expression in 3T3-L1 cells simultaneously does not induce the adipocyte hyperplasia phenotype, confirming that SIRT1 controls adipocyte hyperplasia through c-Myc regulation. A better understanding of the molecular mechanisms of adipocyte hyperplasia will open new avenues toward understanding obesity. PMID:26655722

  17. Allium sativum Compared to Cilostazol as an Inhibitor of Myointimal Hyperplasia

    PubMed Central

    Lima, Paulo Roberto da Silva; Bandeira, Francisco Chavier Vieira; Rolim, Janio Cipriano; Nogueira, Manuel Ricardo Sena; Pordeus, Mizael Armando Abrantes; de Oliveira, Andressa Feitosa Bezerra; Pitta, Guilherme Benjamin Brandão

    2016-01-01

    Objective Intimal hyperplasia is associated with graft failure and vascular sutures in the first year after surgery and in postangioplasty restenosis. Allium sativum (common garlic) lowers cholesterol and has antioxidant effects; it also has antiplatelet and antitumor properties and, therefore, has great potential to reduce or inhibit intimal hyperplasia of the arteries. Our objective is to determine if the garlic has an efficacy to inhibit myointimal hyperplasia compared to cilostazol. Methods Female New Zealand rabbits were divided into the following groups (n=10 each) according to treatment: group A, garlic, 800 µg×kg-1×day-1, orally; group C, cilostazol, 50 mg.day-1, orally; group PS, 10 ml of 0.9% physiological saline solution, orally. Our primary is the difference of the mean of myointimal hyperplasia. Statistical analysis was performed by using ANOVA and Tukey tests, as well as the Chi-square test. We calculated the 95% confidence interval for each point estimate, and the P value was set as < 0.05. Results Group PS had a mean hyperplasia rate of 35.74% (95% CI, 31.76–39.71%); group C, 16.21% (95% CI, 13.36–19.05%); and group A, 21.12% (95% CI, 17.26–25.01%); P<0.0001. Conclusion We conclude that Allium sativum had the same efficacy in inhibiting myointimal hyperplasia when compared to the positive control, cilostazol. PMID:27849301

  18. Periostin contributes to epidermal hyperplasia in psoriasis common to atopic dermatitis

    PubMed Central

    Arima, Kazuhiko; Ohta, Shoichiro; Takagi, Atsushi; Shiraishi, Hiroshi; Masuoka, Miho; Ontsuka, Kanako; Suto, Hajime; Suzuki, Shoichi; Yamamoto, Ken-ichi; Ogawa, Masahiro; Simmons, Olga; Yamaguchi, Yukie; Toda, Shuji; Aihara, Michiko; Conway, Simon J.; Ikeda, Shigaku; Izuhara, Kenji

    2016-01-01

    Background Epidermal hyperplasia is a histological hallmark observed in both atopic dermatitis (AD) and psoriasis, although the clinical features and the underlying immunological disorders of these diseases are different. We previously showed that periostin, a matricellular protein, plays a critical role in epidermal hyperplasia in AD, using a mouse model and a 3-dimensional organotypic coculture system. In this study, we explore the hypothesis that periostin is involved in epidermal hyperplasia in psoriasis. Methods To examine expression of periostin in psoriasis patients, we performed immunohistochemical analysis on skin biopsies from six such patients. To investigate periostin’s role in the pathogenesis of psoriasis, we evaluated periostin-deficient mice in a psoriasis mouse model induced by topical treatment with imiquimod (IMQ). Results Periostin was substantially expressed in the dermis of all investigated psoriasis patients. Epidermal hyperplasia induced by IMQ treatment was impaired in periostin-deficient mice, along with decreased skin swelling. However, upon treatment with IMQ, periostin deficiency did not alter infiltration of inflammatory cells such as neutrophils; production of IL-17, –22, or –23; or induction/expansion of IL-17– and IL-22–producing group 3 innate lymphoid cells. Conclusions Periostin plays an important role during epidermal hyperplasia in IMQ-induced skin inflammation, independently of the IL-23–IL-17/IL-22 axis. Periostin appears to be a mediator for epidermal hyperplasia that is common to AD and psoriasis. PMID:25572557

  19. Renal and adrenal tumours in children

    PubMed Central

    2007-01-01

    The differential diagnosis of renal and supra-renal masses firstly depends on the age of the child. Neuroblastoma (NBL) may be seen antenatally or in the newborn period; this tumour has a good prognosis unlike NBL seen in older children (particularly NBL in those aged 2–4 years). Benign renal masses predominate in early infancy but beyond the first year of life Wilms' tumour is the most common renal malignancy, until adolescence when renal cell carcinoma has similar or increased frequency as children get older. Adrenal adenomas and carcinomas also occur in childhood; these tumours are indistinguishable on imaging but criteria for the diagnosis of adrenal carcinoma include size larger than 5 cm, a tendency to invade the inferior vena cava and to metastasise. The most topical dilemmas in the radiological assessment of renal and adrenal tumours are presented. Topics covered include a proposed revision to the staging of NBL, the problems inherent in distinguishing nephrogenic rests from Wilms' tumour and the current recently altered approach regarding small lung nodules in children with Wilms' tumour. PMID:17339140

  20. Adrenal crisis in treated Addison's disease: a predictable but under-managed event.

    PubMed

    White, Katherine; Arlt, Wiebke

    2010-01-01

    Adrenal crisis is a life-threatening event that occurs regularly in Addison's patients receiving standard replacement therapy. Patient reports suggest that it is an underestimated and under-managed event. To assess the frequency of adrenal crisis in diagnosed patients and to understand the factors contributing to the risks of adrenal crisis. We conducted a postal survey of Addison's patients in four countries, UK (n=485), Canada (n=148), Australia (n=123) and New Zealand (n=85) in 2003, asking about patients' experiences of adrenal crisis and their demographic characteristics. In 2006, a shorter follow-up survey was conducted in the UK (n=261). The frequency and causes of adrenal crisis were compared across both surveys. Demographic data from the 2003 survey were analysed to establish the main variables associated with an elevated risk of crisis. Around 8% of diagnosed cases can be expected to need hospital treatment for adrenal crisis annually. Exposure to gastric infection is the single most important factor predicting the likelihood of adrenal crisis. Concomitant diabetes and/or asthma increase the frequency of adrenal crises reported by patients. The endocrinologist has a responsibility to ensure that Addison's patients have adequate access to life-saving emergency injection materials and repeated, practical training sessions in how to use them, while the general practitioner plays a vital role as in arranging prompt emergency admissions.

  1. [Adrenal incidentaloma: a clinical problem related to imaging].

    PubMed

    de Bruijne, E L E; Burgmans, J P J; Krestin, G P; Pols, H A P; van den Meiracker, A H; de Herder, W W

    2005-08-13

    Two female patients, 68 and 67 years of age, were referred for right abdominal pain and pyelonephritis, respectively. During the diagnostic work-up, an unsuspected adrenal mass was found in both patients. Hormonal evaluation and imaging showed a benign non-hyperactive functioning adenoma in one patient and a pheochromocytoma in the other. Both patients were successfully treated with endoscopic adrenalectomy. Wider application and improvement of abdominal imaging procedures have caused an increase of incidentally detected adrenal masses, posing a common clinical problem. Typically, a diagnosis can be made on the basis of the characteristic radiological image. The exact nature of the defect is often unclear and further evaluation is required to determine functionality and possible malignancy. An algorithm is presented for the management of adrenal incidentalomas.

  2. Regulation of the Adrenal Cortex Function During Stress

    NASA Technical Reports Server (NTRS)

    Soliman, K. F. A.

    1978-01-01

    A proposal to study the function of the adrenal gland in the rat during stress is presented. In the proposed project, three different phases of experimentation will be undertaken. The first phase includes establishment of the circadian rhythm of both brain amines and glucocoticoids, under normal conditions and under chronic and acute stressful conditions. The second phase includes the study of the pharmacokinetics of glucocorticoid binding under normal and stress conditions. The third phase includes brain uptake and binding under different experimental conditions. In the outlined experiments brain biogenic amines will be evaluated, adrenal functions will be measured and stress effect on those parameters will be studied. It is hoped that this investigation can explain some of the complex relationships between the brain neurotransmitter and adrenal function.

  3. [Adrenal incidentaloma and nuclear medicine examination].

    PubMed

    Tenenbaum, F

    2009-03-01

    In the setting of adrenal incidentaloma, nuclear medicine evaluation is only indicated after biological and imaging work-up has been completed. MIBG scintigraphy is helpful to characterize pheochromocytomas. In lesions without MIBG uptake, 18F FDG or 18F DOPA PET can be considered to characterize chromaffin cell tumours. To characterize lesions of the adrenal cortex, iodocholesterol scintigraphy is performed to confirm the origin of the adenoma and the benign or malignant nature of the lesion since benign adenomas show tracer uptake and malignant lesions show no tracer uptake. 18F FDG PET only characterizes the lesion as benign or malignant.

  4. Laparoscopic resection of a large (11 cm) adrenal phaeochromocytoma

    PubMed Central

    Chaudhary, Ranjit; Deshmukh, Abhijeet; Singh, Kulwant; Biswas, Rakesh

    2011-01-01

    Pheochromocytoma is a rare cause of hypertension. Usually the tumour arises in the adrenal and the only cure is surgical extirpation. Laparoscopic adrenalectomy is the gold standard. Traditionally, laparoscopic removal of adrenal tumour of more than 5–6 cm in size is contraindicated. The authors removed a 11×8 cm phaeochromocytoma by laparoscopic approach without any complications. A 52-year-old male presented with complaints of throbbing headache with palpitations. On evaluation, he was found to be severely hypertensive and his blood sugar levels were moderately elevated. Radiological investigations revealed a 11×8 cm left supra renal mass. A provisional diagnosis of left pheochromocytoma was made which was strengthened by the fact that 24 hourly urine sample revealed elevated vanillylmandelic acid levels. The authors decided to surgically extirpate the adrenal mass. This was successfully accomplished by a laparoscopic transperitoneal approach. No complications were encountered. Histopathology showed pheochromocytoma of left adrenal gland without capsular involvement. PMID:22679235

  5. Laparoscopic resection of a large (11 cm) adrenal phaeochromocytoma.

    PubMed

    Chaudhary, Ranjit; Deshmukh, Abhijeet; Singh, Kulwant; Biswas, Rakesh

    2011-09-13

    Pheochromocytoma is a rare cause of hypertension. Usually the tumour arises in the adrenal and the only cure is surgical extirpation. Laparoscopic adrenalectomy is the gold standard. Traditionally, laparoscopic removal of adrenal tumour of more than 5-6 cm in size is contraindicated. The authors removed a 11×8 cm phaeochromocytoma by laparoscopic approach without any complications. A 52-year-old male presented with complaints of throbbing headache with palpitations. On evaluation, he was found to be severely hypertensive and his blood sugar levels were moderately elevated. Radiological investigations revealed a 11×8 cm left supra renal mass. A provisional diagnosis of left pheochromocytoma was made which was strengthened by the fact that 24 hourly urine sample revealed elevated vanillylmandelic acid levels. The authors decided to surgically extirpate the adrenal mass. This was successfully accomplished by a laparoscopic transperitoneal approach. No complications were encountered. Histopathology showed pheochromocytoma of left adrenal gland without capsular involvement.

