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Sample records for bovine adrenal medullary

  1. Upregulation of norepinephrine transporter function by prolonged exposure to nicotine in cultured bovine adrenal medullary cells.

    PubMed

    Itoh, Hideaki; Toyohira, Yumiko; Ueno, Susumu; Saeki, Satoru; Zhang, Han; Furuno, Yumi; Takahashi, Kojiro; Tsutsui, Masato; Hachisuka, Kenji; Yanagihara, Nobuyuki

    2010-09-01

    Nicotine acts on nicotinic acetylcholine receptors in the adrenal medulla and brain, thereby stimulating the release of monoamines such as norepinephrine (NE). In the present study, we examined the effects of prolonged exposure to nicotine on NE transporter (NET) activity in cultured bovine adrenal medullary cells. Treatment of adrenal medullary cells with nicotine increased [(3)H]NE uptake in both a time- (1-5 days) and concentration-dependent (0.1-10 muM) manner. Kinetic analysis showed that nicotine induced an increase in the V (max) of [(3)H]NE uptake with little change in K (m). This increase in NET activity was blocked by cycloheximide, an inhibitor of ribosomal protein synthesis, but not by actinomycin D, a DNA-dependent RNA polymerase inhibitor. [(3)H]NE uptake induced by nicotine was strongly inhibited by hexamethonium and mecamylamine but not by alpha-bungarotoxin, and was abolished by elimination of Ca(2+) from the culture medium. KN-93, an inhibitor of Ca(2+)/calmodulin-dependent protein kinase II, attenuated not only nicotine-induced [(3)H]NE uptake but also (45)Ca(2+) influx in the cells. The present findings suggest that long-term exposure to nicotine increases NET activity through a Ca(2+)-dependent post-transcriptional process in the adrenal medulla.

  2. Dual effects of nobiletin, a citrus polymethoxy flavone, on catecholamine secretion in cultured bovine adrenal medullary cells.

    PubMed

    Zhang, Han; Toyohira, Yumiko; Ueno, Susumu; Shinohara, Yuko; Itoh, Hideaki; Furuno, Yumi; Yamakuni, Tohru; Tsutsui, Masato; Takahashi, Kojiro; Yanagihara, Nobuyuki

    2010-08-01

    Nobiletin, a compound of polymethoxy flavones found in citrus fruits, possesses a wide range of pharmacological activities. Here we report the effects of nobiletin on catecholamine secretion in cultured bovine adrenal medullary cells. Nobiletin (1.0-100 microM) concentration-dependently stimulated catecholamine secretion and (45)Ca(2+) influx. Its stimulatory effect of nobiletin on catecholamine secretion was abolished by deprivation of extracellular Ca(2+) and partially inhibited by specific inhibitors of voltage-dependent Ca(2+) channels and Na(+)/Ca(2+) exchangers. On the other hand, nobiletin suppressed catecholamine secretion and (22)Na(+) and (45)Ca(2+) influx induced by acetylcholine, an agonist of nicotinic acetylcholine receptors, in a concentration-dependent manner. It also inhibited catecholamine secretion, (22)Na(+) influx and/or (45)Ca(2+) influx induced by veratridine, an activator of voltage-dependent Na(+) channels, and 56 mM K(+), an activator of voltage-dependent Ca(2+) channels. In Xenopus oocytes expressing alpha3beta4 neuronal acetylcholine receptors, nobiletin directly inhibited the current evoked by acetylcholine in a concentration-dependent manner similar to that observed in catecholamine secretion. The present findings suggest that nobiletin, by itself, stimulates catecholamine secretion via activation of voltage-dependent Ca(2+) channels or Na(+)/Ca(2+) exchangers, whereas it inhibits catecholamine secretion induced by acetylcholine through the suppression of Na(+) influx and Ca(2+) influx in cultured bovine adrenal medullary cells.

  3. 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

  4. Adrenal cortical and medullary imaging.

    PubMed

    Freitas, J E

    1995-07-01

    Adrenal disease can be manifested by endocrine dysfunction or anatomic abnormalities detected by cross-sectional imaging modalities. With the advent of newer and more reliable in vitro assays and a better understanding of the spectrum of adrenal pathology, the physician can now adopt a more accurate and cost-effective approach to the diagnosis of adrenal disease. Both functional and anatomic imaging modalities can play an important role in the evaluation of the incidental adrenal mass, the early detection of adrenal metastases, differentiation of the various causes of Cushings's syndrome, selection of patients for potentially curative surgery in primary aldosteronism and adrenal hyperandrogenism, and localization of pheochromocytomas and neuroblastomas. The usefulness of the adrenal cortical radiopharmaceutical, 131I-6-beta-iodomethylnorcholesterol (NP-59), and the adrenal medullary radiopharmaceuticals, 131I and 123I-metaiodobenzylguanidine (MIBG), is detailed for these various clinical settings and the role of NP-59 and MIBG is contrasted to that of the cross-sectional modalities, computed tomography and magnetic resonance imaging (MRI). Incidental adrenal masses are common, but malignancies are few. Imaging studies select those patients who require a further evaluation by biopsy examination or adrenalectomy. In the hyperfunctioning endocrine states, such as Cushing's syndrome, primary aldosteronism, adrenal androgenism, and pheochromocytoma, correlation of biochemical findings with both functional and anatomic imaging is necessary to avoid inappropriate and ineffective surgical intervention, yet not miss an opportunity for curative resection. Lastly, MIBG and MRI are complementary in the detection and staging of neuroblastoma.

  5. Inhibition of /sup 22/Na influx by tricyclic and tetracyclic antidepressants and binding of (/sup 3/H)imipramine in bovine adrenal medullary cells

    SciTech Connect

    Arita, M.; Wada, A.; Takara, H.; Izumi, F.

    1987-10-01

    In bovine adrenal medullary cells we investigated the effects of antidepressants on ionic channels and secretion of catecholamines. Tricyclic (imipramine, amitriptyline and nortriptyline) and tetracyclic (maprotiline and mianserin) antidepressants inhibited carbachol-induced influx of /sup 22/Na, /sup 45/Ca and secretion of catecholamines (IC50, 14-96 microM). Influx of /sup 22/Na, /sup 45/Ca and secretion of catecholamines due to veratridine also were inhibited by these drugs (IC50, 10-17 microM). However, antidepressants did not suppress high concentration of K-induced 45Ca influx and catecholamine secretion, suggesting that antidepressants do not inhibit voltage-dependent Ca channels. (/sup 3/H)Imipramine bound specifically to adrenal medullary cells. Binding was saturable, reversible and with two different equilibrium dissociation constants (13.3 and 165.0 microM). Tricyclic and tetracyclic antidepressants competed for the specific binding of (/sup 3/H)imipramine at the same concentrations as they inhibited /sup 22/Na influx caused by carbachol or veratridine. Carbachol, d-tubocurarine, hexamethonium, tetrodotoxin, veratridine and scorpion venom did not inhibit the specific binding of (/sup 3/H)imipramine. These results suggest that tricyclic and tetracyclic antidepressants bind to two populations of binding sites which are functionally associated with nicotinic receptor-associated ionic channels and with voltage-dependent Na channels, and inhibit Na influx. Inhibition of Na influx leads to the reduction of Ca influx and catecholamine secretion caused by carbachol or veratridine.

  6. Stimulatory effect of nobiletin, a citrus polymethoxy flavone, on catecholamine synthesis through Ser19 and Ser40 phosphorylation of tyrosine hydroxylase in cultured bovine adrenal medullary cells.

    PubMed

    Zhang, Han; Yanagihara, Nobuyuki; Toyohira, Yumiko; Takahashi, Keita; Inagaki, Hirohide; Satoh, Noriaki; Li, Xiaoja; Goa, Xiumei; Tsutsui, Masato; Takahaishi, Kojiro

    2014-01-01

    We previously reported the dual effects of nobiletin, a compound of polymethoxy flavones found in citrus fruits, on catecholamine secretion in cultured bovine adrenal medullary cells. Here, we report the effects of nobiletin on catecholamine synthesis in the cells. Nobiletin increased the synthesis of (14)C-catecholamines from [(14)C]tyrosine in a time (20-30 min)- and concentration (1.0-100 μM)-dependent manner. Nobiletin (10-100 μM) also activated tyrosine hydroxylase activity. The stimulatory effect of nobiletin on (14)C-catecholamine synthesis was not observed when extracellular Ca(2+) was not present in the incubation medium. Protein kinase inhibitors including H-89, an inhibitor of cyclic AMP-dependent protein kinase, and KN-93, an inhibitor of Ca(2+)/calmodulin-dependent protein kinase II, suppressed the stimulatory effects of nobiletin on catecholamine synthesis as well as tyrosine hydroxylase activity. Nobiletin also induced the phosphorylation of tyrosine hydroxylase at Ser(19) and Ser(40). Nobiletin (1.0-100 μM) inhibited (14)C-catecholamine synthesis induced by acetylcholine. The present findings suggest that nobiletin, by itself, stimulates catecholamine synthesis through tyrosine hydroxylase phosphorylation at Ser(19) and Ser(40), whereas it inhibits catecholamine synthesis induced by acetylcholine in bovine adrenal medulla.

  7. Catecholamine release from cultured bovine adrenal medullary chromaffin cells in the presence of 60-Hz magnetic fields.

    PubMed

    Craviso, Gale L; Chatterjee, Indira; Publicover, Nelson G

    2003-04-01

    Effects of powerline frequency (50/60 Hz) electric and magnetic fields on the central nervous system may involve altered neurotransmitter release. This possibility was addressed by determining whether 60-Hz linearly polarized sinusoidal magnetic fields (MFs) alter the release of catecholamines from cultured bovine adrenal chromaffin cells, a well-characterized model of neural-type cells. Dishes of cells were placed in the center of each of two four-coil Merritt exposure systems that were enclosed within mu-metal chambers in matched incubators for simultaneous sham and MF exposure. Following 15-min MF exposure of the cells to flux densities of 0.01, 0.1, 1.0 or 2 mT, norepinephrine and epinephrine release were quantified by high-performance liquid chromatography (HPLC) coupled with electrochemical detection. No significant differences in the release of either norepinephrine or epinephrine were detected between sham-exposed cells and cells exposed to MFs in either the absence or presence of Bay K-8644 (2 microM) or dimethylphenylpiperazinium (DMPP, 10 microM). Consistent with these null findings is the lack of effect of MF exposure on calcium influx. We conclude that catecholamine release from chromaffin cells is not sensitive to 60-Hz MFs at magnetic flux densities in the 0.01-2 mT range.

  8. Differential effects of short and prolonged exposure to carvedilol on voltage-dependent Na(+) channels in cultured bovine adrenal medullary cells.

    PubMed

    Kajiwara, Koji; Yanagita, Toshihiko; Nakashima, Yasuhide; Wada, Akihiko; Izumi, Futoshi; Yanagihara, Nobuyuki

    2002-07-01

    We examined the effects of short and prolonged exposure to carvedilol, an antihypertensive and beta-adrenoceptor blocking drug, on voltage-dependent Na(+) channels in cultured bovine adrenal medullary cells. Carvedilol (1-100 microM) reduced (22)Na(+) influx induced by veratridine, an activator of voltage-dependent Na(+) channels. Carvedilol also suppressed veratridine-induced (45)Ca(2+) influx and catecholamine secretion in a concentration-dependent manner similar to that of (22)Na(+) influx. Prolonged exposure of the cells to 10 microM carvedilol increased [(3)H]saxitoxin ([(3)H]STX) binding, which reached a plateau at 12 h and was still observed at 48 to 72 h. Scatchard analysis of [(3)H]STX binding revealed that carvedilol increased the B(max) value (control, 14.9 +/- 0.9 fmol/10(6) cells; carvedilol, 23.8 +/- 1.2 fmol/10(6) cells) (n = 3, P < 0.05) without altering the K(d) value, suggesting a rise in the number of cell surface Na(+) channels. The increase in [(3)H]STX binding by carvedilol was prevented by cycloheximide, an inhibitor of protein synthesis, whereas carvedilol changed neither alpha- nor beta(1)-subunit mRNA levels of Na(+) channels. The carvedilol-induced increase of [(3)H]STX binding was abolished by brefeldin A and H-89, inhibitors of intracellular vesicular trafficking of proteins from the trans-Golgi network and of cyclic AMP-dependent protein kinase (protein kinase A), respectively. The present findings suggest that short-term treatment with carvedilol reduces the activity of Na(+) channels, whereas prolonged exposure to carvedilol up-regulates cell surface Na(+) channels. This may add new pharmacological effects of carvedilol to our understanding in the treatment of heart failure and hypertension.

  9. 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.

  10. Neural control of adrenal medullary and cortical blood flow during hemorrhage

    SciTech Connect

    Breslow, M.J.; Jordan, D.A.; Thellman, S.T.; Traystman, R.J.

    1987-03-01

    Hemorrhagic hypotension produces an increase in adrenal medullary blood flow and a decrease in adrenal cortical blood flow. To determine whether changes in adrenal blood flow during hemorrhage are neurally mediated, the authors compared blood flow responses following adrenal denervation (splanchnic nerve section) with changes in the contralateral, neurally intact adrenal. Carbonized microspheres labeled with /sup 153/Gd, /sup 114/In, /sup 113/Sn, /sup 103/Ru, /sup 95/Nb or /sup 46/Se were used. Blood pressure was reduced and maintained at 60 mmHg for 25 min by hemorrhage into a pressurized bottle system. Adrenal cortical blood flow decreased to 50% of control with hemorrhage in both the intact and denervated adrenal. Adrenal medullary blood flow increased to four times control levels at 15 and 25 min posthemorrhage in the intact adrenal, but was reduced to 50% of control at 3, 5, and 10 min posthemorrhage in the denervated adrenal. In a separate group of dogs, the greater splanchnic nerve on one side was electrically stimulated at 2, 5, or 15 Hz for 40 min. Adrenal medullary blood flow increased 5- to 10-fold in the stimulated adrenal but was unchanged in the contralateral, nonstimulated adrenal. Adrenal cortical blood flow was not affected by nerve stimulation. They conclude that activity of the splanchnic nerve profoundly affects adrenal medullary vessels but not adrenal cortical vessels and mediates the observed increase in adrenal medullary blood flow during hemorrhagic hypotension.

  11. Determination of catecholamines in single adrenal medullary cells by capillary electrophoresis and laser-induced native fluorescence

    SciTech Connect

    Chang, H.T.; Yeung, E.S. |

    1995-03-15

    The present study demonstrates that native fluroescence detection combined with capillary electrophoresis separation at low pH provides high sensitivity (down to nanomolar), high resolution, high speed, and low interference for the analysis of catecholamines. Further, this method has been employed successfully for the measurement of the amounts of epinephrine and norepinephrine in individual bovine adrenal medullary cells. Application of this method to the study of neurochemistry is promising. 46 refs., 7 figs., 2 tabs.

  12. GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells

    PubMed Central

    Harada, Keita; Matsuoka, Hidetada; Fujihara, Hiroaki; Ueta, Yoichi; Yanagawa, Yuchio; Inoue, Masumi

    2016-01-01

    Gamma-aminobutyric acid (GABA) is produced not only in the brain, but also in endocrine cells by the two isoforms of glutamic acid decarboxylase (GAD), GAD65 and GAD67. In rat adrenal medullary chromaffin cells only GAD67 is expressed, and GABA is stored in large dense core vesicles (LDCVs), but not synaptic-like microvesicles (SLMVs). The α3β2/3γ2 complex represents the majority of GABAA receptors expressed in rat and guinea pig chromaffin cells, whereas PC12 cells, an immortalized rat chromaffin cell line, express the α1 subunit as well as the α3. The expression of α3, but not α1, in PC12 cells is enhanced by glucocorticoid activity, which may be mediated by both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). GABA has two actions mediated by GABAA receptors in chromaffin cells: it induces catecholamine secretion by itself and produces an inhibition of synaptically evoked secretion by a shunt effect. Allopregnanolone, a neuroactive steroid which is secreted from the adrenal cortex, produces a marked facilitation of GABAA receptor channel activity. Since there are no GABAergic nerve fibers in the adrenal medulla, GABA may function as a para/autocrine factor in the chromaffin cells. This function of GABA may be facilitated by expression of the immature isoforms of GAD and GABAA receptors and the lack of expression of plasma membrane GABA transporters (GATs). In this review, we will consider how the para/autocrine function of GABA is achieved, focusing on the structural and molecular mechanisms for GABA signaling. PMID:27147972

  13. Methodology and dosimetry in adrenal medullary imaging with iodine-131 MIBG

    SciTech Connect

    Lindberg, S.; Fjaelling, M.J.; Jacobsson, L.; Jansson, S.; Tisell, L.E.

    1988-10-01

    Iodine-131 MIBG scans were performed in 59 patients in order to localize intra- or extra-adrenal pheochromocytomas (pheos), or to visualize hyperplastic adrenal medulla. Images were obtained from the pelvis to the base of the skull on Days 1, 4, and 7 after tracer injection. The 15 patients with histopathologic confirmation of adrenal medullary disease had positive scans. In three of these, the pheos were visible only on images obtained on Day 7. One scan was false negative. After excluding patients with a predisposition to adrenal medullary disease, nine subjects (28%) without verification of pheo displayed adrenal uptake of the radionuclide. Late images produce a low rate of false-negative scans; the background activity diminishes and even small pheos can be detected. In order to increase the quality of late images, 40 MBq (/sup 131/I)MIBG was used instead of 20 MBq. The dosimetric considerations are discussed.

  14. Interleukin-6-mediated signaling in adrenal medullary chromaffin cells.

    PubMed

    Jenkins, Danielle E; Sreenivasan, Dharshini; Carman, Fiona; Samal, Babru; Eiden, Lee E; Bunn, Stephen J

    2016-12-01

    The pro-inflammatory cytokines, tumor necrosis factor-α, and interleukin-1β/α modulate catecholamine secretion, and long-term gene regulation, in chromaffin cells of the adrenal medulla. Since interleukin-6 (IL6) also plays a key integrative role during inflammation, we have examined its ability to affect both tyrosine hydroxylase activity and adrenomedullary gene transcription in cultured bovine chromaffin cells. IL6 caused acute tyrosine/threonine phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and serine/tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3). Consistent with ERK1/2 activation, IL6 rapidly increased tyrosine hydroxylase phosphorylation (serine-31) and activity, as well as up-regulated genes, encoding secreted proteins including galanin, vasoactive intestinal peptide, gastrin-releasing peptide, and parathyroid hormone-like hormone. The effects of IL6 on the entire bovine chromaffin cell transcriptome were compared to those generated by G-protein-coupled receptor (GPCR) agonists (histamine and pituitary adenylate cyclase-activating polypeptide) and the cytokine receptor agonists (interferon-α and tumor necrosis factor-α). Of 90 genes up-regulated by IL6, only 16 are known targets of IL6 in the immune system. Those remaining likely represent a combination of novel IL6/STAT3 targets, ERK1/2 targets and, potentially, IL6-dependent genes activated by IL6-induced transcription factors, such as hypoxia-inducible factor 1α. Notably, genes induced by IL6 include both neuroendocrine-specific genes activated by GPCR agonists, and transcripts also activated by the cytokines. These results suggest an integrative role for IL6 in the fine-tuning of the chromaffin cell response to a wide range of physiological and paraphysiological stressors, particularly when immune and endocrine stimuli converge. © 2016 International Society for Neurochemistry.

  15. Sporadic bilateral adrenal medullary hyperplasia: apparent false positive MIBG scan and expected MRI findings.

    PubMed

    Yung, B C; Loke, T K; Tse, T W; Tsang, M W; Chan, J C

    2000-10-01

    Adrenal medullary hyperplasia is a rare cause of clinical symptoms and biochemical findings identical to pheochromocytoma occurring mostly in multiple endocrine neoplasia patients. The scenario of positive MIBG scan, but no focal lesion found on CT and MRI led to diagnostic and management difficulties. Like pheochromocytoma, surgical excision can lead to clinical and biochemical recovery. We report this unusual case of sporadic bilateral adrenal medullary hyperplasia, with hypertension and biochemical abnormalities alleviated after surgical adrenalectomy. Based on T2 values reported in literature, high signal focal lesions may not appear on T2-weighted MRI images until development of frank pheochromocytoma. MIBG scan remains the most sensitive imaging modality for this condition.

  16. Angiotensin II binding to cultured bovine adrenal chromaffin cells: identification of angiotensin II receptors

    SciTech Connect

    Boyd, V.L.; Printz, M.P.

    1986-03-05

    Physiological experiments have provided evidence that angiotensin II stimulates catecholamine secretion from the adrenal gland. Their laboratory and others have now shown by receptor autoradiography the presence of angiotensin II receptors (AIIR) in bovine and rat adrenal medulla. In order to extend these studies they have undertaken to define AIIR on cultured bovine adrenal chromaffin cells. Cells were isolated using the method of Levitt including cell enrichment with Percoll gradient centrifugation. Primary cultures of bovine adrenal medullary cells were maintained in DME/F12 medium containing 10% FCS. Cells were characterized by immunocytochemistry for Met- and Leu-enkephalin, PNMT, DBH and Chromagranin A. Cultured cells bind with high affinity and specificity (/sup 125/I)-ANG II yielding a K/sub D/ of 0.74 nM and B/sub max/ of 24,350 sites/cell. After Percoll treatment values of .77 nm and 34,500 sites/cell are obtained. K/sub D/ values are in close agreement with that obtained in adrenal slices by Healy. Competition studies identify a rank order of binding by this receptor similar to that of other tissues. They conclude that cultured chromaffin cells provide a suitable model system for the investigation and characterization of the ANG II receptor and for cellular studies of its functional significance.

  17. Adrenal medullary regulation of rat renal cortical adrenergic receptors

    SciTech Connect

    Sundaresan, P.R.; Guarnaccia, M.M.; Izzo, J.L. Jr. )

    1987-11-01

    The role of the adrenal medulla in the regulation of renal cortical adrenergic receptors was investigated in renal cortical particular fractions from control rats and rats 6 wk after adrenal demedullation. The specific binding of ({sup 3}H)prazosin, ({sup 3}H)rauwolscine, and ({sup 125}I)iodocyanopindolol were used to quantitate {alpha}{sub 1}-, {alpha}{sub 2}-, and {beta}-adrenergic receptors, respectively. Adrenal demedullation increased the concentration of all three groups of renal adrenergic receptors; maximal number of binding sites (B{sub max}, per milligram membrane protein) for {alpha}{sub 1}-, and {alpha}{sub 2}-, and {beta}-adrenergic receptors were increased by 22, 18.5, and 25%, respectively. No differences were found in the equilibrium dissociation constants (K{sub D}) for any of the radioligands. Plasma corticosterone and plasma and renal norepinephrine levels were unchanged, whereas plasma epinephrine was decreased 72% by adrenal demedullation, renal cortical epinephrine was not detectable in control or demedullated animals. The results suggest that, in the physiological state, the adrenal medulla modulates the number of renal cortical adrenergic receptors, presumably through the actions of a circulating factor such as epinephrine.

  18. Effects of cannabinoids on adrenaline release from adrenal medullary cells

    PubMed Central

    Niederhoffer, Nathalie; Hansen, Henrik H; Fernandez-Ruiz, Javier J; Szabo, Bela

    2001-01-01

    The objective of the present study was to analyse the peripheral effects of cannabinoids on adrenaline release from adrenal chromaffin cells. In pithed rabbits with electrically stimulated sympathetic outflow, intravenous injection of the cannabinoid receptor agonists WIN55212-2 and CP55940 (5, 50 and 500 μg kg−1) markedly lowered the plasma adrenaline concentration. The effect of WIN55212-2 was attenuated by the selective CB1 cannabinoid receptor antagonist SR141716A (500 μg kg−1). WIN55212-3 (same doses as WIN55212-2), the enantiomer of WIN55212-2 lacking affinity for cannabinoid receptors, had no effect on the plasma adrenaline concentration. In rabbit isolated adrenal glands, the release of adrenaline elicited by electrical stimulation was measured by fast cyclic voltammetry. Electrically-evoked adrenaline release was inhibited by WIN55212-2 (0.3, 1, 3 and 10 μM) and this effect was antagonized by SR141716A (1 μM). The non-cholinergic component of adrenaline release observed after blockade of nicotinic (by hexamethonium 100 μM) and muscarinic (by atropine 0.5 μM) acetylcholine receptors was not depressed by WIN55212-2. WIN55212-3 (10 μM) had no effect on adrenaline release. No detectable specific CB1 receptor binding and mRNA expression were found in rabbit adrenal glands with autoradiography and in situ hybridization. The results show that cannabinoids inhibit adrenaline secretion in rabbit isolated adrenal glands; the likely mechanism is a presynaptic CB1 receptor-mediated inhibition of acetylcholine release from preganglionic sympathetic neurons. The inhibition of adrenaline secretion in adrenal glands most probably accounts for the decrease in the plasma adrenaline concentration observed after cannabinoid administration in pithed rabbits. PMID:11704653

  19. [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.

  20. Adrenal Medullary Grafts Restore Olfactory Deficits and Catecholamine Levels of 6-OHDA Amygdala Lesioned Animals

    PubMed Central

    Fernández-Ruiz, Juan; Guzmán, Rubén; Martínez, María Dolores; Miranda, María Isabel; Bermúdez-Rattoni, Federico; Drucker-Colín, René

    1993-01-01

    Aside from motor and cognitive deficits, Parkinson patients also manifest a little-studied olfactory deficit. Since in Parkinson's disease there is a dopamine depletion of the amygdala due to mesocorticolimbic system degeneration, we decided to test olfactory and taste performance of 6-OHDA amygdala lesioned rats, as well as the possible restoration of either function with adrenal medullary transplants. Two 6-OHDA lesioned groups and one control group were tested in the potentiation of odor by taste aversion paradigm. On taste aversion none of the groups showed any impairment. In contrast, the 6-OHDA lesioned rats showed a marked impairment in olfactory aversion. At this point, one of the lesioned groups received a bilateral adrenal medullary graft within the lesioned area. After two months, all groups were submitted again to the behavioral paradigm. Taste remained unaffected, but the lesioned only group did not recover either olfactory aversion or normal catecholamine levels. The grafted group, on the other hand, restored olfactory aversion and catecholamine levels. It can be concluded from this study that catecholamine depletion of the amygdala is sufficient to produce a selective olfactory deficit, not accompanied by taste impairments, and that such a deficit can be reversed by adrenal medullary transplants, which in turn restore catecholamine levels. PMID:7948179

  1. Spontaneous proliferative lesions of the adrenal medulla in aging Long-Evans rats. Comparison to PC12 cells, small granule-containing cells, and human adrenal medullary hyperplasia.

    PubMed

    Tischler, A S; DeLellis, R A; Perlman, R L; Allen, J M; Costopoulos, D; Lee, Y C; Nunnemacher, G; Wolfe, H J; Bloom, S R

    1985-10-01

    Aging rats of the Long-Evans strain spontaneously develop diffuse and nodular hyperplasia of the adrenal medulla in association with other abnormalities commonly encountered in human multiple endocrine neoplasia syndromes. The cells which comprise the adrenal nodules resemble those in the parent tumor of the rat PC12 pheochromocytoma cell line in that they show varying degrees of spontaneous or nerve growth factor-induced neurite outgrowth in culture and they contain little or no epinephrine. In addition, cells from at least some of the nodules contain immunoreactive neurotensin and neuropeptide-Y, which are also found in PC12 cells. There are a number of striking resemblances between the cells in adrenal nodules and the small granule-containing cells in the normal rodent adrenal. The findings suggest that spontaneous rat adrenal medullary nodules and PC12 cells might be derived from small granule-containing cells, or that cells within the nodules might regain properties of immature chromaffin cells and acquire characteristics of small granule-containing cells and of PC12 cells in the course of neoplastic progression. They further suggest a possible relationship between proliferative capacity and neurotransmitter phenotype in the adult rat adrenal medulla. By virtue of their sparse epinephrine content and their small granules, the cells in adrenal medullary nodules of Long-Evans rats differ from those in adrenal medullary nodules of humans with multiple endocrine neoplasia syndromes.

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

    SciTech Connect

    Bunce, O.R.; Badary, O.A.; Abou El-Ela, S.; Hartle, D.K. )

    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 15 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.

  3. 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.

  4. Modulation of NMDA receptor expression in the rat spinal cord by peripheral nerve injury and adrenal medullary grafting.

    PubMed

    Hama, A T; Unnerstall, J R; Siegan, J B; Sagen, J

    1995-07-31

    Excessive activation of N-methyl-D-aspartate (NMDA) receptors in the spinal cord consequent to peripheral injury has been implicated in the initiation of neuropathologic events leading to a state of chronic hyperexcitability and persistence of exaggerated sensory processing. In other CNS disease or injury states, NMDA-mediated neurotoxic damage is associated with a loss of NMDA receptors, and outcome may be improved by agents reducing NMDA activation. Previous findings in our laboratory have demonstrated that the transplantation of adrenal medullary tissue into the spinal subarachnoid space can alleviate sensory abnormalities and reduce the induction of a putative nitric oxide synthase consequent to peripheral nerve injury. In order to determine changes in NMDA receptor expression in the spinal cord following peripheral nerve injury and adrenal medullary grafting, NMDA receptor binding using a high-affinity competitive NMDA receptor antagonist, CGP-39653, and NMDAR1 subunit distribution using immunocytochemistry were investigated. Two weeks following peripheral nerve injury by loose ligation of the right sciatic nerve, either adrenal medullary or striated muscle (control) tissue pieces were implanted in the spinal subarachnoid space. Binding studies revealed a marked reduction in [3H]CGP-39653 binding at L4-L5 levels ipsilateral to peripheral nerve injury in control transplanted animals. In contrast, NMDA binding was normalized in adrenal medullary grafted animals. In addition, NMDAR1 immunoreactivity was reduced in both the dorsal horn neuropil and motor neurons of the ventral horn in animals with peripheral nerve injury, while levels in adrenal medullary grafted animals appeared similar to intact controls. These results suggest that adrenal medullary transplants reduce abnormal sensory processing resulting from peripheral injury by intervening in the spinal NMDA-excitotoxicity cascade.

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

    PubMed

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

    2007-04-15

    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 (8 microg 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.

  6. Adrenal medullary transplantation to the caudate nucleus in Parkinson's disease. Initial clinical results in 18 patients.

    PubMed

    Allen, G S; Burns, R S; Tulipan, N B; Parker, R A

    1989-05-01

    Results from a pilot study of adrenal medullary autotransplantation for Parkinson's disease are presented. Eighteen patients were studied; 12 were followed up for 1 year, and 6 were followed up for 6 months. Four of 12 patients showed distinct improvement in the signs and symptoms of their disease, as assessed using the Columbia Rating Scale, at 1 year; none showed distinct deterioration. The 6 patients who were followed up for only 6 months were an average of 20 years older and generally more severely affected. None distinctly improved. Morbidity was considered to be minor and transient among the first 12 patients, while 4 of the last 6 patients experienced alteration in mental status lasting as long as several months. This problem has led us to conclude that older patients with preexisting cognitive impairment should not be included in future studies until the benefits are more clearly established. However, we believe that the distinct and persistent improvement seen in some of the younger patients warrants the initiation of a well-designed, randomized, and controlled trial of adrenal medullary autotransplantation for the purpose of confirming these results and assessing the effect of the procedure on the natural progression of Parkinson's disease.

  7. Neuropsychological effects of brain autograft of adrenal medullary tissue for the treatment of Parkinson's disease.

    PubMed

    Ostrosky-Solís, F; Quintanar, L; Madrazo, I; Drucker-Colín, R; Franco-Bourland, R; Leon-Meza, V

    1988-09-01

    We describe the pre- and postoperative neuropsychological profiles of seven patients who received an autograft of adrenal medullary tissue to the caudate nucleus for the treatment of Parkinson's Disease (PD). The preoperative neuropsychological evaluations revealed specific cognitive deficits of varying degree. The patients showed frontal lobe-type deficits with alterations in behavioral programming leading to difficulties in the organization of motor sequences and alternating programs. They also showed memory disorders and visuospatial and visuoperceptual deficiences such as a loss of figure-ground perspective and fragmentation. Postoperative evaluations, carried out 3 months after neurosurgery, revealed a significant amelioration of the frontal lobe-type symptoms and visuospatial deficits, as well as an improvement in memory tasks that require an active organization of the response. Immediate and delayed memory difficulties remained unchanged. These observations were compared to neuropsychological data obtained from neurologically intact subjects and from unoperated PD patients. The improvements of the operated PD patients resulted in performance levels close to normal values and clearly distinguishable from those of unoperated PD patients, and were unrelated to improved mood, increased alertness, or sustained attention. Autotransplantation of adrenal medullary tissue to the caudate nucleus of PD patients showing a decreased effective response to L-dopa therapy can partially restore motor functions and frontal-type cognitive symptoms.

  8. Early diagnosis of and surgical strategy for adrenal medullary disease in MEN II gene carriers

    SciTech Connect

    Jansson, S.; Tisell, L.E.; Fjaelling, M.L.; Lindberg, S.; Jacobsson, L.; Zachrisson, B.F.

    1988-01-01

    Sixteen multiple endocrine neoplasia type II (MEN II) gene carriers--12 who had undergone thyroidectomy because of medullary carcinoma of the thyroid and 4 whose thyroid glands had been removed because of C cell hyperplasia--were examined for the presence of pheochromocytomas. No patient had sought medical advice for pheochromocytoma symptoms. Fourteen patients had MEN IIa syndromes, one patient had a MEN IIb and another patient had a mixed syndrome of von Recklinghausen's neurofibromatosis and MEN II. Eight patients had undergone unilateral adrenalectomy for pheochromocytoma 11 +/- 4 years before. The patients underwent clinical examination, determination of the urinary excretion of catecholamines and metabolites, and /sup 131/I-metaiodobenzylguanidine (/sup 131/I-MIBG) and CAT scans. /sup 131/I-MIBG scanning was performed with images 1, 4, and 7 days after the radionuclide injection. In seven of eight patients who had undergone unilateral adrenalectomies, the /sup 131/I-MIBG scans showed accumulation of the radionuclide in the remaining adrenal gland. Bilateral adrenal accumulation of the radionuclide was demonstrated in seven of eight MEN IIa gene carriers who had not undergone adrenalectomy. Five patients, two of whom had undergone adrenalectomy, were found to have unilateral pheochromocytomas less than 2 cm in diameter. Only one of these five patients had an elevated excretion of urinary catecholamines. Between day 4 and day 7 after /sup 131/I-MIBG injection, adrenal glands with pheochromocytomas increased their relative accumulation of the radionuclide significantly more (p less than 0.02) than did adrenal glands without any demonstrable pheochromocytomas. All the pheochromocytomas were viewed by means of CAT scans.

  9. Molecular mechanisms supporting a paracrine role of GABA in rat adrenal medullary cells

    PubMed Central

    Matsuoka, Hidetada; Harada, Keita; Endo, Yutaka; Warashina, Akira; Doi, Yoshiaki; Nakamura, Jun; Inoue, Masumi

    2008-01-01

    GABA is known to produce membrane depolarization and secretion in adrenal medullary (AM) cells in various species. However, whether the GABAergic system is intrinsic or extrinsic or both in the adrenal medulla and the role that GABA plays are controversial. Therefore, these issues were addressed by combining a biochemical and functional analysis. Glutamic acid decarboxylase (GAD), a GABA synthesizing enzyme, and vesicular GABA transporter (VGAT) were expressed in rat AM cells at the mRNA and protein levels, and the adrenal medulla had no nerve fibre-like structures immunoreactive to an anti-GAD Ab. The double staining for VGAT and chromogranin A indicates that GABA was stored in chromaffin granules. The α1, α3, β2/3, γ2 and δ subunits of GABAA receptors were identified in AM cells at the mRNA and protein levels. Pharmacological properties of GABA-induced Cl− currents, immunoprecipitation experiments and immunocytochemistry indicated the expression of not only γ2-, but also δ-containing GABAA receptors, which have higher affinities for GABA and neurosteroids. Expression of GATs, which are involved in the clearance of GABA at GABAergic synapses, were conspicuously suppressed in the adrenal medulla, compared with expression levels of GABAA receptors. Increases in Ca2+ signal in AM cells evoked trans-synaptically by nerve stimulation were suppressed during the response to GABA, and this suppression was attributed to the shunt effect of the GABA-induced increase in conductance. Overall Ca2+ responses to electrical stimulation and GABA in AM cells were larger or smaller than those to electrical stimulation alone, depending on the frequency of stimulation. The results indicate that GABA functions as a paracrine in rat AM cells and this function may be supported by the suppression of GAT expression and the expression of not only γ2-, but also δ-GABAA receptors. PMID:18755746

  10. Porcine brain natriuretic peptide receptor in bovine adrenal cortex

    SciTech Connect

    Higuchi, K.; Hashiguchi, T.; Ohashi, M.; Takayanagi, R.; Haji, M.; Matsuo, H.; Nawata, H.

    1989-01-01

    The action of porcine brain natriuretic peptide (pBNP) on the steroidogenesis was investigated in cultured bovine adrenocortical cells. Porcine BNP induced a significant dose-dependent inhibition of both ACTH- and A II-stimulated aldosterone secretion. 10/sup /minus/8/M and 10/sup /minus/7/M pBNP also significantly inhibited ACTH-stimulated cortisol and dehydroepiandrosterone (DHEA) secretions. Binding studies of (/sup 125/I)-pBNP to bovine adrenocortical membrane fractions showed that adrenal cortex had high-affinity and low-capacity pBNP binding sites, with a dissociation constant (Kd) of 1.70 x 10/sup /minus/10/M and a maximal binding capacity (Bmax) of 19.9 fmol/mg protein. Finally, the 135 Kd radioactive band was specially visualized in the affinity labeling of bovine adrenal cortex with disuccinimidyl suberate (DSS). These results suggest that pBNP may have receptor-mediated suppressive actions on bovine adrenal steroidogenesis, similar to that in atrial natriuretic peptide (ANP).

  11. Adrenal medullary autograft transplantation into the striatum of patients with Parkinson's disease.

    PubMed

    Kelly, P J; Ahlskog, J E; van Heerden, J A; Carmichael, S W; Stoddard, S L; Bell, G N

    1989-03-01

    In eight patients with advanced Parkinson's disease, we performed autograft transplantation of adrenal medulla to the head of the caudate nucleus. Our technique was similar to that developed by Madrazo and co-workers in Mexico City. No major perioperative complications occurred except for somnolence in one patient for 8 days postoperatively. The follow-up period has been at least 6 months in seven of the patients, and only limited benefit has been apparent. The early morning Parkinson examination score in the "off" (unmedicated) state was significantly improved in one patient and slightly better in the other six. Diary card entries suggested a mild trend toward improvement (not statistically significant). Four of the seven patients were taking less levodopa 6 months after the operation than they had been preoperatively; three of five patients were no longer taking dopamine agonists postoperatively. We cannot exclude a placebo effect contributing to any of this improvement. A reduction in medication-induced dyskinesia was also noted, but this result may have been due to adjustments in doses or a slightly less potent effect of medication (or both factors). In summary, we have not yet been able to replicate the dramatic success reported for adrenal medullary transplantation by Madrazo's group, although our patients may have experienced mild to moderate improvement. We continue to maintain follow-up surveillance of these patients.

  12. Secretion of Catecholamines from Adrenal Gland by a Single Electrical Shock: Electrotonic Depolarization of Medullary Cell Membrane

    NASA Astrophysics Data System (ADS)

    Wakade, Arun R.; Wakade, Taruna D.

    1982-05-01

    Transmural stimulation of the isolated adrenal gland of the rat and guinea pig results in secretion of catecholamines. The secretion is due to activation of cholinergic receptors of the adrenal medulla by acetylcholine released from splanchnic nerve terminals after transmural stimulation. Our aim was to see whether the same experimental technique could be used to directly excite the adrenal medullary cell membrane by electrical stimulation and whether such stimulation would result in secretion of catecholamines. We demonstrate here that a single electrical shock to the perfused adrenal gland of the rat results in massive secretion of epinephrine and norepinephrine. The secretion is directly related to the strength and duration of the applied stimulus over a wide range. Catecholamine secretion is unaffected by tetrodotoxin or hexamethonium/atropine but is abolished by Ca2+ lack or 3 mM Mn2+. We suggest that the adrenal medullary membrane undergoes nonpropagated electrotonic depolarization on electrical stimulation and thereby voltage-dependent Ca2+ channels are opened to initiate secretion.

  13. [Changes in the activity of sympathetic-adrenal medullary system and hypothalamic-pituitary-adrenal system in humans exposed to psychogenic stressors and their effects on immunoreactivity].

    PubMed

    Simić, Natasa

    2010-10-01

    This paper gives an account of the functioning of the two systems in different stress induced situations. The activation of the sympathetic-adrenal medullary system is accompanied by the release of catecholamines, while the increased activity of the hypothalamic-pituitary-adrenal system results in the increased release of corticosteroids, especially cortisol. The role of the sympathetic-adrenal medullary system was investigated in immunologic changes induced by laboratory stressors. In the real, as in laboratory conditions, the effects of different stressors on the level of cortisol were studied, as it is the final product of the hypothalamic-pituitary-adrenal system activity. Additional (negative) effects on the functioning of these systems could induce some variables, as an increased consumption of alcohol, smoking, and sleeping disorder. Furthermore, the methodological shortcomings and the selection of subjects in previous studies are discussed. Previous results are also discussed, such as the immunosuppressive effects of cortisol, as well as the mediator and moderator variables in relation to stress and immunoreactivity.

  14. Histologic and immunohistochemical classification of 41 bovine adrenal gland neoplasms.

    PubMed

    Grossi, A B; Leifsson, P S; Jensen, H E; Vainer, B; Iburg, T

    2013-05-01

    Tumors of the adrenal glands are among the most frequent tumors in cattle; however, few studies have been conducted to describe their characteristics. The aim of this study was to classify 41 bovine adrenal neoplasms from 40 animals based on macroscopic and histologic examination, including electron microscopy and immunohistochemistry for melan A, synaptophysin, chromogranin A, vimentin, pan-cytokeratin, 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNPase), and Ki-67. The tumors were classified as 23 adrenocortical adenomas, 12 adrenocortical carcinomas, 2 schwannomas, 2 pheochromocytomas (1 malignant), and 1 ganglioneuroma. Five histologic features were characteristic of metastasizing adrenocortical tumors: invasion of the capsule, vascular invasion, diffuse growth pattern, spindle-cell morphology, and nuclear pleomorphism. Adrenocortical tumors with at least 3 of these features were classified as malignant. Immunohistochemically, adrenocortical tumors expressed melan A (16/19), vimentin (14/26), cytokeratin (11/26), and chromogranin A (9/27), whereas pheochromocytomas expressed chromogranin A (2/2), synaptophysin (2/2), and vimentin (1/2). Both schwannomas expressed CNPase. An immunohistochemistry panel consisting of antibodies against melan A, synaptophysin, and CNPase was considered most useful to classify bovine adrenal tumors. However, the distinction between benign and malignant adrenocortical tumors was based on histologic features as in human medicine.

  15. The adrenal medullary transplant operation for Parkinson's disease: clinical observations in five patients.

    PubMed

    Penn, R D; Goetz, C G; Tanner, C M; Klawans, H L; Shannon, K M; Comella, C L; Witt, T R

    1988-06-01

    The recent report by Madrazo and coworkers on the successful treatment of Parkinson's disease using adrenal medullary tissue transplanted to the caudate nucleus has aroused international interest in the procedure. The present article reports our initial experiences with the operation in five patients and discusses the postoperative effects of the procedure, the protocol used to monitor motor performance, and the need for cooperation with the two registries that have been created to follow morbidity, mortality, and efficacy. We intend to alert the neurosurgeon to important side effects, but not to assess the long term efficacy of the procedure. Postoperatively, a number of transient effects were seen in our patients, the most striking being somnolence, delusions, and lack of significant pain in spite of a large abdominal incision. The only complications have been respiratory. After the early postoperative period, gradual improvement of on-off times and Schwab-England disability scores was seen over 20 weeks. Long term cooperative studies are needed to demonstrate the efficacy of this procedure. neurosurgeons doing transplant operations are urged to join the registries so that uniform information can be collected.

  16. Effect of MPTP on primate chromaffin cells in vitro: relevance for adrenal medullary cell transplantation.

    PubMed

    Notter, M F; Kaniuki, M; Felten, S Y; Hansen, J T; Gash, D M

    1991-01-01

    Primate adrenal medullary cells were exposed to l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) in vitro to examine the effect of this neurotoxic agent on chromaffin cells. Chromaffin cells from monkey and humans were cultured in the presence of 100 ng/ml nerve growth factor for 1 week and then exposed to 150 μM MPTP or its active metabolite methylpyridinium ion (MPP+) for an additional week. Cells which had extended neurites in the presence of NGF showed no morphological effect in response to MPTP or MPP+ at the light microscopic level. However, there was a significant loss in catecholamines as seen by histofluorescence and high performance liquid chromotography (HPLC). Electron microscopy revealed a depletion in dense-core vesicles in chromaffin cells after chronic exposure to MPTP while the mitochondria appeared similar to those observed in control cells. Replacement of MPTP medium with standard medium stimulated restoration of catecholamine histofluorescence after 7 days. An acute 15 min pretreatment of chromaffin cells with MPTP or MPP+ induced secretion of catecholamines over a 1 h pulse, with MPP+ producing the maximum and more rapid secretion as determined by HPLC. These data indicate that MPTP induces a dramatic loss in catecholamines in primate chromaffin cells in vitro after both acute and chronic exposures; however, removal of the toxic agent permits restoration of catecholamines without permanent effect on the integrity of these cells.

  17. Kidney-Tonifying Recipe Can Repair Alterations in Adrenal Medullary Chromaffin Cells in Asthmatic Rats

    PubMed Central

    Hu, Cheng-Ping; Zou, Jun-Tao; Zou, Ye-Qiang; Li, Xiao-Zhao; Feng, Jun-Tao

    2012-01-01

    Traditional Chinese medicine suggests that renal deficiency is a causative factor of asthma, and tonifying kidney drugs are believed to be an appropriate and beneficial treatment. The adrenal medullary chromaffin cells (AMCC) transition to the neuronal phenotype is known to occur in asthma, as evidenced by degranulation of chromaffin granules, decline of epinephrine (EPI) and phenylethanolamine-n-methyl transferase (PNMT), and obvious alterations in cellular architecture. In this study, rats were sensitized and challenged with ovalbumin, then treated with Kidney-Tonifying Recipe (KTR) to evaluate the therapeutic effect. Tissues were evaluated for changes in pathology and EPI, PNMT, and peripherin expression. Degranulation of chromaffin granules and appearance of neurite-like process were found in AMCC from asthmatic rats, and these changes were corrected by KTR treatment. EPI and PNMT expressions were decreased in asthmatic rats and increased by KTR treatment. Peripherin expression was increased in asthmatic rats and decreased in the KTR-treated group. Morphological changes and decreases in EPI were observed when cultured AMCC were exposed to sera from asthmatic rats in vitro, and these changes were attenuated with the addition of sera from KRT-treated rats. These results suggest that the Kidney-Tonifying Recipe is capable of repairing asthma-associated alterations in endocrine function and the ultrastructure of AMCC. PMID:22474509

  18. Extracellular Ionic Composition Alters Kinetics of Vesicular Release of Catecholamines and Quantal Size During Exocytosis at Adrenal Medullary Cells

    DTIC Science & Technology

    1994-07-05

    cytosolic calcium concentration in single bovine adrenal chromaffin cells form video imaging of fura - 2 , EMBO J. 8, 401-411. Pollard, H. B., Ornberg, R...Key words: chromaffin cells, catecholamine, barium induced exocytosis, fura - 2 , calcium independent exocytosis Running title: Effects of extracellular...calibration of the fluorescent calcium indicator Fura - 2 , Cell Calcium 11, 75-83. Winkler, H. (1976) The Composition of Adrenal Chromaffin Granules

  19. Identification of D-2 dopaminergic receptors in bovine adrenal cortex

    SciTech Connect

    Missale, C.; Liberini, P.; Memo, M.; Carruba, M.O.; Spano, P.

    1985-12-30

    Dopamine receptors in bovine adrenal cortex have been studied by using /sup 3/H-(-) atsulpiride as selective ligand. The specific binding is saturable and the Scatchard analysis reveals a single component with a Kd of 6.2 nM and a Bmax of 8 fmoles/mg protein. The characterization indicates that the binding is rapid, reversible, stereospecific, Na/sup +/ - and temperature-dependent. Moreover its pharmacological profile is superimposable to that of D-2 receptors in the striatum, thus suggesting that central and peripheral D-2 receptors are identical. 27 references, 6 figures, 1 table.

  20. Changes of adrenomedullin and natriuretic peptides in patients with adrenal medullary hyperplasia prior to and following pharmacological therapy and adrenalectomy

    PubMed Central

    Zhou, Pang-Hu; Shi, Lei; Hu, Wei; Zhang, Xiao-Bin; Wang, Wei; Zhang, Li-Jun

    2016-01-01

    The aim of the present study was to investigate the pathophysiological functions of adrenomedullin (ADM), atrial and brain natriuretic peptides (ANP and BNP) in patients with adrenal medullary hyperplasia (AMH). Plasma ADM, ANP and BNP concentrations were measured in 20 patients with AMH, 35 patients with essential hypertension (EH), and 40 healthy control subjects. Following effective antihypertensive therapy, the values in AMH and EH patients were measured again and laparoscopic adrenalectomy was performed for AMH patients. At 2 weeks after surgery, the three peptides were measured again. The AMH patients had higher plasma concentrations of ADM, ANP and BNP compared with the EH and control subjects. There were significant differences in the values of ADM, ANP and BNP between adrenal vein and inferior vena cava and between AMH and contralateral adrenal vein. Plasma ADM concentration was correlated with serum epinephrine and norepinephrine and urine vanillylmandelic acid, in addition to systolic and diastolic blood pressure, left ventricular ejection fraction, left ventricular mass index and ANP and BNP values in the AMH group. Following antihypertensive treatment, ADM, ANP and BNP were significantly decreased in EH patients, but remained unchanged in AMH subjects. However, these concentrations significantly decreased following surgery. Therefore, the present results suggest that ADM, ANP and BNP may be involved in regulating adrenal medulla functions. PMID:27446289

  1. Selective blockade of nicotinic acetylcholine receptors by pimobendan, a drug for the treatment of heart failure: reduction of catecholamine secretion and synthesis in adrenal medullary cells.

    PubMed

    Toyohira, Yumiko; Kubo, Tatsuhiko; Watanabe, Miyabi; Uezono, Yasuhito; Ueno, Susumu; Shinkai, Koji; Tsutsui, Masato; Izumi, Futoshi; Yanagihara, Nobuyuki

    2005-02-01

    Pimobendan, a Ca(2+) sensitizer, is used clinically in the treatment of chronic heart failure. Although chronic heart failure is associated with activation of the sympathetic nervous system, it remains unknown whether pimobendan affects the function of sympathetic neurons and the adrenal medulla. Here, we report the inhibitory effects of pimobendan on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Pimobendan decreased the catecholamine secretion (IC(50)=29.5 microM) elicited by carbachol, an agonist at nicotinic acetylcholine receptors, but not that elicited by veratridine, an activator of voltage-dependent Na(+) channels, or by high K(+), an activator of voltage-dependent Ca(2+) channels. Pimobendan also inhibited carbachol-induced influx of (22)Na(+) (IC(50)=25.9 microM) and (45)Ca(2+) (IC(50)=26.0 microM), but not veratridine-induced (22)Na(+) influx or high K(+)-induced (45)Ca(2+) influx. The reduction of catecholamine secretion caused by pimobendan was not overcome by increasing the concentration of carbachol. UD-CG 212, an active metabolite of pimobendan, lowered carbachol-induced catecholamine secretion with a concentration/inhibition curve similar to that of pimobendan. In experiments in situ, pimobendan suppressed both basal and carbachol-stimulated (14)C-catecholamine synthesis (IC(50)=5.3 and 4.9 microM) from [(14)C] tyrosine [but not from L: -3, 4-dihydroxyphenyl [3-(14)C] alanine ([(14)C]DOPA)], as well as tyrosine hydroxylase activity (IC(50)=3.8 and 4.3 microM). These findings suggest that pimobendan inhibits carbachol-induced catecholamines secretion and synthesis through suppression of nicotinic acetylcholine receptors.

  2. Calcium dynamics in bovine adrenal medulla chromaffin cell secretory granules.

    PubMed

    Santodomingo, Jaime; Vay, Laura; Camacho, Marcial; Hernández-Sanmiguel, Esther; Fonteriz, Rosalba I; Lobatón, Carmen D; Montero, Mayte; Moreno, Alfredo; Alvarez, Javier

    2008-10-01

    The secretory granules constitute one of the less well-known compartments in terms of Ca2+ dynamics. They contain large amounts of total Ca2+, but the free intragranular [Ca2+] ([Ca2+]SG), the mechanisms for Ca2+ uptake and release from the granules and their physiological significance regarding exocytosis are still matters of debate. We used in the present work an aequorin chimera targeted to the granules to investigate [Ca2+]SG homeostasis in bovine adrenal chromaffin cells. We found that most of the intracellular aequorin chimera is present in a compartment with 50-100 microM Ca2+. Ca2+ accumulation into this compartment takes place mainly through an ATP-dependent mechanism, namely, a thapsigargin-sensitive Ca2+-ATPase. In addition, fast Ca2+ release was observed in permeabilized cells after addition of inositol 1,4,5-trisphosphate (InsP3) or caffeine, suggesting the presence of InsP3 and ryanodine receptors in the vesicular membrane. Stimulation of intact cells with the InsP3-producing agonist histamine or with caffeine also induced Ca2+ release from the vesicles, whereas acetylcholine or high-[K+] depolarization induced biphasic changes in vesicular[Ca2+], suggesting heterogeneous responses of different vesicle populations, some of them releasing and some taking up Ca2+during stimulation. In conclusion, our data show that chromaffin cell secretory granules have the machinery required for rapid uptake and release of Ca2+, and this strongly supports the hypothesis that granular Ca2+ may contribute to its own secretion.

  3. Composite paraganglioma-ganglioneuroma concomitant with adrenal metastasis of medullary thyroid carcinoma in a patient with multiple endocrine neoplasia type 2B: A case report.

    PubMed

    Yamasaki, Mutsushi; Sato, Yoshiyasu; Nomura, Takeo; Sato, Fuminori; Uchino, Shinya; Mimata, Hiromitsu

    2017-02-01

    Multiple endocrine neoplasia type 2 (MEN2) is an autosomal-dominant cancer syndrome with major components of medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. MEN2B is the most aggressive and rarest of the MEN2 variants. Pheochromocytoma in MEN2 is virtually always located in the adrenal medulla, but MEN2-associated extra-adrenal pheochromocytomas (paraganglioma) are rare. A 59-year-old man who has been diagnosed with MEN2B consulted our hospital for surgical treatment of a 10-mm left adrenal mass and a 30-mm retroperitoneal mass. He had paroxysmal elevations in blood pressure and in urinary metanephrine and vanillylmandelic acid values. Laparoscopic excision of the left adrenal gland and retroperitoneal mass was performed. We experienced an extremely rare case of composite paraganglioma-ganglioneuroma concomitant with adrenal metastasis of medullary thyroid carcinoma in a patient with MEN2B. © 2016 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

  4. Autologous adrenal medullary, fetal mesencephalic, and fetal adrenal brain transplantation in Parkinson's disease: a long-term postoperative follow-up.

    PubMed

    Madrazo, I; Franco-Bourland, R; Aguilera, M; Ostrosky-Solis, F; Madrazo, M; Cuevas, C; Catrejon, H; Guizar-Zahagun, G; Magallon, E

    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) implantation, 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 rigidity, 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.

  5. 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

  6. The innervation of the adrenal gland. IV. Innervation of the rat adrenal medulla from birth to old age. A descriptive and quantitative morphometric and biochemical study of the innervation of chromaffin cells and adrenal medullary neurons in Wistar rats.

    PubMed Central

    Tomlinson, A; Coupland, R E

    1990-01-01

    The innervation of the adrenal medulla has been investigated in normal Wistar rats from birth to old age and ultrastructural findings compared with biochemical markers of the cholinergic innervation of the adrenal gland and catecholamine storage. Morphological evidence of the immaturity of the innervation during the first postnatal week is provided and using quantitative morphometry the innervation of chromaffin cells is shown to reach a mean total of 5.4 synapses per chromaffin cell during the period 26 days to 12 weeks of age. The variation in contents of synaptic profiles is discussed in the light of recent work that demonstrates a major sensory as well as visceral efferent innervation of the gland. Adrenal medullary neurons usually occur in closely packed groups, intimately associated with Schwann cells. Axodendritic and axosomatic synapses on these neurons are described and the likely origin of axonal processes innervating the neurons discussed. In old age the density of innervation remains the same as in young adult animals even though the medulla shows evidence of hyperplasia and hypertrophy of individual chromaffin cells. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 Fig. 20 Fig. 21 Fig. 22 Fig. 23 Fig. 24 Fig. 25 PMID:2384334

  7. Mass spectrometry-based neuropeptidomics of secretory vesicles from human adrenal medullary pheochromocytoma reveals novel peptide products of prohormone processing.

    PubMed

    Gupta, Nitin; Bark, Steven J; Lu, Weiya D; Taupenot, Laurent; O'Connor, Daniel T; Pevzner, Pavel; Hook, Vivian

    2010-10-01

    Neuropeptides are required for cell-cell communication in the regulation of physiological and pathological processes. While selected neuropeptides of known biological activities have been studied, global analyses of the endogenous profile of human peptide products derived from prohormones by proteolytic processing in vivo are largely unknown. Therefore, this study utilized the global, unbiased approach of mass spectrometry-based neuropeptidomics to define peptide profiles in secretory vesicles, isolated from human adrenal medullary pheochromocytoma of the sympathetic nervous system. The low molecular weight pool of secretory vesicle peptides was subjected to nano-LC-MS/MS with ion trap and QTOF mass spectrometry analyzed by different database search tools (InsPecT and Spectrum Mill). Peptides were generated by processing of prohormones at dibasic cleavage sites as well as at nonbasic residues. Significantly, peptide profiling provided novel insight into newly identified peptide products derived from proenkephalin, pro-NPY, proSAAS, CgA, CgB, and SCG2 prohormones. Previously unidentified intervening peptide domains of prohormones were observed, thus providing new knowledge of human neuropeptidomes generated from precursors. The global peptidomic approach of this study demonstrates the complexity of diverse neuropeptides present in human secretory vesicles for cell-cell communication.

  8. Identification of pro-opiomelanocortin and secretion of its peptide fragments in bovine adrenals

    SciTech Connect

    Tennov, A.V.; Dmitriev, A.D.; Kizim, E.A.; Ustinova, E.E.

    1986-01-01

    This paper describes the results of an investigation to show that biosynthesis of POMC, its proteolytic processing, an secretion of the peptide products of that processing take place in the bovine adrenals. Rabbit antisera against endorphins were obtained and used for radioimmunoassay of peptides. I 125-labeled peptides were obtained by the chloramine method and purified from free I 125 on Sephadex G-10 (0.7 x 5 cm, centrifugation for 10 min at 1500 g). To detect secretion of peptide fragments of POMC in the adrenals experiments were undertaken to determine the beta-endorphin content in perfusates obtained during retrograde perfusion of the bovine adrenals. It was found that immunoreactive compounds, indistinguishable in their immunochemical properties from beta-endorphin, are present in the perfusates, just as in the tissue extracts.

  9. [Isoenzymatic forms and distribution of adenylate kinase and creatine kinase in the bovine adrenal medulla].

    PubMed

    Miras-Portugal, M T; Orera, A; Millaruelo, A

    1982-01-01

    Adenylate kinase, creatine kinase as well as their substrate and product levels have been investigated in the adrenal medullary tissue. The concentration of adenine nucleotides and creatine + creatine phosphate are 12.6 +/- 0.4 and 6.9 +/- 0.4 mumol/g wet weight respectively. Adenylate kinase is mainly in the cytosol; only 4% was found in mitochondria. The cytosol enzyme presents a Km for AMP of 5 X 10(-4) M and a Ki for diadenosine pentaphosphate of 0.6 X 10(-6) M. In gel electrophoresis, only one band of adenylate kinase activity can be seen, and its mobility is different from that of the brain enzyme. Creatine kinase from adrenal medulla is mainly found in cytosol; only 3-4% was associated with mitochondria. The cytosolic enzyme is mainly the BB isozyme form.

  10. Tetrodotoxin-insensitive Na+ channel activator palytoxin inhibits tyrosine uptake into cultured bovine adrenal chromaffin cells

    SciTech Connect

    Morita, K.; Teraoka, K.; Azuma, M.; Oka, M.; Hamano, S. )

    1991-07-01

    The effects of the tetrodotoxin-insensitive Na+ channel activator palytoxin on both the secretion of endogenous catecholamines and the formation of 14C-catecholamines from (14C)tyrosine were examined using cultured bovine adrenal chromaffin cells. Palytoxin was shown to cause the stimulation of catecholamine secretion in a concentration-dependent manner. However, this toxin caused the reduction rather than the stimulation of 14C-catecholamine formation at the same concentrations. Palytoxin failed to cause any alteration in the activity of tyrosine hydroxylase prepared from bovine adrenal medulla. Furthermore, the uptake of (14C)tyrosine into the cells was shown to be inhibited by this toxin under the conditions in which the suppression of 14C-catecholamine formation was observed, and this inhibitory action on tyrosine uptake was closely correlated with that on catecholamine formation. The inhibitory action of palytoxin on tyrosine uptake into the cells was observed to be noncompetitive, and this effect was not altered by the removal of Na+ from the incubation mixture. These results suggest that palytoxin may be able to inhibit the uptake of (14C)tyrosine into the cells, resulting in the suppression of 14C-catecholamine formation, probably through its direct action on the plasma membranes of bovine adrenal chromaffin cells.

  11. Endothelial Cells from Bovine Adrenal Medulla Develop Capillary-Like Growth Patterns in Culture

    NASA Astrophysics Data System (ADS)

    Banerjee, Dipak K.; Ornberg, Richard L.; Youdim, Moussa B. H.; Heldman, Eli; Pollard, Harvey B.

    1985-07-01

    The endocrine barrier between chromaffin cells and the blood stream in the adrenal medulla is made of capillary endothelial cells. We have now succeeded in isolating endothelial cells from adrenal medullary tissue, which are probably derived from this barrier. These cells grow on plastic surfaces in the absence of special growth factors or collagen overlays and differentiate into organized structures quite similar to true capillaries. The cells contain factor VIII:R, a marker for endothelial cells, and form intercellular junctions characteristic of capillary endothelial cells. They also synthesize and secrete basal lamina structures and engage in transcytosis, a characteristic ultrastructural and functional combination of exocytosis and endocytosis across the thin endothelial cell processes. These endothelial cells can take up and deaminate catecholamines by A-type monoamine oxidase, an enzyme functionally distinct from the B-type monoamine oxidase found in chromaffin cells. These data indicate that the chromaffin cell and its endothelial cell neighbor may constitute the functional unit of catecholamine metabolism in the adrenal medulla.

  12. Calcium gradients and exocytosis in bovine adrenal chromaffin cells.

    PubMed

    Marengo, Fernando D

    2005-08-01

    The relationship between the localized Ca(2+) concentration and depolarization-induced exocytosis was studied in patch-clamped adrenal chromaffin cells using pulsed-laser Ca(2+) imaging and membrane capacitance measurements. Short depolarizing voltage steps induced Ca(2+) gradients and small "synchronous" increases in capacitance during the pulses. Longer pulses increased the capacitance changes, which saturated at 16 fF, suggesting the presence of a small immediately releasable pool of fusion-ready vesicles. A Hill plot of the capacitance changes versus the estimated Ca(2+) concentration in a thin (100 nm) shell beneath the membrane gave n = 2.3 and K(d) = 1.4 microM. Repetitive stimulation elicited a more complex pattern of exocytosis: early pulses induced synchronous capacitance increases, but after five or more pulses there was facilitation of the synchronous responses and gradual increases in capacitance continued between pulses (asynchronous exocytosis) as the steep submembrane Ca(2+) gradients collapsed. Raising the pipette Ca(2+) concentration led to early facilitation of the synchronous response and early appearance of asynchronous exocytosis. We used this data to develop a kinetic model of depolarization-induced exocytosis, where Ca(2+)-dependent fusion of vesicles occurs from a small immediately releasable pool with an affinity of 1-2 microM and vesicles are mobilized to this pool in a Ca(2+)-dependent manner.

  13. Spontaneous and electrically-evoked catecholamine secretion from long-term cultures of bovine adrenal chromaffin cells.

    PubMed

    Noga, Brian R; Pinzon, Alberto

    2013-09-05

    Catecholamine release was measured from bovine adrenal medullary chromaffin cell (CC) cultures maintained over a period of three months. Cells were plated over simple biocompatible cell platforms with electrical stimulation capability and at specified times transferred to an acrylic superfusion chamber designed to allow controlled flow of superfusate over the culture. Catecholamine release was measured from the superfusates using fast cyclic voltammetry before, during and after electrical stimulation of the cells. Immunocytochemical staining of CC cultures revealed that they were composed of epinephrine (EP) and/or norepinephrine (NE) type cells. Both spontaneous and evoked-release of catecholamines from CCs were observed throughout the testing period. EP predominated during spontaneous release, whereas NE was more prevalent during electrically-evoked release. Electrical stimulation for 20 s, increased total catecholamine release by 60-130% (measured over a period of 500 s) compared to that observed for an equivalent 20 s period of spontaneous release. Stimulus intensity was correlated with the amount of evoked release, up to a plateau which was observed near the highest intensities. Shorter intervals between stimulation trials did not significantly affect the initial amount of release, and the amount of evoked release was relatively stable over time and did not decrease significantly with age of the culture. The present study demonstrates long-term survival of CC cultures in vitro and describes a technique useful for rapid assessment of cell functionality and release properties of cultured monoaminergic cell types that later can be transplanted for neurotransmitter replacement following injury or disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Enhancement by GABA of the stimulation-evoked catecholamine release from cultured bovine adrenal chromaffin cells.

    PubMed

    Kitayama, S; Morita, K; Dohi, T; Tsujimoto, A

    1990-05-01

    The possible involvement of GABAergic mechanisms in the catecholamine (CA) release from adrenal medulla was investigated in a primary culture of bovine adrenal chromaffin cells. GABA elicited CA release and enhanced acetylcholine (ACh)-, excess K(+)- and veratridine-evoked CA release. Muscimol, a selective GABAA receptor agonist, mimicked the action of GABA on CA release. On the other hand, baclofen, a GABAB receptor agonist, failed to affect basal or evoked CA release. Furthermore, bicuculline and picrotoxin blocked the enhancement by GABA of veratridine-evoked CA release without affecting basal CA release and CA release evoked by veratridine. In Ca2(+)-free medium, GABA failed to affect basal and caffeine-evoked CA release. ACh-evoked CA release was slightly reduced by bicuculline, whereas excess K(+)-evoked CA release was not, suggesting the involvement of endogenous GABA in CA release evoked by ACh. These results suggest a facilitatory modulation by GABA of basal and evoked release of CA from bovine adrenal medulla through GABAA receptor-mediated mechanisms.

  15. Association of the GTP-binding protein Rab3A with bovine adrenal chromaffin granules

    SciTech Connect

    Darchen, F.; Hammel, F.; Monteils, M.P.; Scherman, D. ); Zahraoui, A.; Tavitian, A. )

    1990-08-01

    The Rab3A protein belongs to a large family of small GTP-binding proteins that are present in eukaryotic cells and that share amino acid identities with the Ras proteins (products of the ras protooncogenes). Rab3A, which is specifically located in nervous and endocrine tissues, is suspected to play a key role in secretion. Its localization was investigated in bovine adrenal gland by using a polyclonal antibody. Rab3A was detected in adrenal medulla but not in adrenal cortex. In cultured adrenal medulla cells, Rab3A was specifically expressed in the catecholamine-secreting chromaffin cells. Subcellular fractionation suggested that Rab3A is about 30% cytosolic and that particulate Rab3A is associated with the membrane of chromaffin granules (the catecholamine storage organelles) and with a second compartment likely to be the plasma membrane. The Rab3A localization on chromaffin granule membranes was confirmed by immunoadsorption with an antibody against dopamine {beta}-hydroxylase. Rab3A was not extracted from this membrane by NaCl or KBr but was partially extracted by urea and totally solubilized by Triton X-100, suggesting either an interaction with an intrinsic protein or a membrane association through fatty acid acylation. This study suggests that Rab3A, which may also be located on other secretory vesicles containing noncharacterized small GTP-binding proteins, is involved in their biogenesis or in the regulated secretion process.

  16. Purification and characterization of bovine adrenal cytochrome b561 expressed in insect and yeast cell systems.

    PubMed

    Liu, Wen; Kamensky, Yury; Kakkar, Reva; Foley, Erin; Kulmacz, Richard J; Palmer, Graham

    2005-04-01

    Bovine adrenal chromaffin granule cytochrome (cyt) b561 is a transmembrane hemoprotein that plays a key role in transporting reducing equivalents from ascorbate to dopamine-beta-hydroxylase for catecholamine synthesis. We have developed procedures for expression and purification of functional bovine adrenal cyt b561 in insect and yeast cell systems. The bovine cyt b561 coding sequence, with or without a hexahistidine-tag sequence at the C-terminus, was cloned into the pVL1392 transfer vector under the control of the polyhedrin promoter to generate recombinant baculovirus for protein expression in Sf9 insect cells (approximately 0.5 mg detergent-solubilized cyt b561/L culture). For the yeast system, the cyt b561 cDNA was modified with a hexahistidine-tag sequence at the C-terminus, and inserted into the pPICZB vector under the control of the alcohol oxidase promoter. The recombinant plasmid was transformed into Pichia pastoris GS115 competent cells to give methanol-inducible cyt b561 expression (approximately 0.7 mg detergent-solubilized cyt b561/L culture). Recombinant His-tagged cyt b561 expressed in Sf9 or Pichia cells was readily solubilized from membrane fractions with dodecyl maltoside and purified to electrophoretic homogeneity by one-step chromatography on Ni-NTA affinity resin. The purified recombinant cytochrome from both systems had a heme to protein ratio close to two and was fully functional, as judged by comparison with the spectroscopic and kinetic parameters of the endogenous cytochrome from chromaffin granules. A novel procedure for isolation of chromaffin granule membranes was developed to utilize frozen adrenal glands instead of fresh tissue.

  17. Mobile and immobile calcium buffers in bovine adrenal chromaffin cells.

    PubMed Central

    Zhou, Z; Neher, E

    1993-01-01

    1. The calcium binding capacity (kappa S) of bovine chromaffin cells preloaded with fura-2 was measured during nystatin-perforated-patch recordings. 2. Subsequently, the perforated patch was ruptured to obtain a whole-cell recording situation, and the time course of kappa S was monitored during periods of up to one hour. 3. No rapid change (within 10-20 s) of kappa S was observed upon transition to whole-cell recording, as would be expected, if highly mobile organic anions contributed significantly to calcium buffering. However, approximately half of the cells investigated displayed a drop in kappa S within 2-5 min, indicative of the loss of soluble Ca2+ binding proteins in the range of 7-20 kDa. 4. The average Ca2+ binding capacity (differential ratio of bound calcium over free calcium) was 9 +/- 7 (mean +/- S.E.M.) for the poorly mobile component and 31 +/- 10 for the fixed component. It was concluded that a contribution of 7 from highly mobile buffer would have been detected, if present. Thus, this value can be considered as an upper bound to highly mobile Ca2+ buffer. 5. Both mobile and fixed calcium binding capacity appeared to have relatively low Ca2+ affinity, since kappa S did not change in the range of Ca2+ concentrations between 0.1 and 3 microM. 6. It was found that cellular autofluorescence and contributions to fluorescence of non-hydrolysed or compartmentalized dye contribute a serious error in estimation of kappa S. 'Balanced loading', a degree of fura-2 loading such that the calcium binding capacity of fura-2 equals cellular calcium binding capacity, minimizes these errors. Also, changes in kappa S at the transition from perforated-patch to whole-cell recording can be most faithfully recorded for similar degrees of loading in both situations. 7. Nystatin was found unable to make pores from inside of the plasma membrane of chromaffin cells. With careful preparation and storage the diluted nystatin solution maintained its high activity of membrane

  18. Theoretical conformational analysis of the bovine adrenal medulla 12 residue peptide molecule

    NASA Astrophysics Data System (ADS)

    Akhmedov, N. A.; Tagiyev, Z. H.; Hasanov, E. M.; Akverdieva, G. A.

    2003-02-01

    The spatial structure and conformational properties of the bovine adrenal medulla 12 residue peptide Tyr1-Gly2-Gly3-Phe4-Met5-Arg6-Arg7-Val8-Gly9-Arg10-Pro11-Glu12 (BAM-12P) molecule were studied by theoretical conformational analysis. It is revealed that this molecule can exist in several stable states. The energy and geometrical parameters for the low-energy conformations are obtained. The conformationally rigid and labile segments of this molecule were revealed.

  19. Interaction of urokinase with specific receptors stimulates mobilization of bovine adrenal capillary endothelial cells

    SciTech Connect

    Fibbi, G.; Ziche, M.; Morbidelli, L. ); Magnelli, L.; Del Rosso, M. )

    1988-12-01

    On the basis of {sup 125}I-labeled plasminogen activator binding analysis the authors have found that bovine adrenal capillary endothelial cells have specific receptors for human urinary-type plasminogen activator on the cell membrane. Each cell exposes about 37,000 free receptors with a K{sub d} of 0.8958{times}10{sup {minus}12} M. A monoclonal antibody against the 17,500 proteolytic fragment of the A chain of the plasminogen activator, not containing the catalytic site of the enzyme, impaired the specific binding, thus suggesting the involvement of a sequence present on the A chain in the interaction with the receptor, as previously shown in other cell model systems. Both the native molecule and the A chain are able to stimulate endothelial cell motility in the Boyden chamber, when used at nanomolar concentrations. The use of the same monoclonal antibody that can inhibit ligand-receptor interaction can impair the plasminogen activator and A-chain-induced endothelial cell motility, suggesting that under the conditions used in this in vitro model system, the motility of bovine adrenal capillary endothelial cells depends on the specific interaction of the ligand with free receptors on the surface of endothelial cells.

  20. Fetal substantia nigra and adrenal medullary grafts placed contralateral to the nigrostriatal lesion side induce a decrease in turning behavior but not in dopamine receptor density.

    PubMed

    Mendoza-Ramírez, J L; Aguilar-Roblero, R; Zainos-Rosales, A; Drucker-Colín, R

    1991-01-01

    Motor asymmetries as well as changes in the density of postsynaptic dopamine receptors produced by unilateral denervation of the striatum have been reduced by both substantia nigra (SN) and adrenal medullary (AM) grafts. Since to this date all studies have placed the grafts on the side ipsilateral to the lesion, the purpose of this study was to determine whether similar effects can be obtained when grafts are placed contralateral to the denervated side. The results of this study showed that 6-hydroxydopamine-lesioned rats followed up to 150 days with contralaterally placed intraventricular fetal substantia nigra grafts and fetal adrenal medulla grafts have a reduction of turning behavior of 41% and 34% respectively. However, contrary to ipsilateral grafts no normalization of dopamine receptor density as measured by [3H]spiperone autoradiography was observed 6 months after SN grafts, however, after AM grafts normalization did occur except in the anterior portion of the striatum. These results suggest that the compensatory motor changes induced by the grafted tissues could be mediated by mechanisms unrelated to changes in receptor density.

  1. Renal tubular and adrenal medullary tumors in the 2-year rat study with canagliflozin confirmed to be secondary to carbohydrate (glucose) malabsorption in the 15-month mechanistic rat study.

    PubMed

    De Jonghe, Sandra; Johnson, Mark D; Mamidi, Rao N V S; Vinken, Petra; Feyen, Bianca; Lammens, Godelieve; Proctor, Jim

    2017-09-12

    During preclinical development of canagliflozin, an SGLT2 inhibitor, treatment-related pheochromocytomas, renal tubular tumors (RTT), and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. In a previous 6-month rat mechanistic study, feeding a glucose free diet prevented canagliflozin effects on carbohydrate malabsorption as well as the increase in cell proliferation in adrenal medulla and kidneys, implicating carbohydrate malabsorption as the mechanism for tumor formation. In this chronic study male Sprague-Dawley rats were dosed orally with canagliflozin at high dose-levels (65 or 100 mg/kg/day) for 15 months and received either a standard diet or a glucose-free diet. Canagliflozin-dosed rats on standard diet showed presence of basophilic renal tubular tumors (6/90) and an increased incidence of adrenal medullary hyperplasia (35/90), which was fully prevented by feeding a glucose-free diet (no RTT's; adrenal medullary hyperplasia in ≤5/90). These data further confirm that kidney and adrenal medullary tumors in the 2-year rat study were secondary to carbohydrate (glucose) malabsorption and were not due to a direct effect of canagliflozin on these target tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Functional reconstitution of prostaglandin E receptor from bovine adrenal medulla with guanine nucleotide binding proteins

    SciTech Connect

    Negishi, M.; Ito, S.; Yokohama, H.; Hayashi, H.; Katada, T.; Ui, M.; Hayaishi, O.

    1988-05-15

    Prostaglandin E/sub 2/ (PEG/sub 2/) was found to bind specifically to a 100,000 x g pellet prepared from bovine adrenal medulla. The PGE receptor was associated with a GTP-binding protein (G-protein) and could be covalently cross-linked with this G-protein by dithiobis(succinimidyl propionate) in the 100,000 x g pellet. In order to characterize the G-protein associated with the PGE receptor and reconstitute these proteins in phospholipid vesicles, the authors purified the G-protein to apparent homogeneity from the 100,000 x g pellet. The G-protein served as a substrate of pertussis toxin but differed in its ..cap alpha.. subunit from two known pertussis toxin substrate G-proteins (G/sub i/ and G/sub 0/) purified from bovine brain. The molecular weight of the ..cap alpha.. subunit was 40,000, which is between those of G/sub i/ and G/sub 0/. The purified protein was also distinguished immunologically from G/sub i/ and G/sub 0/ and was referred to as G/sub am/. Reconstitution of the PGE receptor with pure C/sub am/, G/sub i/, or G/sub 0/ in phospholipid vesicles resulted in a remarkable restoration of (/sup 3/H)PGE/sub 2/ binding activity in a GTP-dependent manner. The efficiency of these three G-proteins in this capacity was roughly equal. When pertussis toxin- or N-ethylmaleimide-treated G-proteins, instead of the native ones, were reconstituted into vesicles, the restoration of binding activity was no longer observed. These results indicate that the PGE receptor can couple functionally with G/sub am/, G/sub i/, or G/sub 0/ in phospholipid vesicles and suggest that G/sub am/ may be involved in signal transduction of the PGE receptor in bovine adrenal medulla.

  3. Mouse Adrenal Chromaffin Cell Isolation

    PubMed Central

    Kolski-Andreaco, Aaron; Cai, Haijiang; Currle, D. Spencer; Chandy, K. George; Chow, Robert H.

    2007-01-01

    Adrenal medullary chromaffin cell culture systems are extremely useful for the study of excitation-secretion coupling in an in vitro setting. This protocol illustrates the method used to dissect the adrenals and then isolate the medullary region by stripping away the adrenal cortex. The digestion of the medulla into single chromaffin cells is then demonstrated. PMID:18830430

  4. Alpha-human atrial natriuretic polypeptide (. cap alpha. -hANP) specific binding sites in bovine adrenal gland

    SciTech Connect

    Higuchi, K.; Nawata, H.; Kato, K.I.; Ibayashi, H.; Matsuo, H.