  6. Ca(2+) signaling mechanisms in bovine adrenal chromaffin cells.

    PubMed

    Weiss, Jamie L

    2012-01-01

    Calcium (Ca(2+)) is a crucial intracellular messenger in physiological aspects of cell signaling. Adrenal chromaffin cells are the secretory cells from the adrenal gland medulla that secrete catecholamines, which include epinephrine and norepinephrine important in the 'fight or flight' response. Bovine adrenal chromaffin cells have long been used as an important model for secretion -(exocytosis) not only due to their importance in the short-term stress response, but also as a neuroendocrine model of neurotransmtter release, as they have all the same exocytotic proteins as neurons but are easier to prepare, culture and use in functional assays. The components of the Ca(2+) signal transduction cascade and it role in secretion has been extensively characterized in bovine adrenal chromaffin cells. The Ca(2+) sources, signaling molecules and how this relates to the short-term stress response are reviewed in this book chapter in an endeavor to generally -overview these mechanisms in a concise and uncomplicated manner.

  7. Extensive Focal Epithelial Hyperplasia: A Case Report.

    PubMed

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis.

  8. [Effects of medullary ischemia on respiratory and blood pressure induced by ligating basilar artery in cat].

    PubMed

    Zhuang, Xu; Guo, Jun-Xia; Zhang, Cheng-Wu; Zheng, Yu

    2003-11-01

    Observations on medullary ischemia region, the morphology of neurons and changes of respiration and blood pressure were made, in order to give evidences on how medullary ischemia affects respiration and circulation and give some advices on how to protect from it. Using cats as the experimental animals, the different parts of the basilar artery trunk were ligated. The changes in the density of blood vessels, the morphology of neurons in the brainstem, the electromyogram (EMG) of the diaphragm and the blood pressure of the femoral artery were investigated. The density of blood vessels notably decreased in the medulla after ligating the basilar artery trunk. The ischemic range induced by ligation of the different parts of the basilar artery trunk overlapped, mainly locating in the medulla rostral to the obex. The soma were swelled and the Nissl bodies decreased in some of neurons in the ischemic region of medulla. The duration of inspiration (T1) and expiration (TE) shortened, respiratory frequency (RF) increased, and mean blood pressure (MBP) decreased in the experimental groups (P < 0.05). There is an obvious overlap of the areas in which blood supplied by different parts of the basilar artery trunk. Medullary ischemia can involve in changes of respiration and blood pressure. The ischemic damage of neurons in the medulla might be the structural basis of the changes in the respiratory and circulatory functions.

  9. Role of Hyperplasia of Gingival Lymphatics in Periodontal Inflammation.

    PubMed

    Papadakou, P; Bletsa, A; Yassin, M A; Karlsen, T V; Wiig, H; Berggreen, E

    2017-04-01

    Lymphatic vessels are important for maintenance of tissue fluid homeostasis and afferent antigen transport. In chronic inflammation, lymphangiogenesis takes place and is characterized by lymphatic endothelial cell proliferation and lymphatic hyperplasia. Vascular endothelial growth factor C (VEGFC) is the main known lymphangiogenic growth factor, and its expression is increased in periodontitis, a common chronic infectious disease that results in tissue destruction and alveolar bone loss. The role of lymphangiogenesis during development of periodontitis is unknown. Here, we test if transgenic overexpression of epithelial VEGFC in a murine model is followed by hyperplasia of lymphatic vessels in oral mucosa and if the lymphatic drainage capacity is altered. We also test if lymphatic hyperplasia protects against periodontal disease development. Transgenic keratin 14 (K14)-VEGFC mice had significant hyperplasia of lymphatics in oral mucosa, including gingiva, without changes in blood vessel vasculature. The basal lymph flow was normal but slightly lower than in wild-type mice when oral mucosa was challenged with lipopolysaccharide from Porphyromonas gingivalis. Under normal conditions, K14-VEGFC mice exhibited an increased number of neutrophils in gingiva, demonstrated enhanced phagocyte recruitment in the cervical lymph nodes, and had more alveolar bone when compared with their wild-type littermates. After induction of periodontitis, no strain differences were observed in the periodontal tissues with respect to granulocyte recruitment, bone resorption, angiogenesis, cytokines, and bone-related protein expressions or in draining lymph node immune cell proportions and vascularization. We conclude that overexpression of VEGFC results in hyperplastic lymphatics, which do not enhance lymphatic drainage capacity but facilitate phagocyte transport to draining lymph nodes. Hyperplasia of lymphatics does not protect against development of ligature-induced periodontitis.

  10. [Effect of drinking boron on microtructure of adrenal gland in rats].

    PubMed

    Li, Shenghe; Wang, Jue; Zhou, Jinxing; Jin, Guangming; Gu, Youfang; Xu, Wanxiang

    2012-09-01

    The effects of drinking boron exposure on the mass, organ indexes and structure of adrenal gland were studied in the paper. Methods 192 Sprague-Dawley rats (28 +/- 2 days) with no bacteria infecting were divided into six groups (n = 32, male = female) randomly. Treated rats drunk the distilled water which supplemented with boron of 0, 40, 80, 160, 320 and 640 mg/L, respectively, for 60 days. At the 30th and the 60th day of experiment, 16 rats (n = 8, male = female) of each group were selected and made into narcosis with 10% Chloral Hydrate. The adrenal glands were obtained, weighted and fixed after dissection, then the samples were made into paraffin sections, stained with HE stain and chromaffin, observed and photographed by Olympus CH-30 microphotograph system. Compared with control group, the average mass of adrenal gland of male rats in each experiment group decreased significantly or most significantly at the 30th day of experiment (P < 0.05 or P < 0.01), but the index of adrenal gland of male rats in the group of 640 mg/L boron at 60th day of experiment increased significantly (P < 0.05). Under the microscope, the microstructure of adrenal gland of rats in the group of 40 mg/L boron were better obviously than control group, and the numbers of chromaffin granules in chromaffin cell increased obviously. The histopathological changes of different degree could be observed in the group of 80 to 640 mg/L boron, and they became remarkable with the boron supplementation. By comparative observation, the damage of cells in adrenal medulla appeared ahead of them in adrenal cortex, and the pathological change of adrenal gland in male rats were obvious than female rats. Drinking supplemented with 40 mg/L boron could prompt the structure of adrenal gland in rats, but could cause different degree damage, or even obvious toxic effect when the concentration of boron supplementation in drinking from 80 to 640 mg/L.

  11. Acute adrenal insufficiency: an aide-memoire of the critical importance of its recognition and prevention.

    PubMed

    Gargya, A; Chua, E; Hetherington, J; Sommer, K; Cooper, M

    2016-03-01

    Adrenal crisis is a life-threatening emergency that causes significant excess mortality in patients with adrenal insufficiency. Delayed recognition by medical staff of an impending adrenal crisis and failure to give timely hydrocortisone therapy within the emergency department continue to be commonly encountered, even in metropolitan teaching hospitals. Within the authors' institutions, several cases of poorly handled adrenal crises have occurred over the last 2 years. Anecdotal accounts from members of the Addison's support group suggest that these issues are common in Australia. This manuscript is a timely reminder for clinical staff on the critical importance of the recognition, treatment and prevention of adrenal crisis. The manuscript: (i) outlines a case and the clinical outcome of sub-optimally managed adrenal crisis, (ii) summarises the clinical features and acute management of adrenal crisis, (iii) provides recommendations on the prevention of adrenal crisis and (iv) provides guidance on the management of 'sick days' in patients with adrenal insufficiency. © 2016 Royal Australasian College of Physicians.

  12. 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

  13. [Association between Williams syndrome and adrenal insufficiency].

    PubMed

    Rchachi, Meryem; Larwanou, Maazou Mahamane; El Ouahabi, Hanan; Ajdi, Farida

    2017-01-01

    Williams syndrome is a developmental disorder including dysmorphia, cardiovascular malformations and a specific neuropsychological profile together with other associated disorders. We report the case of a 17-year old girl, born of a non-inbred marriage, with Williams syndrome discovered during an assessment of degree of failure to thrive. Its association with primary adrenal insufficiency makes it unique. Diagnosis is confirmed by cytogenetic and molecular analysis. Its management consists of the implementation of treatment for adrenal insufficiency associated with a clinico-biological monitoring.

  14. High grade primary adrenal intravascular large B-cell lymphoma manifesting as Addison disease.

    PubMed

    Venizelos, I; Venizelos, J; Tamiolakis, D; Lambropoulou, M; Alexiadis, G; Petrakis, G; Papadopoulos, N

    2007-08-01

    We report a rare case of a 68 aged male who presented with adrenal failure and was diagnosed of high grade large B-cell lymphoma primarily arising in the adrenal glands. The patient was administrated with additional chemotherapy but he passed away 7 months later due to infection in the lungs. Intravascular lymphoma should be suspected in patients with bilateral adrenal masses who present with rapidly progressive adrenal insufficiency.

  15. Effect of extracellular acid–base disturbances on the intracellular pH of neurones cultured from rat medullary raphe or hippocampus

    PubMed Central

    Bouyer, Patrice; Bradley, Stefania Risso; Zhao, Jinhua; Wang, Wengang; Richerson, George B; Boron, Walter F

    2004-01-01

    Previous reports suggest that an important characteristic of chemosensitive neurones is an unusually large change of steady-state intracellular pH in response to a change in extracellular pH (ΔpHi/ΔpHo). To determine whether such a correlation exists between neurones from the medullary raphe (a chemosensitive brain region) and hippocampus (a non-chemosensitive region), we used BCECF to monitor pHi in cultured neurones subjected to extracellular acid–base disturbances. In medullary raphe neurones, respiratory acidosis (5% → 9% CO2) caused a rapid fall in pHi (ΔpHi ∼0.2) with no recovery and a large ΔpHi/ΔpHo of 0.71. Hippocampal neurones had a similar response, but with a slightly lower ΔpHi/ΔpHo (0.59). We further investigated a possible link between pHi regulation and chemosensitivity by following the pHi measurements on medullary raphe neurones with an immunocytochemistry for tryptophan hydroxylase (a marker of serotonergic neurones). We found that the ΔpHi/ΔpHo of 0.69 for serotonergic neurones (which are stimulated by acidosis) was not different from either the ΔpHi/ΔpHo of 0.75 for non-serotonergic neurones (most of which are not chemosensitive), or from the ΔpHi/ΔpHo of hippocampal neurones. For both respiratory alkalosis (5% → 3% CO2) and metabolic alkalosis (22 mm → 35 mm HCO3−), ΔpHi/ΔpHo was 0.42–0.53 for all groups of neurones studied. The only notable difference between medullary raphe and hippocampal neurones was in response to metabolic acidosis (22 mm → 14 mm HCO3−), which caused a large pHi decrease in ∼80% of medullary raphe neurones (ΔpHi/ΔpHo = 0.71), but relatively little pHi decrease in 70% of the hippocampal neurones (ΔpHi/ΔpHo = 0.09). Our comparison of medullary raphe and hippocampal neurones indicates that, except in response to metabolic acidosis, the neurones from the chemosensitive region do not have a uniquely high ΔpHi/ΔpHo. Moreover, regardless of whether neurones were cultured from the

  16. Multiple Endocrine Neoplasia Type 2B Unmasked by 18 F-FDG PET/CT and 131 I-MIBG SPECT/CT.

    PubMed

    Sun, Xun; Arnous, Maher Mohamad Rajab; Lan, Xiaoli

    2017-04-01

    F-FDG PET/CT was performed to detect an occult malignancy in a 26-year-old woman with complicated medical history which included paroxysmal hypertension and significantly elevated tumor marker. The images revealed lesions in the thyroid, lymph nodes, and bilateral adrenal glands. Further I-MIBG SPECT/CT revealed intense activity in the lesion in the left adrenal gland, which was consistent with pheochromocytoma. The pathology examination after subsequent neck biopsy demonstrated medullary thyroid carcinoma. A diagnosis of multiple endocrine neoplasia type 2B was eventually made.

  17. Alveolar Soft Part Sarcoma Presenting as Hypervascular Adrenal Metastasis

    PubMed Central

    Goroshi, Manjunath; Lila, Anurag R.; Bandgar, Tushar; Shah, Nalini S.

    2018-01-01

    Hypervascular adrenal masses include pheochromocytoma, metastases caused by clear renal cell carcinoma/hepatocellular carcinoma. Alveolar soft part sarcoma (ASPS) causing hypervascular metastases is not described in the literature. Here, we describe the first case of ASPS presenting as hypervascular metastasis. Our case was a 23-year-old male incidentally detected right adrenal mass during the evaluation of pain in the abdomen. On computed tomography (CT), adrenal mass showed bright enhancement in early arterial phase (unenhanced Hounsfield unit [HU]-45.3; arterial phase HU-158.2). 18- flurodeoxyglucose positron emission tomography/CT showed multiple lesions and was confirmed histologically to be due to ASPS. PMID:29398970

  18. Risk Factors for Atherosclerosis and the Development of Pre-Atherosclerotic Intimal Hyperplasia

    PubMed Central

    Cizek, Stephanie M.; Bedri, Shahinaz; Talusan, Paul; Silva, Nilsa; Lee, Hang; Stone, James R.

    2007-01-01

    Summary Intimal hyperplasia or thickening is considered to be the precursor lesion for atherosclerosis in humans; however the factors governing its formation are unclear. In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood after the 4th decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking. Background Intimal hyperplasia, or thickening, is considered to be the precursor lesion for atherosclerosis in humans; however, the factors governing its formation are unclear. To gain insight into the etiology of pre-atherosclerotic intimal hyperplasia, traditional risk factors for atherosclerosis were correlated with the intimal hyperplasia in an atherosclerosis-resistant vessel, the internal thoracic artery. Methods Paired internal thoracic arteries were obtained from 89 autopsies. Multivariate logistic regression and multiple regression models were used to examine the association of pre-atherosclerotic intimal hyperplasia with traditional risk factors for atherosclerosis: age, gender, hypertension, smoking, body mass index, diabetes, and hypercholesterolemia. Results Atherosclerotic lesions consisting of fatty streaks and/or type III intermediate lesions were identified in 19 autopsies. Only age >75 years was found to be significantly correlated with atherosclerotic lesion development (P=0.01). Multiple regression model of the intima/media ratio in all 89 cases revealed age >75 years (P<0.0001), age 51–75years (P=0.0012), smoking (P=0.008) and hypertension (P=0.02) to be significantly correlated with intimal thickness. In the 70 cases without atherosclerosis, only age 51–75 years (P=0.006) and smoking (P=0.028) were found to be significantly associated with pre-atherosclerotic intimal thickening. Conclusions In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood

  19. Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks.

    PubMed

    Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

    2018-05-01

    Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic-pituitary-adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases.

  20. Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks

    PubMed Central

    Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

    2018-01-01

    Abstract Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic–pituitary–adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases. PMID:29713692

  1. 8D.04: CLINICAL BENEFITS OF ADMINISTERING SUPER-SELECTIVE SEGMENTAL ADRENAL VENOUS SAMPLING AND PERFORMING ADRENAL SPARING SURGERY IN THE PATIENTS WITH PRIMARY ALDOSTERONISM.

    PubMed

    Satoh, F; Morimoto, R; Ono, Y; Iwakura, Y; Omata, K; Kudo, M; Satani, N; Ota, H; Seiji, K; Takase, K; Nakamura, Y; Sasano, H; Ito, S

    2015-06-01

    Adrenal venous sampling (AVS) has been well known to play pivotal roles in clinical differential diagnosis of unilateral aldosterone producing adenoma (APA) from bilateral idiopathic hyperaldosteronism (IHA). However, it is also true that a central vein AVS or c-AVS which collects the blood from right and left central adrenal veins can by no means discriminate bilateral APA from BHA. There have been no published studies reporting the reliable clinical differential diagnosis between bilateral APA and IHA, especially IHA cases with bilateral non-functioning adenomas (NFA), which has been considered practically impossible in clinical differential diagnosis. As an attempt to this clinical dilemma, segmental AVS (S-AVS), which could evaluate segmental effluents from adrenal tributary veins, has been recently developed. We have performed S-AVS in these patients above following C-AVS, via the insertion of a microcatheter in up to three intra-adrenal first-degree tributary veins on bilateral adrenals. S-AVS did enable us to evaluate the intra-adrenal localization of corticosteroidogenesis. These data did indicate that S-AVS should be performed in the PA patients who had increased aldosterone levels in bilateral central vein and demonstrated space occupying lesions in the bilateral adrenals in order to avoid bilateral adrenalectomy or long lasting medical treatment toward persistent PA. In addition to the situations above, we have administere S-AVS to the following patients; those who had clinically suspected APA but not sufficiently high lateralization indexes according to the results of C-AVS, very young ones with higher clinical probability of recurrence and those who could benefit from partial adrenalectomy by demonstrating the sites of specific steroidogenesis. However, it is also entirely true that S-AVS is more expensive, time-consuming and labor-intensive compared to C-AVS.(Figure is included in full-text article.)The angiography during S-AVS (A, B), the coronal CT

  2. Rare presentation of sebaceous hyperplasia

    PubMed Central

    Lester, Rachael A; Torgerson, Rochelle R; Sandhu, Nicole P

    2014-01-01

    A 23-year-old woman presented with an 8-month history of asymptomatic thickening of the central areola bilaterally and oily nipple discharge. On examination, there were yellowish-pink papules coalescing into plaques bilaterally. Biopsy showed ectopic sebaceous glands (Montgomery tubercles), known as bilateral areolar sebaceous hyperplasia. PMID:24759166

  3. Effectiveness of Neuromuscular Electrical Stimulation on Patients With Dysphagia With Medullary Infarction.

    PubMed

    Zhang, Ming; Tao, Tao; Zhang, Zhao-Bo; Zhu, Xiao; Fan, Wen-Guo; Pu, Li-Jun; Chu, Lei; Yue, Shou-Wei

    2016-03-01

    To evaluate and compare the effects of neuromuscular electrical stimulation (NMES) acting on the sensory input or motor muscle in treating patients with dysphagia with medullary infarction. Prospective randomized controlled study. Department of physical medicine and rehabilitation. Patients with dysphagia with medullary infarction (N=82). Participants were randomized over 3 intervention groups: traditional swallowing therapy, sensory approach combined with traditional swallowing therapy, and motor approach combined with traditional swallowing therapy. Electrical stimulation sessions were for 20 minutes, twice a day, for 5d/wk, over a 4-week period. Swallowing function was evaluated by the water swallow test and Standardized Swallowing Assessment, oral intake was evaluated by the Functional Oral Intake Scale, quality of life was evaluated by the Swallowing-Related Quality of Life (SWAL-QOL) Scale, and cognition was evaluated by the Mini-Mental State Examination (MMSE). There were no statistically significant differences between the groups in age, sex, duration, MMSE score, or severity of the swallowing disorder (P>.05). All groups showed improved swallowing function (P≤.01); the sensory approach combined with traditional swallowing therapy group showed significantly greater improvement than the other 2 groups, and the motor approach combined with traditional swallowing therapy group showed greater improvement than the traditional swallowing therapy group (P<.05). SWAL-QOL Scale scores increased more significantly in the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups than in the traditional swallowing therapy group, and the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups showed statistically significant differences (P=.04). NMES that targets either sensory input or motor muscle coupled with

  4. Prevention of Bronchial Hyperplasia by EGFR Pathway Inhibitors in an Organotypic Culture Model

    PubMed Central

    Lee, Jangsoon; Ryu, Seung-Hee; Kang, Shin Myung; Chung, Wen-Cheng; Gold, Kathryn Ann; Kim, Edward S.; Hittelman, Walter N.; Hong, Waun Ki; Koo, Ja Seok

    2011-01-01

    Lung cancer is the leading cause of cancer-related mortality worldwide. Early detection or prevention strategies are urgently needed to increase survival. Hyperplasia is the first morphologic change that occurs in the bronchial epithelium during lung cancer development, followed by squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumor. The current study was designed to determine the molecular mechanisms that control bronchial epithelium hyperplasia. Using primary normal human tracheobronchial epithelial (NHTBE) cells cultured using the 3-dimensional organotypic method, we found that the epidermal growth factor receptor (EGFR) ligands EGF, transforming growth factor-alpha, and amphiregulin induced hyperplasia, as determined by cell proliferation and multilayered epithelium formation. We also found that EGF induced increased cyclin D1 expression, which plays a critical role in bronchial hyperplasia; this overexpression was mediated by activating the mitogen-activated protein kinase pathway but not the phosphoinositide 3-kinase/Akt signaling pathway. Erlotinib, an EGFR tyrosine kinase inhibitor, and U0126, a MEK inhibitor, completely inhibited EGF-induced hyperplasia. Furthermore, a promoter analysis revealed that the activator protein-1 transcription factor regulates EGF-induced cyclin D1 overexpression. Activator protein-1 depletion using siRNA targeting its c-Jun component completely abrogated EGF-induced cyclin D1 expression. In conclusion, we demonstrated that bronchial hyperplasia can be modeled in vitro using primary NHTBE cells maintained in a 3-dimensional (3-D) organotypic culture. EGFR and MEK inhibitors completely blocked EGF-induced bronchial hyperplasia, suggesting that they have a chemopreventive role. PMID:21505178

  5. Massive adrenal vein aneurysm mimicking an adrenal tumor in a patient with hemophilia A: a case report and review of the literature.