    1986-06-13

    The effects of synthetic ..cap alpha..-human atrial natriuretic polypeptide (..cap alpha..-hANP) on steroidogenesis in bovine adrenocortical cells in primary monolayer culture were investigated. ..cap alpha..-hANP did not inhibit basal aldosterone secretion. ..cap alpha..-hANP induced a significant dose-dependent inhibition of basal levels of cortisol and dehydroepiandrosterone (DHEA) secretion and also of aCTH (10/sup -8/M)-stimulated increases in aldosterone, cortisol and DHEA secretion. Visualization of (/sup 125/I) ..cap alpha..-hANP binding sites in bovine adrenal gland by an in vitro autoradiographic technique demonstrated that these sites were highly localized in the adrenal cortex, especially the zona glomerulosa. These results suggest that the adrenal cortex may be a target organ for direct receptor-mediated actions of ..cap alpha..-hANP.

  5. Identification and characterization of an angiotensin II receptor on cultured bovine adrenal chromaffin cells

    SciTech Connect

    Boyd, V.L.

    1987-01-01

    The presence of an angiotensin II receptor on cultured bovine adrenal chromaffin cells was demonstrated by radioligand binding. A single class of finding sites with a K/sub D/ of 0.7 nM was characterized. The use of radioligands also allows the localization of receptors by autoradiography. Autoradiography demonstrated that approximately 50% of the isolated cells bound angiotensin II. It was of interest to see if angiotensin II bound to a cell that possessed a certain phenotype. In order to evaluate this possibility a technique was developed that combined autoradiography and immunocytochemistry. Results indicated that angiotensin II binding sites were not localized preferentially to either norepinephrine or epinephrine cells. Binding of angiotensin II was associated with the release of intracellular catecholamine stores. Cells were pre-loaded with /sup 3/H-norepinephrine and secretion was monitored by following radioactivity released into the supernatant. Alternatively, release of endogenous catecholamines was determined by fluorometric assay.

  6. Photoaffinity crosslinking of etorphine with opioid binding sites in the bovine adrenal medulla

    SciTech Connect

    Cantau, P.; Bourhim, N.; Giraud, P.; Oliver, C.; Castanas, E.

    1987-04-01

    The covalent crosslinking of (/sup 3/H)etorphine with opioid binding sites in the bovine adrenal medulla is reported. Of all the radiolabeled opiates tested (ethylketocyclazocine, etorphine, (D-Ala2, D-Leu5)enkephalin, (D-Ala2, Me-Phe4, Gly5-ol)enkephalin only etorphine could be crosslinked under uv irradiation. In our conditions (black uv lamp, 160 W, peak mean 360 nm, from a distance of 10 cm) maximum covalent binding was observed after a 10-min irradiation. Protein concentration was a crucial factor for the irreversible/total binding ratio. A good ratio (50%) was obtained at protein concentrations of about 1.0 mg/ml. Covalent binding of nonmodified opiates could be of interest for the biochemical characterization of their binding sites.

  7. Processing of enkephalin-containing peptides in isolated bovine adrenal chromaffin granules.

    PubMed Central

    Fleminger, G; Ezra, E; Kilpatrick, D L; Udenfriend, S

    1983-01-01

    Intact chromaffin granules isolated from bovine adrenal medulla were incubated at 37 degrees C for up to 22 hr. Processing of enkephalin-containing (EC) peptides in the granules was followed by the change in their size distribution as shown by chromatography on Sephadex G-75 columns. A gradual shift toward lower molecular weight EC peptides was observed during the incubation, indicating processing of the higher molecular weight to lower molecular weight EC peptides. The total amount of [Met]-enkephalin, free and in peptide linkage, remained constant indicating that little or no nonspecific degradation occurred during the experiment. HPLC resolution of the fraction containing the low molecular weight EC peptides showed that free enkephalins as well as [Met]enkephalin-Arg6-Phe7 and [Met]enkephalin-Arg6-Gly7-Leu8 accumulated while [Met]enkephalin-Arg6 and [Met]enkephalin-Lys6 disappeared. All the above data indicate the presence of an atypical trypsin activity and the presence of a carboxypeptidase B-like activity within the granules. From the rates of accumulation of the low molecular weight EC peptides and the disappearance of the higher molecular weight EC peptides, a processing rate of 65-70 pmol/g tissue per hr was estimated, which calculates to a lifetime of 6-8 days for EC peptides in the granules. Under steady-state conditions this rate of processing appears to be too low to produce significant amounts of free enkephalins from larger EC peptides. This is well in accord with previous observations that relatively small amounts of free enkephalins are found in bovine adrenal medulla. PMID:6578517

  8. Monolayer co-culture of rat heart cells and bovine adrenal chromaffin paraneurons.

    PubMed

    Trifaró, J M; Tang, R; Novas, M L

    1990-04-01

    This paper describes a method for the preparation of co-cultures of rat heart cells and bovine adrenal chromaffin paraneurons. The most suitable condition for heart cell isolation was when a combination of trypsin-DNAse I in Locke's solution was used for digestion. The best co-culture conditions were obtained when 10(6) heart cells were plated on 7- to 8-d-old adrenal chromaffin paraneuron cultures containing 0.5 x 10(6) cells per 35-mm diameter culture dishes. Measurements of DNA (heart cells and chromaffin paraneurons), monitoring of beating frequency (heart cells), and catecholamine (chromaffin paraneurons) levels and release indicated that both cell types remain viable and functional for several weeks. Heart cells started their characteristic contractile activity 24 h earlier when plated either on viable or lysed chromaffin paraneurons, an effect apparently due to faster surface adhesion of heart cells. The beating frequency of heart cells increased after treatment of co-cultures with either noradrenaline or nicotine, with the latter agent acting indirectly through the release of chromaffin paraneuron catecholamines. Propranolol produced a dose-related inhibition of the responses to either noradrenaline or nicotine, thus suggesting that the increase in myocyte's beating activity was mediated through beta-receptors. Anti-myosin and anti-dopamine-beta-hydroxylase immunostaining was used for cell type identification and for the demonstration of body-to-body and process-to-process contacts between adrenal chromaffin paraneurons and heart cells. This co-culture system will serve as a starting point of further studies directed to understand a) the influence of a cell type on the development and on the phenotypic characteristics of a second cell type and b) the interaction of cells derived from different organs and species.

  9. Muscarinic receptor-mediated inositol tetrakisphosphate response in bovine adrenal chromaffin cells

    SciTech Connect

    Sanborn, B.B.; Schneider, A.S. )

    1990-01-01

    Inositol trisphosphate (IP{sub 3}), a product of the phosphoinositide cycle, mobilizes intracellular Ca{sup 2+} in many cell types. New evidence suggests that inositol tetrakisphosphate (IP{sub 4}), an IP{sub 3} derivative, may act as another second messenger to further alter calcium homeostasis. However, the function and mechanism of action of IP{sub 4} are presently unresolved. We now report evidence of muscarinic receptor-mediated accumulation of IP{sub 4} in bovine adrenal chromaffin cells, a classic neurosecretory system in which calcium movements have been well studied. Muscarine stimulated an increase in ({sup 3}H)IP{sub 4} and ({sup 3}H)IP{sub 3} accumulation in chromaffin cells and this effect was completely blocked by atropine. ({sup 3}H)IP{sub 4} accumulation was detectable within 15 sec, increased to a maximum by 30 sec and thereafter declined. 2,3-diphosphoglycerate, an inhibitor of IP{sub 3} and IP{sub 4} hydrolysis, enhanced accumulation of these inositol polyphosphates. The results provide the first evidence of a rapid inositol tetrakisphosphate response in adrenal chromaffin cells, which should facilitate the future resolution of the relationship between IP{sub 4} and calcium homeostasis.

  10. Metabolism of adrenic acid to vasodilatory 1alpha,1beta-dihomo-epoxyeicosatrienoic acids by bovine coronary arteries.

    PubMed

    Yi, Xiu-Yu; Gauthier, Kathryn M; Cui, Lijie; Nithipatikom, Kasem; Falck, John R; Campbell, William B

    2007-05-01

    Adrenic acid (docosatetraenoic acid), an abundant fatty acid in the vasculature, is produced by a two-carbon chain elongation of arachidonic acid. Despite its abundance and similarity to arachidonic acid, little is known about its role in the regulation of vascular tone. Gas chromatography/mass spectrometric analysis of bovine coronary artery and endothelial cell lysates revealed arachidonic acid concentrations of 2.06 +/- 0.01 and 6.18 +/- 0.60 microg/mg protein and adrenic acid concentrations of 0.29 +/- 0.01 and 1.56 +/- 0.16 microg/mg protein, respectively. In bovine coronary arterial rings preconstricted with the thromboxane mimetic U-46619, adrenic acid (10(-9)-10(-5) M) induced concentration-related relaxations (maximal relaxation = 83 +/- 4%) that were similar to arachidonic acid relaxations. Adrenic acid relaxations were blocked by endothelium removal and the K(+) channel inhibitor, iberiotoxin (100 nM), and inhibited by the cyclooxygenase inhibitor, indomethacin (10 microM, maximal relaxation = 53 +/- 4%), and the cytochrome P-450 inhibitor, miconazole (10 microM, maximal relaxation = 52 +/- 5%). Reverse-phase HPLC and liquid chromatography/mass spectrometry isolated and identified numerous adrenic acid metabolites from coronary arteries including dihomo (DH)-epoxyeicosatrienoic acids (EETs) and DH-prostaglandins. DH-EET [16,17-, 13,14-, 10,11-, and 7,8- (10(-9)-10(-5) M)] induced similar concentration-related relaxations (maximal relaxations averaged 83 +/- 3%). Adrenic acid (10(-6) M) and DH-16,17-EET (10(-6) M) hyperpolarized coronary arterial smooth muscle. DH-16,17-EET (10(-8)-10(-6) M) activated iberiotoxin-sensitive, whole cell K(+) currents of isolated smooth muscle cells. Thus, in bovine coronary arteries, adrenic acid causes endothelium-dependent relaxations that are mediated by cyclooxygenase and cytochrome P-450 metabolites. The adrenic acid metabolite, DH-16,17-EET, activates smooth muscle K(+) channels to cause hyperpolarization and

  11. Bradykinin and histamine-induced cytosolic calcium increase in capillary endothelial cells of bovine adrenal medulla.

    PubMed

    Vinet, Raúl; Cortés, Magdalena P; Alvarez, Rocío; Delpiano, Marco A

    2014-09-01

    We have assessed the effect of bradykinin and histamine on the cytosolic free calcium concentration ([Ca(2+)]i ) of bovine adrenal medulla capillary endothelial cells (BAMCECs). To measure [Ca(2+)]i changes in BAMCECs the intracellular fluorescent probe, fluo-3 AM, was used. Bradykinin (3 µM) produced a transient monophasic increase in [Ca(2+)]i , which was depressed by B1650 (0.1 µM), a B2-bradykinin receptor antagonist (D-Arg-[Hyp(3), Thi(5,8) , D-Phe(7)]-Bradykinin). Similarly, increase in [Ca(2+)]i induced by histamine was also depressed by tripolidine (0.1 µM), an H1-histamine receptor antagonist. [Ca(2+)]i increase induced by both agonists was unaffected in the absence of extracellular Ca(2+) or presence of antagonists of voltage operated Ca(2+) channels (VOCCs). Thapsigargin (1 µM) did not abolish the increase of [Ca(2+)]i produced by bradykinin, but abolished that of histamine. In contrast, caffeine (100 µM), abolished the [Ca(2+)]i response induced by bradykinin (3 µM), but did not affect the [Ca(2+)]i increase induced by histamine (100 µM). The results indicate the presence of B2 bradykinin- and H1 histamine-receptors in BAMCECs. Liberation of Ca(2+) induced by both agonists occurs through 2 different intracellular mechanisms. While bradykinin activates a sarco(endo) plasmic reticulum (SER) containing a SER Ca(2+) -ATPase (SERCA) thapsigargin-insensitive, histamine activates a SER containing a SERCA thapsigargin-sensitive. We suggest that the increase in [Ca(2+)]i induced by bradykinin and histamine could be of physiological relevance, modulating adrenal gland microcirculation.

  12. The four-dimensional stress test: psychological, sympathetic-adrenal-medullary, parasympathetic and hypothalamic-pituitary-adrenal responses following inhalation of 35% CO2.

    PubMed

    Wetherell, Mark A; Crown, Anna L; Lightman, Stafford L; Miles, Jeremy N V; Kaye, Joey; Vedhara, Kavita

    2006-07-01

    Hypercapnia is a threat to homeostasis and results in neuroendocrine, autonomic and anxiogenic responses. The inhalation of carbon dioxide (CO2) may, therefore, provide a good paradigm for exploring the pathways by which stress can lead to increased susceptibility to ill-health through physiological and psychological stress reactivity. The current study was designed, therefore, to assess the psychological and physiological responses to the inhalation of CO2. Healthy participants (N = 24) inhaled a single vital capacity breath of a mixture of CO2 (35%) and oxygen (65%). Blood pressure and heart rate were recorded for 5 min before and after the test and blood and saliva samples were taken immediately before and 2, 10, 20 and 30 min post-inhalation for the measurement of noradrenaline, salivary and serum cortisol and salivary alpha amylase. In addition, psychosomatic symptoms were recorded immediately before and after the test. The same protocol was repeated 4-6 weeks later at the same time of day. A single inhalation of CO2 increased blood pressure, noradrenaline, salivary alpha amylase and psychosomatic symptoms, but decreased heart rate at both testing sessions. Analyses of salivary cortisol data revealed that 70% of the sample could be reliably classified as either responders (i.e. demonstrated a post-CO2 cortisol increase) or non-responders (i.e. responded with a decrease or no change in cortisol following CO2) at both test sessions. Responders also perceived the test to be more aversive than non-responders. Inhalation of 35% CO2 reliably stimulated the key mechanisms involved in the human stress response. The inter-individual differences in the reactivity of the hypothalamic-pituitary-adrenal axis were also related to differences in the perception of the test.

  13. Subcellular compartmentalization of 1-methyl-4-phenylpyridinium with catecholamines in adrenal medullary chromaffin vesicles may explain the lack of toxicity to adrenal chromaffin cells.

    PubMed

    Reinhard, J F; Diliberto, E J; Viveros, O H; Daniels, A J

    1987-11-01

    Cultures of bovine adrenomedullary chromaffin cells accumulated 1-methyl-4-phenylpyridinium (MPP+) in a time- and concentration-dependent manner by a process that was prevented by desmethylimipramine. The subcellular localization of the incorporated [methyl-3H]MPP+ was examined by differential centrifugation and sucrose density gradient fractionation and was found to be predominantly colocalized with catecholamines in chromaffin vesicles, and negligible amounts were detected within the mitochondrial fraction. When chromaffin cell membranes were made permeable with the detergent digitonin in the absence of calcium, there was no increase in the release of [3H]MPP+, indicating that there is negligible accumulation of the neurotoxin in the cytosol. Simultaneous exposure to digitonin and calcium induced cosecretion of MPP+ and catecholamines. Stimulation of the cells with nicotine released both catecholamines and MPP+ at identical rates and percentages of cellular content in a calcium-dependent manner. Last, when cells were incubated with MPP+ in the presence of tetrabenazine (an inhibitor of vesicular uptake), the chromaffin cell toxicity of MPP+ was potentiated. We submit that the ability of the chromaffin cells to take up and store MPP+ in the chromaffin vesicle prevents the toxin's interaction with other structures and, thus, prevents cell damage. As an extension of this hypothesis, the relative resistance of some brain monoaminergic neurons to the toxic actions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine may result from the subcellular sequestration of MPP+ in the storage vesicle.

  14. Multicenter study of autologous adrenal medullary transplantation to the corpus striatum in patients with advanced Parkinson's disease.

    PubMed

    Goetz, C G; Olanow, C W; Koller, W C; Penn, R D; Cahill, D; Morantz, R; Stebbins, G; Tanner, C M; Klawans, H L; Shannon, K M

    1989-02-09

    In 19 patients with severe Parkinson's disease, we replicated the surgical procedures developed by Madrazo et al. for transplantation of the adrenal medulla to the striatum, and followed them for six months after operation. We monitored their motor function with the use of standardized scales and determined the amount and quality of "on" and "off" time (the hours of the waking day when the antiparkinsonian medications were effective and ineffective, respectively). We found significant improvement in focal areas of motor function. The mean percentage of on time during the day increased from 47.6 percent to 75.0 percent (P = 0.012); the mean percentage of on time without chorea increased from 26.6 percent to 59.2 percent (P = 0.006); the mean severity of off time decreased as assessed by both the Activities of Daily Living subscale of the Unified Parkinson's Disease Scale (P = 0.002) and the Schwab and England scale (P = 0.037). In contrast to the finding of Madrazo et al., however, the dosages of antiparkinsonian medications could not be decreased and postoperative morbidity was substantial. Despite cautious optimism, we conclude that the widespread use of this procedure outside of research centers is premature, since the improvement we found was slighter than in the previous cases.

  15. Subcellular compartmentalization of 1-methyl-4-phenylpyridinium with catecholamines in adrenal medullary chromaffin vesicles may explain the lack of toxicity to adrenal chromaffin cells

    SciTech Connect

    Reinhard, J.F. Jr.; Diliberto, E.J. Jr.; Viveros, O.H.; Daniels, A.J.

    1987-11-01

    Cultures of bovine adrenomedullary chromaffin cells accumulated 1-methyl-4-phenylpyridinium (MPP/sup +/) in a time- and concentration-dependent manner by a process that was prevented by desmethylimipramine. The subcellular localization of the incorporated (methyl-/sup 3/H)MPP/sup +/ was examined by differential centrifugation and sucrose density gradient fractionation and was found to be predominantly colocalized with catecholamines in chromaffin vesicles, and negligible amounts were detected within the mitochondrial fraction. When chromaffin cell membranes were made permeable with the detergent digitonin the absence of calcium, there was no increase in the release of (/sup 3/H)MPP/sup +/, indicating that there is negligible accumulation of the neurotoxin in the cytosol. Simultaneous exposure to digitonin and calcium induced cosecretion of MPP/sup +/ and catecholamines. Stimulation of the cells with nicotine released both catecholamines and MPP/sup +/ at identical rates and percentages of cellular content in a calcium-dependent manner. Last, when cells were incubated with MPP/sup +/ in the presence of tetrabenazine (an inhibitor of vesicular uptake), the chromaffin cell toxicity of MPP/sup +/ was potentiated. The authors submit that the ability of the chromaffin cells to take up and store MPP/sup +/ in the chromaffin vesicle prevents the toxin's interaction with other structures and, thus, prevents cell damage. As an extension of this hypothesis, the relative resistance of some brain monoaminergic neurons to the toxic actions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine may result from the subcellular sequestration of MPP/sup +/ in the storage vesicle.

  16. Intrathecal grafting of unencapsulated adrenal medullary tissue can bring CD4 T lymphocytes into CSF: a potentially deleterious event for the graft.

    PubMed

    Tkaczuk, J; Bes, J C; Duplan, H; Sallerin, B; Tafani, M; Charlet, J P; Abbal, M; Lazorthes, Y; Ohayon, E

    2000-01-01

    Adrenal medullary tissue including chromaffin cells was grafted intrathecally in cancer patients to relieve intractable pain. The central nervous system (CNS) is considered an immune privileged site. Therefore, non-HLA-matched and unencapsulated tissue was grafted in 15 patients and 1 sham control in a series of at least 20 grafts. We observed an increase in CSF lymphocyte counts in 15/20 allografts (75%). In contrast to peripheral blood, CD4 T cells predominated in the CSF, but failed to exhibit an activated phenotype (CD25+ CD45RO+ HLA-DR+). The positive effect of graft on pain, the high met-enkephalin levels, the absence of any increase in CSF cytokine levels particularly for IFN-gamma or IL-2 (but not IL-10 and IL-6), indirectly indicated that the graft was tolerated despite the presence of CSF lymphocytes. The single treatment failure and three of four cases of partial efficacy occurred in grafts where CSF lymphocytes were present. Moreover, when assayed (n = 7), the CD4+ CSF lymphocytes still retained the capacity to exhibit ex vivo a normal or enhanced frequency of T CD4 cells producing IFN-gamma and IL-2. Taken together, our observations indicate that impairment of the local immunosuppressive balance can lead to activation of those CSF CD4 T cells and drive a rejection process. This study suggests further work on the purification and/or the immunoisolation of tissues grafted in the CNS will be necessary, particularly when the possibility of long-term and repeated grafting is considered.

  17. Characterization of angiotensin-binding sites in the bovine adrenal and the rat brain

    SciTech Connect

    Rogulja, I.

    1989-01-01

    The first study was designed to determine whether systemically administered MSG affects neurons in the CVOs that are potentially important in mediating angiotensin-dependent responses. Rats were pretreated with MSG and the receptors for angiotensin II were assayed by radioligand binding in brain homogenates from the septum anteroventral third ventricular region (AV3V) and the thalamus/hypothalamus region using {sup 125}I-angiotensin II as the radioligand. The results of this experiment indicate that systematically administered MSG in the rat significantly reduced the number (Bmax) of Ang II receptors in a tissue sample which contained both extra blood-brain barrier organs as well as tissue within the blood-brain barrier with no change in the affinity (Kd) of the binding sites. The second chapter reports the successful solubilization of bovine adrenal {sup 125}I Ang II and {sup 125}I Sar{sup 1},Ile{sup 8}-Ang II binding sites with the detergent CHAPS. The results of our studies indicate the presence of two angiotensin binding sites. The one site is specific for naturally occurring angiotensins as well as sarcosine-1 substituted angiotensin analogues. The other site which can be optimally stabilized be re-addition of 0.3% CHAPS into the incubation assay binds sarcosine-1 substituted angiotensins exclusively. Hydrophobic interaction chromatography experiments suggest that these sites, possibly, represent distinct proteins. The third chapter discusses the successful solubilization and partial characterization of the rat brain angiotensin receptor.

  18. Identification of muscarinic receptor subtypes involved in catecholamine secretion in adrenal medullary chromaffin cells by genetic deletion

    PubMed Central

    Harada, Keita; Matsuoka, Hidetada; Miyata, Hironori; Matsui, Minoru; Inoue, Masumi

    2015-01-01

    Background and Purpose Activation of muscarinic receptors results in catecholamine secretion in adrenal chromaffin cells in many mammals, and muscarinic receptors partly mediate synaptic transmission from the splanchnic nerve, at least in guinea pigs. To elucidate the physiological functions of muscarinic receptors in chromaffin cells, it is necessary to identify the muscarinic receptor subtypes involved in excitation. Experimental Approach To identify muscarinic receptors, pharmacological tools and strains of mice where one or several muscarinic receptor subtypes were genetically deleted were used. Cellular responses to muscarinic stimulation in isolated chromaffin cells were studied with the patch clamp technique and amperometry. Key Results Muscarinic M1, M4 and M5 receptors were immunologically detected in mouse chromaffin cells, and these receptors disappeared after the appropriate gene deletion. Mouse cells secreted catecholamines in response to muscarinic agonists, angiotensin II and a decrease in external pH. Genetic deletion of M1, but not M3, M4 or M5, receptors in mice abolished secretion in response to muscarine, but not to other stimuli. The muscarine-induced secretion was suppressed by MT7, a snake peptide toxin specific for M1 receptors. Similarly, muscarine failed to induce an inward current in the presence of MT7 in mouse and rat chromaffin cells. The binding affinity of VU0255035 for the inhibition of muscarine-induced currents agreed with that for the M1 receptor. Conclusions and Implications Based upon the effects of genetic deletion of muscarinic receptors and MT7, it is concluded that the M1 receptor alone is responsible for muscarine-induced catecholamine secretion. PMID:25393049

  19. Separate [3H]-nitrendipine binding sites in mitochondria and plasma membranes of bovine adrenal medulla.

    PubMed Central

    Ballesta, J. J.; Garcia, A. G.; Gutierrez, L. M.; Hidalgo, M. J.; Palmero, M.; Reig, J. A.; Viniegra, S.

    1990-01-01

    1. Two binding sites for the 1,4-dihydropyridine (DHP) derivative [3H]-nitrendipine have been found in the bovine adrenal medulla. The high-affinity site (Kd = 0.48 nM and Bmax = 128 fmol mg-1 protein) was specifically located in purified plasma membranes. The low-affinity site (Kd = 252 nM and Bmax = 169 pmol mg-1 protein) was located only in mitochondria. Chromaffin granule membranes lacked specific binding sites for [3H]-nitrendipine. 2. Kinetic analysis of the rates of association and dissociation of [3H]-nitrendipine, saturation isotherms and displacement experiments with unlabelled nitrendipine and PN200-110 revealed single, homogeneous populations of high- and low-affinity sites in plasma and mitochondrial membranes, respectively. 3. The high affinity site was sensitive to Ca2+ deprivation and heating; it was practically unaffected by changes in ionic strength of the medium and its optimal pH was slightly alkaline. This site exhibited a strong DHP stereoselectivity; diltiazem increased and verapamil decreased the affinity of [3H]-nitrendipine. 4. In contrast, binding of [3H]-nitrendipine to the low affinity site was more heat resistant and less affected by Ca2+ removal. Its optimal pH was slightly acid and the increase in ionic strength enhanced the number of available sites. The site had no DHP stereoselectivity. Verapamil decreased the dissociation constant of [3H]-nitrendipine acting in a non-competitive manner; diltiazem did not affect equilibrium binding parameters of [3H]-nitrendipine. 5. These results suggest that both biding sites reflect different receptor entities. The high-affinity binding site corresponds to the dihydropyridine receptor associated with the L-type calcium channel. The function of the mitochondrial, low-affinity binding site is, at present, unknown. PMID:1704272

  20. Dopamine Inhibits Angiotensin-Stimulated Aldosterone Biosynthesis in Bovine Adrenal Cells

    PubMed Central

    Mc Kenna, Terence J.; Island, Donald P.; Nicholson, Wendell E.; Liddle, Grant W.

    1979-01-01

    The possibility that dopamine may play a role in the in vivo control of aldosterone production in man was suggested to us by reports from others; (a) that bromocriptine, a dopaminergic agonist, inhibits the aldosterone response to diuresis and to the infusion of angiotensin or ACTH; and (b) that metaclopramide, a dopamine blocking agent, causes elevations in plasma aldosterone levels. To determine whether such effects were direct or indirect, we examined the action of dopamine on aldosterone biosynthesis in isolated, bovine adrenal cells. Dopamine significantly inhibits the aldosterone response to angiotensin (P < 0.001), but does not influence basal aldosterone biosynthesis. It has previously been reported that angiotensin stimulates both the early and late phases of aldosterone biosynthesis. The present experiments demonstrated that the enhancing effect of angiotensin on the conversion of deoxycorticosterone to aldosterone (late phase of aldosterone biosynthesis) was almost completely inhibited by dopamine (P < 0.001). A significant inhibitory effect of dopamine (10 nM) was seen even when aldosterone biosynthesis was stimulated by a grossly supraphysiological concentration of angiotensin II (10 μM). However, these studies did not demonstrate any direct effect of dopamine on the early phase of aldosterone biosynthesis (cholesterol to pregnenolone) basally or when stimulated, or on the late phase of aldosterone biosynthesis under basal conditions. These in vitro studies suggest a direct inhibitory role for dopamine on the late phase of aldosterone biosynthesis, which may account for the in vivo inhibition of the aldosterone response to angiotensin in subjects treated with a dopaminergic agent. PMID:447857

  1. Isolation and characterization of a specific endogenous Na/sup +/, K/sup +/-ATPase inhibitor from bovine adrenal

    SciTech Connect

    Tamura, M.; Lam, T.T.; Inagami, T.

    1988-06-14

    In order to identify a specific endogenous Na/sup +/,K/sup +/-ATPase inhibitor which could possibly be related to salt-dependent hypertension, the authors looked for substances in the methanol extract of bovine whole adrenal which show all of the following properties: (i) inhibitory activity for Na/sup +/,K/sup +/-ATPase; (ii) competitive displacing activity against (/sup 3/H)ouabain binding to the enzyme; (iii) inhibitory activity for /sup 86/Rb uptake into intact human erythrocytes; and (iv) cross-reactivity with sheep anti-digoxin-specific antibody. After stepwise fractionation of the methanol extract of bovine adrenal glands by chromatography on a C/sub 18/ open column, a 0-15% acetonitrile fraction was fractionated by high-performance liquid chromatography on a Zorbax octadecylsilane column. One of the most active fractions in 0-15% acetonitrile was found to exhibit all of the four types of the activities. It was soluble in water and was distinct from various substances which have been known to inhibit Na/sup +/,K/sup +/-ATPase. These results strongly suggest that this water-soluble nonpeptidic Na/sup +/,K/sup +/-ATPase inhibitor may be a specific endogenous regulator for the ATPase.

  2. In vitro activation of a soluble cholesterol esterase from bovine adrenals by a cAMP-dependent protein kinase.

    PubMed

    Wallat, S; Kunau, W H

    1976-07-01

    Properties and partial purification of the bovine adrenal cholesterol esterase from the 100000 X g supernatant fraction were investigated. Variations of the enzyme activity with time-dependent (enzymatic) and time-dependent (non enzymatic) effects have been demonstrated. Mg2 has been proved to inhibit the enzyme activity by a non-enzymatic effect in 50mM Tris/HCl buffer, pH 7.4. A time-dependent inactivation of the cholesterol esterase has been observed in the same buffer. The enzyme could be protected from this enzymatic inactivation by its substrate, cholesterol oleate. cAMP, ATP and Mg2 cuase a time-dependent stimulation of the enzyme in 50mM Tris/HCl buffer, pH 7.4. This result suggests that corticotropin activates the soluble cholesterol esterase from bovine adrenals via cAMP-dependent protein kinase. This view is strengthened by the incorporation of 32P radioactivity from [gamma-32P] ATP into the protein fraction of the 100,000 X g supernatant. The protein-bound 32P radioactivity could be co-purified with the enzyme activity during the partial purification of the soluble cholesterol esterase.

  3. Electrophysiological and morphological features underlying neurotransmission efficacy at the splanchnic nerve-chromaffin cell synapse of bovine adrenal medulla.

    PubMed

    de Diego, Antonio M G

    2010-02-01

    The ability of adrenal chromaffin cells to fast-release catecholamines relies on their capacity to fire action potentials (APs). However, little attention has been paid to the requirements needed to evoke the controlled firing of APs. Few data are available in rodents and none on the bovine chromaffin cell, a model extensively used by researchers. The aim of this work was to clarify this issue. Short puffs of acetylcholine (ACh) were fast perifused to current-clamped chromaffin cells and produced the firing of single APs. Based on the currents generated by such ACh applications and previous literature, current waveforms that efficiently elicited APs at frequencies up to 20 Hz were generated. Complex waveforms were also generated by adding simple waveforms with different delays; these waveforms aimed at modeling the stimulation patterns that a chromaffin cell would conceivably undergo upon strong synaptic stimulation. Cholinergic innervation was assessed using the acetylcholinesterase staining technique on the supposition that the innervation pattern is a determinant of the kind of stimuli chromaffin cells can receive. It is concluded that 1) a reliable method to produce frequency-controlled APs by applying defined current injection waveforms is achieved; 2) the APs thus generated have essentially the same features as those spontaneously emitted by the cell and those elicited by fast-ACh perifusion; 3) the higher frequencies attainable peak at around 30 Hz; and 4) the bovine adrenal medulla shows abundant cholinergic innervation, and chromaffin cells show strong acetylcholinesterase staining, consistent with a tight cholinergic presynaptic control of firing frequency.

  4. Cloning and expression of cDNA encoding a bovine adrenal cytochrome P-450 specific for steroid 21-hydroxylation.

    PubMed Central

    White, P C; New, M I; Dupont, B

    1984-01-01

    We isolated a cDNA clone encoding a bovine adrenal cytochrome P-450 specific for steroid 21-hydroxylation (P-450C21). Serum from rabbits immunized with purified P-450C21 precipitated a single protein from the products of an in vitro translation reaction using bovine adrenal mRNA. This protein migrated with P-450C21 on NaDodSO4/polyacrylamide gel electrophoresis. After sucrose gradient sedimentation, mRNA encoding P-450C21 was found in the 19S fraction. This fraction was reverse transcribed into double-stranded cDNA and inserted into the Pst I site of pBR322 by the dC X dG tailing procedure. Escherichia coli cells transformed with recombinant plasmids were screened with an in situ immunoassay using anti-P-450C21 serum and 125I-labeled staphylococcal protein A. Two colonies consistently bound anti-P-450C21 serum. They were identified as carrying the same plasmid by restriction mapping. This plasmid, pC21a, contains an insert of 520 base pairs. It hybridizes with mRNA encoding P-450C21. The peptide encoded by the insert in pC21a is highly homologous to two peptides isolated from porcine P-450C21 and shows limited homology to the P-450 induced by phenobarbital in rat liver. This clone may be useful in studying the molecular genetics of human congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Images PMID:6609358

  5. Characterization of insulin-like growth factor I and insulin receptors on cultured bovine adrenal fasciculata cells. Role of these peptides on adrenal cell function

    SciTech Connect

    Penhoat, A.; Chatelain, P.G.; Jaillard, C.; Saez, J.M.

    1988-06-01

    We have characterized insulin-like growth factor I (IGF-I) and insulin receptors in cultured bovine adrenal cells by binding and cross-linking affinity experiments. At equilibrium the dissociation constant and the number of binding sites per cell for IGF-I were 1.4 +/- (SE) 0.3 x 10(-9) M and 19,200 +/- 2,100, respectively. Under reduction conditions, disuccinimidyl suberate cross-linked (/sup 125/I)iodo-IGF-I to one receptor complex with an Mr of 125,000. Adrenal cells also contain specific insulin receptors with an apparent dissociation constant (Kd) of 10(-9) M. Under reduction conditions (/sup 125/I)iodo-insulin binds to one band with an approximate Mr of 125,000. IGF-I and insulin at micromolar concentrations, but not at nanomolar concentrations, slightly stimulated DNA synthesis, but markedly potentiated the mitogenic action of fibroblast growth factor. Adrenal cells cultured in a serum-free medium containing transferrin, ascorbic acid, and insulin (5 micrograms/ml) maintained fairly constant angiotensin-II (A-II) receptor concentration per cell and increased cAMP release on response to ACTH and their steroidogenic response to both ACTH and A-II. When the cells were cultured in the same medium without insulin, the number of A-II receptors significantly decreased to 65% and the increased responsiveness was blunted. Treatment of such cells for 3 days with increasing concentrations of IGF-I (1-100 ng/ml) produced a 2- to 3-fold increase in A-II receptors and enhanced the cAMP response (3- to 4-fold) to ACTH and the steroidogenic response (4- to 6-fold) to ACTH and A-II. These effects were time and dose dependent (ED50 approximately equal to 10(-9) M). Insulin at micromolar concentrations produced an effect similar to that of IGF-I, but at nanomolar concentrations the effect was far less.

  6. Direct visualization of secretion from single bovine adrenal chromaffin cells by laser-induced native fluorescence imaging microscopy

    SciTech Connect

    Tong, W.; Yeung, E.S.

    1998-03-01

    Direct visualization of the secretion process of individual bovine adrenal chromaffin cells was achieved with laser-induced native fluorescence imaging microscopy. By monitoring the native fluorescence of catecholamines excited by the 275 nm laser line with an intensified charge-coupled-device (CCD) camera, we obtained good temporal and spatial resolution simultaneously without using additional fluorescent probes. Large variations were found among individual cells in terms of the amounts of catecholamines secreted and the rates of secretion. Different regions of a cell also behave differently during the secretion process. However, the degree of this local heterogeneity is smaller than in neurons and neuralgia. The influence of deep-ultraviolet (UV) laser excitation on cells is also discussed. This quantitative imaging technique provides a useful noninvasive approach for the study of dynamic cellular changes and the understanding of the molecular mechanisms of secretory processes. {copyright} {ital 1998} {ital Society for Applied Spectroscopy}

  7. Stimulatory actions of bioflavenoids on tyrosine uptake into cultured bovine adrenal chromaffin cells

    SciTech Connect

    Morita, K.; Hamano, S.; Oka, M.; Teraoka, K. )

    1990-09-28

    The effects of flavenoids on L-({sup 14}C)tyrosine uptake into cultured adrenal chromaffin cells were examined. Flavone markedly stimulated tyrosine uptake into these cells in a manner dependent on its concentration. Apigenin also caused a moderate stimulatory action, but quercetin had no significant effect on the uptake. Flavone also stimulated the uptake of histidine, but did not affect the uptake of serine, lysine, or glutamic acid. These results are considered to propose the possibility that flavonoids may be able to stimulate the precursor uptake into the cells, resulting in an enhancement of the biogenic amine production.

  8. A study of the bovine adrenal chromaffin nicotinic receptor using patch clamp and concentration-jump techniques.

    PubMed Central

    Maconochie, D J; Knight, D E

    1992-01-01

    1. Voltage clamp records have been obtained from bovine adrenal chromaffin cells in the outside-out and whole-cell configurations, in response to step changes of acetylcholine (ACh) concentration. The concentrations used ranged from 50 nM to 20 mM. 2. At high acetylcholine concentrations, the activation and desensitization kinetics of the nicotinic receptor, as observed in outside-out patches, may be described by a model incorporating a single, fast agonist binding step, and relatively slow isomerization to the open state. The affinity of the closed receptor for ACh is 310 microM, the channel opening rate constant is 460 s-1, and the closing rate constant is 29 s-1. 3. Single channel events, observed when nanomolar ACh concentrations are applied to whole cells, have two distinct channel lifetimes: 0.6 ms and 11-15 ms. The variation of the frequencies of the events with ACh concentration, suggests that the short lifetimes are openings of a singly liganded receptor and the longer lifetimes are openings of a doubly liganded receptor. 4. Only a single exponential associated with receptor desensitization is seen with outside-out patches, but two are seen with whole cells. It is postulated that there are two nicotinic receptor types present on adrenal chromaffin cells. 5. The rate of desensitization (9 s-1 and 26 s-1, whole cells; 24 s-1, patches), is fast enough to be significant in determining the open channel lifetime. 6. A sudden increase in current (rebound) is observed when a high concentration of ACh is abruptly removed from outside-out patches. This is evidence for a blocked state. The affinity of the blocking site for ACh is 1400 microM (outside-out patches). 7. The total number of activatable nicotinic channels per whole cell is estimated to be 2600. PMID:1282154

  9. Halothane inhibits the cholinergic-receptor-mediated influx of calcium in primary culture of bovine adrenal medulla cells

    SciTech Connect

    Yashima, N.; Wada, A.; Izumi, F.

    1986-04-01

    Adrenal medulla cells are cholinoceptive cells. Stimulation of the acetylcholine receptor causes the influx of Ca to the cells, and Ca acts as the coupler of the stimulus-secretion coupling. In this study, the authors investigated the effects of halothane on the receptor-mediated influx of /sup 45/Ca using cultured bovine adrenal medulla cells. Halothane at clinical concentrations (0.5-2%) inhibited the influx of /sup 45/Ca caused by carbachol, with simultaneous inhibition of catecholamine secretion. The influx of /sup 45/Ca and the secretion of catecholamines caused by K depolarization were inhibited by a large concentration of Mg, which competes with Ca at Ca channels, but not inhibited by halothane. Inhibition of the /sup 45/Ca influx by halothane was not overcome by increase in the carbachol concentration. Inhibition of the /sup 45/Ca influx by halothane was examined in comparison with that caused by a large concentration of Mg by the application of Scatchard analysis as the function of the external Ca concentration. Halothane decreased the maximal influx of /sup 45/Ca without altering the apparent kinetic constant of Ca to Ca channels. On the contrary, a large concentration of Mg increased the apparent kinetic constant without altering the maximal influx of /sup 45/Ca. Based on these findings, the authors suggest that inhibition of the /sup 45/Ca influx by halothane was not due to the direct competitive inhibition of Ca channels, nor to the competitive antagonism of agonist-receptor interaction. As a possibility, halothane seems to inhibit the receptor-mediated activation of Ca channels through the interference of coupling between the receptor and Ca channels.