    PubMed

    Sleightholm, Richard; Wahlmeier, Steven; Carson, Jeffrey S; Drincic, Andjela; Lazenby, Audrey; Foster, Jason M

    2016-12-01

    Visceral venous aneurysms are exceedingly rare, and until now, there have been no reports of this phenomenon in the adrenal vasculature. This report details the first adrenal venous aneurysm reported in the literature. The aneurysm presented as an 18-cm mass that was initially suspected to be a hematoma or tumor on the basis of the complex medical history of the patient, which included hemophilia A and testicular cancer. After surgical excision, pathologic examination confirmed this mass to be a 15.9-cm adrenal vein aneurysm, the largest aneurysm of any type or location recorded in the medical literature. A 58-year-old caucasian male with hemophilia A presented to the emergency room of another institution with abdominal pain, blood in the stool, and a history of diverticulosis and symptomatic hemorrhoids. A large, left-sided adrenal mass was detected by computed tomography, and because of the patient's hemophilia A and imaging consistent with a hemorrhagic mass, a hematoma was initially suspected. The patient was transferred to our institution, monitored for further bleeding with a stable hospital course, and discharged from the hospital under close monitoring. After 7-8 weeks with no change in the size of the mass, concerns grew regarding increasing symptoms of both satiety and mass effects from the large anomaly, as well as about the patient's complicated medical history, which also included cancer. Surgical excision was recommended because of the concerns about increasing symptoms and the possibility of a malignancy. Correction and maintenance of factor VIII levels were incorporated pre-, intra-, and postoperatively, and en bloc surgical resection was performed to minimize bleeding and provide oncologic extirpation of the mass. A bowling ball-sized mass was removed, and careful pathologic examination revealed the mass to be a venous adrenal aneurysm. After a brief hospital stay, the patient made a full recovery. Extensive review of the literature revealed 11

  6. Lymphoid papillary hyperplasia of the palatine tonsil: a Chinese case report

    PubMed Central

    Zhao, Ming; Yu, Jingjing; Li, Changshui

    2013-01-01

    Lymphoid papillary hyperplasia is a rare abnormality of the tonsils with a predilection for affecting young Asian girls. Herein, we report a 31-year-old Chinese woman presented as right lateral recurrent tonsillar hypertrophy with odynophagia and dysphagia over the past 5 years, worsening over a period of for half a year. Clinically, this lesion was similar to papillomatosis or lymphoid polyposis. However, histopathologic study showed a distinctive form of lymphoid hyperplasia with considerable distinct finger-like projections composed of many phyllodes which contained remarkable follicular lymphoid hyperplasia. This is the only Chinese case of lymphoid papillary hyperplasia of the palatine tonsils that has been reported in the most recent English literature so far. The importance of recognizing this disorder rests in the fact that in spite of the clinical features suggestive of both a benign and a malignant tumor, however, the process is a benign tumor-like proliferation, probably non-neoplastic, could easily be cured by tonsillectomy. PMID:24040465

  7. Heterogeneous levels of oxidative phosphorylation enzymes in rat adrenal glands.

    PubMed

    Ogawa, Koichi; Harada, Keita; Endo, Yutaka; Sagawa, Sueko; Inoue, Masumi

    2011-01-01

    Mitochondria are organelles that produce ATP and reactive oxygen species, which are thought to be responsible for a decline in physiological function with aging. In this study, we morphologically and biochemically examined mitochondria in the rat adrenal gland. Immunohistochemistry showed that the rank order for intensity of immunolabelling for complex IV was zona reticularis > zona fasciculata > adrenal medulla, whereas for complex V α and β subunits, it was zona fasciculata > zona reticularis and adrenal medulla. The immunolabelling for complex I was homogeneous in the adrenal gland. The difference in immunolabelling between complexes I and IV indicates that the ratio of levels of complex I to that of complex IV in the zona reticularis was smaller than that in the zona fasciculata and the adrenal medulla. Electron microscopy revealed that aging rats had zona reticularis cells with many lysosomes and irregular nuclei. The result suggests that the level of proteins involved in oxidative phosphorylation is coordinated within the complex, but differs between the complexes. This might be responsible for degeneration of zona reticularis cells with aging. Copyright © 2009 Elsevier GmbH. All rights reserved.

  8. Anatomical Variations of the Right Adrenal Vein: Concordance Between Multidetector Computed Tomography and Catheter Venography.

    PubMed

    Omura, Kensuke; Ota, Hideki; Takahashi, Yuuki; Matsuura, Tomonori; Seiji, Kazumasa; Arai, Yoichi; Morimoto, Ryo; Satoh, Fumitoshi; Takase, Kei

    2017-03-01

    Adrenal venous sampling is the most reliable diagnostic procedure to determine surgical indications in primary aldosteronism. Because guidelines recommend multidetector computed tomography (CT) to evaluate the adrenal gland, some past reports used multidetector CT as a guide for adrenal venous sampling. However, the detailed anatomy of the right adrenal vein and its relationship with an accessory hepatic vein remains uncertain. The purpose of this study was to describe detailed anatomical variations of the right adrenal vein and to determine the concordance between CT and catheter venography in patients with primary aldosteronism. In total, 440 consecutive patients who underwent adrenal venous sampling were included. Four-phase dynamic CT was performed. Anatomical locations and variations of the right adrenal vein and its relationship with the accessory hepatic vein were compared with catheter venographic findings. Successful catheterization was achieved in 437 patients (99%). The right adrenal vein was visualized in the late arterial phase with CT in 420 patients (95%). The right adrenal vein formed a common trunk with the accessory hepatic vein in 87 patients (20%). CT identified the correct craniocaudal level of the orifice in 354 patients (84%). Anatomical variations, location, and angle of inflow of the right adrenal vein based on CT demonstrated high concordance with catheter venography. CT may provide useful information for preparation before adrenal venous sampling. © 2017 American Heart Association, Inc.

  9. Hypertensive crisis caused by electrocauterization of the adrenal gland during hepatectomy.

    PubMed

    Doo, A Ram; Son, Ji-Seon; Han, Young-Jin; Yu, Hee Chul; Ko, Seonghoon

    2015-02-14

    Hypertensive crisis (i.e., systolic blood pressure over 300 mmHg) is very rare during operation except pheochromocytoma, but it can be a fatal and embarrassing to surgeons and anesthesiologists. The right adrenal gland can be electrocauterized during a right hemi-hepatectomy. We report a case of hypertensive crisis during right hemi-hepatectomy in which the right adrenal gland was stimulated by monopolar electrocautery in a patient with normal neuroendocrine function. A 73-year-old man with hepatocellular carcinoma was scheduled to undergo right hemi-hepatectomy. Three hours into the surgery, the patient's blood pressure increased abruptly from 100/40 to over 350/130 mmHg (the maximum measurement pressure of the monitor; 350 mmHg). The surgeon had cauterized the right adrenal gland using monopolar electrocautery to separate the liver from the adrenal gland immediately prior to the event. Approximately 3 minutes after suspending the operation, blood pressure returned to baseline levels. After the event, the operation was successfully completed without any complication. Hormonal studies and iodine-123 meta-iodobenzylguanidine scintigraphy revealed no neuroendocrine tumor such as a pheochromocytoma. Operations such as hepatectomy that stimulate the adrenal gland may lead to an unexpected catecholamine surge and result in hypertensive crisis, even if neuroendocrine function of the adrenal gland is normal.

  10. Brain serotonin and pituitary-adrenal functions

    NASA Technical Reports Server (NTRS)

    Vernikos-Danellis, J.; Berger, P.; Barchas, J. D.

    1973-01-01

    It had been concluded by Scapagnini et al. (1971) that brain serotonin (5-HT) was involved in the regulation of the diurnal rhythm of the pituitary-adrenal system but not in the stress response. A study was conducted to investigate these findings further by evaluating the effects of altering brain 5-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. In a number of experiments brain 5-HT synthesis was inhibited with parachlorophenylalanine. In other tests it was tried to raise the level of brain 5-HT with precursors.

  11. Endoscopic Ultrasound in Endocrinology: Imaging of the Adrenals and the Endocrine Pancreas.

    PubMed

    Kann, Peter Herbert

    2016-01-01

    Endoscopic ultrasound (EUS) imaging of adrenal glands and its application to diagnostic procedures of adrenal diseases has been reported since 1998. It can be considered a relevant advantage in the field of adrenal diseases. Indeed, EUS allows the detection of adrenal lesions (even very small ones) and their characterization, the assessment of malignancy criteria, the early detection of neoplastic recurrences, the preoperative identification of morphologically healthy parts of the glands, the differentiation of extra-adrenal from adrenal tumors, and of the pathological entities associated with adrenal insufficiency, and the fine-needle aspiration biopsy (EUS-FNA) of suspicious lesions. At the same time, its clinical relevance depends on the experience of the endosonographer. Moreover, EUS is also by far the best and most sensitive imaging technique to detect and assess the follow-up of pancreatic manifestation of MEN1 disease. It furthermore enables the preoperatively localization of insulinomas and critical structures in their neighborhood, and may be relevant in planning surgical strategy. A positive EUS in a case of insulinoma furthermore confirms the endocrine diagnosis, especially considering the differential diagnosis of hypoglycemia factitia by oral antidiabetics. It can be supplemented by EUS-FNA. Again, it has to be considered that EUS may reveal false positive and false negative results, and the quality of the findings largely depends on the endosonographer's skills and experience. The most important technical details together with the advantages and limitations of EUS, and the pathognomonic characteristic of benign and malignant disorders of the adrenals and pancreas are presented here. © 2016 S. Karger AG, Basel.

  12. Intimal hyperplasia induced by vascular intervention causes lipoprotein retention and accelerated atherosclerosis.

    PubMed

    Kijani, Siavash; Vázquez, Ana Maria; Levin, Malin; Borén, Jan; Fogelstrand, Per

    2017-07-01

    Accelerated atherosclerosis diminishes the long term patency of vascular interventions, such as percutaneous coronary intervention and implantation of saphenous vein grafts. However, the cause of this accelerated atherosclerosis is unclear. In this study, we tested the hypothesis that intimal hyperplasia formed following vascular intervention promotes retention of atherogenic lipoproteins. Intimal hyperplasia was surgically induced in the mouse common carotid artery. The surgery was combined with different mouse models of hypercholesterolemia to obtain different cholesterol levels and to control the onsets of hypercholesterolemia. Three weeks after surgery, samples were immunostained for apoB lipoproteins, smooth muscle cells and leukocytes. Already at mild hypercholesterolemia (193 mg/dL), pronounced apoB lipoprotein retention was found in the extracellular matrix in both intimal hyperplasia and the injured underlying media. In contrast, minimal retention was detected in the uninjured proximal region of the same vessel, or in vessels from mice with normal cholesterol levels (81 mg/dL). Induction of aggravated hypercholesterolemia 3 weeks after surgery, when a mature intimal hyperplasia had been formed, caused a very rapid development of atherosclerotic lesions. Mechanistically, we show that lipoprotein retention was almost exclusively dependent on electrostatic interactions to proteoglycan glycosaminoglycans, and the lipoprotein retention to intimal hyperplasia could be inhibited in vivo using glycosaminoglycan-binding antibodies. Thus, formation of intimal hyperplasia following vascular intervention makes the vessel wall highly susceptible for lipoprotein retention and accelerated atherosclerosis. The increased lipoprotein retention in intimal hyperplasia can be targeted by blocking the interaction between apoB lipoproteins and glycosaminoglycans in the extracellular matrix. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on

  13. Saw palmetto for benign prostatic hyperplasia.

    PubMed

    Bent, Stephen; Kane, Christopher; Shinohara, Katsuto; Neuhaus, John; Hudes, Esther S; Goldberg, Harley; Avins, Andrew L

    2006-02-09

    Saw palmetto is used by over 2 million men in the United States for the treatment of benign prostatic hyperplasia and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration. In this double-blind trial, we randomly assigned 225 men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo. The primary outcome measures were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects. There was no significant difference between the saw palmetto and placebo groups in the change in AUASI scores (mean difference, 0.04 point; 95 percent confidence interval, -0.93 to 1.01), maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, -0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels during the one-year study. The incidence of side effects was similar in the two groups. In this study, saw palmetto did not improve symptoms or objective measures of benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00037154.). Copyright 2006 Massachusetts Medical Society.

  14. Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids.

    PubMed

    Yarnell, Kelly; Purcell, Rebecca S; Walker, Susan L

    2016-04-25

    Adrenal activity can be assessed in the equine species by analysis of feces for corticosterone metabolites. During a potentially aversive situation, corticotrophin releasing hormone (CRH) is released from the hypothalamus in the brain. This stimulates the release of adrenocorticotrophic hormone (ACTH) from the pituitary gland, which in turn stimulates release of glucocorticoids from the adrenal gland. In horses the glucocorticoid corticosterone is responsible for several adaptations needed to support equine flight behaviour and subsequent removal from the aversive situation. Corticosterone metabolites can be detected in the feces of horses and assessment offers a non-invasive option to evaluate long term patterns of adrenal activity. Fecal assessment offers advantages over other techniques that monitor adrenal activity including blood plasma and saliva analysis. The non-invasive nature of the method avoids sampling stress which can confound results. It also allows the opportunity for repeated sampling over time and is ideal for studies in free ranging horses. This protocol describes the enzyme linked immunoassay (EIA) used to assess feces for corticosterone, in addition to the associated biochemical validation.

  15. Is there a role for segmental adrenal venous sampling and adrenal sparing surgery in patients with primary aldosteronism?

    PubMed

    Satoh, Fumitoshi; Morimoto, Ryo; Seiji, Kazumasa; Satani, Nozomi; Ota, Hideki; Iwakura, Yoshitsugu; Ono, Yoshikiyo; Kudo, Masataka; Nezu, Masahiro; Omata, Kei; Tezuka, Yuta; Kawasaki, Yoshihide; Ishidoya, Shigeto; Arai, Yoichi; Takase, Kei; Nakamura, Yasuhiro; McNamara, Keely; Sasano, Hironobu; Ito, Sadayoshi

    2015-10-01

    Adrenal venous sampling (AVS) is critical to determine the subtype of primary aldosteronism (PA). Central AVS (C-AVS)--that is, the collection of effluents from bilateral adrenal central veins (CV)--sometimes does not allow differentiation between bilateral aldosterone-producing adenomas (APA) and idiopathic hyperaldosteronism. To establish the best treatment course, we have developed segmental AVS (S-AVS); that is, we collect effluents from the tributaries of CV to determine the intra-adrenal sources of aldosterone overproduction. We then evaluated the clinical utility of this novel approach in the diagnosis and treatment of PA. We performed C-AVS and/or S-AVS in 297 PA patients and assessed the accuracy of diagnosis based on the results of C-AVS (n=138, 46.5%) and S-AVS (n=159, 53.5%) by comparison with those of clinicopathological evaluation of resected specimens. S-AVS demonstrated both elevated and attenuated secretion of aldosterone from APA and non-tumorous segments, respectively, in patients with bilateral APA and recurrent APA. These findings were completely confirmed by detailed histopathological examination after surgery. S-AVS, but not C-AVS, also served to identify APA located distal from the CV. Compared to C-AVS, S-AVS served to identify APA in some patients, and its use should expand the pool of patients eligible for adrenal sparing surgery through the identification of unaffected segments, despite the fact that S-AVS requires more expertise and time. Especially, this new technique could enormously benefit patients with bilateral or recurrent APA because of the preservation of non-tumorous glandular tissue. © 2015 European Society of Endocrinology.

  16. Adrenal venous sampling in primary aldosteronism: multinomial regression modeling to detect aldosterone secretion lateralization when right adrenal sampling is missing.

    PubMed

    Durivage, Camille; Blanchette, Rémi; Soulez, Gilles; Chagnon, Miguel; Gilbert, Patrick; Giroux, Marie-France; Bourdeau, Isabelle; Oliva, Vincent L; Lacroix, André; Therasse, Eric

    2017-02-01

    Difficulty to recognize or canulate the right adrenal vein is the most frequent cause of adrenal venous sampling (AVS) failure. We aimed to assess multinomial regression modeling (MRM) of peripheral and left adrenal vein samplings to detect lateralization of aldosterone secretion when the right AVS is missing. Simultaneous bilateral AVS samplings were performed before (basal) and after intravenous cosyntropin injection in 188 consecutive patients between December 1989 and September 2015. Different reference standards for lateralization of aldosterone secretion were defined for basal and for postcosyntropin AVS and according to lateralization index cutoffs at least 2 and at least 4. MRMs were built to detect lateralization of aldosterone secretion according to these reference standards using only peripheral and left adrenal veins samplings (without the right AVS). Detection accuracy was assessed by the area under the receiver operating characteristic (AUROC) curves and detection sensitivities were reported for specificity at least 95%. For basal AVS with lateralization index at least 2, AUROC were respectively 0.931 [95% confidence interval (CI) 0.894-0.968] and 0.922 (95% CI 0.882-0.962) for right and left lateralization of aldosterone secretion detection and MRM could detect respectively 65.5 and 62.7% of the right and left lateralization of aldosterone secretion. For AVS after cosyntropin with lateralization index at least 4, AUROC were respectively 0.964 (95% CI: 0.940-0.987) and 0.955 (95% CI: 0.927-0.983) for right and left lateralization of aldosterone secretion, and MRM could detect respectively 77.2 and 72.9% of the right and left lateralization of aldosterone secretion. MRM can detect lateralization of aldosterone secretion without the right AVS in most patients and could eliminate the need for repeat AVS when right adrenal vein canulation is nonselective or impossible.

  17. Severe polyuria after the resection of adrenal pheochromocytoma.

    PubMed

    Tobe, Musashi; Ito, Keiichi; Umeda, Shun; Sato, Akinori; Adaniya, Noriaki; Tanaka, Yuji; Hayakawa, Masamichi; Asano, Tomohiko

    2010-12-01

    A 73-year-old male patient with hypertension and hyperglycemia was referred to our hospital because of a diagnosis regarding his left adrenal tumor. Because the levels of urinary metanephrine and normetanephrine were elevated, and (131) I-MIBG scintigraphy showed intense uptake in the adrenal tumor, the tumor was diagnosed as a pheochromocytoma. An adrenalectomy was carried out. Severe polyuria, which was accompanied by a rapid decrease in central venous pressure, started 1 hour after the operation. Urine output of more than 8000 mL/day continued until the 16th postoperative day. Plasma antidiuretic hormone (ADH) levels were within the normal range. Plasma human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were elevated postoperatively, and the elevation of these peptides was one possible cause for the severe polyuria. Because ADH levels in the tumor fluid were not elevated, the tumor was not an ADH-secreting tumor. Urinary β2-microglobulin was significantly elevated after the operation, thus suggesting that renal tubule dysfunction might also have been involved in the polyuria. However, the mechanism of polyuria after the resection of adrenal pheochromocytoma is not fully understood. Polyuria after the resection of adrenal pheochromocytoma is extremely rare, and the present subject is the second case to date. © 2010 The Japanese Urological Association.

  18. Multiple endocrine neoplasia type 1 knockout mice develop parathyroid, pancreatic, pituitary and adrenal tumours with hypercalcaemia, hypophosphataemia and hypercorticosteronaemia.