  10. Muscarinic and opioid receptor modulation of release of (Met/sup 5/-enkephalin immunoreactive material and catecholamines from the bovine adrenal gland

    SciTech Connect

    Barron, B.A.

    1985-01-01

    Retrogradely perfused bovine adrenal glands were stimulated by acetylcholine (ACh) and 1,1-dimethyl-4-phenyl-piperazinium (DMPP), with or without: hexamethonium (C-6), atropine, imipramine, methacholine, pilocarpine, etorphine, or diprenorphine. Stimulation by either ACh DMPP resulted in an increased release of both (Met/sup 5/)-enkephalin immunoreactive material (ME-IRM) and catecholamines as measured by radioimmunoassay and high performance liquid chromatography with electrochemical detection, respectively. ACh (5 x 10/sup -5/ M) and DMPP (5 x 10/sup -5/ M) stimulated the release of norepinephrine greater than the release of epinephrine. The action of these agents was antagonized by C-6(5 x 10/sup -4/ M). Atropine (5 x 10/sup -7/ M) antagonized the action of ACh to stimulate norepinephrine and MI-IRM release while having no effect on DMPP-stimulated release. Imipramine (5 x 10/sup -6/ M) had no effect on either ACh or DMPP-stimulated release. Methacholine (4 x 10/sup -5/ M) potentiated the DMPP (1 x 10/sup -5/ M) stimulation of ME-IRM and catecholamine release; pilocarpine (4 x 10/sup -5/ M) significantly potentiated only the DMPP-stimulated release of norepinephrine. Pilocarpine (5 x 10/sup -5/ M) and muscarine (5 x 10/sup -5/ M) had no effect on the secretion of MI-IRM and catecholamines from the bovine adrenal gland. Etorphine (5 x 10/sup -7/ M) significantly decreased the ACh and DMPP stimulation ME-IRM and catecholamine release. The activity of a muscarinic cholinergic receptor in the bovine adrenal medulla in stimulus-secretion coupling has been controversial. The binding of /sup 3/H-quinuclidinyl benzilate to chromaffin granule membranes was investigated to further characterize muscarinic receptors in the bovine adrenal gland.

  11. Compensatory and excess retrieval: two types of endocytosis following single step depolarizations in bovine adrenal chromaffin cells

    PubMed Central

    Engisch, Kathrin L; Nowycky, Martha C

    1998-01-01

    Endocytosis following exocytosis evoked by single step depolarizations was examined in bovine adrenal chromaffin cells using high resolution capacitance measurements in perforated-patch voltage clamp recordings. Endocytosis was detected as a smooth exponential decline in membrane capacitance to either the pre-stimulus level (‘compensatory retrieval’) or far below the pre-stimulus level (‘excess retrieval’). During excess retrieval, > 10 % of the cell surface could be internalized in under 5 s. Compensatory retrieval was equal in magnitude to stimulus-evoked exocytosis for membrane additions > 100 fF (about fifty large dense-cored vesicles). In contrast, excess retrieval surpassed both the stimulus-evoked exocytosis, and the initial capacitance level recorded at the onset of phase-tracking measurements. Cell capacitance was not maintained at the level achieved by excess retrieval but slowly returned to pre-stimulus levels, even in the absence of stimulation. A large percentage of capacitance increases < 100 fF, usually evoked by 40 ms depolarizations, were not accompanied by membrane retrieval. Compensatory retrieval could occur with any amount of Ca2+ entry, but excess retrieval was never triggered below a threshold Ca2+ current integral of 70 pC. The kinetics of compensatory and excess retrieval differed by an order of magnitude. Compensatory retrieval was usually fitted with a single exponential function that had a median time constant of 5.7 s. Excess retrieval usually occurred with double exponential kinetics that had an extremely fast first time constant (median, 670 ms) and a second time constant indistinguishable from that of compensatory retrieval. The speed of compensatory retrieval was Ca2+ dependent: the largest mono-exponential time constants occurred for the smallest amounts of Ca2+ entry and decreased with increasing Ca2+ entry. The Ca2+ dependence of mono-exponential time constants was disrupted by cyclosporin A (CsA), an inhibitor of the Ca2

  12. Formation of inositol 1,3,4,6-tetrakisphosphate during angiotensin II action in bovine adrenal glomerulosa cells

    SciTech Connect

    Balla, T.; Guillemette, G.; Baukal, A.J.; Catt, K.J.

    1987-10-14

    Angiotensin II stimulates the formation of several inositol polyphosphates in cultured bovine adrenal glomerulosa cells prelabelled with (/sup 3/H) inositol. Analysis by high performance anion exchange chromatography of the inositol-phosphate compounds revealed the existence of two additional inositol tetrakisphosphate (InsP4) isomers in proximity to Ins-1,3,4,5-P4, the known phosphorylation product of Ins-1,4,5-trisphosphate and precursor of Ins-1,3,4-trisphosphate. Both of these new compounds showed a slow increase after stimulation with angiotensin II. The structure of one of these new InsP4 isomers, which is a phosphorylation product of Ins-1,3,4-P3, was deduced by its resistance to periodate oxidation to be Ins-1,3,4,6-P4. The existence of multiple cycles of phosphorylation-dephosphorylation reactions for the processing of Ins-1,4,5-P4 may represent a new aspect of the inositol-lipid related signalling mechanism in agonist-activated target cells.

  13. The rat adrenal medulla.

    PubMed

    Tischler, A S

    1989-01-01

    Adult adrenal medullary cells, in many strains of rats, develop diffuse and nodular hyperplasia and neoplasia under a variety of conditions. Both endogenous and exogenous factors affect the development of these proliferative changes. The former include the animals' strain, age, and sex. The latter include drugs and other environmental agents, diet, and perhaps stress. Adrenal medullary neoplasms which arise under diverse circumstances often closely resemble each other both morphologically and functionally, and exhibit characteristics of immature chromaffin cells. Recent data indicate that normal, mature-appearing epinephrine- and norepinephrine-type chromaffin cells are able to divide, and suggest that signals which regulate chromaffin cell function also regulate cell proliferation. Prolongation of these signals or superimposed abnormalities might initiate pathological proliferative states. It remains to be determined whether the mechanisms which promote or prevent cell proliferation in the adult adrenal are related to those involved in normal development.

  14. Characterization of a novel, hydrophilic dihydropyridine, NKY-722, as a Ca2+ antagonist in bovine cultured adrenal chromaffin cells.

    PubMed Central

    Ohue, T.; Lee, K.; Koshimura, K.; Miwa, S.

    1991-01-01

    1. To characterize NKY-722, a novel hydrophilic dihydropyridine derivative, as a Ca2+ antagonist, we examined its effects on 45Ca2+ influx, intracellular free Ca2+ concentrations [( Ca2+]i), and release of noradrenaline and adrenaline in bovine cultured adrenal chromaffin cells. 2. NKY-722 had little effect on basal 45Ca2+ influx into the resting cells, but inhibited high K+ (35.9 mM)-evoked 45Ca2+ influx in a concentration-dependent manner with an IC50 value of 5.2 nM. 3. NKY-722 inhibited high K(+)-evoked increases in [Ca2+]i in a concentration-dependent manner without effect on the resting [Ca2+]i. 4. NKY-722 had little effect on basal release of noradrenaline and adrenaline but inhibited high K(+)-evoked release of noradrenaline and adrenaline in a concentration-dependent manner with IC50 values of 5.0 nM and 4.8 nM, respectively. 5. Nicardipine, a prototype of NKY-722, also inhibited high K(+)-evoked 45Ca2+ influx and release of noradrenaline and adrenaline in a concentration-dependent manner: the IC50 value for high K(+)-evoked 45Ca2+ influx was 51 nM, and the values for high K(+)-evoked release of noradrenaline and adrenaline were 52 nM and 50 nM, respectively. 6. These results show that NKY-722 is a hydrophilic Ca2+ antagonist ten times more potent than nicardipine. PMID:1912977

  15. Effects of nonylphenol on the calcium signal and catecholamine secretion coupled with nicotinic acetylcholine receptors in bovine adrenal chromaffin cells.

    PubMed

    Liu, Pei-Shan; Liu, Ging-Hui; Chao, Wei-Liang

    2008-02-03

    Nonylphenol (NP) is the most critical metabolite of alkylphenol polyethoxylate detergents. NP is known as an endocrine disruptor with estrogenic activities and as an inhibitor of endoplasmic reticulum Ca(2+)-ATPase. Estrogen has modulatory roles on ligand-gated ion channels, such as nicotinic acetylcholine receptors (nAChRs). Ca(2+)-ATPase inhibitors can modulate the cytosolic calcium concentration ([Ca(2+)](c)]) and thus can affect the calcium signaling coupled with nAChRs. Therefore, NP is predicted to have complex effects on the Ca(2+) signaling and secretion coupled with nAChRs. This study investigated these effects using bovine adrenal chromaffin cells. The results show that NP suppressed the Ca(2+) signaling coupled with nAChRs and voltage-operated Ca(2+) channels in a dose-dependent manner, with IC(50)s of 1 and 5.9 microM, respectively. Estradiol exhibits similar suppression but much lower inhibitory potencies. NP alone induced a transient rise in [Ca(2+)](c) in the presence or absence of extracellular calcium. Thapsigargin, an endoplasmic reticulum Ca(2+)-ATPase inhibitor, partially suppressed the [Ca(2+)](c) rise induced by NP, but NP totally blocked the [Ca(2+)](c) rise induced by thapsigargin. This illustrates that NP can cause Ca(2+) release from thapsigargin-insensitive pools. Thapsigargin suppressed the Ca(2+) signaling coupled with nAChRs but increased that coupled with voltage-operated Ca(2+) channels. We propose that three routes are responsible for the effects of NP on nAChRs: named receptor channels, voltage-gated Ca(2+) channels, and Ca(2+)-induced Ca(2+) release. Three routes are related to the characteristics of NP as steroid-like compounds and Ca(2+)-ATPase inhibitor.

  16. Hypertension and adrenal disorders.

    PubMed

    Blumenfeld, J D

    1993-03-01

    Abnormalities of adrenal cortical and medullary function are important causes of hypertension in adults. Mineralocorticoid hypertension, characterized by spontaneous hypokalemia with excessive kaliuresis and low plasma renin activity, is most commonly caused by aldosterone-producing adenoma or, less frequently, by nonadenomatous adrenal hyperplasia. However, recent evidence indicates that this classification oversimplifies the pathophysiologic diversity of this syndrome. Advances in steroid biochemistry and molecular biology have improved our ability to identify patients with various forms of mineralocorticoid hypertension and also provide evidence that they are underdiagnosed. Pheochromocytomas are most commonly located in the adrenal medulla, where they may overproduce norepinephrine or epinephrine. Appropriate screening of norepinephrine, epinephrine, and their metabolites is essential because tumors that secrete epinephrine exclusively may not present with hypertension and, thus, can be overlooked. Extra-adrenal pheochromocytomas are more prevalent than previously considered and pose special problems because they may be multicentric, difficult to locate, and more likely to be malignant than are adrenal pheochromocytomas.

  17. Adrenal imaging (Part 1): Imaging techniques and primary cortical lesions

    PubMed Central

    Panda, Ananya; Das, Chandan J.; Dhamija, Ekta; Kumar, Rakesh; Gupta, A. K.

    2015-01-01

    Adrenal glands can be affected by a variety of lesions. Adrenal lesions can either be primary, of adrenal origin, or secondary to other pathologies. Primary adrenal lesions can further be either of cortical or medullary origin. Functioning adrenal lesions can also give clues to the histologic diagnosis and direct workup. Over the years, various imaging techniques have been developed that have increased diagnostic accuracy and helped in better characterization of adrenal lesions non-invasively. In the first part of the two part series, we review adrenal imaging techniques and adrenal cortical tumors such as adenomas, adrenocortical tumors, adrenal hyperplasia and oncocytomas. PMID:25593820

  18. 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 ...

  19. Detection of disease-associated prion protein in the optic nerve and the adrenal gland of cattle with bovine spongiform encephalopathy by using highly sensitive immunolabeling procedures.

    PubMed

    Okada, Hiroyuki; Iwamaru, Yoshifumi; Fukuda, Shigeo; Yokoyama, Takashi; Mohri, Shirou

    2012-04-01

    A sensitive immunohistochemical procedure, the tyramide signal amplification (TSA) system, was applied to detect the localization of immunolabeled disease-associated prion protein (PrP(Sc)) in cattle affected with bovine spongiform encephalopathy (BSE). In this procedure, immunolabeling could be visualized in the optic nerve and the adrenal medulla. In the optic nerve, the dual immunofluorescent technique showed that the granular PrP(Sc) was occasionally detected in the astrocytes, microglia, and myelin sheath adjacent to the axon. Clustered PrP(Sc) was also scattered in association with microglial cells and astrocytes of the optic nerve. In the adrenal gland, PrP(Sc) immunolabeling was confined within the sympathetic nerve fibers and endings. The results suggest that (1) PrP(Sc) might centrifugally spread within and between glial cells and/or the non-axonal (also known as ad-axonal) region of nerve fibers, rather than the axonal and/or extracellular space pathway in the optic nerve, and (2) the sympathetic innervations might be important for the trafficking of BSE agent in the adrenal glands of cattle. This study also suggests that tyramide-based immunochemical analysis should be performed to detect immunolabeled PrP(Sc) in the extracerebral tissues of BSE-affected cattle.

  20. Detection of Disease-associated Prion Protein in the Optic Nerve and the Adrenal Gland of Cattle with Bovine Spongiform Encephalopathy by Using Highly Sensitive Immunolabeling Procedures

    PubMed Central

    Iwamaru, Yoshifumi; Fukuda, Shigeo; Yokoyama, Takashi; Mohri, Shirou

    2012-01-01

    A sensitive immunohistochemical procedure, the tyramide signal amplification (TSA) system, was applied to detect the localization of immunolabeled disease-associated prion protein (PrPSc) in cattle affected with bovine spongiform encephalopathy (BSE). In this procedure, immunolabeling could be visualized in the optic nerve and the adrenal medulla. In the optic nerve, the dual immunofluorescent technique showed that the granular PrPSc was occasionally detected in the astrocytes, microglia, and myelin sheath adjacent to the axon. Clustered PrPSc was also scattered in association with microglial cells and astrocytes of the optic nerve. In the adrenal gland, PrPSc immunolabeling was confined within the sympathetic nerve fibers and endings. The results suggest that (1) PrPSc might centrifugally spread within and between glial cells and/or the non-axonal (also known as ad-axonal) region of nerve fibers, rather than the axonal and/or extracellular space pathway in the optic nerve, and (2) the sympathetic innervations might be important for the trafficking of BSE agent in the adrenal glands of cattle. This study also suggests that tyramide-based immunochemical analysis should be performed to detect immunolabeled PrPSc in the extracerebral tissues of BSE-affected cattle. PMID:22260993

  1. Differential effects of heparin on inositol 1,4,5-trisphosphate binding, metabolism, and calcium release activity in the bovine adrenal cortex.

    PubMed

    Guillemette, G; Lamontagne, S; Boulay, G; Mouillac, B

    1989-03-01

    In a wide variety of cells, inositol-1,4,5-triphosphate is a second messenger that interacts with specific intracellular receptors and triggers the release of sequestered Ca2+ from an intracellular store. We have looked at the influence of heparin on the action and metabolism of inositol-1,4,5-triphosphate in the bovine adrenal cortex. Heparin blocked inositol-1,4,5-trisphosphate binding with half-maximal efficiency around 10 micrograms/ml. Scatchard analyses revealed that heparin did not change the affinity but decreased the number of available binding sites. The Ca2+-releasing activity of inositol-1,4,5-trisphosphate was monitored with the fluorescent indicator, fura-2. Heparin blocked this activity with half-maximal effeciency around 10 micrograms/ml. The effect of heparin could be overcome by a supramaximal dose of inositol-1,4,5-trisphosphate (25 microM). The activity of inositol-1,4,5-trisphosphate-3-kinase from bovine adrenal cortex cytosol was also studied. Heparin inhibited the activity of the kinase with a half-maximal effeciency around 0.4 microgram/ml. Lineweaver-Burk plots revealed that this potent effect was noncompetitive. Finally, we observed that heparin is without effect on inositol-1,4,5-trisphosphate-5-phosphatase (at concentrations as high as 2 mg/ml). These results are consistent with the suggestion that the binding sites for inositol-1,4,5-trisphosphate are the intracellular receptors responsible for the Ca2+-mobilizing effects of inositol-1,4,5-trisphosphate. These results also show that the kinase, the phosphatase, and the receptor are three different molecular entities, which are affected in a different manner by heparin.

  2. The adrenal medulla and Parkinson's disease.

    PubMed

    Stoddard, S L

    1994-01-01

    This paper reviews the literature describing the condition of the adrenal medulla in Parkinson's disease. Parkinson's disease is a neurodegenerative disorder that is characterized primarily by the loss of dopaminergic neurons in the substantia nigra. Clinical observations have revealed that Parkinson's disease is also frequently accompanied by a variety of autonomic symptoms. The adrenal medulla is a major component of the autonomic nervous system. However, until recently this organ has not been of particular interest in Parkinson's disease. Early studies found histologic abnormalities in adrenal medullary cells, and several groups measured urinary and plasma catecholamines to determine general autonomic status. In the late 1980s adrenal medullary tissue was first transplanted to the caudate nucleus in an attempt to augment the decreased levels of dopamine, and thus treat the symptoms of Parkinson's disease. At this time the status of the adrenal medulla in this disease became clinically important. We measured the total catecholamine content of the parkinsonian adrenal medulla in tissue collected both at autopsy and in conjunction with adrenal-caudate transplants. Adrenal medullary catecholamines and several neuropeptides were severely depressed in parkinsonian glands. Thus, the adrenal medulla appears to be a target of the peripheral manifestations of Parkinson's disease.

  3. Mas-related G-protein-coupled receptor c agonist bovine adrenal medulla 8-22 attenuates bone cancer pain in mice

    PubMed Central

    Sun, Yu-E; Lu, Cui-E; Lei, Yishan; Liu, Yue; Ma, Zhengliang; Gu, Xiaoping

    2015-01-01

    Objectives: The aim of this study is to investigate the effects of Mas-related G-protein-coupled receptor C (MrgC) agonist bovine adrenal medulla 8-22 (BAM8-22) on bone cancer pain and mirror-image pain. Methods: Bone cancer pain was induced by intramedullary injection of NC2472 fibrosarcoma cells in the mice. BAM8-22 and/or anti-MrgC antibody were injected intrathecally at day 14 after bone cancer induction and their effects on pain behaviors were detected. The pain behaviours were assessed by the number of spontaneous foot lifts and paw withdrawal mechanical threshold (PWMT) tests. MrgC expression was detected using western blot analysis and immunofluorescence assay. Results: There were increased bone cancer pain and mirror-image pain in the tumor-bearing mice while not in the sham-treated mice. BAM8-22 attenuated bone cancer pain in mice dose dependently with the highest effects at 2 hr after BAM8-22 administration, and anti-MrgC antibody reversed the effects of BAM8-22. However, intrathecal administration of BAM8-22 did not affect the mirror-image pain. Furthermore, BAM8-22 stimulated the expression of MrgC in the spinal dorsal horn. Conclusions: MrgC agonist BAM8-22 could attenuate bone cancer pain in mice. This study may provide a novel strategy for the treatment of bone cancer pain. PMID:26884930

  4. [Characteristics of steroid metabolism in transgenic Nicotiana tabacum plants bearing the CYP11A1 cDNA of cytochrome P450(SCC) from the bovine adrenal cortex].

    PubMed

    Spivak, S G; Berdichevets, I N; Litvinovskaia, R P; Drach, S V; Kartel', N A; Shpakovskiĭ, G V

    2010-01-01

    In the mitochondria of animal steroidogenic tissues, cytochrome P450(SCC), encoded by the CYP11A1 gene, catalyzes the conversion of cholesterol into pregnenolone - the general precursor of all steroid hormones. In this work, we study the steroid metabolism in transgenic tobacco plants carrying the CYP11A1 cDNA cytochrome P450(SCC)from the bovine adrenal cortex. The transgenic plants under investigation markedly surpass the control wild-type plants by size and are characterized by a shortened period of vegetative growth (by rapid flowering); their leaves contain pregnenolone - the product of a reaction catalyzed by cytochrome P450(SCC). The level of progesterone in transgenic tobacco leaves is higher than in the control plants of the wild type. The seeds of the transgenic plants contain less (24R)-brassinosteroids than the wild-type tobacco plants. The results obtained indicate that the synthesis of an active P450(SCC) cytochrome in transgenic Nicotiana tabacum plants has a profound effect on steroid metabolism and is responsible for the specific phenotypic features of transgenic plants bearing CYP11A1 cDNA.

  5. 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.

  6. Adrenocortical hemorrhagic necrosis: the role of catecholamines and retrograde medullary-cell embolism

    SciTech Connect

    Szabo, S.; McComb, D.J.; Kovacs, K.; Huettner, I.

    1981-10-01

    We investigated the pathogenesis of adrenal necrosis using animal models of the disease (induced by administration of acrylonitrile, cysteamine, or pyrazole) and human cases. Results of electron-microscopic and histochemical time-response studies with rat models revealed an early, retrograde embolization of medullary cells and cell fragments in the cortical capillaries that showed prominent endothelial injury. The experimental adrenal lesions were prevented by surgical removal of the medulla one month before administration of adrenocorticolytic chemicals, or by the administration of the alpha-adrenergic antagonist phenoxybenzamine hydrochloride. Histochemical staining for medullary (argyrophil) granules in human cases of adrenal necrosis demonstrated tissue fragments that stained positively for silver in vascular cortical spaces in nine of ten autopsy specimens and in all four surgical cases we reviewed. Thus, catecholamines released from the adrenal medulla and from the retrograde medullary emboli in the cortex may have a role in the pathogenesis of adrenocortical necrosis.

  7. Bradshaw lecture, 1976. Thyroid medullary carcinoma.

    PubMed Central

    Taylor, S.

    1977-01-01

    The main characteristics of medullary carcinoma of the thyroid are its non-follicular histological appearance, resulting from its origin from the parafollicular C cells, its secretion of calcitonin, providing a relatively simple diagnostic test, and its equal sex incidence, in contrast to all other diseases of the thyroid. Sporadic cases are seen and it occurs in familial groups, with autosomal dominant inheritance, when it is associated with phaeochromocytoma and parathyroid hyperplasia to form the second type of multiple endocrine adenomatosis (MEA2). These last features make it necessary in every case of medullary carcinoma of the thyroid to examine other members of the family and to investigate the possibility of concomitant adrenal and parathyroid disease. The priorities of treatment when these are present and the indications for total thyroidectomy are discussed. Images Fig. 1 PMID:20027

  8. Frequency of varicella zoster virus DNA in human adrenal glands.

    PubMed

    Badani, Hussain; White, Teresa; Schulick, Nicole; Raeburn, Christopher D; Topkaya, Ibrahim; Gilden, Don; Nagel, Maria A

    2016-06-01

    Varicella zoster virus (VZV) becomes latent in ganglionic neurons derived from neural crest cells. Because the adrenal gland also contains medullary chromaffin cells of neural crest origin, we examined human adrenal glands and medullary chromaffin cell tumors (pheochromocytomas) for VZV and herpes simplex virus type 1 (HSV-1). We found VZV, but not HSV-1, DNA in 4/63 (6 %) normal adrenal glands. No VZV transcripts or antigens were detected in the 4 VZV DNA-positive samples. No VZV or HSV-1 DNA was found in 21 pheochromocytomas.

  9. Properties of soluble and membrane bound dopamine-beta-monooxygenase from bovine adrenal medulla cross-linked with dimethyl suberimidate.

    PubMed

    Miras-Portugal, M T; Millaruelo, A; Vara, F

    1980-12-10

    Bovine dopamine-beta-monooxygenase from chromaffin granules in its soluble and membrane-bound forms was cross-linked with the bifunctional reagent dimethyl suberimidate, and its structural and kinetic properties were studied. 1. The cross-linking reaction does not affect the activity of soluble dopamine-beta-monooxygenase; it produces a ten percent inactivation in the membrane-bound enzyme, possibly because the linkage to other membrane proteins hinders its activity. 2. The soluble dopamine-beta-monooxygenase reaction mixture was analyzed by sodium dodecyl sulfate gel electrophoresis, showing appreciable amounts of dimer and tetramer, but only small amounts of trimer. In membrane-bound dopamine-beta-monooxygenase, subjected to the same treatment, appreciable amounts of dimer and higher aggregates were found. 3. The kinetic properties of soluble dopamine-beta-monooxygenase after the crosslinking reaction are the same as those of the native enzyme, with a ping-pong kinetic mechanism and the same real Michaelis constants for tyramine and ascorbate: KmT = 0.36 mM and KmA = 0.32 mM. Membrane-bound dopamine-beta-monooxygenase does not present a ping-pong mechanism before or after cross-linking; its real Michaelis constants are slightly modified by the cross-linking reaction: KmT = 0.4 mM and KMA = 0.4 mM.

  10. Adrenal glands

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002219.htm Adrenal glands To use the sharing features on this page, please enable JavaScript. The adrenal glands are two triangle-shaped glands. One gland is ...

  11. Adrenal insufficiency.

    PubMed

    Auron, Moises; Raissouni, Nouhad

    2015-03-01

    Adrenal insufficiency is a life-threatening condition that occurs secondary to impaired secretion of adrenal glucocorticoid and mineralocorticoid hormones. This condition can be caused by primary destruction or dysfunction of the adrenal glands or impairment of the hypothalamic-pituitary-adrenal axis. In children, the most common causes of primary adrenal insufficiency are impaired adrenal steroidogenesis (congenital adrenal hyperplasia) and adrenal destruction or dysfunction (autoimmune polyendocrine syndrome and adrenoleukodystrophy), whereas exogenous corticosteroid therapy withdrawal or poor adherence to scheduled corticosteroid dosing with long-standing treatment constitute the most common cause of acquired adrenal insufficiency. Although there are classic clinical signs (eg, fatigue, orthostatic hypotension, hyperpigmentation, hyponatremia, hyperkalemia, and hypoglycemia) of adrenal insufficiency, its early clinical presentation is most commonly vague and undefined, requiring a high index of suspicion. The relevance of early identification of adrenal insufficiency is to avoid the potential lethal outcome secondary to severe cardiovascular and hemodynamic insufficiency. The clinician must be aware of the need for increased corticosteroid dose supplementation during stress periods.

  12. Conus medullaris stroke

    PubMed Central

    Alanazy, Mohammed H.

    2016-01-01

    Absent F wave in the stage of spinal shock has been described in cases of traumatic spinal cord injury. The role of F wave in predicting prognosis after conus medullaris infarct has not been described. We describe herein a middle aged-man with a conus medullaris infarct. Both tibial and peroneal F waves were absent on day 4. The left tibial F wave reappeared in the following study on day 18. All F waves reappeared on day 56 at which time the patient was still wheelchair bound. He regained walking on day 105. We hypothesize that reappearance of initially absent F waves post conus medullaris infarct is a good prognostic sign for the return of ambulation. The applicability of this observation requires further research. We also discuss clinical and diagnostic caveats in this case. PMID:27356660

  13. Adrenal autotransplantation.

    PubMed

    Srougi, M; Gittes, R F

    1978-04-01

    New tools for the diagnosis of adrenal diseases and the development of successful techniques to treat patients with bilateral tumors of the kidney have increased the number of procedures involving removal of both adrenals. Offering to these patients an adrenal autograft represents more than a superfluous medical exercise, since a successful outcome of the graft will relieve them of the burdens and risks of long-term postoperative steroid replacement therapy. The aim of this review is to bring to mind the possibility of autografting adrenal glands in some clinical situations and to emphasize some points that could be relevant in obtaining successful results. The available data justify clinical trials with the procedure.

  14. [Pheochromocytomas as adrenal gland incidentalomas].

    PubMed

    Cerović, Snezana; Cizmić, Milica; Milović, Novak; Ajdinović, Boris; Brajusković, Goran

    2002-07-01

    Adrenal incidentalomas are a heterogeneous group of pathological entities, including benign or malignant adrenocortical or medullary tumors, hormonally active or inactive lesions, which are identified incidentally during the examination of nonadrenal-related abdominal complaints. About 1.5% to 23% of adrenal incidentalomas are pheochromocytomas. Composite pheochromocytoma is a rare tumour of adrenal medulla with divergente clinical course. This type of pheochromocytoma is designated "composite" or "mixed," depending on whether pheochromocytoma and nonpheochromocytoma components show the same embryologic origin. Nonpheochromocytoma components found in the composite pheochromocytoma include ganglioneuroma, ganglioneuroblastoma, neuroblastoma, and malignant schwannoma. The biologic behavior of composite pheochromocytomas may be as difficult to predict as more traditional pheochromocytomas; based on the number of cases reported to date the presence of areas resembling ganglioneuroblastoma or neuroblastoma does not necessary indicate a poor prognosis. Some may behave in a malignant fashion with metastasis by a component of the tumour which has neural features. Pheochromocytomas and paragangliomas are well-defined entities. Some of their nonsporadic associations and unusual morphological appearances are not universally appreciated. We report on a rare association of left adrenal CP, with typical right adrenal phochromocytoma and retroperitoneal paraganglioma, and a review of literature. We analyzed the clinical and immunohistochemical features in a 24-year-old woman with composite pheochromocytoma localized in the left adrenal gland and associated with blood pressure of 200/140 mmHg. Abdominal computed tomography and 131-J MIBG revealed a 65 x 60 mm mass in the right adrenal gland, but no revealed 45 x 40 mm retroperitoneal mass and 20 x 20 mm mass in the left adrenal region. Serum and urinary adrenaline levels were high, and catecholamine levels in the blood sample of

  15. 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 ...

  16. 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.

  17. Renal Medullary Interstitial Cells

    NASA Astrophysics Data System (ADS)

    Rao, Reena; Hao, Chuan-Ming; Breyer, Matthew D.

    2007-04-01

    Renal medullary interstitial cells (RMICs) are specialized fibroblast-like cells that reside in the renal medulla among the vasa recta, the thin limbs of Henle's loop, and medullary collecting ducts. These cells are characterized by abundant lipid droplets in the cytoplasm. The lipid droplets are composed of triglycerides, cholesterol esters and free long-chain fatty acids, including arachidonic acid. RMICs are also a major site of cyclooxygenase2 (COX-2) expression, and thus a major site of COX-2 derived prostanoid biosynthesis. RMICs are also a potential target of hormones such as angiotensin II and endothelin. The RMIC COX-2 expression and the abundance of lipid droplets change with salt and water intake. These properties of RMICs are consistent with an important role of these cells in modulating physiologic and pathologic processes of the kidney.

  18. Adipose tissue and adrenal glands: novel pathophysiological mechanisms and clinical applications.

    PubMed

    Kargi, Atil Y; Iacobellis, Gianluca

    2014-01-01

    Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unknown whether these changes in adrenal endocrine function are in part responsible for the pathogenesis of obesity and related comorbidities or represent an adaptive response. In turn, adipose tissue hormones or "adipokines" have direct effects on the adrenal glands and interact with adrenal hormones at several levels. Here we review the emerging evidence supporting the existence of "cross talk" between the adrenal gland and adipose tissue, focusing on the relevance and roles of their respective hormones in health and disease states including obesity, metabolic syndrome, and primary disorders of the adrenals.

  19. Diagnosis of adrenal tumors with radionuclide imaging

    SciTech Connect

    Beierwaltes, W.H.; Sisson, J.C.; Shapiro, B.

    1984-01-01

    The development of radiolabeled cholesterols in 1969 as precursors of adrenocortical steroid production allowed the first noninvasive imaging of the adrenal cortices. FDA-NDA approval in 1984 should allow routine use of these agents in most hospitals. NP-59 is most commonly used in the diagnosis and management of Cushing syndrome; the second most common use is in the diagnosis of primary aldosteronism. It is also helpful in the differential diagnosis of adrenal and ovarian hyperandrogenism and hirsutism, and is the only noninvasive method of detecting unilateral adrenocortical hypofunction. The newest and most popular use is in the differential diagnosis of asymptomatic masses in the region of the adrenal gland discovered incidentally with CT scan (incidentalomas). In this situation, the NP-59 scan can define whether the tumor is in the adrenal gland and if it is functional or nonfunctional. The authors believe that, in the future, radiolabeled enzyme inhibitors might offer better diagnostic imaging of the adrenal cortex, although these agents will probably not be available for routine use for some time. The development of a radioiodinated guanethidine analog, /sup 131/I-MIBG, has allowed differentiation of normal adrenal medullary function from bilateral adrenal medullary hyperplasia before the development of hypertension or tachycardia, diagnostic increases in plasma or urinary catecholamines, or abnormal CT scans. The search for a pheochromocytoma should begin with /sup 131/I-MIBG scintigraphy. While over 90% of primary pheochromocytomas occur in the abdomen, neither a survey of the abdomen nor the finding of a single tumor should conclude the search.

  20. Stimulation of catecholamine synthesis through unique estrogen receptors in the bovine adrenomedullary plasma membrane by 17{beta}-estradiol

    SciTech Connect

    Yanagihara, Nobuyuki . E-mail: yanagin@med.uoeh-u.ac.jp; Liu, Minhui; Toyohira, Yumiko; Tsutsui, Masato; Ueno, Susumu; Shinohara, Yuko; Takahashi, Kojiro; Tanaka, Kazumi

    2006-01-13

    Incubation of cultured bovine adrenal medullary cells with 17{beta}-estradiol (E{sub 2}) (0.3-100 nM) or membrane-impermeable E{sub 2}-bovine serum albumin (100 nM) acutely increased {sup 14}C-catecholamine synthesis from [{sup 14}C]tyrosine. The stimulatory effect of E{sub 2} was not inhibited by ICI182,780, a nuclear estrogen receptor inhibitor. E{sub 2} also increased tyrosine hydroxylase activity and p44/42MAPK phosphorylation, the former of which was attenuated by U0126, an inhibitor of p44/42MAPK kinase. The plasma membrane isolated from the gland showed two classes of specific binding sites of [{sup 3}H]E{sub 2} with apparent K {sub d}s of 3.2 and 106 nM, and B {sub max}s of 0.44 and 8.5 pmol/mg protein, respectively. The high-affinity binding of [{sup 3}H]E{sub 2} was most strongly inhibited by E{sub 2} and phytoestrogens, and to lesser extents by other steroid hormones, while it was enhanced by ICI182,780 and environmental estrogenic pollutants. These findings suggest that E{sub 2} acutely stimulates catecholamine synthesis via activation of p44/42MAPK through unique estrogen receptors in the plasma membrane of bovine adrenal medulla.

  1. [Adrenal mass and adrenal insufficiency].

    PubMed

    Martínez Albaladejo, M; García López, B; Serrano Corredor, S; Alguacil García, G

    1996-12-01

    Primary adrenal insufficiency is a non frequent disease, that is declared in young adults and in the most of the cases is produced from an autoimmune mechanism or a tuberculous disease. The incidence of these forms in the different geographic areas is dependent of degree of irradication of the tuberculosis. We report the case of a patient with latent chronic adrenal insufficiency of tuberculous origin who was affected for an addisonian crisis during an intercurrent infectious disease, which permitted the diagnosis of the addisonian crisis, and Mal of Pott was moreover detected. Evolution with corticosteroid and specific treatment was very favorable.

  2. Medullary thyroid carcinoma.

    PubMed

    Leboulleux, Sophie; Baudin, Eric; Travagli, Jean-Paul; Schlumberger, Martin

    2004-09-01

    Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells that produce calcitonin (CT), and accounts for 5-10% of all thyroid cancers. MTC is hereditary in about 25% of cases. The discovery of a MTC in a patient has several implications: disease extent should be evaluated, phaeochromocytoma and hyperparathyroidism should be screened for and whether the MTC is sporadic or hereditary should be determined by a direct analysis of the RET proto-oncogene. In this review, pathological characteristics, tumour markers and genetic abnormalities in MTC are discussed. The diagnostic and therapeutic modalities applied to patients with clinical MTC and those identified with preclinical disease through familial screening are also described. Progresses concerning genetics, initial treatment, follow-up, screening and treatment of pheochromocytoma have permitted an improvement in the long-term outcome. However, there is no effective treatment for distant metastases, and new therapeutic modalities are urgently needed.

  3. Three siblings with familial non-medullary thyroid carcinoma: a case series.

    PubMed

    Rashid, Muhammad Owais; Haq, Naeemul; Farooq, Saad; Kiran, Zareen; Siddique, Sabeeh; Pervez, Shahid; Islam, Najmul

    2016-08-02

    In 2015, thyroid carcinoma affected approximately 63,000 people in the USA, yet it remains one of the most treatable cancers. It is mainly classified into medullary and non-medullary types. Conventionally, medullary carcinoma was associated with heritability but increasing reports have now begun to associate non-medullary thyroid carcinoma with a genetic predisposition as well. It is important to identify a possible familial association in patients diagnosed with non-medullary thyroid carcinoma because these cancers behave more destructively than would otherwise be expected. Therefore, it is important to aggressively manage such patients and screening of close relatives might be justified. Our case series presents a diagnosis of familial, non-syndromic, non-medullary carcinoma of the thyroid gland in three brothers diagnosed over a span of 6 years. We report the history, signs and symptoms, laboratory results, imaging, and histopathology of the thyroid gland of three Pakistani brothers of 58 years, 55 years, and 52 years from Sindh with non-medullary thyroid carcinoma. Only Patients 1 and 3 had active complaints of swelling and pruritus, respectively, whereas Patient 2 was asymptomatic. Patients 2 and 3 had advanced disease at presentation with lymph node metastasis. All patients underwent a total thyroidectomy with Patients 2 and 3 requiring a neck dissection as well. No previous exposure to radiation was present in any of the patients. Their mother had died from adrenal carcinoma but also had a swelling in the front of her neck which was never investigated. All patients remained stable at follow-up. Non-medullary thyroid carcinoma is classically considered a sporadic condition. Our case report emphasizes a high index of suspicion, a detailed family history, and screening of first degree relatives when evaluating patients with non-medullary thyroid carcinoma to rule out familial cases which might behave more aggressively.

  4. 3 Beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase from bovine adrenals: mechanism of inhibition by 3-oxo-4-aza steroids and kinetic mechanism of the dehydrogenase.

    PubMed

    Brandt, M; Levy, M A

    1989-01-10

    Several 3-oxo-4-aza steroids (1) have been identified as inhibitors of the 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase catalyzed conversion of pregnenolone to progesterone. By kinetically decoupling the two enzyme activities isolated from bovine adrenal cortex, it has been demonstrated that inhibition by 1 occurs through interference of both activities. A preferred ordered association of substrates to the 3 beta-hydroxy-delta 5-steroid dehydrogenase in which the cofactor binds prior to steroid was determined by isotope exchange at equilibrium. With this result, the dead-end inhibition patterns of 1 with the dehydrogenase were interpreted to originate from a preferred association of inhibitor within an enzyme ternate containing NADH; this proposal is supported by data from multiple inhibition analysis indicating synergistic binding of NADH and 1. Similarly, inhibition of the 3-keto-delta 5-steroid isomerase by the 3-oxo-4-aza steroids was enhanced in the presence of the positive effector NADH. On the basis of pH profiles upon Vm, Vm/Km, and 1/Ki for both enzyme activities, inhibition is proposed to result from the structural similarity of 1 to intermediate states formed upon enzyme catalysis.