    PubMed

    Harding, Brian; Lemos, Manuel C; Reed, Anita A C; Walls, Gerard V; Jeyabalan, Jeshmi; Bowl, Michael R; Tateossian, Hilda; Sullivan, Nicky; Hough, Tertius; Fraser, William D; Ansorge, Olaf; Cheeseman, Michael T; Thakker, Rajesh V

    2009-12-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized in man by parathyroid, pancreatic, pituitary and adrenal tumours. The MEN1 gene encodes a 610-amino acid protein (menin) which is a tumour suppressor. To investigate the in vivo role of menin, we developed a mouse model, by deleting Men1 exons 1 and 2 and investigated this for MEN1-associated tumours and serum abnormalities. Men1(+/-) mice were viable and fertile, and 220 Men1(+/-) and 94 Men1(+/+) mice were studied between the ages of 3 and 21 months. Survival in Men1(+/-) mice was significantly lower than in Men1(+/+) mice (<68% vs >85%, P<0.01). Men1(+/-) mice developed, by 9 months of age, parathyroid hyperplasia, pancreatic tumours which were mostly insulinomas, by 12 months of age, pituitary tumours which were mostly prolactinomas, and by 15 months parathyroid adenomas and adrenal cortical tumours. Loss of heterozygosity and menin expression was demonstrated in the tumours, consistent with a tumour suppressor role for the Men1 gene. Men1(+/-) mice with parathyroid neoplasms were hypercalcaemic and hypophosphataemic, with inappropriately normal serum parathyroid hormone concentrations. Pancreatic and pituitary tumours expressed chromogranin A (CgA), somatostatin receptor type 2 and vascular endothelial growth factor-A. Serum CgA concentrations in Men1(+/-) mice were not elevated. Adrenocortical tumours, which immunostained for 3-beta-hydroxysteroid dehydrogenase, developed in seven Men1(+/-) mice, but resulted in hypercorticosteronaemia in one out of the four mice that were investigated. Thus, these Men1(+/-) mice are representative of MEN1 in man, and will help in investigating molecular mechanisms and treatments for endocrine tumours.

  19. 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.

  20. Adrenal 11-beta hydroxysteroid dehydrogenase activity in response to stress.

    PubMed

    Zallocchi, Marisa; Matković, Laura; Damasco, María C

    2004-06-01

    This work studied the effect of stresses produced by simulated gavage or gavage with 200 mmol/L HCl two hours before adrenal extraction, on the activities of the 11beta-hydroxysteroid dehydrogenase 1 and 11beta-hydroxysteroid dehydrogenase 2 isoforms present in the rat adrenal gland. These activities were determined on immediately prepared adrenal microsomes following incubations with 3H-corticosterone and NAD+ or NADP+. 11-dehydrocorticosterone was measured as an end-product by TLC, and controls were adrenal microsomes from rats kept under basal (unstressed) conditions. 11beta-hydroxysteroid dehydrogenase 1 activity, but not 11beta-hydroxysteroid dehydrogenase 2 activity, was increased under both stress-conditions. Homeostatically, the stimulation of 11beta-hydroxysteroid dehydrogenase 1 activity would increase the supply of glucocorticoids. These, in turn, would activate the enzyme phenylethanolamine N-methyl transferase, thereby improving the synthesis of epinephrine as part of the stress-response.

  1. Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex.

    PubMed

    Prüss, Harald; Tedeschi, Andrea; Thiriot, Aude; Lynch, Lydia; Loughhead, Scott M; Stutte, Susanne; Mazo, Irina B; Kopp, Marcel A; Brommer, Benedikt; Blex, Christian; Geurtz, Laura-Christin; Liebscher, Thomas; Niedeggen, Andreas; Dirnagl, Ulrich; Bradke, Frank; Volz, Magdalena S; DeVivo, Michael J; Chen, Yuying; von Andrian, Ulrich H; Schwab, Jan M

    2017-11-01

    Acute spinal cord injury (SCI) causes systemic immunosuppression and life-threatening infections, thought to result from noradrenergic overactivation and excess glucocorticoid release via hypothalamus-pituitary-adrenal axis stimulation. Instead of consecutive hypothalamus-pituitary-adrenal axis activation, we report that acute SCI in mice induced suppression of serum norepinephrine and concomitant increase in cortisol, despite suppressed adrenocorticotropic hormone, indicating primary (adrenal) hypercortisolism. This neurogenic effect was more pronounced after high-thoracic level (Th1) SCI disconnecting adrenal gland innervation, compared with low-thoracic level (Th9) SCI. Prophylactic adrenalectomy completely prevented SCI-induced glucocorticoid excess and lymphocyte depletion but did not prevent pneumonia. When adrenalectomized mice were transplanted with denervated adrenal glands to restore physiologic glucocorticoid levels, the animals were completely protected from pneumonia. These findings identify a maladaptive sympathetic-neuroendocrine adrenal reflex mediating immunosuppression after SCI, implying that therapeutic normalization of the glucocorticoid and catecholamine imbalance in SCI patients could be a strategy to prevent detrimental infections.

  2. AgNORs in hyperplasia, papilloma and oral squamous cell carcinoma.

    PubMed

    Fonseca, L M; do Carmo, M A

    2000-01-01

    Ten inflammatory fibrous hyperplasias, ten papillomas, and nineteen oral squamous cell carcinomas were analyzed by the AgNOR technique to determine if different disturbances of oral epithelia presented different AgNOR counts. The papilloma group showed higher mean AgNOR counts (3.15 +/- 0.58) than the hyperplasia group (1.98 +/- 0.24) and smaller than the well-differentiated oral squamous cell carcinoma group (6.56 +/- 1.25) and poorly differentiated oral squamous cell carcinoma group (7.07 +/- 1.60). The differences among the groups of lesions were statistically significant (P < 0.05) except between the well differentiated oral squamous cell carcinoma group and the poorly differentiated oral squamous cell carcinoma group. Our findings suggest that the cellular proliferation ratio in papillomas is greater than hyperplasias and smaller than carcinomas.

  3. Aldo-Keto Reductases 1B in Adrenal Cortex Physiology

    PubMed Central

    Pastel, Emilie; Pointud, Jean-Christophe; Martinez, Antoine; Lefrançois-Martinez, A. Marie

    2016-01-01

    Aldose reductase (AKR1B) proteins are monomeric enzymes, belonging to the aldo-keto reductase (AKR) superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates, such as aliphatic and aromatic aldehydes or ketones. Due to the involvement of human aldose reductases in pathologies, such as diabetic complications and cancer, AKR1B subgroup enzymatic properties have been extensively characterized. However, the issue of AKR1B function in non-pathologic conditions remains poorly resolved. Adrenal activities generated large amount of harmful aldehydes from lipid peroxidation and steroidogenesis, including 4-hydroxynonenal (4-HNE) and isocaproaldehyde (4-methylpentanal), which can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase (PGFS) activity, suggesting that, in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, the adrenal gland is one of the major sites for human and murine AKR1B expression, suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover, chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms. This review presents the molecular mechanisms accounting for the adrenal-specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions. PMID:27499746

  4. Abnormal gel flotation caused by contrast media during adrenal vein sampling.

    PubMed

    Lima-Oliveira, Gabriel; Lippi, Giuseppe; Salvagno, Gian Luca; Gelati, Matteo; Bassi, Antonella; Contro, Alberto; Pizzolo, Francesca; Guidi, Gian Cesare

    2016-10-15

    During adrenal venous sampling (AVS) procedure, radiologists administer a contrast agent via the catheter to visualize the proper catheter position. A patient with primary aldosteronism diagnostic-hypothesis was admitted for AVS. A venogram was performed to
confirm the catheter's position with 2mL of Iopamidol 300 mg/mL. Samples were collected with syringe connected to a hydrophilic coated catheter by low-pressure aspiration from each of the four collection sites: inferior vena cava in the suprarenal portion, inferior vena cava in the infrarenal portion, left adrenal vein, and right adrenal vein; then immediately transferred from syringe to tubes with gel separator. All tubes were centrifuged at 1200 x g for 10 minutes. At the end of centrifugation process, primary blood tubes containing blood from inferior vena cava and left adrenal vein exhibited the standard gel separator barrier, while tubes from right adrenal vein showed abnormal flotation of gel separator. The radiologist confirmed the usage of 2.6 mL instead of 2.0 mL of Iopamidol 300 mg/mL. This iodinated contrast media, with 1.33 g/cm 3 of density, was used close to the right adrenal vein due to some difficulty to access it. The abnormal flotation of gel separator in samples taken from right adrenal vein can be explained by the usage of the iodinated
contrast media. We suggest using plain-tubes (without gel separator) for AVS in order to avoid preanalytical nonconformities. Moreover, a blood volume equivalent to twice the catheter extension should be discarded to eliminate residual contrast media before collection of samples for laboratory assays.

  5. Abnormal gel flotation caused by contrast media during adrenal vein sampling

    PubMed Central

    Lima-Oliveira, Gabriel; Lippi, Giuseppe; Salvagno, Gian Luca; Gelati, Matteo; Bassi, Antonella; Contro, Alberto; Pizzolo, Francesca; Guidi, Gian Cesare

    2016-01-01

    Introduction During adrenal venous sampling (AVS) procedure, radiologists administer a contrast agent via the catheter to visualize the proper catheter position. Materials and methods A patient with primary aldosteronism diagnostic-hypothesis was admitted for AVS. A venogram was performed to
confirm the catheter’s position with 2mL of Iopamidol 300 mg/mL. Samples were collected with syringe connected to a hydrophilic coated catheter by low-pressure aspiration from each of the four collection sites: inferior vena cava in the suprarenal portion, inferior vena cava in the infrarenal portion, left adrenal vein, and right adrenal vein; then immediately transferred from syringe to tubes with gel separator. All tubes were centrifuged at 1200 x g for 10 minutes. Results At the end of centrifugation process, primary blood tubes containing blood from inferior vena cava and left adrenal vein exhibited the standard gel separator barrier, while tubes from right adrenal vein showed abnormal flotation of gel separator. The radiologist confirmed the usage of 2.6 mL instead of 2.0 mL of Iopamidol 300 mg/mL. This iodinated contrast media, with 1.33 g/cm3 of density, was used close to the right adrenal vein due to some difficulty to access it. Conclusion The abnormal flotation of gel separator in samples taken from right adrenal vein can be explained by the usage of the iodinated
contrast media. We suggest using plain-tubes (without gel separator) for AVS in order to avoid preanalytical nonconformities. Moreover, a blood volume equivalent to twice the catheter extension should be discarded to eliminate residual contrast media before collection of samples for laboratory assays. PMID:27812311

  6. Reversion of gingival hyperplasia in a heart transplant patient upon interruption of cyclosporine therapy.

    PubMed

    Somacarrera, M L; Lucas, M; Acero, J

    1996-01-01

    A heart transplant patient undergoing a combined cyclosporine and prednisone treatment was monitored during the 18 months following transplantation. A complete oral and dental examination was performed in each of the first six months after transplantation, and then in the 9th, 12th, 15th, and 18th months. The data collected included gingival hyperplasia secondary to cyclosporine use, and clinical and periodontal variables. Histological studies were also conducted on gingival tissue samples in months 1, 3, 9, 15, and 18. Cyclosporine treatment was replaced by azathioprine treatment in month 10 because the patient was experiencing nephrotoxicity. Between months 9 and 18, gingival hyperplasia regressed by 26.5% due to a reduction in the fibrous connective tissue mass, fibroblasts, and inflammatory infiltration. The control group included 13 heart transplant patients subject to equivalent conditions except discontinuance of cyclosporine treatment; seven of the patients had developed hyperplasia by month 9. Average hyperplasia in the control group increased by 2% between months 9 and 18; only one patient showed a 6.2% decrease in hyperplasia. This provides further evidence for the causal relationship between cyclosporine therapy and gingival hyperplasia, and suggests that this side-effect is reversible.

  7. Direct effects of endogenous pyrogen on medullary temperature-responsive neurons in rabbits.

    PubMed

    Sakata, Y; Morimoto, A; Takase, Y; Murakami, N

    1981-01-01

    The effect of endogenous pyrogen (E.P.) injected directly into the tissue near the recording site were examined on the activities of the medullary temperature-responsive (TR) neurons in rabbits anesthetized with urethane. Endogenous pyrogen prepared from rabbit's whole blood was administered by a fine glass cannula (100-200 micrometer in diameter) in a fluid volume of 1 to 4 microliter. The cannula was fixed to the manipulator in parallel with a microelectrode and their tips were less than 0.05 mm apart. In rabbits with the intact preoptic/anterior hypothalamic (PO/AH) region, 4 warm-responsive neurons out of 7 were inhibited and 6 cold-responsive neuron out of 7 were excited by the direct administration of the E.P. In rabbits with lesions of the PO/AH, 5 warm-responsive neurons out of 9 were inhibited and 6 cold-responsive neurons out of 8 were facilitated by E.P. Antipyretics administered locally after the E.P. antagonized the pyretic effect, causing a return of the discharge of TR neuron to the control rate within 2.4 +/- 1.2 (mean +/- S.D.) min. The medullary TR neuron itself has the ability to respond to the E.P. and contributes to the development of fever.

  8. CLINICAL FACTORS ASSOCIATED WITH BIOCHEMICAL ADRENAL-CORTISOL INSUFFICIENCY IN HOSPITALIZED PATIENTS

    PubMed Central

    Ben-Shlomo, Anat; Mirocha, James; Liu, Ning-Ai; Sheinin, Renee C.; Melmed, Shlomo

    2014-01-01

    Background Diagnosis of adrenal-cortisol insufficiency is often misleading in hospitalized patients as clinical and biochemical features overlap with co-morbidities. We analyzed clinical determinants associated with a biochemical diagnosis of adrenal-cortisol insufficiency in non-ICU hospitalized patients. Methods In a retrospective cohort study we reviewed 4668 inpatients with random morning cortisol levels ≤15 μg/dL hospitalized in our center between 2003 and 2010. Using serum cortisol threshold level of 18 μg/dL 30 and/or 60 minutes after cortrosyn (250 μg) injection to define biochemical adrenal-cortisol status, we characterized and compared insufficient (n=108, serum cortisol ≤18 μg/dL) and sufficient ( n=394; serum cortisol >18 μg/dL) non-ICU hospitalized patients. Results Commonly reported clinical and routine biochemical adrenal-cortisol insufficiency features were similar between insufficient and sufficient inpatients. Biochemical adrenal-cortisol insufficiency was associated with increased frequency of liver disease, specifically hepatitis C (p=0.01) and prior orthotopic liver transplantation (p<0.001), HIV (p=0.005) and reported preexisting male hypogonadism (p<0.001) as compared to biochemical adrenal-cortisol sufficiency group. Forty percent of insufficient inpatients were not treated with glucocorticoids after diagnosis. Multivariable logistic analysis demonstrated that inpatients with higher cortisol levels (p=0.0001), higher diastolic blood pressure (p=0.05) and females (p=0.009) were more likely not to be treated, while those with previous short-term glucocorticoid treatment (p=0.002), had other co-existing endocrine diseases (p=0.005) or received an inhospital endocrinology consultation (p<0.0001) were more likely to be replaced with glucocorticoids. Conclusions Commonly reported adrenal-cortisol insufficiency features do not reliably identify hospitalized patients biochemically confirmed to have this disorder. Co-morbidities including

  9. [Vascular adrenal cyst causing difficult to control high blood pressure].

    PubMed

    García Escudero, D; Torres Roca, M; Hernández Contreras, M E; Sánchez Rodríguez, C; Oñate Celdrán, J

    Hypertension is a prevalent disease in developed countries. Adrenal masses, and especially adrenal cysts, are a rare and usually asymptomatic finding, which can go unnoticed or be detected as incidental findings in imaging tests. These circumstances make the multidisciplinary approach mandatory. The case is presented on a 72 year-old woman with uncontrolled high blood pressure referred to the Urology Department due to the incidental finding of a right retroperitoneal mass. A functional and imaging study was performed, establishing a diagnosis of adrenal cyst causing hypertensive symptoms. A literature search was performed in order to assess diagnostic and therapeutic approaches. With the diagnosis of adrenal cyst causing uncontrolled high blood pressure, a right laparoscopic adrenalectomy was performed. After surgery the patient has maintained blood pressure within the normal range. A multidisciplinary approach is necessary for the management of rare diseases. The surgical approach, if possible, should be laparoscopic. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Simultaneous peritoneal and retroperitoneal splenosis mimics metastatic right adrenal mass.

    PubMed

    Hashem, Abdelwahab; Elbaset, M A; Zahran, Mohamed H; Osman, Yasser

    2018-06-05

    Right retroperitoneal splenosis is rare with few reported cases. We report, here, the case of simultaneous peritoneal and retroperitoneal splenosis mimics metastatic right adrenal mass. A 28-year-old man who had previously undergone post traumatic splenectomy at childhood and subsequently presented with an large incidental non-functioning right adrenal mass with presence of extra-hepatic peritoneal focal lesion diagnosed as metastasis by magnetic resonance imaging (MRI). Adrenalectomy with metatstectomy was performed, and both masses were identified to be splenosis. Adrenal incidentalomas (AIs) is defined as asymptomatic masses >1 cm. on cross-sectional imaging studies. AIs have significant malignant potential for masses > 6 cm. Splenosis are found most frequently in the left retroperitoneum in cases involving retroperitoneal splenosis. However, right retroperitoneal splenosis have been reported. Traditional imaging techniques cannot differentiate splenosis from malignancy. Large right adrenal incidentalomas present with other abdominal, peritoneal masses could be splenosis in patient following post-traumatic splenectomy. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  11. Partial recovery of adrenal function in a patient with autoimmune Addison's disease.

    PubMed

    Smans, L C C J; Zelissen, P M J

    2008-07-01

    To our knowledge, no case of remission in autoimmune Addison's disease has previously been reported. We describe a patient with primary adrenal insufficiency caused by autoimmune adrenalitis in whom partial remission was observed after 7 yr. A 39-yr-old male was referred because of extreme fatigue, weight loss, anorexia, nausea, and bouts of fever. During physical examination hyperpigmentation was seen. Laboratory tests showed a plasma cortisol of 0.02 micromol/l (08:30 h). Cortisol failed to increase during the ACTH stimulation test (0.02 to 0.03 micromol/l) and ACTH was markedly elevated (920 pmol/l). Adrenal auto-antibodies were weakly positive. A CT-scan showed no evidence of calcifications or other abnormalities of the adrenal glands. The diagnosis of autoimmune Addison's disease was made and replacement therapy with hydrocortisone and fludrocortisone was started. During the following years the dose of hydrocortisone was gradually decreased. Eventually, the patient decided to stop his medication completely. A repeated ACTH-stimulation test revealed a basal cortisol of 0.25 micromol/l and a peak cortisol of 0.30 micromol/l with a basal ACTH of 178 pmol/l. The patient did not have any complaints. Recovery of adrenal insufficiency, due to causes other than autoimmune adrenalitis, has been reported in the past. If our case of partial recovery of autoimmune adrenalitis is not unique this could have profound effects on treatment and follow-up of Addison's disease.

  12. Hypogammaglobulinemia associated with nodular lymphoid hyperplasia of the intestine and pernicious anaemia.

    PubMed

    Ouakaa-Kchaou, Asma; Trad, Dorra; Boussourra, Houda; Bibani, Norsaf; Elloumi, Héla; Kochlef, Asma; Gargouri, Dalila; Kharrat, Jamel

    2015-11-01

    Nodular lymphoid hyperplasia of the gastrointestinal tract, recurrent acute pulmonary infections and autoimmune disease are well-recognized complications of common variable immunodeficiency. We aimed to focus on clinical presentation and differential diagnosis of diffuse nodular lymphoid and hyperplasia of the gastrointestinal tract coexisting with hypogammaglobulinemia. We report the case of nodular lymphoid hyperplasia associated with pernicious anaemia in a young man with hypogammaglobulinemia and a long history of pulmonary infections. The considerable point was a mismatch primary clinical diagnosis of familial adenomatous polyposis, due to prominent polyplike endoscopic appearance of the lesions throughout the digestive tract.

  13. Adrenal haemorrhage due to heparin-induced thrombocytopenia.

    PubMed

    Ketha, Siva; Smithedajkul, Patrick; Vella, Adrian; Pruthi, Rajiv; Wysokinski, Waldemar; McBane, Robert

    2013-04-01

    Adrenal haemorrhage (AH) is a rare but potentially devastating complication of heparin-induced thrombocytopenia (HIT). Neither the prevalence nor the natural history of AH due to HIT are known. The objectives of this study were to identify the spectrum of AH causes, to characterise the frequency of AH due to HIT and determine the natural history of HIT-associated AH. All patients with incident adrenal haemorrhage from January 2002 through June 2012 seen at the Mayo Clinic were identified. Over this time frame, there were a total of 115 patients with AH of which 11 cases (10%; mean age 67 ± 8 years; 73% female) were associated with HIT. Of these, all but one occurred in the postoperative setting and involved both adrenal glands (89%) with acute adrenal insufficiency at the time of diagnosis. Cases were found incidentally during an evaluation for fever, shock, abdominal pain or mental status changes. All HIT patients experienced venous thrombosis at other locations including deep venous thromboses (n=14), pulmonary emboli (n= 4) and arterial thrombosis (n=2). Four patients undergoing total knee arthroplasty had "spontaneous HIT" with AH in the absence of identifiable heparin exposure. Other causes of AH included trauma (29%), sepsis (15%), antiphospholipid antibody syndrome (10%), and metastatic disease (12%). In conclusion, AH is an important but seldom recognised presumed thrombotic complication of HIT, which usually occurs in the postoperative period, especially after orthopaedic procedures. This syndrome can occur in the apparent absence of heparin exposure, especially following major joint replacement surgery.