  5. Medullary sponge kidney.

    PubMed

    Gambaro, Giovanni; Danza, Francesco M; Fabris, Antonia

    2013-07-01

    After it was first described in 1939, medullary sponge kidney (MSK) received relatively little attention. This was because it was believed to have a low prevalence and because it was considered a benign condition. Studies in recent years have been changing these convictions however, hence the present review. Insight has been obtained on the genetic basis of this disease, supporting the hypothesis that MSK is due to a disruption at the 'ureteric bud-metanephric mesenchyme' interface. This explains why so many tubular defects coexist in this disease, and particularly a distal tubular acidification defect of which the highly prevalent metabolic bone disease is one very important consequence. In addition to the typical clinical phenotype of recurrent stone disease, other clinical profiles have now been recognized, that is, an indolent, almost asymptomatic MSK, and a rare form characterized by intractable, excruciating pain. Findings suggest the need for a more comprehensive clinical characterization of MSK patients. The genetic grounds for the condition warrant further investigation, and reliable methods are needed to diagnose MSK.

  6. Pediatric Medullary Thyroid Carcinoma.

    PubMed

    Starenki, Dmytro; Park, Jong-In

    Medullary thyroid carcinoma (MTC), which originates from thyroid parafollicular C cells, accounts for 3 to 5% of thyroid malignancies. MTC occurs either sporadically or in an inherited autosomal dominant manner. Hereditary MTC occurs as a familial MTC or as a part of multiple endocrine neoplasia (MEN) type 2A and B syndromes. A strong genotype-phenotype correlation has been observed between hereditary MTC and germ-line "gain of function" mutations of the RET proto-oncogene. Most cases of pediatric MTC are hereditary whereas sporadic MTC is rare in children and is usually diagnosed in adults. Therefore, MTC in children is most often diagnosed in the course of a familial genetic investigation. The standard treatment of MTC mainly requires surgery involving total thyroidectomy and central neck node dissection before extrathyroidal extension occurs. To prevent MTC development in hereditary syndromes, prophylactic thyroidectomy is performed in presymptomatic patients. An appropriate age at which the surgery should take place is determined based upon the data from genotyping, serum calcitonin measurements, and ultrasonography. For the treatment of advanced MTC cases, the broad spectrum receptor tyrosine kinase inhibitors vandetanib and cabozantinib, which also inhibit RET, are used although they are not always effective.

  7. Renal Medullary Carcinoma; A Rare Entity

    PubMed Central

    Çalışkan, Selahattin; Gökçe, Ali Murat; Gümrükçü, Gülistan; Önenerk, Mine

    2017-01-01

    Renal medullary carcinoma (RMC) is an uncommon aggressive neoplasm of the kidney. RMC is biologically aggressive with a very poor prognosis, and metastasis is seen in up to 95% of the patients at diagnosis or shortly thereafter. The common sites of metastasis are respectively lymph nodes, lungs, livers, and adrenal glands in order of frequency. The presence of poorly differentiated eosinophilic cells in a characteristic fibro-inflammatory stroma is seen in histological examination. The origin and pathogenesis of RMC are unclear. The radiographical and pathological findings suggest that RMC probably originates in the calyceal epithelium in or near the renal papillae, which could be the result of chronic ischemic damage in the renal papillae epithelium by sickled erythrocytes. Positivity of VEGF and HIF-1α supports the chronic hypoxia that may be caused in the pathogenesis of RMC. Other factors such as genetic or environmental factors are important. Although hemoglobinopathy is very common, RMC is very rare. An understanding of the molecular and genetic factors of this rare disease is important for its prevention and treatment. We herein describe an adult Turkish patient, who presented with hematuria. The diagnosis was RMC after pathological examination. PMID:28360450

  8. Involvement of adrenal medulla grafts in the open field behavior.

    PubMed

    Jousselin-Hosaja, M; Venault, P; Tobin, C; Joubert, C; Delacour, J; Chapouthier, G

    2001-06-01

    Immunohistochemical and behavioral techniques were used to study the effects of adrenal medulla grafts, implanted in striatum after bilateral kainic acid (KA) lesions of this structure, on the open field behavior of mice. KA-induced behavioral changes in leaning, grooming and locomotor activity of the open field test were significantly improved after grafting of the adrenal medulla, and in some respects, fully restored. Immunohistochemical identification showed that grafts contained neuron-like cells with a tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase, gamma-aminobutyric acid (GABA), choline acetyltransferase (ChAT), and enkephalin-like immunostainings. A likely interpretation of this complex pattern of results is that adrenal medullary grafts may restore the deficits of GABAergic neurons which in turn reverse the abnormalities in emotionality and locomotion. Neurobiologically, these behavioral improvements probably involve GABAergic and catecholaminergic factors of adrenal medulla grafts, although other neuroactive substances, such as acetylcholine and enkephalins, cannot be excluded.

  9. Primary structure of bovine pituitary secretory protein I (chromogranin A) deduced from the cDNA sequence

    SciTech Connect

    Ahn, T.G.; Cohn, D.V.; Gorr, S.U.; Ornstein, D.L.; Kashdan, M.A.; Levine, M.A.

    1987-07-01

    Secretory protein I (SP-I), also referred to as chromogranin A, is an acidic glycoprotein that has been found in every tissue of endocrine and neuroendocrine origin examined but never in exocrine or epithelial cells. Its co-storage and co-secretion with peptide hormones and neurotransmitters suggest that it has an important endocrine or secretory function. The authors have isolated cDNA clones from a bovine pituitary lambdagt11 expression library using an antiserum to parathyroid SP-I. The largest clone (SP4B) hybridized to a transcript of 2.1 kilobases in RNA from parathyroid, pituitary, and adrenal medulla. Immunoblots of bacterial lysates derived from SP4B lysognes demonstrated specific antibody binding to an SP4B/..beta..-galactosidase fusion protein (160 kDa) with a cDNA-derived component of 46 kDa. Radioimmunoassay of the bacterial lystates with SP-I antiserum yielded parallel displacement curves of /sup 125/I-labeled SP-I by the SP4B lysate and authentic SP-I. SP4B contains a cDNA of 1614 nucleotides that encodes a 449-amino acid protein (calculated mass, 50 kDa). The nucleotide sequences of the pituitary SP-I cDNA and adrenal medullary SP-I cDNAs are nearly identical. Analysis of genomic DNA suggests that pituitary, adrenal, and parathyroid SP-I are products of the same gene.

  10. Metastatic tumors to the adrenal glands in domestic animals.

    PubMed

    Labelle, P; De Cock, H E V

    2005-01-01

    Although metastases to the adrenals are common in humans, they have not been thoroughly studied in animals. The purpose of this retrospective study was to document the types of malignant tumors that metastasize to canine, feline, equine, and bovine adrenals, and the rate at which they do so. The average rate of adrenal involvement in metastatic cancer was 112/534 (21.0%) in dogs, 12/81 (14.8%) in cats, 18/67 (26.9%) in horses, and 5/16 (31.3%) in cattle. In dogs, 26 different tumor types metastasized to the adrenals. Pulmonary, mammary, prostatic, gastric, and pancreatic carcinomas, and melanoma had the highest rates of metastasis to the adrenal glands in dogs. Hemangiosarcoma and melanoma had high rates of adrenal involvement in horses. In cats and cattle, relevant data were only available for lymphoma. Adrenal metastases usually occurred in the late stages of the disease. One dog had developed Addison's disease (hypoadrenocorticism) secondary to lymphoma. Metastatic lesions represented 126/472 (26.7%) of canine, 12/20 (60.0%) of feline, 21/80 (26.3%) of equine, and 5/9 (55.5%) of bovine adrenal neoplasms. This study shows that adrenal glands should be thoroughly examined during both clinical work-up and postmortems when disseminated neoplasia is suspected.

  11. Adrenal metabolism of mitotane and related compounds

    SciTech Connect

    Djanegara, T.K.S.

    1989-01-01

    Mitotane (o,p{prime}-DDD; 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane) has been used in the treatment of Cushing's syndrome due to adrenal hyperfunction and it the drug of choice for adrenocortical carcinoma. The object of this investigation is to study the biotransformation of o,p{prime}-DDD and p,p{prime}-DDD in dogs and bovine adrenal cortex to explain its selective toxicity and mechanism of action. The in vitro biotransformation of {sup 14}C-labeled o,p{prime}-DDD and p,p{prime}-DDD by dog and bovine adrenal cortex as studied. Of the cortex subcellular fractions, the cytosol fraction was found to be the most active in metabolizing the substrates, followed by the mitochondrial fraction. This metabolism including that in cytosolic fractions, did not take place with boiled enzyme preparations and required an NADPH generating system. This study has been directed towards establishing the metabolic activation mechanism which may account for the adrenocorticolytic effect of mitotane in contrast to detoxication by the liver. HPLC and TLC metabolic profiles have been generated from incubations of bovine and dog adrenal cortex homogenates and their subfractions for {sup 14}C-labeled p,p{prime}-DDD, o,p{prime}-DDD and its monochloroethylene derivative, o,p{prime}-DDMU.

  12. Adrenal gland disorders.

    PubMed

    Berry, Matthew E

    2009-01-01

    Medical imaging of the adrenal glands is an important aspect of the diagnosis of any adrenal gland disorder. This article discusses the normal anatomy and functions of the adrenal glands, as well as specific adrenal gland disorders and how they are diagnosed and treated. Radiologic technologists need to understand the causes, signs, symptoms, diagnosis and management of disorders that prevent the adrenal glands from functioning properly.

  13. Adrenal Pathology in the Adult: A Urological Pathologist's Perspective.

    PubMed

    Hansel, Donna E; Reuter, Victor E

    2016-09-01

    Adrenal gland diagnostics can pose significant challenges. In most academic and community practice settings, adrenal gland resections are encountered less frequently than other endocrine or genitourinary specimens, leading to less familiarity with evolving classifications and criteria. The unique dichotomy between cortical and medullary lesions reflects the developmental evolution of these functionally independent components. Adrenal cortical lesions at resection include hyperplasia, adenoma, and carcinoma, with some cases straddling the boundary between these distinct clinical classifications. The lack of immunohistochemical or molecular markers to definitively categorize these intermediate lesions enhances the diagnostic challenge. In addition, modified terminology for oncocytic and myxoid cortical lesions has been proposed. Medullary lesions are somewhat easier to categorize; however, the prediction of aggressive behavior in pheochromocytomas remains a challenge due to a lack of reliable prognostic biomarkers. Recent work by the Cancer Genome Atlas Project and other research groups has identified a limited subset of molecular and signaling pathway alterations in these 2 major neoplastic categories. Ongoing research to better define prognostic and predictive biomarkers in cortical and medullary lesions has the potential to enhance both pathologic diagnosis and patient therapy.

  14. Activation of spinal MrgC-Gi-NR2B-nNOS signaling pathway by Mas oncogene-related gene C receptor agonist bovine adrenal medulla 8-22 attenuates bone cancer pain in mice.

    PubMed

    Sun, Yu'e; Zhang, Juan; Lei, Yishan; Lu, Cui'e; Hou, Bailing; Ma, Zhengliang; Gu, Xiaoping

    2016-01-01

    In the present study, we investigate the effects of Mas oncogene-related gene (Mrg) C receptors (MrgC) on the expression and activation of spinal Gi protein, N-methyl-D-aspartate receptor subunit 2B (NR2B), and neuronal nitric oxide synthase (nNOS) in mouse model of bone cancer pain. The number of spontaneous foot lift (NSF) and paw withdrawal mechanical threshold (PWMT) were measured after inoculation of tumor cells and intrathecal injection of MrgC agonist bovine adrenal medulla 8-22 (BAM8-22) or MrgC antagonist anti-MrgC for 14 days after operation. Expression of spinal MrgC, Gi protein, NR2B and nNOS and their phosphorylated forms after inoculation was examined by immunohistochemistry and Western blotting. Double labeling was used to identify the co-localization of NR2B or nNOS with MrgC in spinal cord dorsal horn (SCDH) neurons. The effects of intrathecal injection of BAM8-22 or anti-MrgC on nociceptive behaviors and the corresponding expression of spinal MrgC, Gi protein, NR2B and nNOS were also investigated. The expression of spinal MrgC, Gi protein, NR2B, and nNOS was higher in tumor-bearing mice in comparison to sham mice or normal mice. Intrathecal injection of MrgC agonist BAM8-22 significantly alleviated bone cancer pain, up-regulated MrgC and Gi protein expression, and down-regulated the expression of spinal p-NR2B, t-nNOS and p-nNOS in SCDH on day 14 after operation, whereas administration of anti-MrgC produced the opposite effect. Meanwhile, MrgC-like immunoreactivity (IR) co-localizes with NR2B-IR or nNOS-IR in SCDH neurons. The present study demonstrates that MrgC-activated spinal Gi-NR2B-nNOS signaling pathway plays important roles in the development of bone cancer pain. These findings may provide a novel strategy for the treatment of bone cancer pain.

  15. Activation of spinal MrgC-Gi-NR2B-nNOS signaling pathway by Mas oncogene-related gene C receptor agonist bovine adrenal medulla 8-22 attenuates bone cancer pain in mice

    PubMed Central

    Sun, Yu’e; Zhang, Juan; Lei, Yishan; Lu, Cui’e; Hou, Bailing; Ma, Zhengliang; Gu, Xiaoping

    2016-01-01

    Objectives: In the present study, we investigate the effects of Mas oncogene-related gene (Mrg) C receptors (MrgC) on the expression and activation of spinal Gi protein, N-methyl-D-aspartate receptor subunit 2B (NR2B), and neuronal nitric oxide synthase (nNOS) in mouse model of bone cancer pain. Methods: The number of spontaneous foot lift (NSF) and paw withdrawal mechanical threshold (PWMT) were measured after inoculation of tumor cells and intrathecal injection of MrgC agonist bovine adrenal medulla 8-22 (BAM8-22) or MrgC antagonist anti-MrgC for 14 days after operation. Expression of spinal MrgC, Gi protein, NR2B and nNOS and their phosphorylated forms after inoculation was examined by immunohistochemistry and Western blotting. Double labeling was used to identify the co-localization of NR2B or nNOS with MrgC in spinal cord dorsal horn (SCDH) neurons. The effects of intrathecal injection of BAM8-22 or anti-MrgC on nociceptive behaviors and the corresponding expression of spinal MrgC, Gi protein, NR2B and nNOS were also investigated. Results: The expression of spinal MrgC, Gi protein, NR2B, and nNOS was higher in tumor-bearing mice in comparison to sham mice or normal mice. Intrathecal injection of MrgC agonist BAM8-22 significantly alleviated bone cancer pain, up-regulated MrgC and Gi protein expression, and down-regulated the expression of spinal p-NR2B, t-nNOS and p-nNOS in SCDH on day 14 after operation, whereas administration of anti-MrgC produced the opposite effect. Meanwhile, MrgC-like immunoreactivity (IR) co-localizes with NR2B-IR or nNOS-IR in SCDH neurons. Conclusions: The present study demonstrates that MrgC-activated spinal Gi-NR2B-nNOS signaling pathway plays important roles in the development of bone cancer pain. These findings may provide a novel strategy for the treatment of bone cancer pain. PMID:27158400

  16. Adrenal microvascularization in the common tree shrew (Tupaia glis) as revealed by scanning electron microscopy of vascular corrosion casts.

    PubMed

    Thongpila, S; Rojananeungnit, S; Chunhabundit, P; Cherdchu, C; Samritthong, A; Somana, R

    1998-01-01

    The blood supply of the adrenal gland in the common tree shrew (Tupaia glis) was studied by use of transmission electron microscopy and vascular corrosion cast/scanning electron microscopy techniques. It was found that the gland receives its blood supply from branches of the inferior phrenic, aorta and renal arteries. Upon reaching the gland, these arteries divide into cortical and medullary arteries. The cortical arteries give rise to the subcapsular capillary plexuses which partially enclose the clusters of cells in the zona glomerulosa (ZG) and appear as lobular-like microvascular networks before running among the cellular cords in the zona fasciculata (ZF) and zona reticularis (ZR). It was noted that the capillaries in ZG and ZR are with more anastomoses than those in the ZF. Capillaries from the ZR become the sinusoidal capillaries in the adrenal medulla before proceeding to the peripheral radicles of the central vein. The medullary arteries penetrate the adrenal cortex and occasionally give off small branches to supply the inner cortex, especially the ZR. Their main branches break up into small or conventional capillaries in the adrenal medulla. These capillaries drain the blood into the peripheral radicles of the central vein and medullary collecting veins which proceed further into a very large central vein. The present findings illustrate that the adrenal medulla receives two blood supplies that yield somewhat different influences upon the adrenal medulla. The portal blood vessel could not be illustrated in the tree shrew adrenal gland.

  17. Adrenal Steroidogenesis and Congenital Adrenal Hyperplasia

    PubMed Central

    Turcu, Adina F.; Auchus, Richard J.

    2015-01-01

    Synopsis Adrenal steroidogenesis is a dynamic process, reliant on de novo synthesis from cholesterol, under the stimulation of ACTH and other regulators. The syntheses of mineralocorticoids, glucocorticoids and adrenal androgens occur in separate adrenal cortical zones, each expressing specific enzymes. Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive enzymatic defects in cortisol biosynthesis. 21-hydroxylase (21OHD) deficiency accounts for over 90% of CAH cases and when milder or nonclassic forms are included, 21OHD is one of the most common genetic diseases. This review discusses in detail the epidemiology, genetics, diagnostic, clinical aspects and management of 21OHD. PMID:26038201

  18. Adrenal Gland Disorders

    MedlinePlus

    ... adrenal gland disorders include Genetic mutations Tumors including pheochromocytomas Infections A problem in another gland, such as the pituitary, which helps to regulate the adrenal gland Certain medicines Treatment depends on which problem you have. Surgery or ...

  19. 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 ...

  20. 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 - ...

  1. Acute adrenal crisis

    MedlinePlus

    ... adrenal gland is damaged due to, for example, Addison disease or other adrenal gland disease, and surgery The ... Call your health care provider if you have Addison disease and are unable to take your glucocorticoid medicine ...

  2. Plasminogen activator inhibitor (type-1) in rat adrenal medulla.

    PubMed

    Eriksen, J; Kristensen, P; Pyke, C; Danø, K

    1989-01-01

    Plasminogen activator inhibitor type-1 (PAI-1) was identified in extracts of rat adrenal medulla, and its immunohistochemical localization was studied together with that of tissue-type plasminogen activator (t-PA). By staining of adjacent sections and by double-staining of the same section we demonstrate that the same cells of the adrenal medulla contain both PAI-1 and t-PA immunoreactivity in the cytoplasm. In addition a few ganglion cells of the adrenal medulla were found to contain PAI-1 but not t-PA. Neither of the components were found in the adrenal cortex. Analysis of extracts from isolated adrenal medulla using reverse zymography showed the presence of a plasminogen activator inhibitor with Mr approximately 46,000. The inhibitory activity disappeared when the extract was passed through a column with sepharose-coupled anti-PAI-1 IgG, while the run-through from a similar column coupled with preimmune IgG still contained the inhibitor. The present findings suggest that PAI-1 could play a role in the regulation of t-PA activity in the rat adrenal gland medullary cells.

  3. Histogenesis of the human adrenal medulla. An evaluation of the ontogeny of chromaffin and nonchromaffin lineages.

    PubMed

    Cooper, M J; Hutchins, G M; Israel, M A

    1990-09-01

    The authors previously evaluated the expression of a panel of chromaffin-related genes during histogenesis of the human adrenal medulla. In these studies, chromaffin and nonchromaffin adrenal neuroblasts were identified. To better characterize these nonchromaffin neuroblasts, the authors evaluated two additional markers: HNK-1, an antibody recognizing the migratory neural crest cell; and S-100, a protein expressed by sustentacular cells of the adrenal medulla. HNK-1 immunoreactivity was found in both chromaffin and nonchromaffin cell types at different times during development, marking the nonchromaffin lineage during the second trimester of gestation as well as the chromaffin lineage in the neonatal period. In addition, S-100 expression was noted in some nonchromaffin neuroblasts, and sustentacular cells were first identified at approximately 28 weeks of gestational age. These data suggest a model of human adrenal medullary histogenesis that incorporates the chromaffin, ganglionic, and sustentacular lineages known to constitute the adult adrenal medulla.

  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. Multiple endocrine neoplasia similar to human subtype 2A in a dog: Medullary thyroid carcinoma, bilateral pheochromocytoma and parathyroid adenoma

    PubMed Central

    Arias, E.A. Soler; Castillo, V.A.; Trigo, R.H.; Caneda Aristarain, M.E.

    2016-01-01

    Human multiple endocrine neoplasia subtype 2A (MEN 2A) is characterized by medullary thyroid carcinoma, pheochromocytoma and parathyroid hyperplasia or adenoma in the same individual. In this report, a case of a female Rottweiler with medullary thyroid carcinoma, bilateral pheochromocytoma and parathyroid adenoma was described. Clinical manifestations of muscle weakness, polydipsia, polyuria, diarrhea and weight loss were observed. Two adrenal neoplasms were identified incidentally by ultrasonography, and tumor in the left thyroid lobe was identified by palpation. Primary hyperparathyroidism was diagnosed by biochemical testing. Histopathology report was consistent with diagnosis of bilateral pheochromocytoma and parathyroid adenoma. Immunohistochemical staining was positive for calcitonin and synaptophysin, and negative for thyroglobulin, which confirmed medullary thyroid carcinoma. This case in a dog is presenting neoplastic characteristics similar to human MEN 2A and emphasizing the importance of using immunohistochemistry for confirmation. PMID:27822452

  7. Concurrent Medullary, Papillary, and Follicular Thyroid Carcinomas and Simultaneous Cushing's Syndrome.

    PubMed

    Mazeh, Haggi; Orlev, Amir; Mizrahi, Ido; Gross, David J; Freund, Herbert R

    2015-03-01

    Papillary thyroid carcinoma is the most common thyroid cancer (85%). Follicular thyroid carcinoma is the second most common type of thyroid cancer, accounting for up to 10% of all thyroid cancers. Medullary thyroid carcinoma accounts for only 5-8% of thyroid cancers. Concurrent medullary, follicular, and papillary carcinomas of the thyroid gland are extremely rare and reported scarcely. A 72-year-old male presented with nonspecific neck pain. The workup revealed a nodular thyroid gland with a follicular lesion on fine-needle aspiration. Total thyroidectomy was performed and pathological examination identified a 25-mm follicular carcinoma, two papillary microcarcinomas, and two medullary microcarcinomas. The genetic workup was negative and no other family members were diagnosed with any endocrinopathy. Two months after surgery, the patient was diagnosed with Cushing's syndrome that was treated with laparoscopic left adrenalectomy. On 3-year follow-up, the patient is asymptomatic with no evidence of recurrent disease. We present a rare case of a patient with follicular, papillary, and medullary thyroid carcinoma, and Cushing's syndrome. To date, no known genetic mutation or syndrome can account for this combination of neoplastic thyroid and adrenal pathologies, although future research may prove differently.

  8. Imaging of Renal Medullary Carcinoma

    PubMed Central

    Faiella, Eliodoro; Santucci, Domiziana; Mallio, Carlo Augusto; Nezzo, Marco; Quattrocchi, Carlo Cosimo; Beomonte Zobel, Bruno; Grasso, Rosario Francesco

    2017-01-01

    Renal medullary carcinoma (RMC) is a rare, highly aggressive tumor recognized as an independent pathological entity. African-descent adolescents and young adults with sickle cell hemoglobinopathy are the most affected groups. This rare subtype of renal cell carcinoma has its own morphogenetic and pathological characteristics. The major clinical manifestations include gross hematuria, abdominal or flank pain, and weight loss. The prognosis is very poor, with 95% of cases diagnosed at an advanced stage of the disease. In this review, we summarize the morphologic and dynamic characteristics of RMC under various imaging modalities such as ultrasound, computed tomography, and magnetic resonance. Differential diagnosis and management strategies are also discussed. PMID:28405543

  9. Medullary sponge kidney in childhood

    SciTech Connect

    Patriquin, H.B.; O'Regan, S.

    1985-08-01

    Medullary sponge kidney is reported in six children aged 2-18 years. One child was asymptomatic; the others had hematuria or a urine-concentrating defect. Renal function and size were otherwise normal, as was liver function. The diagnosis was made at excretory urography according to criteria established in adults. Sonography revealed hyperechogenic pyramids, at first at the periphery, later generalized. Computed tomography is very sensitive to the pyramidal nephrocalcinosis that complicates this disease and explains the frequent presenting symptom of hematuria in these children.

  10. Medullary sponge kidney associated with congenital hemihypertrophy.

    PubMed

    Indridason, O S; Thomas, L; Berkoben, M

    1996-08-01

    Medullary sponge kidney is a developmental disorder characterized by ectatic and cystic malformation of the collecting ducts and tubules. Clinical manifestations include urinary tract infections, renal stones, and hematuria. It can be associated with other developmental disorders. A case of medullary sponge kidney associated with congenital hemihypertrophy, complicated by nephrocalcinosis and nephrolithiasis, is reported here.

  11. [Pediatric emergency: adrenal insufficiency and adrenal crisis].

    PubMed

    Martínez, Alicia; Pasqualini, Titania; Stivel, Mirta; Heinrich, Juan Jorge

    2010-04-01

    Adrenal insufficiency is defined by impaired secretion of adrenocortical hormones. It is classified upon the etiology in primary and secondary. Rapid recognition and therapy of adrenocortical crisis are critical to survival. Patients often have nonspecific symptoms: anorexia, vomiting, weakness, fatigue and lethargy. They are followed by hypotension, shock, hypoglicemia, hyponatremia and hyperkalemia. All patients with adrenal insufficiency require urgent fluid reposition, correction of hypoglycemia and glucocorticoid replacement, in order to avoid serious consequences of adrenal crisis. After initial crisis treatment, maintenance dose of corticoids should be indicated. Mineralocorticoids replacement, if necessary, should also be initiated.

  12. Hashimoto's Thyroiditis and Medullary Carcinoma of Thyroid.

    PubMed

    Dasgupta, S; Chakrabarti, S; Mandal, P K; Das, S

    2014-01-01

    Hashimoto's thyroiditis (HT) has been found to be associated with lymphoma, papillary carcinoma and Hürthle cell neoplasms of thyroid. In contrast, there are only a few reports of co-existence of HT with medullary carcinoma of thyroid. An overall prevalence of medullary carcinoma of only 0.35% has been reported in HT patients. Such a rare combination is being presented here. A 33 year old female presented with history of goiter for one year. Fine needle aspiration cytology (FNAC) of the swelling revealed cytological features suggestive of medullary carcinoma of thyroid. Histopathological examination of total thyroidectomy specimen revealed Hashimoto's thyroiditis along with medullary carcinoma of thyroid. Although Hashimoto's thyroiditis can uncommonly co-exist with thyroid neoplasm, its association with medullary carcinoma is extremely rare and hence being presented.

  13. Nonreutilizaton of adrenal chromaffin granule membranes following secretion

    SciTech Connect

    Nobiletti, J.B.

    1985-01-01

    The intracellular postexocytotic fate of the adrenal chromaffin granule membrane (reutilization vs. nonreutilization) was addressed through two experimental approaches. First, (/sup 3/H) leucine pulse-chase labeling experiments were conducted in two systems - the isolated retrograde perfused cat adrenal gland and cultured bovine adrenal chromaffin cells to compare chromaffin granule soluble dopamine-B-hydroxylase (DBH) turnover (marker for granule soluble content turnover) to that of membrane-bound DBH (marker for granule membrane turnover). Experiments in cat adrenal glands showed that at all chase periods the granule distribution of radiolabeled DBH was in agreement with the DBH activity distribution (73% membrane-bound/27% soluble) - a result consistent with parallel turnover of soluble and membrane-bound DBH. Experiments in cultured bovine cells showed that labeled soluble and membrane-bound DBH had parallel turnover patterns and at all chase period, the distribution of radiolabeled DBH between the soluble contents and membranes was similar to the DBH activity distribution (50% soluble/50% membrane-bound). The above experiments showed that the soluble contents and membranes turnover in parallel and are consistent with nonreutilization of chromaffin granule membranes following exocytosis. Isolated retrograde perfused bovine adrenal glands were subjected to repetitive acetylcholine stimulation to induce exocytosis and then the dense and less-dense chromaffin granule fractions were isolated. Since both approaches gave results consistent with membrane nonreutilization, the authors conclude that once a chromaffin granule is involved in exocytosis, its membrane is not reutilized for the further synthesis, storage, and secretion of catecholamines.

  14. Tyrosine hydroxylase, chromogranin A, and steroidogenic acute regulator as markers for successful separation of human adrenal medulla

    PubMed Central

    Fliedner, Stephanie M. J.; Breza, Jan; Kvetnansky, Richard; Powers, James F.; Tischler, Arthur S.; Wesley, Robert; Merino, Maria; Lehnert, Hendrik

    2016-01-01

    Progress in high throughput “-omic” techniques now allows the simultaneous measurement of expression levels of thousands of genes and promises the improved understanding of the molecular biology of diseases such as cancer. Detection of the dysfunction of molecular pathways in diseases requires healthy control tissue. This is difficult to obtain from pheochromocytomas (PHEOs), rare chromaffin tumors derived from adrenal medulla. The two options for obtaining adrenal tissue are: (1) whole organ removal post-mortem or during radical nephrectomy; (2) removal during PHEO surgery. Access to high quality normal adrenal tissue is limited. Removal of whole adrenals during nephrectomy is rare, because of improved surgical techniques. For adrenals removed post-mortem, the lag time to proper organ perfusion causes uncontrolled tissue degradation. Adjacent normal adrenal tissue can almost never be obtained from resected PHEOs, because they often replace the entire medulla or are well-encapsulated. If a margin of normal adrenal is attached to a resected PHEO, it seldom contains any medulla. The clean separation of medulla and cortex is further complicated, because their border is convoluted, and because adult adrenal consists of ~90% cortex. Thus, the quality of separation has to be evaluated with specific medullary and cortical markers. We describe the successful dissection of highly pure, medullary tissue from adrenals snap-frozen upon resection during radical nephrectomy or after brain death. Separation quality has been verified by quantitative reverse transcription with polymerase chain reaction for the medullary enzymes, tyrosine hydroxylase, and chromogranin A, and for the cortical enzyme, steroidogenic acute regulator. PMID:20440513

  15. Congenital Adrenal Hyperplasia

    PubMed Central

    Speiser, Phyllis W.

    2015-01-01

    Congenital adrenal hyperplasia associated with deficiency of steroid 21-hydroxylase is the most common inborn error in adrenal function and the most common cause of adrenal insufficiency in the pediatric age group. As patients now survive into adulthood, adult health-care providers must also be familiar with this condition. Over the past several years, F1000 has published numerous commentaries updating research and practical guidelines for this condition. The purposes of this review are to summarize basic information defining congenital adrenal hyperplasia and to highlight current knowledge and controversies in management. PMID:26339484

  16. Adrenal cortex carcinomas with distant metastases in beef cattle at slaughter.

    PubMed

    Edwards, J F; Ralston, K E

    2013-07-01

    Ten cases of adrenal cortex carcinomas with distant metastases were collected as subclinical lesions at slaughter of approximately 14,000 adult cattle. The primary lesion in the adrenal gland and the distant metastases, to either the lung or liver, were characterized by light microscopy and immunohistochemistry. Carcinomas were usually detected by noting metastases in the lungs as polypoid, soft, red or red and yellow masses. All adrenal tumours were unilateral and none were seen in bulls. In six of 10 carcinomas there was gross evidence of invasion of the vena cava via the adrenal vein. Normal bovine adrenal cortex labelled positively with S100, calretinin, α inhibin and melan-A; however, adenomas and seven of 10 carcinomas were labelled best by melan-A and α inhibin. Three carcinomas, grossly identical to the other seven, had numerous calcific granules and a slightly different microscopical appearance. In addition to melan-A and α-inhibin, these variant carcinomas labelled with S100. This variant may be derived from a different layer of the adrenal cortex. Because of the similarity of the bovine and human adrenal cortices, cultures of spontaneously arising bovine adrenal tumours may be a useful resource for study of human neoplasia.

  17. A rare adrenal incidentaloma: adrenal schwannoma.

    PubMed

    Adas, Mine; Ozulker, Filiz; Adas, Gokhan; Koc, Bora; Ozulker, Tamer; Sahin, Ilknur Mansuroglu

    2013-01-01

    Adrenal schwannoma is an extremely uncommon cause of incidentaloma. It originates from neural sheath Schwann cells of the adrenal gland. We report the case of a left adrenal schwannoma incidentally discovered in a 32-year-old woman during examination of bloated feeling and stomach ache. The patient was incidentally found to have a left adrenal mass of 9 cm on abdominal ultrasonography. Computed tomography (CT) of the abdomen and [(18)F] fluorodeoxyglucose positron emission tomography (PET) were also performed. Metabolic evaluation was unremarkable. Due to the large size of the tumor, left adrenalectomy was performed. The postoperative course was uneventful. Histological examination established the diagnosis of schwannoma. This diagnosis was supported by immunohistochemistry of S-100 and vimentin positivity. In conclusion, adrenal schwannoma is an extremely rare entity and can grow considerably in size. The present case report emphasizes that clinicians should be aware of the possibility of retroperitoneal schwannoma. Total excision of benign schwannoma is associated with a favorable outcome. To our knowledge, there are case reports of schwannoma with CT and magnetic resonance imaging findings in the literature, although this is the first schwannoma case with PET-CT imaging.

  18. Adrenal Gland Microenvironment and Its Involvement in the Regulation of Stress-Induced Hormone Secretion during Sepsis

    PubMed Central

    Kanczkowski, Waldemar; Sue, Mariko; Bornstein, Stefan R.

    2016-01-01

    Survival of all living organisms depends on maintenance of a steady state of homeostasis, which process relies on its ability to react and adapt to various physical and emotional threats. The defense against stress is executed by the hypothalamic–pituitary–adrenal axis and the sympathetic–adrenal medullary system. Adrenal gland is a major effector organ of stress system. During stress, adrenal gland rapidly responds with increased secretion of glucocorticoids (GCs) and catecholamines into circulation, which hormones, in turn, affect metabolism, to provide acutely energy, vasculature to increase blood pressure, and the immune system to prevent it from extensive activation. Sepsis resulting from microbial infections is a sustained and extreme example of stress situation. In many critical ill patients, levels of both corticotropin-releasing hormone and adrenocorticotropin, the two major regulators of adrenal hormone production, are suppressed. Levels of GCs, however, remain normal or are elevated in these patients, suggesting a shift from central to local intra-adrenal regulation of adrenal stress response. Among many mechanisms potentially involved in this process, reduced GC metabolism and activation of intra-adrenal cellular systems composed of adrenocortical and adrenomedullary cells, endothelial cells, and resident and recruited immune cells play a key role. Hence, dysregulated function of any of these cells and cellular compartments can ultimately affect adrenal stress response. The purpose of this mini review is to highlight recent insights into our understanding of the adrenal gland microenvironment and its role in coordination of stress-induced hormone secretion. PMID:28018291

  19. Adrenal Gland Microenvironment and Its Involvement in the Regulation of Stress-Induced Hormone Secretion during Sepsis.

    PubMed

    Kanczkowski, Waldemar; Sue, Mariko; Bornstein, Stefan R

    2016-01-01

    Survival of all living organisms depends on maintenance of a steady state of homeostasis, which process relies on its ability to react and adapt to various physical and emotional threats. The defense against stress is executed by the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal medullary system. Adrenal gland is a major effector organ of stress system. During stress, adrenal gland rapidly responds with increased secretion of glucocorticoids (GCs) and catecholamines into circulation, which hormones, in turn, affect metabolism, to provide acutely energy, vasculature to increase blood pressure, and the immune system to prevent it from extensive activation. Sepsis resulting from microbial infections is a sustained and extreme example of stress situation. In many critical ill patients, levels of both corticotropin-releasing hormone and adrenocorticotropin, the two major regulators of adrenal hormone production, are suppressed. Levels of GCs, however, remain normal or are elevated in these patients, suggesting a shift from central to local intra-adrenal regulation of adrenal stress response. Among many mechanisms potentially involved in this process, reduced GC metabolism and activation of intra-adrenal cellular systems composed of adrenocortical and adrenomedullary cells, endothelial cells, and resident and recruited immune cells play a key role. Hence, dysregulated function of any of these cells and cellular compartments can ultimately affect adrenal stress response. The purpose of this mini review is to highlight recent insights into our understanding of the adrenal gland microenvironment and its role in coordination of stress-induced hormone secretion.

  20. Adrenal cortex ontogenesis.

    PubMed

    Lalli, Enzo

    2010-12-01

    During the early phases of development, adrenal glands share a common origin with kidneys and gonads. The action of diverse transcription factors, signalling pathways and endocrine signals is required for the individualization of the adrenal primordium and its subsequent differentiation into an adult adrenal gland, with massive remodelling taking place around the time of birth in humans. Here I summarize the most important steps by which the adrenal cortex is shaped and present an overview of the current understanding of the genes and molecular pathways implicated in adrenal development and involved in the pathogenesis of its congenital diseases. Evidence is accumulating that some pivotal factors acting during adrenocortical development also play an important role to regulate the growth of adrenocortical tumors, representing promising therapeutical targets for a biology-oriented therapy. 2010 Elsevier Ltd. All rights reserved.

  1. Medullary cystic disease: a family study.

    PubMed

    Chen, H C; Chang, J M; Tsai, J H; Lai, Y H

    1998-03-01

    Medullary cystic disease of the kidney is characterized by progressive tubulointerstitial disease with medullary cyst formation and secondary glomerular sclerosis. We treated a patient with chronic renal failure and investigated the family history of renal disease. The patient, an 18-year-old woman, was admitted due to poor appetite and fatigue for several months. Findings on physical examination were normal except for a pale conjunctiva. Urinalysis revealed only mild proteinuria with clear sediment. The hemogram showed normocytic normochromic anemia with hemoglobin 86 g/L. The patient was azotemic and her creatinine clearance rate was 10.7 mL/min. Renal sonography showed contraction of both kidneys with a marked increase in cortical echogenicity. One small cyst was found in the medullary area. Computed tomography (CT) and magnetic resonance imaging revealed several medullary cysts. Percutaneous renal biopsy showed focal and periglomerular sclerosis, marked tubular atrophy, and interstitial fibrosis. Ten of her family members were examined for renal function, and by sonography and CT. Five had medullary cysts, and three of the five showed abnormal renal function. Medullary cystic disease should be considered in the differential diagnosis of patients with renal disease and a positive family history.

  2. Adrenomedullin receptor is found exclusively in noradrenaline-secreting cells of the rat adrenal medulla.

    PubMed

    Renshaw, D; Thomson, L M; Michael, G J; Carroll, M; Kapas, S; Hinson, J P

    2000-04-01

    Adrenomedullin, originally identified in the adrenal medulla, has binding sites in the adrenal gland; however, its role in the adrenal medulla is unclear. This study was designed to characterise adrenomedullin binding sites in the rat adrenal medulla, using ligand binding studies, immunocytochemistry, and mRNA analysis. A single population of specific adrenomedullin receptors was identified in adrenal medullary homogenates. 125I-Adrenomedullin was displaced only by adrenomedullin1-50 and not by calcitonin gene-related peptide or amylin at concentrations up to 100 nmol/L. The receptor K(D) was 3.64 nmol/L with a receptor density of 570 fmol/mg of protein. Analysis of mRNA revealed that the genes encoding both the putative adrenomedullin receptors, termed calcitonin receptor-like receptor (CRLR) and L1, were expressed in the rat adrenal medulla. Dual-colour indirect-labelled immunofluorescence was used to localise phenylethanolamine N-methyltransferase (PNMT) and the adrenomedullin receptor in the same section. PNMT is the enzyme that converts noradrenaline to adrenaline and is not expressed in noradrenaline-secreting cells. These studies revealed that both CRLR and L1 were expressed only in cells that did not express PNMT, suggesting that adrenomedullin receptors are only found in noradrenaline-secreting cells. Further evidence to support this conclusion was provided by the demonstration of colocalisation of adrenomedullin receptors with dopamine beta-hydroxylase, confirming the presence of the receptors in medullary chromaffin cells. Taken together, these data suggest that adrenomedullin acts through a specific adrenomedullin receptor in the rat adrenal medulla. RT-PCR and northern blot analysis revealed greater abundance of mRNA for L1 than for CRLR, possibly suggesting that L1 may be the major adrenomedullin receptor expressed in this tissue. As it has been reported that adrenomedullin is synthesised predominantly by adrenaline-secreting cells, it appears likely

  3. [Ectopic adrenal cortical adenoma in the spinal canal: A case report and a review of the literature].

    PubMed

    Konstantinov, A S; Shelekhova, K V

    2016-01-01

    Ectopic adrenal cortical neoplasms are extremely rare. The authors describe their own case of intradural, extramedullary conus medullaris adenoma that occurred in a 55-year-old woman, which was clinically accompanied by lumbar pains, left leg numbness, and left foot weakness during 10 years. The mass was histologically composed of rounded and polygonal cell fields with rounded, regular nuclei and abundant eosinophilic and clear cytoplasm. There were no necroses or mitoses. The cells were immunohistochemically positive for cytokeratin AE1/3, vimentin, inhibin-α, melan-A, and synaptophysin. An ectopic adrenocortical adenoma was diagnosed after ruling out myxopapillary ependymoma, meningioma with oncocytic transformation, paraganglioma, metastatic renal cell carcinoma, and adrenal cortical carcinoma. In the opinion of most investigators, extra-adrenal tumors develop from ectopic adrenal cortical tissue. To date, only eight intraspinal adrenal cortical tumors have been described. These tumors should be considered in the differential diagnosis of central nervous system masses located in the lower spinal canal.

  4. Morphology of the adrenal medulla indicating multiple neuroectodermal abnormalities in pheochromocytoma patients.

    PubMed

    Jansson, S; Tisell, L E; Hansson, G

    1988-01-01

    25 of 85 (29.4%) consecutive patients operated on for pheochromocytoma had other neuroectodermal abnormalities. Medullary thyroid carcinoma was the most common associated neuroectodermal abnormality followed by von Recklinghausen's neurofibromatosis. Other abnormalities were intracranial tumors, parathyroid hyperplasia and midgut carcinoid. The adrenal medulla was studied to find out morphological characteristics in patients with associated neuroectodermal abnormalities. All patients with multiple pheochromocytomas (n = 7) and all patients with hyperplasia of the extratumoral adrenal medulla (n = 13) had other neuroectodermal abnormalities. It is important to detect the associated neuroectodermal abnormalities because they can be lethal. Patients with associated neuroectodermal abnormalities often have hereditary syndromes.

  5. Management of Adrenal Masses.

    PubMed

    Bhat, Hattangadi Sanjay; Tiyadath, Balagopal Nair

    2017-03-01

    An adrenal mass can be either symptomatic or asymptomatic in the form of adrenal incidentalomas (AIs) in up to 8 % in autopsy and 4 % in imaging series. Once a diagnosis of adrenal mass is made, we need to differentiate whether it is functioning or nonfunctioning, benign, or malignant. In this article, we provide a literature review of the diagnostic workup including biochemical evaluation and imaging characteristics of the different pathologies. We also discuss the surgical strategies with laparoscopy as the mainstay with partial adrenalectomy in select cases and adrenalectomy in large masses. Follow-up protocol of AIs and adrenocortical carcinoma is also discussed.

  6. Managing Adrenal Insufficiency

    MedlinePlus

    ... the body. • Surgical removal of the adrenals Temporary AI is caused by some medications, infections, and/or surgeries. Causes of temporary AI include the following: • Transsphenoidal surgery for Cushing’s disease ...

  7. Correlation between catecholamine secretion from bovine isolated chromaffin cells and [3H]-ouabain binding to plasma membranes

    PubMed Central

    Aunis, Dominique; García, Antonio G.

    1981-01-01

    1 Secretion of catecholamines (CA) evoked by ouabain, chlormadinone acetate (CMA), phenoxybenzamine (Pbz) and vanadate, four agents known to inhibit Na+, K+-dependent Mg2+-activated adenosine triphosphatase (ATPase) activity has been studied in suspensions of bovine isolated adrenal medullary cells. 2 Acetylcholine (ACh) evoked a 5 fold increase of the basal CA secretion from isolated cells suspended in oxygenated Krebs-bicarbonate solution kept at 27°C. Secretion was antagonized by Ca2+-deprivation or hexamethonium, indicating good functional viability of the cells. 3 Ouabain (10-7 to 10-4 M) evoked a progressive, dose-dependent release of CA from cell suspensions. Study of the time course of the secretory response for 2 h allowed the separation of two components in the secretory response at all doses studied: a slow initial component (0.011 pg/min CA) and a second faster component (0.032 pg/min CA). 4 CMA evoked a clear-cut CA secretory response. The ED50 for CMA was 10-4 M, as compared to 3 × 10-6 M for ouabain. Pbz and vanadate did not induce CA release. 5 [3H]-ouabain was taken up and bound to intact isolated cells by a non-saturable binding process. However, in semi-purified plasma membranes from bovine adrenal medulla a saturable specific [3H]-ouabain binding process was observed with a KD of 8.1 nM. Binding to the membranes was ATP-dependent and antagonized by K+. 6 [3H]-ouabain specific binding to membranes was antagonized by ouabain and CMA, but not by Pbz or vanadate; the ID50 for ouabain and CMA were 10-6 and 10-5 M respectively. 7 Ouabain partially inhibited, in a dose-dependent manner, Na+, K+-Mg2+ ATPase activity of the semi-purified plasma membranes. 8 The results demonstrate a good correlation between the ability of different drugs, known to inhibit ATPase activity, to displace [3H]-ouabain binding to adreno—medullary plasma membranes and their capacity to evoke a CA secretory response from isolated chromaffin cells. The data also suggest that

  8. Adrenal gland and bone.

    PubMed

    Hardy, Rowan; Cooper, Mark S

    2010-11-01

    The adrenal gland synthesizes steroid hormones from the adrenal cortex and catecholamines from the adrenal medulla. Both cortisol and adrenal androgens can have powerful effects on bone. The overproduction of cortisol in Cushing's disease leads to a dramatic reduction in bone density and an increase risk of fracture. Overproduction of adrenal androgens in congenital adrenal hyperplasia (CAH) leads to marked changes in bone growth and development with early growth acceleration but ultimately a significant reduction in final adult height. The role of more physiological levels of glucocorticoids and androgens on bone metabolism is less clear. Cortisol levels measured in elderly individuals show a weak correlation with measures of bone density and change in bone density over time with a high cortisol level associated with lower bone density and more rapid bone loss. Cortisol levels and the dynamics of cortisol secretion change with age which could also explain some age related changes in bone physiology. It is also now clear that adrenal steroids can be metabolized within bone tissue itself. Local synthesis of cortisol within bone from its inactive precursor cortisone has been demonstrated and the amount of cortisol produced within osteoblasts appears to increase with age. With regard to adrenal androgens there is a dramatic reduction in levels with aging and several studies have examined the impact that restoration of these levels back to those seen in younger individuals has on bone health. Most of these studies show small positive effects in women, not men, but the skeletal sites where benefits are seen varies from study to study.

  9. Association of adrenal medullar and cortical nodular hyperplasia: a report of two cases with clinical and morpho-functional considerations.

    PubMed

    Valdés, Gloria; Roessler, Eric; Salazar, Iván; Rosenberg, Helmar; Fardella, Carlos; Martínez, Pedro; Velasco, Alfredo; Velasco, Soledad; Orellana, Pilar

    2006-12-01

    Arterial hypertension of adrenal etiology is mainly attributed to primary hyperaldosteronism. However, subtle expressions of hyperadrenergic or glucocorticoid excess can also generate arterial hypertension. The present report describes two hypertensive patients cataloged as resistant essential hypertensives, in whom adrenal masses were found incidentally, who highlight the need to recognize these tenuous clinical or laboratory presentations. Case 1 was a 50-yr-old female with hyperadrenergic hypertension associated to a left adrenal node, normal cortisol and aldosterone:renin ratio, marginally increased urinary normetanephrine, and a positive 131I MIBG radioisotope scan. Adrenalectomy normalized blood pressure and urinary metanephrines. Pathology showed a hyperplastic adrenal medulla associated to a multinodular cortical hyperplasia. Case 2 was a 62- yr-old female with progressive hypertension, a slight Cushing phenotype, non-suppressible hypercortisolism, normal urinary metanephrines, and bilateral adrenal nodes. Bilateral adrenalectomy and subsequent replacement normalized blood pressure and phenotypic stigmata. Pathology demonstrated bilateral cortical multinodular hyperplasia and medullary hyperplasia. The clinical study in both patients was negative for MEN. The apparently rare association of cortical and medullary lesions presented by both patients is probably overlooked in routine pathology exams, but should be meticulously searched since the crosstalk between the adrenal cortex and medulla may prompt dual abnormalities.

  10. Immunolocalization of steroidogenic enzymes in equine fetal adrenal glands during mid-late gestation.

    PubMed

    Weng, Qiang; Tanaka, Yumiko; Taniyama, Hiroyuki; Tsunoda, Nobuo; Nambo, Yasuo; Watanabe, Gen; Taya, Kazuyoshi

    2007-10-01

    To elucidate the relationship between steroidogenic hormones and developing adrenal glands, we investigated the immunolocalization of steroidogenic enzymes in equine fetal adrenal glands during mid-late gestation. Fetal adrenal glands were obtained from three horses at 217, 225 and 235 days of gestation. Steroidogenic enzymes were immunolocalized using polyclonal antisera raised against bovine adrenal cholesterol side-chain cleavage cytochrome P450 (P450scc), human placental 3beta-hydroxysteroid dehydrogenase (3betaHSD), porcine testicular 17alpha-hydroxylase cytochrome P450 (P450c17) and human placental aromatase cytochrome P450 (P450arom). Histologically, cortex and medulla cells were clearly observed in the three fetal adrenal gland tissue samples. P450scc and P450c17 were identified in cortex cells close to medulla cells and in some medulla cells in the fetal adrenal glands. P450arom was present in both cortex and medulla cells in the fetal adrenal glands. However, 3betaHSD was not found in any of the equine fetal adrenal gland tissue samples. These results suggest that equine fetal adrenal glands have the ability to synthesize androgen and estrogen, which may play an important physiological role in the development of equine fetal adrenal glands.

  11. 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.

  12. Alterations in prealbumin concentration after adrenal autotransplantation for Parkinson's disease.

    PubMed

    Abram, S R; Kruskal, J B; Allen, G S; Burns, R S; Parker, R; Tulipan, N

    1990-05-01

    The cerebrospinal fluid of eight patients with Parkinson's disease who underwent adrenal medullary autotransplantation was analyzed using SDS-polyacrylamide gel electrophoresis. A protein, subsequently identified as prealbumin, was noted to change in concentration over the intraoperative to 18-month postoperative time course. The qualitative changes observed on visual inspection were confirmed and quantified using laser densitometry. The concentration of prealbumin increased by an average of 90% when the intraoperative and 12-month samples were compared. This increase persisted at 18 months. The ratio of prealbumin to albumin also increased from intraoperative to 12 months by an average of 56%. This suggests that the increases in PA are the result of choroid plexus activation rather than a nonspecific breakdown of the blood-brain barrier. Given the association of prealbumin with other nervous system diseases, as well as its known ability to bind multiple substances, these findings may have important implications. Alterations in prealbumin may be responsible for the improvement seen in some patients who receive adrenal medullary autotransplants. Alternatively, prealbumin may be implicated in the pathophysiology of Parkinson's disease.

  13. Bilateral Thyroid and Ultimobranchial Medullary Carcinoma.

    PubMed

    Patey, Martine; Flament, Jean Bernard; Caron, Jean; Delisle, Marie Joelle; Delemer, Brigitte; Pluot, Michel

    1996-01-01

    The ultimobranchial bodies in human embryos develop from the fourth and fifth branchial pouch complexes along with thymic and parathyroid tissue. They become incorporated within the lateral thyroid lobes and are believed to be involved in the development of C-cells. We report a case of an unusual bilateral thyroid and neck prelaryngeal medullary carcinoma in a 23-year-old male patient who belongs to a multiple endocrine neoplasia type 2a (MEN type 2a) family with thyroid tumors and pheochromocytomas. The medullary carcinoma was located in an abnormal cystic structure that seems to be a remnant of the ultimobranchial body (UBB) in the neck. Within the contralateral thyroid lobe, the medullary carcinoma was associated with C-cell hyperplasia.

  14. Biological relevance of medullary thyroid microcarcinoma.

    PubMed

    Machens, Andreas; Dralle, Henning

    2012-05-01

    The clinical relevance of medullary thyroid microcarcinoma, a calcitonin-secreting malignancy, as a valid target for biochemical screening programs has been called into doubt. This investigation aimed at clarifying the intensity of lymphatic spread and exploring the potential for biochemical cure in medullary thyroid microcarcinoma. This was a retrospective analysis. The setting was a tertiary referral center. Included were 233 patients with hereditary (126 patients) or sporadic (107 patients) medullary thyroid microcarcinoma. The intervention was compartment-oriented surgery. Clinical-histopathological variables were stratified by primary tumor diameter (2-mm increments) and biochemical cure. With incremental tumor diameter, increasingly more patients with medullary thyroid microcarcinoma harbored lymph node metastases: from 6 to 62% of patients (P < 0.001) for hereditary and from 13 to 43% of patients (P = 0.01) for sporadic disease. The corresponding biochemical cure rates declined from 96 to 71% (P = 0.001) and from 85 to 77% (P = 0.01). Distant disease (two instances of lung metastasis and one instance of bone and liver metastasis) was exceptional, affecting 1.3% of patients with medullary thyroid microcarcinoma. Strongest predictors of a patient's failure to achieve normal calcitonin serum levels were positive nodal status (79 vs. 11% in hereditary and 79 vs. 12% in sporadic disease; both P < 0.001) and the number of involved nodes (means of 6.6 vs. 0.3 nodes in hereditary and 8.8 vs. 0.4 nodes in sporadic disease; both P < 0.001). Sporadic and hereditary medullary thyroid microcarcinoma carry a significant risk of lymph node metastasis and postoperative calcitonin elevation.

  15. [Pheochromocytomas in adrenal medulla or extra-adrenal and multiple endocrine neoplasms:a clinicopathologic analysis of 181 cases].

    PubMed

    Jiang, Chang-xin; Zeng, Zhi; Wang, Ting; Liu, Xin; Liu, Rong; Li, Ying

    2011-11-01

    , which were younger than patients with malignant pheochromocytomas (51.6 years, P < 0.05); the mean age of patients with benign and potentially malignant pheochromocytomas in extra-adrenal sites was 43.1 years (ranged from 20 - 75 years) and 45.2 years (28 - 65 years) that were older than those with malignant (37.8 years, ranged from 14 - 58 years, P < 0.05). It was spectacular that patients with malignant pheochromocytoma in adrenal medulla (51.6 years) were older than that in extra-adrenal sites (37.8 years); all the patients with MEN2 were female benign pheochromocytoma in adrenal medulla, whose age (38.9 years) was younger than that of benign lesions (42.7 years, P < 0.05), in which thyroid medullary carcinoma appeared early than pheochromocytomas in adrenal medulla. The detectable rate of hypertension in patients with malignant pheochromocytomas in adrenal medulla and in extra-adrenal sites were less than that in benign and potentially malignant ones (P < 0.05). The bilateral lesions more commonly found in malignant pheochromocytoma (25.0%) than benign (15.7%) and potentially malignant pheochromocytomas (6.9%) only in adrenal medulla. Relapse rates in both adrenal and extra-adrenal tumors were rising from benign (11.8%, 0), potentially malignant (13.8%, 25.0%), to malignant (33.3%, 37.5%) groups; the average diameter of pheochromocytomas in both adrenal and extra-adrenal sites was increasing from benign (4.2 cm, 4.0 cm), potentially malignant (5.3 cm, 5.6 cm) to malignant (7.3 cm, 6.9 cm) groups (P < 0.05). The diagnostic criteria of benign, potentially malignant and malignant pheochromocytomas in adrenal medulla and in extra-adrenal sites are well established according to the WHO classification of endocrine tumors (2004). The closer relationship is found between clinical manifestations and pathologic changes. The definite type and nature of pheochromocytomas are mainly rested upon the pathologic examination.

  16. [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.

  17. What Is Adrenal Cortical Cancer?

    MedlinePlus

    ... include pheochromocytomas (which are most often benign) and neuroblastomas . This document is about tumors and cancers of ... does not discuss tumors of the adrenal medulla. Neuroblastoma s are covered in a separate document . Adrenal cortex ...

  18. Adrenal gland hormone secretion (image)

    MedlinePlus

    The adrenal gland secretes steroid hormones such as cortisol and aldosterone. It also makes precursors that can be converted to ... steroids (androgen, estrogen). A different part of the adrenal gland makes adrenaline (epinephrine). When the glands produce more ...

  19. Congenital adrenal hyperplasia.

    PubMed

    Merke, Deborah P; Bornstein, Stefan R

    Congenital adrenal hyperplasia (CAH) due to deficiency of 21-hydroxylase is a disorder of the adrenal cortex characterised by cortisol deficiency, with or without aldosterone deficiency, and androgen excess. Patients with the most severe form also have abnormalities of the adrenal medulla and epinephrine deficiency. The severe classic form occurs in one in 15,000 births worldwide, and the mild non-classic form is a common cause of hyperandrogenism. Neonatal screening for CAH and gene-specific prenatal diagnosis are now possible. Standard hormone replacement fails to achieve normal growth and development for many children with CAH, and adults can experience iatrogenic Cushing's syndrome, hyperandrogenism, infertility, or the development of the metabolic syndrome. This Seminar reviews the epidemiology, genetics, pathophysiology, diagnosis, and management of CAH, and provides an overview of clinical challenges and future therapies.

  20. Catecholamine secretion and adrenal nerve activity in response to movements of normal and inflamed knee joints in cats.

    PubMed Central

    Sato, A; Sato, Y; Schmidt, R F

    1986-01-01

    The effects of articular stimulation on adrenal catecholamine secretion and adrenal sympathetic nerve activity were studied using halothane anaesthetized cats. Various natural passive movements were applied to the normal and inflamed knee joints. Rhythmic flexions and extensions as well as rhythmic inward and outward rotation of normal knee joints within their physiological range of motion did not change nerve activity or the secretion of adrenal catecholamines. Static outward rotation in the normal working range was also ineffective. However, as soon as this static rotation was extended into the noxious range, significant increases in both of these variables were elicited. In the acutely inflamed knee joint, various passive movements produced increases in both adrenal sympathetic and catecholamine secretion. Especially noteworthy was the finding that movements of the inflamed knee joint that were within the normal range of motion produced increases in all variables. Articularly induced increases in adrenal sympathetic nerve activity were diminished by severing various hind-limb somatic afferent nerves and abolished by complete denervation of the knee joint. Additionally, section of the adrenal sympathetic nerves eliminated the catecholamine secretion response. From these data it was concluded that the responses observed in these experiments were reflexes having an afferent limb in hind-limb nerves and an efferent limb in the adrenal sympathetic nerves. A contribution of supraspinal structures was suggested for the reflex responses of sympatho-adrenal medullary function evoked by knee joint stimulations, since spinal transection at the C2 level completely abolished the responses. PMID:3795070

  1. Expression and externalization of annexin 1 in the adrenal gland: structure and function of the adrenal gland in annexin 1-null mutant mice.

    PubMed

    Davies, Evelyn; Omer, Selma; Buckingham, Julia C; Morris, John F; Christian, Helen C

    2007-03-01

    Annexin 1 (ANXA1) is a member of the annexin family of phospholipid- and calcium-binding proteins with a well demonstrated role in early delayed (30 min to 3 h) inhibitory feedback of glucocorticoids in the hypothalamus and pituitary gland. This study used adrenal gland tissue from ANXA1-null transgenic mice, in which a beta-galactosidase (beta-Gal) reporter gene was controlled by the ANXA1 promoter, and wild-type control mice to explore the potential role of ANXA1 in adrenal function. RT-PCR and Western blotting revealed strong expression of ANXA1 mRNA and protein in the adrenal gland. Immunofluorescence labeling of ANXA1 in wild-type and beta-Gal expression in ANXA1-null adrenals localized intense staining in the outer perimeter cell layers. Immunogold electron microscopy identified cytoplasmic and nuclear ANXA1 labeling in outer cortical cells and capsular cells. Exposure of adrenal segments in vitro to dexamethasone (0.1 mum, 3 h) caused an increase in the amount of ANXA1 in the intracellular compartment and attached to the surface of the cells. The N-terminal peptide ANXA1(Ac2-26) inhibited corticosterone release. Corticosterone release was significantly greater from ANXA1-null adrenal cells compared with wild type in response to ACTH (10 pm to 5 nm). In contrast, basal and ACTH-stimulated aldosterone release from ANXA1-null adrenal cells was not different from wild type. Morphometry studies demonstrated that ANXA1 null adrenal glands were smaller than wild-type, and the cortical/medullary area ratio was significantly reduced. These results suggest ANXA1 is a regulator of adrenocortical size and corticosterone secretion.

  2. Adrenal Gland Disorders: Condition Information

    MedlinePlus

    ... source of sex steroids, such as estrogen and testosterone. What are adrenal gland disorders? Adrenal gland disorders occur when the adrenal glands do not work properly. They can be classified into disorders that occur when too much hormone is produced or when too little hormone is produced. These ...

  3. 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

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

    PubMed

    Builes-Montaño, Carlos Esteban; 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.

  5. Congenital adrenal hyperplasia

    MedlinePlus

    ... or inappropriately). Congenital adrenal hyperplasia can affect both boys and girls. About 1 in 10,000 to 18,000 ... penis but normal testes Well-developed muscles Both boys and girls will be tall as children, but much shorter ...

  6. PET studies of parkinsonian patients treated with autologous adrenal implants.

    PubMed

    Guttman, M; Burns, R S; Martin, W R; Peppard, R F; Adam, M J; Ruth, T J; Allen, G; Parker, R A; Tulipan, N B; Calne, D B

    1989-08-01

    Transplantation of autologous adrenal medulla tissue into the striatum has recently been proposed as a treatment for Parkinson's disease. We report the use of positron emission tomography (PET) to evaluate patients who had adrenal implants placed into the right caudate. 6-[18F] fluoro-L-dopa (6-FD) scans were performed to study the integrity and activity of the implant, and the nigrostriatal dopamine system before and six weeks after transplantation surgery. [68Ga] Gallium-ethylenediaminetetraacetate (Ga) scans were also performed to assess the blood brain barrier. The Ga scans performed on two patients showed increased permeability of the blood brain barrier at the surgical site. 6-FD PET scans in five patients did not show a consistent change in striatal uptake following adrenal medullary implantation after six weeks. Further assessment of implant viability with 6-FD PET scans after longer follow up may provide useful information if the blood-brain barrier becomes re-established with the passage of time.

  7. Medullary carcinoma in a lingual thyroid.

    PubMed

    Yaday, S; Singh, I; Singh, J; Aggarwal, N

    2008-03-01

    Total ectopia of thyroid is a rare phenomenon and malignant change in an ectopic thyroid is even rarer. We report a case of medullary carcinoma in a total ectopic lingual thyroid occurring in a 45-year-old woman who presented with dysphagia, plummy voice and a round sessile mass at the base of the tongue. The mass was extirpated using Trotter's midline approach. Upon examination, it was found to be medullary carcinoma in an ectopic thyroid. Permanent substitution therapy with thyroxine secured the euthyroid status of the patient. The embrylogical basis and a review of literature regarding carcinomatous change in an ectopic thyroid are also discussed. There is a need to investigate for an ectopic thyroid, or even total ectopia, in the case of any smooth mass found at the base of the tongue.

  8. Schwannosis induced medullary compression in VACTERL syndrome.

    PubMed

    Treacy, A; Redmond, M; Lynch, B; Ryan, S; Farrell, M; Devaney, D

    2009-01-01

    A 7-year-old boy with a history of VACTERL syndrome was found collapsed in bed. MRI had shown basilar invagination of the skull base and narrowing of the foramen magnum. Angulation, swelling and abnormal high signal at the cervicomedullary junction were felt to be secondary to compression of the medulla. Neuropathologic examination showed bilateral replacement of the medullary tegmentum by an irregularly circumscribed cellular lesion which was composed of elongated GFAP/S 100-positive cells with spindled nuclei and minimal atypia. The pathologic findings were interpreted as intramedullary schwannosis with mass effect. Schwannosis, is observed in traumatized spinal cords where its presence may represent attempted, albeit aberrant, repair by inwardly migrating Schwann cells ofperipheral origin. In our view the compressive effect of the basilar invagination on this boy's medulla was of sufficient magnitude to have caused tumoral medullary schwannosis with resultant intermittent respiratory compromise leading to reflex anoxic seizures.

  9. Medial medullary infarction: abnormal ocular motor findings.

    PubMed

    Kim, J Soo; Choi, K-D; Oh, S-Y; Park, S-H; Han, M-K; Yoon, B-W; Roh, J-K

    2005-10-25

    In 20 consecutive patients with isolated medial medullary infarction, abnormal ocular motor findings included nystagmus (n = 8), ocular contrapulsion (n = 5), and contralesional ocular tilt reaction (n = 2). The nystagmus was ipsilesional (n = 4), gaze-evoked (n = 5), upbeating (n = 4), and hemiseesaw (n = 1). The ocular motor abnormalities may be explained by involvements of the nucleus prepositus hypoglossi, medial longitudinal fasciculus or efferent fibers from the vestibular nuclei, climbing fibers, and cells of the paramedian tracts.

  10. Concurrent medullary and papillary carcinoma of thyroid.

    PubMed

    Ateşpare, Altay; Çalış, Aslı Batur; Çelik, Öner; Yener, Neşe; Vural, Çetin

    2015-01-01

    Simultaneous occurrence of papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) in the same thyroid gland is a rare condition. These tumors derive from different cells; PTC originates from follicular cells whereas MTC originates from parafollicular cells. Because of this, the treatment of these tumors also differs. This article describes two rare cases of the simultaneous occurrence of MTC and PTC in the thyroid gland.

  11. Normal conus medullaris: CT criteria for recognition

    SciTech Connect

    Grogan, J.P.; Daniels, D.L.; Williams, I.L.; Rauschning, W.; Haughton, V.M.

    1984-06-01

    The normal CT configuration and dimension of the conus medullaris and adjacent spinal cord were determined in 30 patients who had no clinical evidence of conus compression. CT studies were also correlated with anatomic sections in cadavers. The normal conus on CT has a distinctive oval configuration, an arterior sulcus, and a posterior promontory. The anteroposterior diameter ranged from 5 to 8 mm; the transverse diameter from 8 to 11 mm. Intramedullary processes altered both the dimensions and configuration of the conus.

  12. The NANETS Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors: Pheochromocytoma, Paraganglioma & Medullary Thyroid Cancer

    PubMed Central

    Chen, Herbert; Sippel, Rebecca S.; Pacak, Karel

    2012-01-01

    Pheochromocytomas, intra-adrenal paraganglioma, and extra-adrenal sympathetic and parasympathetic paragangliomas are neuroendocrine tumors derived from adrenal chromaffin cells or similar cells in extra-adrenal sympathetic and parasympathetic paraganglia, respectively. Serious morbidity and mortality rates associated with these tumors are related to the potent effects of catecholamines on various organs, especially those of the cardiovascular system. Before any surgical procedure is done, pre-operative blockade is necessary to protect the patient against significant release of catecholamines due to anesthesia and surgical manipulation of the tumor. Treatment options vary with the extent of the disease with laparoscopic surgery being the preferred treatment for removal of primary tumors. Medullary thyroid cancer (MTC) is a malignancy of the thyroid C-cells or parafollicular cells. Thyroid c-cells elaborate a number of peptides and hormones, such as calcitonin, CEA, and chromogranin A. Some or all of these markers are elevated in patients with MTC and can be used to confirm the diagnosis as well as to follow patients longitudinally for recurrence. MTC consists of a spectrum of disease that ranges from extremely indolent tumors that are stable for many years to aggressive types associated with a high mortality rate. Genetic testing for RET mutations has allowed identification of familial cases and prophylactic thyroidectomy for cure. The only curative treatment is complete surgical resection. PMID:20664475

  13. Two distinct aquaporin-4 cDNAs isolated from medullary cone of quail kidney.

    PubMed

    Yang, Yimu; Cui, Yujun; Fan, Zheng; Cook, George A; Nishimura, Hiroko

    2007-05-01

    Water deprivation or arginine vasotocin upregulates aquaporin-2 (AQP2) expression in apical and subapical regions of medullary collecting duct (CD) cells of Coturnix coturnix quail (q) kidneys. We therefore aimed to determine whether the CD has AQPs mediating water exit from the intracellular to the extracellular (interstitial) space. Using a homologue cloning technique, we isolated two distinct qAQP4 cDNAs from quail medullary cones; long (L, open reading frames) and short (S) cDNA encoded 335 (qAQP4-L) and 301 (qAQP4-S) amino acids with, respectively, 80% and 87% identity to human long- and short-form AQP4. qAQP4-S is identical to qAQP4-L from the second initiation site. Both isoforms have two NPA motifs, but lack cysteine at the known mercury-sensitive site. qAQP4-L and qAQP4-S are expressed in membranes of Xenopus laevis oocytes, but both failed to increase the water permeability (P(f)) of oocytes exposed to a hypotonic solution. Glutamate (Q242) replacement with histidine did not increase P(f). With conventional RT-PCR and real-time PCR, qAQP4-L/S mRNA signals were detected in the brain, lung, heart, intestine, adrenal gland, skeletal muscle, liver, and kidney (higher in medulla than in cortical region). qAQP4-L mRNA was detected only in the brain and adrenal gland. Orthogonal arrays of intramembranous particles were not detected in quail CDs. The results suggest that although qAQP4-L and qAQP4-S have high homology to mammalian AQP4, their physiological function may be different.

  14. A morphological and histological examination of the pan-tropical spotted dolphin (Stenella attenuata) and the spinner dolphin (Stenella longirostris) adrenal gland.

    PubMed

    Clark, L S; Cowan, D F; Pfeiffer, D C

    2008-04-01

    The morphology and histology of the cetacean adrenal gland are poorly understood. Therefore, this study examined 32 pairs of adrenal glands from 18 pan-tropical spotted dolphins (Stenella attenuata) and 14 spinner dolphins (Stenella longirostris). In both species, the cortex was pseudolobulated and contained a typical mammalian zonation. Medullary protrusions (0-3 per section) and a medullary band were identified in both species. For S. attenuata, no statistical differences were found in the cortex to medulla (CM) ratio or the percent cross-sectional area (PCA) of the adrenal glands compared with sex or sexual maturity. The mean CM ratio for S. attenuata was 2.34 and the PCA was 64.4% cortex, 29.4% medulla and 6.2%'other'. 'Other' indicates blood vessels, connective tissue and the gland capsule itself. For S. longirostris, there was no statistical difference in the CM ratio compared with sexual maturity. However, a statistical difference was found between the CM ratio and sex, suggesting sexual dimorphism (female CM ratio = 2.46 and males = 3.21). No statistical differences were found in the PCA of S. longirostris adrenal glands by sexual maturity. However, a statistical difference was found between the PCA by sex. Female S. longirostris adrenal glands consisted of 65.0% cortex, 27.3% medulla and 7.7% 'other', whereas male adrenal glands consisted of 71.7% cortex, 22.7% medulla and 5.6% 'other'.

  15. Quantitation of the prominent medullary pyramid: a reappraisal.

    PubMed

    Paling, M R; Black, W C

    1986-06-01

    We propose a revised objective measurement of the size of the renal medullary pyramid in the assessment of the prominent renal pyramid: the medullary-renal ratio (MRR). (Formula: see text). This is a more accurate assessment of the size of the renal pyramid relative to the size of the kidney than the previously proposed medullary pyramid index, which fails to take into account the varying morphology of otherwise normal kidneys.

  16. Upregulation of neuronal nitric oxide synthase mRNA and protein in adrenal medulla of water-deprived rats.

    PubMed

    Lai, Feng-Jie; Huang, Shiue-Shin; Hsieh, Ming-Chia; Hsin, Shih-Chie; Wu, Chin-Han; Hsin, Ya-Chieh; Shin, Shyi-Jang

    2005-01-01

    Experiments were performed to investigate whether adrenal neuronal nitric oxide synthase (nNOS) mRNA and protein expression are responsive to alterations in body volume. Using an RT-PCR technique, the relative quantities of nNOS mRNA as well as the tyrosine hydroxylase and phenylethanolamine N-methyltransferase mRNA in the adrenals of water-deprived rats significantly increased from 12 hr to 4 days. In situ hybridization and immunohistochemical study showed that water deprivation activated nNOS mRNA and protein expression in the adrenal medulla. Four days after water deprivation, nNOS protein expression determined by Western blot significantly increased in the adrenal gland. Our results are the first to demonstrate that nNOS syntheses in the adrenal medulla are markedly increased in water-deprived rats. This study also indicates that the upregulation of nNOS synthesis of the adrenal medulla is associated with the activation of adrenal medullary function in the face of volume depletion.

  17. CT demonstration of bilateral adrenal hemorrhage

    SciTech Connect

    Ling, D.; Korobkin, M.; Silverman, P.M.; Dunnick, N.R.

    1983-08-01

    Bilateral adrenal hemorrhage with subsequent adrenal insufficiency is a recognized complication of anticoagulant therapy. Because the clinical manifestations are often nonspecific, the antemortem diagnosis of adrenal hemorrhage has been a difficult clinical problem. Computed tomography (CT) provides detailed images of the adrenal glands that are not possible with conventional imaging methods. The CT findings of bilateral adrenal hemorrhage in an anticoagulated patient are reported.

  18. The renal medullary interstitium: focus on osmotic hypertonicity.

    PubMed

    Sadowski, Janusz; Dobrowolski, Leszek

    2003-03-01

    1. There has been continued interest in the functional role of the renal medullary interstitium and intense research in this area has furnished new information regarding the extent, dynamics and mechanisms determining fluctuations in medullary osmotic hypertonicity. 2. Any change in the tonicity (interstitial solute concentration) indicates an imbalance of the rate of solute delivery to the interstitium (by tubular transport) and solute removal therefrom (by the microcirculation). It is often difficult to establish whether alteration of the delivery or removal triggered the change in medullary tissue tonicity. 3. Newer in vivo studies have confirmed earlier predictions and indirect evidence indicating that the rate of NaCl transport in the ascending limb of the loop of Henle is the major determinant of medullary ionic hypertonicity. 4. The hypothesis of a 'washout' of medullary solutes during increased medullary blood flow (MBF) has been re-evaluated. A novel experimental approach has provided direct evidence of a modest dissipation of medullary solutes with increasing MBF and a modest accumulation of solutes with decreasing MBF. 5. Increasing evidence is reviewed indicating that medullary tonicity is not only a regulated variable, but also that it may itself modulate the activity of multiple local endocrine and paracrine control systems and thereby affect local microcirculation and the function of medullary interstitial and tubular cells.

  19. Congenital lipoid adrenal hyperplasia

    PubMed Central

    2014-01-01

    Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most fatal form of CAH, as it disrupts adrenal and gonadal steroidogenesis. Most cases of lipoid CAH are caused by recessive mutations in the gene encoding steroidogenic acute regulatory protein (StAR). Affected patients typically present with signs of severe adrenal failure in early infancy and 46,XY genetic males are phenotypic females due to disrupted testicular androgen secretion. The StAR p.Q258X mutation accounts for about 70% of affected alleles in most patients of Japanese and Korean ancestry. However, it is more prevalent (92.3%) in the Korean population. Recently, some patients have been showed that they had late and mild clinical findings. These cases and studies constitute a new entity of 'nonclassic lipoid CAH'. The cholesterol side-chain cleavage enzyme, P450scc (CYP11A1), plays an essential role converting cholesterol to pregnenolone. Although progesterone production from the fetally derived placenta is necessary to maintain a pregnancy to term, some patients with P450scc mutations have recently been reported. P450scc mutations can also cause lipoid CAH and establish a recently recognized human endocrine disorder. PMID:25654062

  20. 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

  1. Synthesis, internalization, and localization of atrial natriuretic peptide in rat adrenal medulla

    SciTech Connect

    Morel, G.; Chabot, J.G.; Garcia-Caballero, T.; Gossard, F.; Dihl, F.; Belles-Isles, M.; Heisler, S.

    1988-07-01

    Some, though not all studies, have indicated that atrial natriuretic peptide (ANP) can bind to adrenal medullary cells. ANP-like immunoreactivity (ANP-LI) has also been identified in catecholamine-secreting cells. Together, these findings suggest that ANP may be taken up and/or synthesized in the adrenal medulla. The present study was designed to ascertain, by in situ hybridization, whether adrenal chromaffin cells could synthesize ANP, to define by an in vivo ultrastructural autoradiographic approach, whether ANP could, in fact, bind to rat adrenal medulla cells, to determine whether there was a cellular (noradrenaline (NA) vs. adrenaline (A)) selectivity in the binding process, and to establish whether extracellular (125I)ANP could be internalized by these cells. The cellular and subcellular distribution of endogenous ANP-LI was also investigated in both cell types by cryoultramicrotomy and immunocytochemical approaches. The in situ hybridization studies indicate the presence of mRNA to ANP in about 15% of adrenal medullary cells. Intravenous injection of (125I)ANP resulted in a 3-fold, preferential and specific radiolabeling of A-as compared to NA-containing cells. In A-containing cells, plasma membranes were significantly labeled 2 and 5 min post injection; cytoplasmic matrix, mitochondria, and secretory granules throughout the time course studied (1-30 min post injection). Lysosomes, rough endoplasmic reticulum, Golgi apparatus, and nuclei were not labeled. ANP-LI was identified in both NA- and A-containing cells; in the former, it was almost exclusively localized in secretory vesicles, in the latter it was detected in plasma membranes, cytoplasmic matrix, nuclear euchromatin, some mitochondria and relatively fewer granules than in NA-containing cells.

  2. Development of adrenal cortex zonation.

    PubMed

    Xing, Yewei; Lerario, Antonio M; Rainey, William; Hammer, Gary D

    2015-06-01

    The human adult adrenal cortex is composed of the zona glomerulosa (zG), zona fasciculata (zF), and zona reticularis (zR), which are responsible for production of mineralocorticoids, glucocorticoids, and adrenal androgens, respectively. The final completion of cortical zonation in humans does not occur until puberty with the establishment of the zR and its production of adrenal androgens; a process called adrenarche. The maintenance of the adrenal cortex involves the centripetal displacement and differentiation of peripheral Sonic hedgehog-positive progenitors cells into zG cells that later transition to zF cells and subsequently zR cells.

  3. [Sonography of the adrenal glands].

    PubMed

    Rüeger, R

    2005-03-02

    In the abdominal ultrasonography, the representation of normal adrenal glands is frequently problematic, also for experienced practitioners in ultrasonography. During a seminary at the congress of the SGUM in Davos, in June 2004, it was specially entered to this problematic by anatomical illustrations and live demonstrations. These statements will be summarized in the following article. Also, the technics of examination of the adrenal glands will be explained, especially in comparison to anatomical cut-preparations. It will be entered to particular pathological statements of the adrenal glands. The proceeding will be described by the localisation of accidentally detected tumours of adrenal glands.