  14. Catecholamines of the adrenal medula and their morphological changes during adaptation to repeated immobilization stress

    NASA Technical Reports Server (NTRS)

    Kvetnansky, R.; Mitro, A.; Mikulaj, L.; Hocman, G.

    1980-01-01

    Changes of the adrenal medulla of rats were studied in the course of adaptation to repeated immobilization stress. An increase in the number of cells in the adrenal medulla was found in the adapted animals; this increase was confirmed by weight indices of the medulla and by cell counts per surface unit. Simultaneous karyometric measurements of the nuclei of adrenal medulla cells and an analysis of the catecholamine contents in the adrenals explain the increased activity of the adrenal medulla in the course of adaptation.

  15. Thymic involution in the suspended rat - Adrenal hypertrophy and glucocorticoid receptor content

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1986-01-01

    The relationship between thymic involution and adrenal hypertrophy is studied. The thymus, adrenal glands, and tissue water content are evaluated in male Sprague rats suspended in antiorthostatic (AO) or orthostatic (O) positions. A 50 percent decrease in the wet weight of the thymus and hypertrophy of the adrenal glands are observed during the seven days of AO suspension. After seven days of recovery the thymus weight is increased to control level; however, the hypertrophy of the adrenal glands remains unchanged. Thymic and renal responses in O postioned rats are similar to AO reactions. Thymic glucocorticoid (GC) receptor concentrations in the rats are analyzed; a 20 percent decrease in GC receptor site concentration, which is related to thymic involution, is detected in both AO and O rats. It is concluded that there is a temporal correlation between thymic involution and adrenal hypertrophy, which is not affected by AO positioning, and thymic involution is not associated with an increased sensitivity to GC.

  16. Inflammatory papillary hyperplasia: A systematic review

    PubMed Central

    Gual-Vaqués, Patricia; Jané-Salas, Enric; Egido-Moreno, Sonia; Ayuso-Montero, Raúl; Marí-Roig, Antoni

    2017-01-01

    Introduction Inflammatory papillary hyperplasia (IPH) is a benign lesion of the palatal mucosa. It is usually found in denture-wearers but also has been reported in patients without a history of use of a maxillary prosthesis use. Objetives The aim of this study is to review the literature to assess the prevalence of denture stomatitis and inflammatory papillary hyperplasia and the etiological factors associated. Material and Methods A search was carried out in PubMed (January 2005 to October 2015) with the key words “inflammatory papillary hyperplasia”, “denture stomatitis”, “granular stomatitis” and “Newton’s type III” The inclusion criteria were studies including at least a sample of 50 apparently healthy patients, articles published from 2005 to 2015 written in English. The exclusion criteria were reviews and non-human studies. Results Out of the 190 studies obtained initially from the search 16 articles were selected to be included in our systematic review. The prevalence of denture stomatitis was 29.56% and 4.44% for IPH. We found 5 cases of denture stomatitis among non-denture-wearer individuals. All IPH cases were associated with the use of prosthesis. Smoking and continued use of ill-fitting dentures turned out to be the most frequent risk factors for developing IPH. Conclusions IPH is a rare oral lesion and its pathogenesis still remains unclear. Its presentation among non-denture-wearers is extremely unusual. Key words:Inflammatory papillary hyperplasia, denture stomatitis, prevalence, granular stomatitis, Newton’s type III stomatitis. PMID:27918740

  17. Molecular classification of benign prostatic hyperplasia: A gene expression profiling study in a rat model.

    PubMed

    Hata, Junya; Satoh, Yuichi; Akaihata, Hidenori; Hiraki, Hiroyuki; Ogawa, Soichiro; Haga, Nobuhiro; Ishibashi, Kei; Aikawa, Ken; Kojima, Yoshiyuki

    2016-07-01

    To characterize the molecular features of benign prostatic hyperplasia by carrying out a gene expression profiling analysis in a rat model. Fetal urogenital sinus isolated from 20-day-old male rat embryo was implanted into a pubertal male rat ventral prostate. The implanted urogenital sinus grew time-dependently, and the pathological findings at 3 weeks after implantation showed epithelial hyperplasia as well as stromal hyperplasia. Whole-genome oligonucleotide microarray analysis utilizing approximately 30 000 oligonucleotide probes was carried out using prostate specimens during the prostate growth process (3 weeks after implantation). Microarray analyses showed 926 upregulated (>2-fold change, P < 0.01) and 3217 downregulated genes (<0.5-fold change, P < 0.01) in benign prostatic hyperplasia specimens compared with normal prostate. Gene ontology analyses of upregulated genes showed predominant genetic themes of involvement in development (162 genes, P = 2.01 × 10(-4) ), response to stimulus (163 genes, P = 7.37 × 10(-13) ) and growth (32 genes, P = 1.93 × 10(-5) ). When we used both normal prostate and non-transplanted urogenital sinuses as controls to identify benign prostatic hyperplasia-specific genes, 507 and 406 genes were upregulated and downregulated, respectively. Functional network and pathway analyses showed that genes associated with apoptosis modulation by heat shock protein 70, interleukin-1, interleukin-2 and interleukin-5 signaling pathways, KIT signaling pathway, and secretin-like G-protein-coupled receptors, class B, were relatively activated during the growth process in the benign prostatic hyperplasia specimens. In contrast, genes associated with cholesterol biosynthesis were relatively inactivated. Our microarray analyses of the benign prostatic hyperplasia model rat might aid in clarifying the molecular mechanism of benign prostatic hyperplasia progression, and identifying molecular targets for benign prostatic hyperplasia treatment.

  18. Armc5 deletion causes developmental defects and compromises T-cell immune responses

    PubMed Central

    Hu, Yan; Lao, Linjiang; Mao, Jianning; Jin, Wei; Luo, Hongyu; Charpentier, Tania; Qi, Shijie; Peng, Junzheng; Hu, Bing; Marcinkiewicz, Mieczyslaw Martin; Lamarre, Alain; Wu, Jiangping

    2017-01-01

    Armadillo repeat containing 5 (ARMC5) is a cytosolic protein with no enzymatic activities. Little is known about its function and mechanisms of action, except that gene mutations are associated with risks of primary macronodular adrenal gland hyperplasia. Here we map Armc5 expression by in situ hybridization, and generate Armc5 knockout mice, which are small in body size. Armc5 knockout mice have compromised T-cell proliferation and differentiation into Th1 and Th17 cells, increased T-cell apoptosis, reduced severity of experimental autoimmune encephalitis, and defective immune responses to lymphocytic choriomeningitis virus infection. These mice also develop adrenal gland hyperplasia in old age. Yeast 2-hybrid assays identify 16 ARMC5-binding partners. Together these data indicate that ARMC5 is crucial in fetal development, T-cell function and adrenal gland growth homeostasis, and that the functions of ARMC5 probably depend on interaction with multiple signalling pathways. PMID:28169274

  19. Predictive diagnosis of endometrial hyperplasia and personalized therapeutic strategy in women of fertile age

    PubMed Central

    2013-01-01

    Introduction Endometrial hyperplasia has a high risk for malignant transformation and relapses; existing mini-invasive treatments may lead to irrevocable endometrium destruction. The aims were to analyze receptor systems in endometrial hyperplasia, to evaluate the capabilities of ultrasonography, sonoelastography for diagnosis and treatment control, and to develop treatment algorithm. Materials and methods We included 313 women (20–45 years), assessed into the following: group 1 (n = 112) with glandular cystic hyperplasia, group 2 (n = 98) endometrial polyps, and group 3 (n = 103) atypical hyperplasia; and 82 controls who have undergone hysteroscopy before in vitro fertilization in tubal origin infertility were also included. Patients underwent clinical examination, transvaginal ultrasound, immunohistochemical study, and hormonal therapy/hysteroresectoscopy. Results In patients with glandular hyperplasia, we registered increase of endometrium estrogen receptors (75.6% in the epithelium and 30.9% in the stroma; in controls, 43.3% and 29.6%, respectively); in polyps, there was a significant estrogen receptor increase in the stroma (48.2% vs 29.6% in controls), and in atypical hyperplasia, progesterone receptors significantly increased in the stroma. Ki-67 increased (40% to 50%) in the epithelium without changes in the stroma. Ultrasound has a sensitivity of 96% and a specificity of 85% for early detection of endometrial pathology and prediction outcome of intervention, and sonoelastography has a sensitivity of 91% and a specificity of 83% for polyp diagnosis. Personalized treatment was effective in 88.8%, relapse was diagnosed in 11.2% after 6 months, and conservative treatment of atypical hyperplasia was effective in 45%: in 25.8%, ablative hysteroresectoscopy was performed, while in 22.6% with comorbidities, hystero/oophorectomies were performed. Conclusions The evaluation of receptor status with ultrasound data in patients with endometrial

  20. Rifampicin-induced adrenal crisis in a patient with tuberculosis: a therapeutic challenge.

    PubMed

    Denny, Nicholas; Raghunath, Sarika; Bhatia, Praveen; Abdelaziz, Muntasir

    2016-11-29

    A 55-year-old Indian man presented with productive cough and a large left pleural effusion. Pleural fluid culture grew Mycobacterium tuberculosis, and he was started on antituberculosis therapy. One week later, the patient presented to hospital with drowsiness, dehydration and hypotension. He was transferred to critical care and only improved after starting hydrocortisone and stopping rifampicin. His short synACTHen test subsequently confirmed primary adrenal insufficiency, and a CT of the abdomen showed bilateral adrenal enlargement. Rifampicin is known to accelerate cortisol metabolism. We report the rare case of a rifampicin-induced adrenal crisis as a first presentation of Addison's disease in a patient with tuberculous infiltration of the adrenal glands. 2016 BMJ Publishing Group Ltd.