  4. Adrenal crisis secondary to bilateral adrenal haemorrhage after hemicolectomy

    PubMed Central

    Tsang, Venessa H M; Kabir, Shahrir; Ip, Julian C Y

    2016-01-01

    Summary Adrenal haemorrhage is a rare cause of adrenal crisis, which requires rapid diagnosis, prompt initiation of parenteral hydrocortisone and haemodynamic monitoring to avoid hypotensive crises. We herein describe a case of bilateral adrenal haemorrhage after hemicolectomy in a 93-year-old female with high-grade colonic adenocarcinoma. This patient’s post-operative recovery was complicated by an acute hypotensive episode, hypoglycaemia and syncope, and subsequent computed tomography (CT) scan of the abdomen revealed bilateral adrenal haemorrhage. Given her labile blood pressure, intravenous hydrocortisone was commenced with rapid improvement of blood pressure, which had incompletely responded with fluids. A provisional diagnosis of hypocortisolism was made. Initial heparin-induced thrombocytopenic screen (HITTS) was positive, but platelet count and coagulation profile were both normal. The patient suffered a concurrent transient ischaemic attack with no neurological deficits. She was discharged on a reducing dose of oral steroids with normal serum cortisol levels at the time of discharge. She and her family were educated about lifelong steroids and the use of parenteral steroids should a hypoadrenal crisis eventuate. Learning points: Adrenal haemorrhage is a rare cause of hypoadrenalism, and thus requires prompt diagnosis and management to prevent death from primary adrenocortical insufficiency. Mechanisms of adrenal haemorrhage include reduced adrenal vascular bed capillary resistance, adrenal vein thrombosis, catecholamine-related increased adrenal blood flow and adrenal vein spasm. Standard diagnostic assessment is a non-contrast CT abdomen. Intravenous hydrocortisone and intravenous substitution of fluids are the initial management. A formal diagnosis of primary adrenal insufficiency should never delay treatment, but should be made afterwards. PMID:27855238

  5. The effects of sustained delivery of diosgenin on the adrenal gland of female rats.

    PubMed

    Benghuzzi, Hamed; Tucci, Michelle; Eckie, Rebecca; Hughes, James

    2003-01-01

    Diosgenin is a steroidal saponin, which is extracted from the root of Wild Yam (Dioscorea villosa). It has been reported to have tremendous medical applications. In addition, as an herbal extract it appears to be free of any major adverse effects. Recently, Wild Yam has been used to minimize post-menopausal symptoms and is sold unregulated over the counter at a variety of pharmacy and health food stores. The specific objectives of this study were to continuously deliver diosgenin to adult ovariectomized female rats for 45 days and follow changes in body weight, organ weight and histopathological changes in the adrenal gland. Adult female Sprague Dawley rats were divided into three equal groups (n = 54, 250-300 gm BW). Rats in group I served as the control group, animals in group II were ovariectomized and animals in group II were ovariectomized, and supplemented with tricalcium phosphate (TCP) drug delivery system loaded with 500 mg diosgenin. The results indicated that ovariectomized animals had a significant increase in body weight and spleen weights. Slight increases in wet adrenal weights were observed in the ovariectomized group compared to the control animals. Histopathological evaluation of the adrenal gland revealed an increase in the cortical and medullary adrenal areas of the ovariectomized group and a significant decrease in these areas in the diosgenin treated animals (p < 0.001). The information is considered important because reduction in adrenal mass may poses a potential for major endocrine complications.

  6. 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.

  7. Adrenal glands transabdominal ultrasonography - pictorial essay.

    PubMed

    Chira, Romeo Ioan; Chira, Alexandra; Manzat-Saplacan, Roberta Maria; Nagy, Georgiana; Valea, Ana; Silaghi, Alina Cristina; Mircea, Petru Adrian; Valean, Simona

    2017-05-03

    Adrenal gland ultrasonography is one of the corner stones of the abdominal ultrasonography examination for many medical specialties. The adrenal areas can be easily overlooked though adrenal gland pathology is diverse. We present the normal aspects and various transabdominal ultrasonography findings of the adrenal glands, both common and rare. Even though ultrasound examination is operator and patient dependent, we consider the examination of the adrenal glands very important, due to relatively frequent incidental detection of an adrenal mass.

  8. The Effects of High Intensity Cycle Exercise on Sympatho-Adrenal- Medullary Response Patterns

    DTIC Science & Technology

    1989-01-01

    cap’fib -1) were determined from amylase -periodic acid-Schiff- stained fibers and analyzed by methods previously described (1,2). Maximal lea Power (MLP...This lack of a relationship between endogenous opioid peptides and blood lactate at very high power outputs was observed for beta - endorphin in our...Cytochem. 18: 670-672, 1970. 6. Brooks, S., J. Burrin, M.E. Cheetham, G.M. Hall, T. Yeo, and C. Williams. The responses of catecholamines and beta

  9. Time-Course of Release of Catecholamines from Individual Vesicles During Exocytosis at Adrenal Medullary Cells

    DTIC Science & Technology

    1994-10-12

    microelectrodes. Two electrochemical techniques were employed: cyclic voltammetry and amperometry. Spikes obtained by amperometry had a faster time course than...those measured by cyclic voltammetry , consistent with the different concentration profiles established by each technique. However, the experimental data

  10. Central pontine myelinolysis and medullary myelinolysis.

    PubMed

    Bhagavan, B S; Wagner, J A; Juanteguy, J

    1976-05-01

    Central pontine myelinolysis (CPM) is a rare, acute, and uniformly fatal demyelinative process that involves the pons almost exclusively. Three cases diagnosed at autopsy illustrate the characteristic clinical course and pathologic features of CPM. A unique extrapontine location of a similar process is noted in the medulla of a 6-year-old girl. The term "medullary myelinolysis" is a descriptive designation for demyelination that occurs predominantly in this area. The clinical and pathologic features of CPM are reviewed in detail, together with a brief review of theories of metabolic, nutritional, vascular, and endogenous and exogenous toxic factors that act either singly or in concert in the cause and pathogenesis of CPM.

  11. Medullary trichomalacia in 6 German shepherd dogs.

    PubMed

    Tieghi, Chiara; Miller, William H; Scott, Danny W; Pasquinelli, Gianandrea

    2003-02-01

    Medullary trichomalacia is the name proposed for a hair shaft abnormality that was recognized in 6 German shepherd dogs. Affected dogs had multifocal areas of broken hairs, especially on the dorsolateral trunk. Microscopic examination of hair shafts revealed focal areas of loss of architecture, swelling, and apparent softening of the medulla, followed by longitudinal (length-wise) splitting and breakage of the hair shaft. No cause could be found. Affected dogs were otherwise healthy, and apparent spontaneous recovery was the usual outcome. Relapses may occur.

  12. Adrenal Histoplasmosis in Immunocompetent Patients Presenting as Adrenal Insufficiency.

    PubMed

    Gajendra, Smeeta; Sharma, Rashi; Goel, Shalini; Goel, Ruchika; Lipi, Lipika; Sarin, Hemanti; Guleria, Mridula; Sachdev, Ritesh

    2016-01-01

    Histoplasmosis is an infectious disease caused by the dimorphic fungus Histoplasma capsulatum, endemic in central and eastern states of United States, South America and Africa. India is considered to be non-endemic area for histoplasmosis. Disseminated histoplasmosis may affect almost all systems. Disseminated histoplasmosis with asymptomatic adrenal involvement has been described in immunocompromised patients; whereas isolated adrenal involvement with adrenal insufficiency as the presenting manifestation of the disease is rare. Twelve patients from a non-endemic area with adrenal histoplasmosis, who were immunocompetent and diagnosed as adrenal histoplasmosis by cytology/histopathology between January 2012 to December 2014 were studied. 18F-FDG PET/CT (fluorodeoxyglucose positron emission tomography/computed tomography) was used to assess the extent of involvement. There were a total of 12 immunocompetent males (mean age: 56.9 years). Ten patients had bilateral adrenal involvement and two had a unilateral left adrenal mass. All the patients had histopathologically/cytologically proven adrenal histoplasmosis. Two patients had simultaneous histoplasmosis of other sites, one in the epiglottis and the other in the alveolus. 18F-FDG PET/CT was performed in 10 patients showing high FDG uptake in the adrenals. All these patients received Amphotericin B and/or Itraconazole treatment that led to symptomatic improvement. A diagnosis of invasive fungal infection requires a high index of suspicion, especially in immunocompetent patients who present with nonspecific symptoms, clinical signs, laboratory and radiological features that can resemble adrenal neoplasms. Clinical specimens must be sent for cytopathology/histopathology together with fungal culture for a definite diagnosis and appropriate management.

  13. [Adrenal carcinoma induced hypoglycemia].

    PubMed

    Soutelo, Jimena; Saban, Melina; Borghi Torzillo, Florencia; Lutfi, Ruben; Leal Reyna, Mariela

    2013-01-01

    Adrenal carcinoma is a rare malignancy of poor prognosis. The most common clinical presentation is secondary to hormone production, while the development of symptomatic hypoglycemia is exceptional. We report the case of a 37 year old-woman admitted to hospital with severe hypoglycemia, hypertension, hypokalemia and amenorrhea. In the laboratory we found hypoglycemia, with low insulin levels, and androgen levels in tumor range. CT of abdomen and pelvis showed a heterogeneous lesion of solid appearance without a cleavage plane relative to liver parenchyma, and intense contrast enhancement. Retroperitoneal mass was removed, and the patient evolved without complications, blood glucose and potassium were normalized, blood pressure stabilized and menstrual cycles recovered.

  14. Persistent hypercalcitoninemia in patients with medullary thyroid cancer.

    PubMed

    Misso, Claudia; Calzolari, Filippo; Puxeddu, Efisio; Lucchini, Roberta; Monacelli, Massimo; Giammartino, Camillo; Sanguinetti, Alessandro; d'Ajello, Michele; Ragusa, Mark; Avenia, Nicola

    2009-01-01

    Medullary thyroid carcinoma is a highly malignant and progressive disease. Surgery is the only effective treatment. Calcitonin is a significant marker for medullary thyroid carcinoma, and due to its sensitivity it represents a useful tool for the follow-up. The outcome of patients affected by medullary thyroid carcinoma depends on tumor size, lymph node involvement, and adequacy of primary surgical management. In the present study, the authors reviewed their own experience in the cure of medullary thyroid carcinoma. Forty-one patients operated for sporadic medullary thyroid carcinoma were included. Indications for surgery, inclusive of lymphectomy techniques, timing of redo surgery, and the meaning of calcitonin levels in highlighting disease are extensively discussed. Patients with elevated calcitonin levels and favorable outcome are considered, together with the various diagnostic tools to be employed during patient workup.

  15. The bovine peripheral-type benzodiazepine receptor: A receptor with low affinity for benzodiazepines

    SciTech Connect

    Parola, A.L.; Laird, H.E. II )

    1991-01-01

    The density of bovine peripheral-type benzodiazepine receptors (PBR) in four tissues was highest in adrenal cortex. The adrenal cortex PBR cofractionated with a mitochondrial membrane marker enzyme and could be solubilized with intact ligand binding properties using digitonin. The membrane bound and soluble mitochondrial receptors were pharmacologically characterized and showed the rank order of potency to inhibit ({sup 3}H)PK 11195 binding was PK 11195 > protoporphyrin IX > benzodiazepines. ({sup 3}H)PK 11195 binding to bovine adrenal mitochondria was unaffected by diethylpyrocarbonate, a histidine residue modifying reagent that decreased binding to rat liver mitochondria by 70%. ({sup 3}H)PK 14105 photolabeled the bovine PBR and the Mr was estimated under nondenaturing and denaturing conditions. These results demonstrate the bovine peripheral-type benzodiazepine receptor is pharmacologically and biochemically distinct from the rat receptor, but the receptor component photolabeled by an isoquinoline ligand has a similar molecular weight.

  16. The pathology of preclinical medullary thyroid carcinoma.

    PubMed

    Ashworth, Michael

    2004-01-01

    Medullary carcinoma of the thyroid (MTC) occurs sporadically, or in familial forms in familial medullary thyroid carcinoma and multiple endocrine neoplasia types 2A and 2B. In the familial forms it is associated with well-characterized, germline mutations in the RET protooncogene. The mutation sites differ in MEN2A and MEN2B, and MTC develops at an earlier age and is more aggressive in MEN2B. Screening of relatives of affected individuals for such mutations can identify those at risk of developing MTC and total thyroidectomy can be carried out in the first decade of life before the development of clinical disease. Analysis of such removed thyroid glands shows abnormalities of the parafollicular C-cells in almost all cases. The abnormalities range from C-cell hyperplasia, either diffuse or nodular, to microcarcinoma and occasionally frank MTC. The abnormalities are bilateral and affect the upper two thirds of the thyroid lobes. Microcarcinomas may be visible with the naked eye, but often they are identified only on microscopy. Histopathological examination of the entire gland is essential.

  17. Advanced medullary thyroid cancer: pathophysiology and management

    PubMed Central

    Ferreira, Carla Vaz; Siqueira, Débora Rodrigues; Ceolin, Lucieli; Maia, Ana Luiza

    2013-01-01

    Medullary thyroid carcinoma (MTC) is a rare malignant tumor originating from thyroid parafollicular C cells. This tumor accounts for 3%–4% of thyroid gland neoplasias. MTC may occur sporadically or be inherited. Hereditary MTC appears as part of the multiple endocrine neoplasia syndrome type 2A or 2B, or familial medullary thyroid cancer. Germ-line mutations of the RET proto-oncogene cause hereditary forms of cancer, whereas somatic mutations can be present in sporadic forms of the disease. The RET gene encodes a receptor tyrosine kinase involved in the activation of intracellular signaling pathways leading to proliferation, growth, differentiation, migration, and survival. Nowadays, early diagnosis of MTC followed by total thyroidectomy offers the only possibility of cure. Based on the knowledge of the pathogenic mechanisms of MTC, new drugs have been developed in an attempt to control metastatic disease. Of these, small-molecule tyrosine kinase inhibitors represent one of the most promising agents for MTC treatment, and clinical trials have shown encouraging results. Hopefully, the cumulative knowledge about the targets of action of these drugs and about the tyrosine kinase inhibitor-associated side effects will help in choosing the best therapeutic approach to enhance their benefits. PMID:23696715

  18. Radionuclide bone scanning of medullary chondrosarcoma

    SciTech Connect

    Hudson, T.M.; Chew, F.S.; Manaster, B.J.

    1982-12-01

    /sup 99m/Tc methylene diphosphonate bone scans of 18 medullary chondrosarcomas of bone were correlated with pathologic macrosections of the resected tumors. There was increased scan uptake by all 18 tumors, and the uptake in 15 scans corresponded accurately to the anatomic extent of the tumors. Only three scans displayed increased uptake beyond the true tumor margins; thus, the extended pattern of uptake beyond the true tumor extent is much less common in medullary chondrosarcomas than in many other primary bone tumors. Therefore, increased uptake beyond the apparent radiographic margin of the tumor suggests possible occult tumor spread. Pathologically, there was intense reactive new bone formation and hyperemia around the periphery of all 18 tumors, and there were foci of enchondral ossification, hyperemia, or calcification within the tumor itself in nearly every tumor. Three scans displayed less uptake in the center of the tumors than around their peripheries. One of these tumors was necrotic in the center, but the other two were pathologically no different from tumors that displayed homogeneous uptake on the scan.

  19. Radionuclide bone scanning of medullary chondrosarcoma

    SciTech Connect

    Hudson, T.M.; Chew, F.S.; Manaster, B.J.

    1982-12-01

    Technetium-99m methylene diphosphonate bone scans of 18 medullary chondrosarcomas of bone were correlated with pathologic macrosections of the resected tumors. There was increased scan intake by all 18 tumors, and the uptake in 15 scans corresponded accurately to the anatomic extent of the tumors. Only three scans displayed increased uptake beyond the true tumor margins; thus, the ''extended pattern of uptake'' beyond the true tumor extent is much less common in medullary chondrosarcomas than in many other primary bone tumors. Therefore, increased uptake beyond the apparent radiographic margin of the tumor suggests possible occult tumor spread. Pathologically, there was intense reactive new bone formation and hyperemia around the periphery of all 18 tumors, and there were foci of enchondral ossification, hyperemia, or calcification within the tumor itself in nearly every tumor. Three scans displayed less uptake in the center of the tumors than around their peripheries. One of these tumors was necrotic in the center, but the other two were pathologically no different from tumors that displayed homogenous uptake on the scan.

  20. Elevated luteinizing hormone induces expression of its receptor and promotes steroidogenesis in the adrenal cortex

    PubMed Central

    Kero, Jukka; Poutanen, Matti; Zhang, Fu-Ping; Rahman, Nafis; McNicol, Anne Marie; Nilson, John H.; Keri, Ruth A.; Huhtaniemi, Ilpo T.

    2000-01-01

    Transgenic (TG) female mice expressing bLHβ-CTP (a chimeric protein derived from the β-subunit of bovine luteinizing hormone [LH] and a fragment of the β-subunit of human chorionic gonadotropin [hCG]) exhibit elevated serum LH, infertility, polycystic ovaries, and ovarian tumors. In humans, increased LH secretion also occurs in infertility and polycystic ovarian syndrome, often concomitant with adrenocortical dysfunction. We therefore investigated adrenal function in LH overexpressing bLHβ-CTP female mice. The size of their adrenals was increased by 80% with histological signs of cortical stimulation. Furthermore, adrenal steroid production was increased, with up to 14-fold elevated serum corticosterone. Primary adrenal cells from TG and control females responded similarly to ACTH stimulation, but, surprisingly, the TG adrenals responded to hCG with significantly increased cAMP, progesterone, and corticosterone production. LH receptor (LHR) expression and activity were also elevated in adrenals from female TG mice, but gonadectomized TG females showed no increase in corticosterone, suggesting that the dysfunctional ovaries of the intact TG females promote adrenocortical hyperfunction. We suggest that, in intact TG females, enhanced ovarian estrogen synthesis causes increased secretion of prolactin (PRL), which elevates LHR expression. Chronically elevated serum LH, augmented by enhanced PRL production, induces functional LHR expression in mouse adrenal cortex, leading to elevated, LH-dependent, corticosterone production. Thus, besides polycystic ovaries, the bLHβ-CTP mice provide a useful model for studying human disorders related to elevated LH secretion and adrenocortical hyperfunction. PMID:10712435

  1. Elevated luteinizing hormone induces expression of its receptor and promotes steroidogenesis in the adrenal cortex.

    PubMed

    Kero, J; Poutanen, M; Zhang, F P; Rahman, N; McNicol, A M; Nilson, J H; Keri, R A; Huhtaniemi, I T

    2000-03-01

    Transgenic (TG) female mice expressing bLHbeta-CTP (a chimeric protein derived from the beta-subunit of bovine luteinizing hormone [LH] and a fragment of the beta-subunit of human chorionic gonadotropin [hCG]) exhibit elevated serum LH, infertility, polycystic ovaries, and ovarian tumors. In humans, increased LH secretion also occurs in infertility and polycystic ovarian syndrome, often concomitant with adrenocortical dysfunction. We therefore investigated adrenal function in LH overexpressing bLHbeta-CTP female mice. The size of their adrenals was increased by 80% with histological signs of cortical stimulation. Furthermore, adrenal steroid production was increased, with up to 14-fold elevated serum corticosterone. Primary adrenal cells from TG and control females responded similarly to ACTH stimulation, but, surprisingly, the TG adrenals responded to hCG with significantly increased cAMP, progesterone, and corticosterone production. LH receptor (LHR) expression and activity were also elevated in adrenals from female TG mice, but gonadectomized TG females showed no increase in corticosterone, suggesting that the dysfunctional ovaries of the intact TG females promote adrenocortical hyperfunction. We suggest that, in intact TG females, enhanced ovarian estrogen synthesis causes increased secretion of prolactin (PRL), which elevates LHR expression. Chronically elevated serum LH, augmented by enhanced PRL production, induces functional LHR expression in mouse adrenal cortex, leading to elevated, LH-dependent, corticosterone production. Thus, besides polycystic ovaries, the bLHbeta-CTP mice provide a useful model for studying human disorders related to elevated LH secretion and adrenocortical hyperfunction.

  2. Spontaneous adrenal pheochromocytoma rupture complicated by intraperitoneal hemorrhage and shock

    PubMed Central

    2011-01-01

    MEN2A is a hereditary syndrome characterized by medullary thyroid carcinoma, hyperparathyroidism, and pheochromocytoma. Classically patients with a pheochromocytoma initially present with the triad of paroxysmal headaches, palpitations, and diaphoresis accompanied by marked hypertension. However, although reported as a rare presentation, spontaneous hemorrhage within a pheochromocytoma can present as an abdominal catastrophe. Unrecognized, this transformation can rapidly result in death. We report the only documented case of a thirty eight year old gentleman with MEN2A who presented to a community hospital with hemorrhagic shock and peritonitis secondary to an unrecognized hemorrhagic pheochromocytoma. The clinical course is notable for an inability to localize the source of hemorrhage during an initial damage control laparotomy that stabilized the patient sufficiently to allow emergent transfer to our facility, re-exploration for continued hemorrhage and abdominal compartment syndrome, and ultimately angiographic embolization of the left adrenal artery for control of the bleeding. Following recovery from his critical illness and appropriate medical management for pheochromocytoma, he returned for interval bilateral adrenal gland resection, from which his recovery was unremarkable. Our review of the literature highlights the high mortality associated with the undertaking of an operative intervention in the face of an unrecognized functional pheochromocytoma. This reinforces the need for maintaining a high index of suspicion for pheochromocytoma in similar cases. Our case also demonstrates the need for a mutimodal treatment approach that will often be required in these cases. PMID:21843357

  3. Practical considerations in the scintigraphic evaluation of endocrine hypertension. The adrenal cortex and medulla.

    PubMed

    Hattner, R S

    1993-09-01

    A nuclear scan maps the distribution of a radiopharmaceutical that is specific for a physiologic property of a targeted tissue. As such, it is not limited by the anatomic changes necessary for CT and MR scans. It is just because of this that maps of specific metabolic precursors of adrenal medullary and cortical hormones offer information crucial to the therapeutic strategy of endocrine hypertension. NP-59 and MIBG scans can specify the nature of abnormalities revealed by anatomic images and because of the ease of surveying the whole body can give transcendent information about lesions remote from the adrenals. In instances when the origin of endocrine hypertension is not forthcoming from CT or MR imaging or when the anatomic and biochemical findings are in conflict, NP-59 or MIBG can almost always provide the answer.

  4. Effects of oxalate on IMCD cells: a line of mouse inner medullary collecting duct cells.

    PubMed

    Maroni, Paul D; Koul, Sweaty; Meacham, Randall B; Chandhoke, Paramjit S; Koul, Hari K

    2004-12-01

    Oxalate, a metabolic end product and a major constituent of the majority of renal stones, has been shown to be toxic to renal epithelial cells of cortical origin. However, it is unknown whether inner medullary collecting duct (IMCD) cells that are physiologically exposed to higher concentrations of oxalate also behave in a similar manner. In the present study, we examined the effects of oxalate on IMCD cells. IMCD cells from the mouse were maintained in DMEM/F12 media supplemented with fetal bovine serum and antibiotics. Exposure of IMCD cells to oxalate produced time- and concentration-dependent changes in the light microscopic appearance of the cells. Long-term exposure to oxalate resulted in alterations in cell viability, with net cell loss after exposure to concentrations of 2 mM or greater. The production of free radicals was directly related to the exposure time and the concentration of oxalate. Crystal formation occurred in less than 1 h and cells in proximity to crystals would lose membrane integrity. Compared with IMCD cells, LLC-PK1 cells as well as HK-2 cells showed significant toxicity starting at lower oxalate concentrations (0.4 mM or greater). These results provide the first direct demonstration of toxic effects of oxalate in IMCD cells, a line of renal epithelial cells of the inner medullary collecting duct, and suggest that the cells lining the collecting duct are relatively resistant to oxalate toxicity.

  5. [Lumbar pain and bilateral adrenal masses].

    PubMed

    García, Elena; Sánchez, Raquel; Martínez, Guillermo; Bernal, Carmen; Calatayud, M; Partida, M; Hawkins, Federico

    2009-05-01

    Many problems may arise when defining whether adrenal lesions are primary to the adrenal glands or represent other tissue, whether they are benign or malignant and whether they are functioning or nonfunctioning. Adrenal imaging complements the clinical and hormonal evaluation of these patients. We present a patient with lumbar pain and bilateral adrenal masses.

  6. C-cell hyperplasia and medullary thyroid microcarcinoma.

    PubMed

    Albores-Saavedra, J A; Krueger, J E

    2001-01-01

    Since the discovery of the thyroid C-cell, considerable progress has been made regarding its origin, function, and pathology. In this article an attempt is made to summarize and update our knowledge about physiologic or reactive C-cell hyperplasia, neoplastic C-cell hyperplasia (medullary carcinoma in situ), and medullary microcarcinoma. Seldom recognized preoperatively, physiologic C-cell hyperplasia is associated with inflammatory, metabolic, and neoplastic thyroid disorders as well as with hypercalcemia. However, the pathogenesis is still unclear. Although physiologic C-cell hyperplasia may progress to medullary carcinoma, the full malignant potential is unknown. Problems related to the definition of physiologic C-cell hyperplasia are discussed. Immunohistochemistry and quantitative analysis are required for the diagnosis. By contrast, C-cell hyperplasia associated with MEN II syndromes or familial medullary carcinoma can be diagnosed preoperatively in asymptomatic children or adolescents by the detection of germline mutations of the RET protooncogene. Morphologic and genetic abnormalities support the idea that C-cells in the familial form of C-cell hyperplasia are neoplastic and can be recognized with conventional stains. Therefore, the number of C-cells is irrelevant for the diagnosis. Medullary microcarcinoma is a neoplasm that measures < 1 cm. The sporadic variant is usually an incidental microscopic finding, whereas the familial form can be diagnosed by genetic testing. Its morphologic features and biologic behavior differ from those of larger medullary carcinomas. The frequency of medullary microcarcinoma will probably increase with the use of genetic testing.

  7. Adrenal involvement in non-Hodgkin lymphoma

    SciTech Connect

    Paling, M.R.; Williamson, B.R.J.

    1983-08-01

    Adrenal masses are described in seven cases of non-Hodgkin lymphoma in a series of 173 patients. In all seven patients the lymphoma was diffuse rather than nodular. Three patients had adrenal masses at the time of presentation, whereas in four cases the adrenal gland was a site of tumor recurrence after therapy. Three patients had simultaneous bilateral adrenal involvement by tumor. No characteristic features were recognized that might have distinguished these tumors from other adrenal masses. Appropriate therapy successfully resolved the adrenal masses in all but one case. The latter patient was the only one with evidence of adrenal insufficiency.

  8. Laparoendoscopic single site adrenal surgery.

    PubMed

    Han, Deok Hyun; Lim, Meng Shi; Seo, Joo Wan; Jeong, Byong Chang; Rha, Koong Ho

    2012-04-01

    Laparoscopic adrenal surgery is a standard procedure for the management of benign adrenal pathology and small malignant tumors. There has been an increasing interest over the last few years in the use of laparoendoscopic single-site surgery (LESS). From recent literatures, LESS adrenalectomy was demonstrated that this technique was safe and feasible despite the relatively difficult anatomical location of the adrenal gland. We reviewed the surgical techniques and outcomes of LESS adrenalectomy including robot-assisted approach and gave an overview of the current role of LESS in adrenalectomy.

  9. [Hormonal evaluation of adrenal incidentalomas].

    PubMed

    Le Loupp, Anne-Gaëlle; Cariou, Bertrand; Drui, Delphine; Graveline, Nolwenn; Masson, Damien; Bach-Ngohou, Kalyane

    2014-01-01

    Imaging technological advances and widespread use of abdominal imaging have led to the identification of an increasing number of adrenal incidentalomas in the last decades. Causes of these adrenal masses are multiple, but the most common etiology is the non-functional adenoma. Although in most cases, these masses are benign and non-functional, clinicians have to perform biochemical testing for subclinical cushing's syndrome, pheochromocytoma or primary hyperaldosteronism. This screening is essential for their etiological diagnosis and therapeutic management. We report in this article the biological approach to detect secretory activity of adrenal incidentalomas and the diagnostic accuracy of the biochemical tests used.

  10. Medullary thyroid cancer diagnosis: an appraisal.

    PubMed

    Trimboli, Pierpaolo; Giovanella, Luca; Crescenzi, Anna; Romanelli, Francesco; Valabrega, Stefano; Spriano, Giuseppe; Cremonini, Nadia; Guglielmi, Rinaldo; Papini, Enrico

    2014-08-01

    Since its first description in 1951, a timely diagnosis of medullary thyroid carcinoma (MTC) may represent a diagnostic challenge in clinical practice. Several contributions have been addressed to the treatment and follow-up of MTC, but review articles focused on the diagnostic problems of this cancer in clinical practice are sparse. As a delayed diagnosis and an inadequate initial treatment may severely affect the prognosis of this thyroid malignancy, the appropriate use and the correct interpretation of the available diagnostic tools for MTC are of crucial importance. The purpose of the present article is to provide an easy-to-use guide reviewing the main issues of MTC diagnosis: (1) basal serum calcitonin; (2) stimulated serum calcitonin; (3) additional serum markers for MTC; (4) ultrasound and other imaging techniques; (5) fine-needle aspiration (FNA) cytology; (6) calcitonin measurement on FNA washout; (7) rearranged during transfection (RET) mutations; and (8) scope of the problem. Copyright © 2014 Wiley Periodicals, Inc.

  11. [Dysphagia with lateral medullary infarction (Wallenberg's syndrome)].

    PubMed

    Oshima, Fumiko

    2011-11-01

    Dysphagia after lateral medullary infarction (LMI) is common. The dysphagia of LMI is dynamically characterized by a failure in triggering of the pharyngeal-phase swallowing movements, reduced output, and lack of coordination (swallowing pattern abnormality). Based on accurate evaluation, we can select suitable rehabilitative approaches for individual patients, including respiratory therapy, food modification, postural changes, and oral care. We focused on the absence of upper esophageal sphincter (UES) opening of the unaffected side of the medullae. The movement pattern was defined as failure of bolus passage through the intact side of the UES, occurring at least once during the videofluorographic evaluation of each individual. Three abnormal patterns of UES opening were classified. The passage pattern abnormality shows the failure of the stereotyped motor sequence. For severe cases, it is necessary to consider long-term treatment, including botulinum toxin injection or surgery to prevent aspiration and adequate nutritional management.

  12. Angiotensin converting enzyme in the brain, testis, epididymis, pituitary gland and adrenal gland

    SciTech Connect

    Strittmatter, S.M.

    1986-01-01

    (/sup 3/H)Captopril binds to angiotensin converting enzyme (ACE) in rat tissue homogenates. The pharmacology, regional distribution and copurification of (/sup 3/H)captopril binding with enzymatic activity demonstrate the selectivity of (/sup 3/H)captopril labeling of ACE. (/sup 3/H)Captopril binding to purified ACE reveals differences in cationic dependence and anionic regulation between substrate catalysis and inhibitor recognition. (/sup 3/H)Captopril association with ACE is entropically driven. The selectivity of (/sup 3/H)captopril binding permits autoradiographic localization of the ACE in the brain, male reproductive system, pituitary gland and adrenal gland. In the brain, ACE is visualized in a striatonigral neuronal pathway which develops between 1 and 7 d after birth. In the male reproductive system, (/sup 3/H)captopril associated silver grains are found over spermatid heads and in the lumen of seminiferous tubules in stages I-VIII and XII-XIV. In the pituitary gland, ACE is localized to the posterior lobe and patches of the anterior lobe. The adrenal medulla contains moderate ACE levels while low levels are found in the adrenal cortex. Adrenal medullary ACE is increased after hypophysectomy and after reserpine treatment. The general of ligand binding techniques for the study of enzymes is demonstrated by the specific labeling of another enzyme, enkephaline convertase, in crude tissue homogenates by the inhibitor (/sup 3/H)GEMSA.

  13. Fetal Glucocorticoid Synthesis Is Required for Development of Fetal Adrenal Medulla and Hypothalamus Feedback Suppression

    PubMed Central

    Huang, Chen-Che Jeff; Shih, Meng-Chun Monica; Hsu, Nai-Chi; Chien, Yu

    2012-01-01

    During pregnancy, fetal glucocorticoid is derived from both maternal supply and fetal secretion. We have created mice with a disruption of the Cyp11a1 gene resulting in loss of fetal steroid secretion but preserving the maternal supply. Cyp11a1null embryos have appreciable although lower amounts of circulating corticosterone, the major mouse glucocorticoid, suggesting that transplacental corticosterone is a major source of corticosterone in fetal circulation. These embryos thus provide a means to examine the effect of fetal glucocorticoids. The adrenal in Cyp11a1 null embryos was disorganized with abnormal mitochondria and oil accumulation. The adrenal medullary cells did not express phenylethanolamine N-methyltransferase and synthesized no epinephrine. Cyp11a1 null embryos had decreased diencephalon Hsd11b1, increased diencephalon Crh, and increased pituitary Pomc expression, leading to higher adrenocorticotropin level in the plasma. These data indicate blunted feedback suppression despite reasonable amounts of circulating corticosterone. Thus, the corticosterone synthesized in situ by the fetus is required for negative feedback suppression of the hypothalamus-pituitary-adrenal axis and for catecholamine synthesis in adrenal medulla. PMID:22962254

  14. 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.

  15. Clonidine-induced suppression of plasma catecholamines in states of adrenal medulla hyperfunction.

    PubMed

    Gross, M D; Shapiro, B; Sisson, J C; Zweifler, A

    1987-08-01

    To assess adrenal medulla activity in states of hyperfunction, a single 0.3 mg oral dose of clonidine hydrochloride (Catapres) was given to twelve patients with varying evidence of familial adrenal medullary hyperplasia and pheochromocytomas from kindreds with Multiple Endocrine Neoplasia type 2 syndrome (MEN-2), seven patients with sporadic pheochromocytomas and six normal subjects. Mean arterial blood pressure and plasma norepinephrine (NE) levels were lower than baseline values 2 h after clonidine in the normal subjects. Plasma epinephrine (E) rose in one normal but fell in the remainder after clonidine administration. In sporadic pheochromocytoma patients, E fell slightly in 4 and NE fell in 3 while mean arterial blood pressure was not significantly lower than baseline values in 7 patients 2 h after clonidine. In MEN-2, mean arterial blood pressure fell and there was a variable response of plasma E and NE to clonidine, which appears to be related to the presence of detectable anatomic (CT scan) and functional (131I-mlBG scintigraphy) abnormalities of the adrenal medulla. These findings are thus compatible with the spectrum of adrenal medulla dysfunction and the presumed development of pheochromocytoma in this syndrome.

  16. Cerebellin stimulates the secretory activity of the rat adrenal gland: in vitro and in vivo studies.

    PubMed

    Albertin, G; Malendowicz, L K; Macchi, C; Markowska, A; Nussdorfer, G G

    2000-02-01

    Cerebellin is a 16-aminoacid peptide widely distributed in the central nervous system, where it exerts neuromodulatory functions. Cerebellin is contained in human adrenal medulla, and it has been recently demonstrated that cerebellin elicits catecholamine release by human adrenal in vitro. Aim of the present study was to ascertain whether cerebellin affects adrenal function in the rat. Cerebellin concentration-dependently (from 10(-9)to 10(-7)M) increased norepinephrine (but not epinephrine) and cyclic-AMP production by adrenomedullary tissue in vitro. The norepinephrine response to 10(-7)M cerebellin was blocked by the protein kinase (PK) A inhibitor H-89, but not by the phospholipase C inhibitor U-73122 or the PKC inhibitor calphostin-C. Cerebellin did not affect aldosterone and corticosterone secretion of dispersed zona glomerulosa and zona fasciculata-reticularis adrenocortical cells. Cerebellin concentration-dependently (from 10(-8)to 10(-7)M) enhanced norepinephrine release by in situ perfused rat adrenals. Cerebellin (10(-7)M) also elicited a significant rise in aldosterone and corticosterone output, and this effect was annulled by either the beta1-adrenoceptor antagonist l -alprenolol or H-89. Collectively, the present findings allow us to conclude that cerebellin 1) directly stimulates norepinephrine release via the adenylate cyclase/PKA-dependent signaling pathway; and 2) indirectly enhances adrenocortical secretion in vivo, through a paracrine mechanism involving medullary catecholamine release. Copyright 2000 Harcourt Publishers Ltd.

  17. Adrenal Insufficiency and Addison's Disease

    MedlinePlus

    ... cortisol. If ACTH output is too low, cortisol production drops. Eventually, the adrenal glands can shrink due ... sodium and potassium in the blood. When aldosterone production falls too low, the body loses too much ...

  18. VIP innervation: sharp contrast in fetal sheep and baboon adrenal glands suggests differences in developmental regulation.

    PubMed

    Berghorn, K A; Li, C; Nathanielsz, P W; McDonald, T J

    2000-09-22

    Immunocytochemical technique and light microscopy were used to ascertain the relationship between vasoactive intestinal polypeptide (VIP) and tyrosine hydroxylase in fetal sheep and fetal baboon adrenal cortices and medullae at 85% of gestation. VIP immunostaining was extremely robust in fetal sheep adrenal cortical neurofibers and cells while weak in fibers and nonexistent in cells of fetal baboon. Also, tyrosine hydroxylase-immunopositive cells, present throughout the adrenal cortices of both fetal sheep and baboons, were heavily innervated by VIP-immunoreactive neurofibers in fetal sheep, but not in fetal baboons. Adrenal cortical VIP-immunopositive fibers occurred in greater (P<0.05) frequency in fetal sheep than in fetal baboons (14.82+/-3.10 vs. 0.84+/-0.26 fibers/field), were larger in diameter (2.93+/-0.34 vs. 0.93+/-0.07 microm) and ran for longer distances in the plane of section (127.85+/-5.16 vs. 74.53+/-4.93 microm). VIP immunogenicity in cells (ganglion and chromaffin) and fibers was robust in fetal adrenal medulla of sheep while nonexistent in baboons. VIP fibers in fetal sheep medulla were smaller in diameter compared to fetal sheep cortex (1.22+/-0.13 vs. 2.93+/-0.34 microm, P<0.05), but not compared to extrinsic nerve fibers (1.30+/-0.09 microm). We hypothesize that in fetal sheep of this age, medullary neurofibers derive primarily from extrinsic sources while cortical fibers arise from cortical ganglion cells. We conclude that at 85% of gestation the potential for VIP neural control of paracrine (e.g., glucocorticoid/catecholamine) interactions in both adrenal cortex and medulla is much greater in fetal sheep compared to fetal baboons.

  19. Budesonide-related adrenal insufficiency.

    PubMed

    Arntzenius, Alexander; van Galen, Louise

    2015-10-01

    Iatrogenic adrenal insufficiency is a potential harmful side effect of treatment with corticosteroids. It manifests itself when an insufficient cortisol response to biological stress leads to an Addisonian crisis: a life-threatening situation. We describe a case of a patient who developed an Addisonian crisis after inappropriate discontinuation of budesonide (a topical steroid used in Crohn's disease) treatment. Iatrogenic adrenal insufficiency due to budesonide use has been rarely reported. Prescribers should be aware of the resulting risk for an Addisonian crisis.

  20. [Congenital Adrenal Hyperplasia in Adults].

    PubMed

    Vrbíková, Jana

    2016-01-01

    Congenital adrenal hyperplasia is a life-long disease requiring an integrated therapy. It may negatively influence the quality of life. In childhood, the main problems of the care of these patients involve sex determination and ensuring optimum growth and puberty. The therapeutic goals for adults are the prevention of Addisonian crisis and ensuring the best possible quality of life, including fertility.Key words: androgens - cardiovascular risk - congenital adrenal hyperplasia - bone density - testicular rest tumors.

  1. [Study of Medullary Thyroid Carcinoma from a proband].

    PubMed

    Morlán Herrador, Laura; de Arriba, Antonio; Miguel, Gloria; Ferrera, Marta; Labarta, José I

    2016-12-01

    Thyroid cancer is an uncommon type of cancer, accounting less than 1% of all cancers in adults, and 0.5-3% of all cancers in children. There are four different types: papillary carcinoma (80-90% of cases), follicular (5-10%), medullary (5%) and anaplastic cell (2-3%). Eighty per cent of cases of medullary thyroid cancer are sporadic, but 20% are associated with an inherited syndrome that is divided into three groups: multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma. The inherited forms are caused by a disruption in the RET oncogene, which is located in the long arm of chromosome 10. A hereditary case of medullary thyroid carcinoma is presented. It was detected because of a familial genetic study. The purpose of the paper is emphasize the importance of the early diagnosis and the intervention of multidisciplinary teams of experts.

  2. Oral complications associated with idiopathic medullary aplasia: case report.

    PubMed

    Clercq, Marcel; Gagné-Tremblay, Mélanie

    2008-05-01

    This article describes a patient who experienced serious oral sequelae after severe oral hemorrhage associated with medullary aplasia. These complications required medical, surgical and prosthetic treatments necessitating dental expertise in the hospital setting.

  3. Medullary thyroid carcinoma presenting as a supraglottic mass.

    PubMed

    White, Jeremy; Mohyeldin, Ahmed; Schwartz, Arnold; Bielamowicz, Steven

    2014-01-01

    We report a rare case of medullary thyroid carcinoma that presented as a metastasis to the supraglottic larynx. A 92-year-old man with a 3-month history of voice change and airway obstruction was diagnosed with medullary thyroid carcinoma metastatic to the supraglottis. Excision of the mass, total thyroidectomy, and elective neck dissection were recommended, but the patient declined because of his advanced age. Medullary carcinoma of the thyroid gland is a rare neuroendocrine tumor with a poor prognosis when associated with a distant metastasis. To the best of our knowledge, this is the first case of a medullary carcinoma of the thyroid presenting as a supraglottic mass. Total thyroidectomy, neck dissection, and surgical excision of the entire tumor comprise the treatment of choice.

  4. Orthostatic hypotension associated with dorsal medullary cavernous angioma.

    PubMed

    Idiaquez, J; Araya, P; Benarroch, E

    2009-01-01

    Orthostatic hypotension (OH) is a rare manifestation of medulla oblongata lesions that may be because of interruption of descending sympathoexcitatory axons. To illustrate the location of a medullary lesion that produced OH following resection in relationship to the location of putative sympathoexcitatory pathways. A case with dorsal medullary cavernous angioma presenting with OH is described. The possible localization of lesion was compared with distribution of tyrosine hydroxylase (TH)-immunoreactive axons in a comparable section of the medulla of a control brain. The patient had marked OH after partial removal of the cavernous angioma. Biopsy confirmed the diagnosis. The magnetic resonance imaging location of the lesion overlapped that of TH-immunoreactive axons of the medullary transtegmental tract. A restricted lesion of medullary lesion interrupting the catecholaminergic transtegmental tract arising from the sympathoexcitatory C1 neurons of the rostral ventrolateral medulla could result in severe OH.

  5. The mechanism of calcium channel facilitation in bovine chromaffin cells.

    PubMed Central

    Albillos, A; Gandía, L; Michelena, P; Gilabert, J A; del Valle, M; Carbone, E; García, A G

    1996-01-01

    1. This study was planned to clarify the mechanism of Ca2+ channel facilitation by depolarizing prepulses given to voltage-clamped bovine chromaffin cells. The hypothesis for an autocrine modulation of such channels was tested by studying the effects of a soluble vesicle lysate (SVL) on whole-cell Ba2+ currents (IBa). 2. SVL was prepared from a bovine adrenal medullary homogenate. The ATP content in this concentrated SVL amounted to 3.18 +/- 0.12 mM (n = 4). The concentration of noradrenaline and adrenaline present in the SVL was 11.2 +/- 0.97 and 15.2 +/- 2 mM, respectively (n = 5). A 1:1000 dilution of SVL in the external solution halved the magnitude of IBa and produced a 7-fold slowing of its activation kinetics. The blocking effects of SVL were concentration dependent and quickly reversed upon washout. 3. Inhibition and slowing of the kinetics of IBa by SVL could be partially reversed by strong depolarizing prepulses (+90 mV, 45 ms). This reversal of inhibition, called Ca2+ channel facilitation, persisted in the presence of 3 microM nifedipine. 4. Intracellular dialysis of GDP-beta-S (0.5 mM) or pretreatment of the cells with pertussis toxin (100 ng ml-1 for 18-24 h) prevented the reduction in peak current caused by a 1:100 dilution of SVL; no prepulse facilitation could be observed under these conditions. 5. The receptor blockers naloxone (10 microM) or suramin (100 microM) and PPADS (100 microM) largely antagonized the effects of SVL. Treatment of SVL with alkaline phosphatase or dialysis against a saline buffer to remove low molecular mass materials (< 10 kDa) considerably reduced the activity of SVL. 6. Stopping the flow of the external solution (10 mM Ba2+) gradually reduced the size, and slowed down the activation phase, of the current. Prepulse facilitation of IBa was absent or weak in a superfused cell, but was massive upon flow-stop conditions in the presence or absence of 3 microM nifedipine. 7. Our experiments suggest that facilitation by prepulses

  6. Effects of Cultured Adrenal Chromaffin Cell Implants on Hindlimb Reflexes of the 6-OHDA Lesioned Rat

    PubMed Central

    Pulford, Bruce E.; Mihajlov, Andrea R.; Nornes, Howard O.; Whalen, L. Ray

    1994-01-01

    The effects of implantation of cultured adrenal medullary cells on the recovery of neurotransmitter specific reflex activity were studied in the rat spinal cord using electrophysiological testing methods. Cell suspensions of cultured neonatal adrenal medullary chromaffin (AM) cells (which produce catecholamines), or Schwann (Sc) cells (controls) were implanted into the lumbar region of the spinal cord 2 weeks after catecholamine (CA) denervation by intracisternal injection of 6-hydroxydopamine (6-OHDA). All cells were taken from 7 day neonates and cultured for 10 days in the presence of nerve growth factor (NGF). Three months after implantation, the extent of implant-associated recovery of reflex activity was determined by measuring electromyogram (EMG) activity and force associated with the long latency component of the hindlimb withdrawal reflex (which is CA modulated). After the electrophysiological testing, rats were anesthetized, and the spinal cords were rapidly removed and frozen. Spinal cords were sectioned longitudinally, and implanted cells were visualized using glyoxylic acid techniques. Labelled sections were examined to determine cell survival. Results indicate that 1) chromaffin cells survive for 3 months in the segments of the cord into which they have been implanted and 2) rats implanted with AM cells have significantly more forceful withdrawal reflexes than those that received Sc cells or received no implant after lesioning. PMID:7703294

  7. Prognostic and predictive markers in medullary thyroid carcinoma.

    PubMed

    Erovic, Boban M; Kim, Dae; Cassol, Clarissa; Goldstein, David P; Irish, Jonathan C; Asa, Sylvia L; Mete, Ozgur

    2012-12-01

    Unlike papillary thyroid carcinoma, medullary thyroid carcinoma is insensitive to adjuvant treatment with radioactive iodine. The clinical management of patients with advanced or metastatic disease remains challenging since no effective systemic adjuvant therapy is available. We aimed to identify markers of aggressive disease and novel drugable protein targets that would provide systemic adjuvant treatment for patients with advanced medullary thyroid carcinoma. We therefore examined morphologic features of aggressive behavior and the expression of 41 proteins involved in apoptosis, cell cycle, angiogenesis, inflammation, cell adhesion, tumor-specific markers, and WNT, SHH, and AKT pathways using tissue microarray from 23 patients with medullary thyroid carcinoma. Protein expression was determined using computerized image analysis software. Statistical analysis was carried out to correlate clinical data with the average score for each marker. Angioinvasion proved to be the most reliable predictor of disease recurrence and death. The rate of angioinvasion was 43 %. All angioinvasive medullary thyroid carcinomas had locoregional and/or distant metastasis; 60 % of angioinvasive medullary thyroid carcinomas developed distant metastasis. We identified expression of several potentially important protein targets such as COX-1/2, Bcl-2a, Gst-π, Gli-1, Gli-2, Gli-3, and Bmi-1 that may be therapeutically targeted in medullary thyroid carcinoma. More importantly, the immunohistochemical profile of SSTRs in medullary thyroid carcinoma may also have clinical relevance for the administration of peptide receptor radionuclide treatment. Successful outcome of clinical trials directed against these novel targets would provide much needed systemic adjuvant treatment for patients with advanced medullary thyroid carcinoma, and our data suggest the possibility of stratifying patients who are likely to require adjuvant therapy before their burden of disease precludes successful

  8. Hypercalcitoninemia is not pathognomonic of medullary thyroid carcinoma.

    PubMed

    Toledo, Sergio P A; Lourenço, Delmar M; Santos, Marcelo Augusto; Tavares, Marcos R; Toledo, Rodrigo A; Correia-Deur, Joya Emilie de Menezes

    2009-01-01

    Hypercalcitoninemia has frequently been reported as a marker for medullary thyroid carcinoma. Currently, calcitonin measurements are mostly useful in the evaluation of tumor size and progression, and as an index of biochemical improvement of medullary thyroid carcinomas. Although measurement of calcitonin is a highly sensitive method for the detection of medullary thyroid carcinoma, it presents a low specificity for this tumor. Several physiologic and pathologic conditions other than medullary thyroid carcinoma have been associated with increased levels of calcitonin. Several cases of thyroid nodules associated with increased values of calcitonin are not medullary thyroid carcinomas, but rather are related to other conditions, such as hypercalcemias, hypergastrinemias, neuroendocrine tumors, renal insufficiency, papillary and follicular thyroid carcinomas, and goiter. Furthermore, prolonged treatment with omeprazole (>2-4 months), beta-blockers, glucocorticoids and potential secretagogues, have been associated with hypercalcitoninemia. An association between calcitonin levels and chronic auto-immune thyroiditis remains controversial. Patients with calcitonin levels >100 pg/mL have a high risk for medullary thyroid carcinoma (approximately 90%-100%), whereas patients with values from 10 to 100 pg/mL (normal values: <8.5 pg/mL for men, <5.0 pg/mL for women; immunochemiluminometric assay) have a <25% risk for medullary thyroid carcinoma.In multiple endocrine neoplasia type 2 (MEN2), RET mutation analysis is the gold-standard for the recommendation of total preventive thyroidectomy to relatives at risk of harboring a germline RET mutation (50%). False-positive calcitonin results within MEN2 families have led to incorrect indications of preventive total thyroidectomy to RET mutation negative relatives. In this review, we focus on the differential diagnosis of hypercalcitoninemia, underlining its importance for the avoidance of misdiagnosis of medullary thyroid carcinoma

  9. Hypercalcitoninemia is not Pathognomonic of Medullary Thyroid Carcinoma

    PubMed Central

    Toledo, Sergio PA; Lourenço, Delmar M; Santos, Marcelo Augusto; Tavares, Marcos R; Toledo, Rodrigo A; de Menezes Correia-Deur, Joya Emilie

    2009-01-01

    Hypercalcitoninemia has frequently been reported as a marker for medullary thyroid carcinoma. Currently, calcitonin measurements are mostly useful in the evaluation of tumor size and progression, and as an index of biochemical improvement of medullary thyroid carcinomas. Although measurement of calcitonin is a highly sensitive method for the detection of medullary thyroid carcinoma, it presents a low specificity for this tumor. Several physiologic and pathologic conditions other than medullary thyroid carcinoma have been associated with increased levels of calcitonin. Several cases of thyroid nodules associated with increased values of calcitonin are not medullary thyroid carcinomas, but rather are related to other conditions, such as hypercalcemias, hypergastrinemias, neuroendocrine tumors, renal insufficiency, papillary and follicular thyroid carcinomas, and goiter. Furthermore, prolonged treatment with omeprazole (> 2–4 months), beta-blockers, glucocorticoids and potential secretagogues, have been associated with hypercalcitoninemia. An association between calcitonin levels and chronic auto-immune thyroiditis remains controversial. Patients with calcitonin levels >100 pg/mL have a high risk for medullary thyroid carcinoma (~90%–100%), whereas patients with values from 10 to 100 pg/mL (normal values: <8.5 pg/mL for men, < 5.0 pg/mL for women; immunochemiluminometric assay) have a <25% risk for medullary thyroid carcinoma. In multiple endocrine neoplasia type 2 (MEN2), RET mutation analysis is the gold-standard for the recommendation of total preventive thyroidectomy to relatives at risk of harboring a germline RET mutation (50%). False-positive calcitonin results within MEN2 families have led to incorrect indications of preventive total thyroidectomy to RET mutation negative relatives. In this review, we focus on the differential diagnosis of hypercalcitoninemia, underlining its importance for the avoidance of misdiagnosis of medullary thyroid carcinoma and

  10. Multiple medullary venous malformations decreasing cerebral blood flow: Case report

    SciTech Connect

    Tomura, N.; Inugami, A.; Uemura, K.; Hadeishi, H.; Yasui, N. )

    1991-02-01

    A rare case of multiple medullary venous malformations in the right cerebral hemisphere is reported. The literature review yielded only one case of multiple medullary venous malformations. Computed tomography scan showed multiple calcified lesions with linear contrast enhancement representing abnormal dilated vessels and mild atrophic change of the right cerebral hemisphere. Single-photon emission computed tomography using N-isopropyl-p-({sup 123}I) iodoamphetamine demonstrated decreased cerebral blood flow in the right cerebral hemisphere.

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

    PubMed

    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.

  12. 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

  13. Compensatory adrenal growth - A neurally mediated reflex

    NASA Technical Reports Server (NTRS)

    Dallman, M. F.; Engeland, W. C.; Shinsako, J.

    1976-01-01

    The responses of young rats to left adrenalectomy or left adrenal manipulation were compared to surgical sham adrenalectomy in which adrenals were observed but not touched. At 12 h right adrenal wet weight, dry weight, DNA, RNA, and protein content were increased (P less than 0.05) after the first two operations. Left adrenal manipulation resulted in increased right adrenal weight at 12 h but no change in left adrenal weight. Sequential manipulation of the left adrenal at time 0 and the right adrenal at 12 h resulted in an enlarged right adrenal at 12 h (P less than 0.01), and an enlarged left adrenal at 24 h (P less than 0.05), showing that the manipulated gland was capable of response. Bilateral adrenal manipulation of the adrenal glands resulted in bilateral enlargement of 12 h (P less than 0.01). Taken together with previous results, these findings strongly suggest that compensatory adrenal growth is a neurally mediated reflex.

  14. Diagnosis and treatment of medullary thyroid cancer.

    PubMed

    Modigliani, E; Franc, B; Niccoli-sire, P

    2000-12-01

    Medullary carcinoma of the thyroid (MTC) is a rare tumour derived from thyroid C cells with serum calcitonin as a specific and sensitive marker. MTC is inherited in 25% of cases, with an autosomal dominant transmission, age-related penetrance and variable expressivity. MTC is an obligatory component of multiple endocrine neoplasia type 2 (MEN2), which comprises three well defined syndromes: MEN2A, which may be associated with pheochromocytoma and/or hyperparathyroidism; the much rarer MEN2B, which occurs early and is accompanied by developmental abnormalities; while in contrast, familial MTC (FMTC) is not associated with any endocrinopathy. The RET proto-oncogene is the causative gene of the MEN2 syndromes and mutations in this gene are found in >90% of inherited cases, allowing easier and more reliable family screening than pentagastrin stimulation tests. Nevertheless, the correlation between the genotype and the different clinical phenotypes is not perfect. The prognosis of MTC depends on its staging at presentation, and the early appearance of cervical lymph node metastases emphasizes the need for extensive surgery, although many patients still do not normalize calcitonin levels post-operatively, and they remain a challenge for the further management.

  15. Medullary sponge kidney: state of the art.

    PubMed

    Fabris, Antonia; Anglani, Franca; Lupo, Antonio; Gambaro, Giovanni

    2013-05-01

    Medullary sponge kidney (MSK) is a kidney malformation that generally manifests with nephrocalcinosis and recurrent renal stones; other signs may be renal acidification and concentration defects, and pre-calyceal duct ectasias. MSK is generally considered a sporadic disorder, but an apparently autosomal dominant inheritance has also been observed. As MSK reveals abnormalities in both the lower and the upper nephron and is often associated with urinary tract developmental anomalies, its pathogenesis should probably be sought in one of the numerous steps characterizing renal morphogenesis. Given the key role of the GDNF-RET interaction in kidney and urinary tract development and nephrogenesis, anomalies in these molecules are reasonable candidates for explaining a disorder such as MSK. As a matter of fact, we detected two, hitherto unknown, rare variants of the GDNF gene in MSK patients. We surmise that a defective distal acidification has a central role in MSK and is followed by a chain of events including defective bone mineralization, hypercalciuria, hypocitraturia and stone formation.

  16. Medical Management of Metastatic Medullary Thyroid Cancer

    PubMed Central

    Maxwell, Jessica E.; Sherman, Scott K.; O’Dorisio, Thomas M.; Howe, James R.

    2014-01-01

    Medullary thyroid cancer (MTC) is an aggressive form of thyroid cancer, which occurs in both heritable and sporadic forms. Discovery that mutations in the RET protooncogene predispose to familial cases of this disease has allowed for presymptomatic identification of gene carriers and prophylactic surgery to improve the prognosis of these patients. A significant number of patients with the sporadic type of MTC and even with familial disease, still present with nodal or distant metastases, making surgical cure difficult. Over the past several decades, many different types of therapy for metastatic disease have been attempted, with limited success. Improved understanding of the molecular defects and pathways involved in both familial and sporadic MTC has resulted in new hope for these patients with the development of drugs targeting the specific alterations responsible. This new era of targeted therapy with kinase inhibitors represents a significant step forward from previous trials of chemotherapy, radiotherapy, and hormonal therapy. Although much progress has been made, additional agents and strategies are needed to achieve durable, long-term responses in patients with metastatic MTC. This article reviews the history and results of medical management for metastatic MTC from the early 1970s up until the present day. PMID:24942936

  17. Management of hereditary medullary thyroid carcinoma.

    PubMed

    Pappa, Theodora; Alevizaki, Maria

    2016-07-01

    Hereditary medullary thyroid carcinoma (MTC) represents up to one-third of MTC cases and includes multiple endocrine neoplasia syndrome type 2A (and its variant familial MTC) and 2B. The aim of this paper is to provide an overview of the disease focusing on the management of hereditary MTC patients, who have already developed tumor, as well as discuss the recommended approach for asymptomatic family members carrying the same mutation. A PubMed search was performed to review recent literature on diagnosis, genetic testing, and surgical and medical management of hereditary MTC. The wide use of genetic testing for RET mutations has markedly influenced the course of hereditary MTC. Prophylactic thyroidectomy of RET carriers at an early age eliminates the risk of developing MTC later in life. Pre-operative staging is a strong prognostic factor in patients, who have developed MTC. The use of recently approved tyrosine kinase inhibitors (vandetanib, cabozantinib) holds promising results for the treatment of unresectable, locally advanced, and progressive metastatic MTC. Genetic testing of the RET gene is a powerful tool in the diagnosis and prognosis of MTC. Ongoing research is expected to add novel treatment options for patients with advanced, progressive disease.

  18. Renal medullary carcinomas: histopathologic phenotype associated with diverse genotypes.

    PubMed

    Gatalica, Zoran; Lilleberg, Stan L; Monzon, Federico A; Koul, Manika Sapru; Bridge, Julia A; Knezetic, Joseph; Legendre, Ben; Sharma, Poonam; McCue, Peter A

    2011-12-01

    Chromosomal abnormalities and gene mutations have become major determinants in the classification of kidney carcinomas. Most renal medullary carcinomas develop in patients with hereditary sickle cell disease, but sporadic cases unassociated with sickle cell disease have also been described, for which underlying genetic abnormality is unknown. We evaluated 3 patients with renal medullary carcinoma (1 patient with sickle cell disease and 2 patients without sickle cell disease) for germ line and somatic mutations in genes commonly involved in pathogenesis of renal carcinomas using denaturing high-performance liquid chromatography and direct sequencing. Chromosomal abnormalities were studied by the conventional cytogenetic and SNP arrays analysis. Expression of hypoxia-inducible factor 1α was examined using immunohistochemistry. Two new mutations in the gene for fumarate hydratase were identified in 1 case of medullary renal carcinoma without sickle cell disease: a germ line mutation in exon 6 (R233H) and an acquired (somatic) mutation in exon 8 (P374S). No fumarate hydratase mutations were identified in the other 2 patients. The second sporadic case of renal medullary carcinoma harbored double somatic mutations in von Hippel-Lindau gene, and renal medullary carcinoma in the patient with sickle cell disease showed von Hippel-Lindau gene promoter methylation (epigenetic silencing). No consistent pattern of chromosomal abnormalities was found between 2 cases tested. All 3 cases showed increased hypoxia-inducible factor 1α expression. Medullary renal carcinomas from patients with or without sickle cell disease show involvement of genes important in hypoxia-induced signaling pathways. Generalized cellular hypoxia (in sickle cell disease) or pseudohypoxia (in tumors with fumarate hydratase and von Hippel-Lindau mutations or epigenetic silencing) may act alone or in concert at the level of medullary tubular epithelium to promote development of this rare type of renal

  19. Multi-step approach in a complex case of Cushing's syndrome and medullary thyroid carcinoma.

    PubMed

    Parenti, G; Nassi, R; Silvestri, S; Bianchi, S; Valeri, A; Manca, G; Mangiafico, S; Ammannati, F; Serio, M; Mannelli, M; Peri, A

    2006-02-01

    The diagnosis of Cushing's syndrome (CS) may sometimes be cumbersome. In particular, in ACTH-dependent CS it may be difficult to distinguish between the presence of an ACTH-secreting pituitary adenoma and ectopic ACTH and/or CRH secretion. In such instances, the etiology of CS may remain unknown despite extensive diagnostic workout, and the best therapeutic option for each patient has to be determined. We report here the case of a 54-yr-old man affected by ACTH-dependent CS in association with a left adrenal adenoma and medullary thyroid carcinoma (MTC). He presented with clinical features and laboratory indexes of hypercortisolism associated with elevated levels of calcitonin. Ectopic CS due to MTC was reported previously. In our case hypercortisolism persisted after surgical treatment of MTC. Thorough diagnostic assessment was performed, in order to define the aetiology of CS. He was subjected to basal and dynamic hormonal evaluation, including bilateral inferior petrosal sinus sampling. Extensive imaging evaluation was also performed. Overall, the laboratory data together with the results of radiological procedures suggested that CS might be due to inappropriate CRH secretion. However, the source of CRH secretion in this patient remained unknown. It was then decided to remove the left adenomatous adrenal gland. Cortisol level fell and has remained within the normal range nine months after surgery. This case well depicts the complexity of the diagnostic workout, which is needed sometimes to correctly diagnose and treat CS, and suggests that monolateral adrenalectomy may represent, at least temporarily, a reasonable therapeutic option in occult ACTH-dependent hypercortisolism.

  20. Cushing syndrome due to adrenal tumor

    MedlinePlus

    ... syndrome. It occurs when a tumor of the adrenal gland releases excess amounts of the hormone cortisol. Causes ... hormone cortisol. This hormone is made in the adrenal glands . Too much cortisol can be due to various ...

  1. [Addison's disease, primary adrenal insufficiency in adults].

    PubMed

    Krikke, Maaike; ten Wolde, Marije; Smit, Natalie

    2013-01-01

    Adrenal insufficiency is a rare but fatal disease if left unrecognized. Symptoms often mimic more prevalent diseases. We discuss three patients with primary adrenal insufficiency. These cases illustrate that presenting symptoms such as syncope, nausea, vomiting, weight loss and hypoglycemia are often non-specific and, therefore, often not immediately recognized. When an adrenal crisis is suspected, glucocorticoids should be given promptly. The symptoms are caused by insufficient production of adrenal hormones due to destruction of the adrenal glands by auto-immune adrenalitis. An ACTH stimulation test should confirm the diagnosis when primary adrenal insufficiency is suspected. Treatment consists of glucocorticoid and mineralocorticoid replacement. Primary adrenal insufficiency is a 'master of disguise'. Unexplained syncope, vomiting, weight loss or hypoglycemia should prompt suspicion of this disease.

  2. Adrenal cortex dysfunction: CT findings

    SciTech Connect

    Huebener, K.H.; Treugut, H.

    1984-01-01

    The computed tomographic appearance of the adrenal gland was studied in 302 patients with possible endocrinologic disease and 107 patients undergoing CT for nonendocrinologic reasons. Measurements of adrenal size were also made in 100 adults with no known adrenal pathology. CT proved to be a sensitive diagnostic tool in combination with clinical studies. When blood hormone levels are increased, CT can differentiate among homogeneous organic hyperplasia, nodular hyperplasia, benign adenoma, and malignant cortical adenoma. When blood hormone levels are decreased, CT can demonstrate hypoplasia or metastatic tumorous destruction. Calcifications can be demonstrated earlier than on plain radiographs. When hormone elimination is increased, the morphologic substrate can be identified; tumorous changes can be localized and infiltration of surrounding organs recognized.

  3. Adrenal gland disease in ferrets.

    PubMed

    Simone-Freilicher, Elisabeth

    2008-01-01

    Adrenal gland disease in ferrets is unique to this species, with clinical signs and pathophysiology different from those seen in the dog. Its prevalence is increasing; 70% of pet ferrets in the United States were affected in 2003. The exact causes of the adrenal gland changes that lead to the disease are not known. Early oophorohysterectomies and neutering, combined with the artificially prolonged photoperiod experienced by indoor pet ferrets, and a possible genetic component, may be contributing factors. Signs of adrenal gland disease include progressive hair loss, pruritus, lethargy, atrophy, and, in female ferrets, vulvar swelling. An understanding of the signs and physiologic changes is necessary for diagnosis and treatment. A review of anatomy, physiology, and current surgical and medical options is presented.

  4. 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

  5. Adrenal myelolipoma with osseous metaplasia and hypercortisolism

    PubMed Central

    Kumar, Ujwal; Priyadarshi, Shivam; Tomar, Vinay; Vohra, Rishi Raj

    2017-01-01

    Adrenal myelolipomas are rare adrenal tumors generally diagnosed incidentally. A 42-year-old female reported to us with complaints of left flank pain attributable to her left ureteric calculi. On evaluation, a large adrenal mass was diagnosed along with hypercortisolism. After adrenalectomy, the histopathology revealed adrenal myelolipoma along with osseous metaplasia not reported in English literature, to the best of our knowledge till date. PMID:28216934

  6. HLA-DR and ß2 microglobulin expression in medullary and atypical medullary carcinoma of the breast: histopathologically similar but biologically distinct entities

    PubMed Central

    Feinmesser, M.; Sulkes, A.; Morgenstern, S.; Sulkes, J.; Stern, S.; Okon, E.

    2000-01-01

    Aims—To examine the expression of HLA-DR and ß2 microglobulin in medullary carcinoma and atypical medullary carcinoma of the breast to determine if the effective presentation of tumour antigens to the immune system can differentiate between these two histopathologically similar entities. Methods—Expression of HLA-DR and ß2 microglobulin was examined by immunohistochemical methods in five samples of medullary carcinoma of the breast, which has a relatively favourable prognosis, six samples of atypical medullary carcinoma of the breast, which has a prognosis closer to that of regular invasive duct carcinoma, and 20 samples of invasive duct carcinomas, 10 with an accompanying lymphocytic infiltrate. Results—A positive and significant correlation was found between tumour type and both HLA-DR and ß2 microglobulin expression. Expression was most prominent in medullary carcinoma, followed by atypical medullary carcinoma and invasive duct carcinoma with and without lymphocytic infiltrates. The mean intensity and percentage of HLA-DR tumour immunostaining were significantly higher in medullary carcinoma than in the other three tumour groups, as was the mean intensity of ß2 microglobulin immunostaining. Mean percentage of ß2 microglobulin immunostaining was significantly higher in medullary carcinoma than in invasive duct carcinoma without lymphocytic infiltrates, and showed a trend to increase from invasive duct carcinoma with lymphocytic infiltrates to atypical medullary carcinoma and medullary carcinoma. Conclusions—Medullary carcinoma and atypical medullary carcinoma of the breast differ in their expression of HLA-DR and ß2 microglobulin. The relatively favourable prognosis of medullary carcinoma of the breast may be related to effective tumour antigen presentation to the immune system through MHC-I and MHC-II expression. Immunotherapy aimed at MHC-I and MHC-II induction might have a beneficial effect in breast cancer. Key Words: medullary carcinoma of the

  7. Sporadic Medullary Thyroid Carcinoma: Clinical Data From A University Hospital

    PubMed Central

    Correia-Deur, Joya Emilie M.; Toledo, Rodrigo A.; Imazawa, Alice T.; Lourenço, Delmar M.; Ezabella, Marilza C. L.; Tavares, Marcos R.; Toledo, Sergio P. A.

    2009-01-01

    INTRODUCTION: Medullary thyroid carcinoma may occur in a sporadic (s-medullary thyroid carcinoma, 75%) or in a multiple endocrine neoplasia type 2 form (MEN2, 25%). These clinical forms differ in many ways, as s-medullary thyroid carcinoma cases are RET-negative in the germline and are typically diagnosed later than medullary thyroid carcinoma in MEN2 patients. In this study, a set of cases with s-medullary thyroid carcinoma are documented and explored. PURPOSE: To document the phenotypes observed in s-medullary thyroid carcinoma cases from a university group and to attempt to improve earlier diagnosis of s-medullary thyroid carcinoma. Some procedures for diagnostics are also recommended. METHOD: Patients (n=26) with apparent s-medullary thyroid carcinoma were studied. Their clinical data were reviewed and peripheral blood was collected and screened for RET germline mutations. RESULTS: The average age at diagnosis was 43.9 years (± 10.82 SD) and did not differ between males and females. Calcitonin levels were increased in all cases. Three patients presented values that were 100-fold greater than the normal upper limit. Most (61.54%) had values that were 20-fold below this limit. Carcinoembryonic antigen levels were high in 70.6% of cases. There was no significant association between age at diagnosis, basal calcitonin levels or time of disease onset with thyroid tumor size (0.6–15 cm). Routine thyroid cytology yielded disappointing diagnostic accuracy (46.7%) in this set of cases. After total thyroidectomy associated with extensive cervical lymph node resection, calcitonin values remained lower than 5 pg/mL for at least 12 months in eight of the cases (30.8%). Immunocyto- and histochemistry for calcitonin were positive in all analyzed cases. None of the 26 cases presented germline mutations in the classical hotspots of the RET proto-oncogene. CONCLUSION: Our cases were identified late. The basal calcitonin measurements and immunostaining for calcitonin were

  8. Radionuclide therapy of adrenal tumors.

    PubMed

    Carrasquillo, Jorge A; Pandit-Taskar, Neeta; Chen, Clara C

    2012-10-01

    Adrenal tumors arising from chromaffin cells will often accumulate radiolabeled metaiodobenzylguanidine (MIBG) and thus are amenable to therapy with I-131 MIBG. More recently, therapy studies have targeted the somatostatin receptors using Lu-177 or Y-90 radiolabeled somatostatin analogs. Because pheochromocytoma (PHEO)/paraganglioma (PGL) and neuroblastoma (NB), which often arise from the adrenals, express these receptors, clinical trials have been performed with these reagents. We will review the experience using radionuclide therapy for targeting PHEO/PGL and NBs. Copyright © 2012 Wiley Periodicals, Inc.

  9. [Immunoendocrine associations in adrenal glands].

    PubMed

    Sterzl, I; Hrdá, P

    2010-12-01

    Immune and endocrine systems are basic regulatory mechanisms of organism and, including the nervous system, maintain the organism's homeostasis. The main immune system representatives are mononuclear cells, T- and B-cells and their products, in the endocrine system the main representatives are cells of the glands with inner secretion and their products. One of the most important glands for maintaining homeostasis are adrenal glands. It has been proven that either cells of the immune system, either endocrine cells can, although in trace amounts, produce mutually mediators of both systems (hormones, cytokines). Disorders in one system can lead to pathological symptoms in the other system. Also here represent adrenals an important model.

  10. Somatostatin receptor expression in non-medullary thyroid carcinomas.

    PubMed

    Pazaitou-Panayiotou, Kalliopi; Tiensuu Janson, Eva; Koletsa, Triantafyllia; Kotoula, Vassiliki; Stridsberg, Mats; Karkavelas, Georgios; Karayannopoulou, Georgia

    2012-01-01

    Peptide receptor radionuclide therapy (PRRT) is dependent upon binding of radiolabelled peptides to their respective receptor expressing cells. The main objective of this study was to characterize the expression of somatostatin receptor (SSTR) subtypes in non-medullary thyroid cancers in order to be able to recommend the use of PRRT as a treatment option in patients with progressive local or metastatic disease. We constructed tissue microarrays from paraffin blocks prepared from 47 cases of non-medullary thyroid carcinomas and related normal thyroid tissue. Immunohistochemical staining was performed with five different polyclonal SSTR antibodies. SSTR subtypes sst2 and sst3 were expressed in all non-medullary thyroid carcinomas, sst1 and sst5 in 75%, and sst4 in 38%. Coexpression of more than three subtypes was detected in 36 of the 47 cases. The expression of SSTR subtypes in normal thyroid tissue was low or absent. Non-medullary thyroid carcinomas frequently express all SSTR subtypes. This expression provides a basis for further studies with the aim of exploring PRRT as a possible new treatment for iodine-131 refractory metastatic non-medullary thyroid carcinomas.

  11. Spontaneous bilateral adrenal hemorrhage following cholecystectomy.

    PubMed

    Dahan, Meryl; Lim, Chetana; Salloum, Chady; Azoulay, Daniel

    2016-06-01

    Postoperative bilateral adrenal hemorrhage is a rare but potentially life-threatening complication. This diagnosis is often missed because the symptoms and laboratory results are usually nonspecific. We report a case of bilateral adrenal hemorrhage associated with acute primary adrenal insufficiency following laparoscopic cholecystectomy. The knowledge of this uncommon complication following any abdominal surgery allows timey diagnosis and rapid treatment.

  12. Spontaneous Retroperitoneal Hemorrhage from Adrenal Artery Aneurysm

    SciTech Connect

    Gonzalez Valverde, F.M. Balsalobre, M.; Torregrosa, N.; Molto, M.; Gomez Ramos, M.J.; Vazquez Rojas, J.L.

    2007-04-15

    Spontaneous adrenal hemorrhage is a very rare but serious disorder of the adrenal gland that can require emergent treatment. We report on a 42-year-old man who underwent selective angiography for diagnosis and treatment of retroperitoneal hemorrhage from small adrenal artery aneurysm. This case gives further details about the value of transluminal artery embolization in the management of visceral aneurysm rupture.

  13. The adrenal glands and their functions.

    PubMed

    De Silva, Deepthi C; Wijesiriwardene, Bandula

    2007-09-01

    The adrenal glands secrete hormones essential for metabolism, regulation of blood pressure, and sodium and glucose homeostasis. Hypo- or hypersecretion of these hormones is life threatening. Understanding the physiological functions of adrenal hormones is a prerequisite to the management of adrenal gland disease.

  14. Spontaneous bilateral adrenal hemorrhage following cholecystectomy

    PubMed Central

    Dahan, Meryl; Lim, Chetana; Salloum, Chady

    2016-01-01

    Postoperative bilateral adrenal hemorrhage is a rare but potentially life-threatening complication. This diagnosis is often missed because the symptoms and laboratory results are usually nonspecific. We report a case of bilateral adrenal hemorrhage associated with acute primary adrenal insufficiency following laparoscopic cholecystectomy. The knowledge of this uncommon complication following any abdominal surgery allows timey diagnosis and rapid treatment. PMID:27275469

  15. Medullary thyroid cancer with undetectable serum calcitonin.

    PubMed

    Brutsaert, Erika F; Gersten, Adam J; Tassler, Andrew B; Surks, Martin I

    2015-02-01

    Calcitonin is a sensitive biomarker that is used for diagnosis and follow-up in medullary thyroid cancer (MTC). In patients with tumors > 1 cm, it is uncommon for preoperative serum calcitonin to be in the normal laboratory reference range in patients with MTC, and even more unusual for serum calcitonin to be undetectable. A 39-year-old woman was found to have a left thyroid nodule on magnetic resonance imaging done for neck pain. Ultrasound and fine-needle aspiration biopsy were performed, and cytopathology was positive for malignant cells. The cells also had features suggestive of a neuroendocrine tumor, and the specimen was immune-stained with calcitonin. There was positive immunoreactivity for calcitonin in isolated cells of the cytospin, highly favoring a diagnosis of MTC. Serum calcitonin was < 2 pg/mL (<6 pg/mL), and serum carcinoembryonic antigen was 3.1 ng/mL (<5.2 ng/mL). Given the low calcitonin levels, procalcitonin was also tested and was elevated at 0.21 ng/mL (< 0.1 ng/mL). The patient subsequently underwent a total thyroidectomy and central and ipsilateral lateral lymph node dissection. Histopathology confirmed a 2.6 × 2.0 × 1.2-cm MTC, with strong, diffuse immunostaining for calcitonin. Postoperatively, serum calcitonin has remained undetectable, carcinoembryonic antigen has remained within the reference range, and procalcitonin has become undetectable. We present a rare case of a patient with MTC with undetectable preoperative serum calcitonin, whose tumor demonstrated strong, diffuse immunohistochemical staining for calcitonin. We discuss the possible pathogenesis of calcitonin-negative MTC and the challenges in following patients with this condition.

  16. 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.

  17. Adrenal Insufficiency and Addison's Disease

    MedlinePlus

    ... used if the diagnosis remains unclear. What other tests might a health care provider perform after diagnosis of adrenal insufficiency? After ... skin. A nurse or lab technician performs the test in a health care provider’s office; a patient does not need anesthesia. ...

  18. Anesthetic Considerations on Adrenal Gland Surgery

    PubMed Central

    Domi, Rudin; Sula, Hektor; Kaci, Myzafer; Paparisto, Sokol; Bodeci, Artan; Xhemali, Astrit

    2015-01-01

    Adrenal gland surgery needs a multidisciplinary team including endocrinologist, radiologist, anesthesiologist, and surgeon. The indications for adrenal gland surgery include hormonal secreting and non-hormonal secreting tumors. Adrenal hormonal secreting tumors present to the anesthesiologist unique challenges requiring good preoperative evaluation, perioperative hemodynamic control, corrections of all electrolytes and metabolic abnormalities, a detailed and careful anesthetic strategy, overall knowledge about the specific diseases, control and maintaining of postoperative adrenal function, and finally a good collaboration with other involved colleagues. This review will focus on the endocrine issues, as well as on the above-mentioned aspects of anesthetic management during hormone secreting adrenal gland tumor resection. PMID:25368694

  19. [Frequency of Kongenital Adrenal Hyperplasia (author's transl)].

    PubMed

    Müller, W; Prader, M; Kofler, J; Glatzl, J; Geir, W

    1979-01-01

    The frequency of homozygous congenital adrenal hyperplasia in Tyrol is found to be 1 : 8991, the gene-frequency for congenital adrenal hyperplasia 1 : 95 and the frequency of heterozygous congenital adrenal hyperplasia 1 : 48. Our data is compared on a numerical and statistical base with that in Zürich and Munich with regard to the frequency of congenital adrenal hyperplasia, to its distribution with and without salt loss and to its sex-distribution. According to our study one may assume a frequency of homozygous congenital adrenal hyperplasia in Tyrol, Zürich and Munich of 1 : 7000--10,000.

  20. Dysphagia in unilateral medullary infarction: lateral vs medial lesions.

    PubMed

    Kwon, Miseon; Lee, Jae H; Kim, Jong S

    2005-09-13

    To study dysphagia in pure, unilateral medullary infarction using video fluoroscopic swallowing (VFS) tests and to compare the results between lateral medullary infarction (LMI) and medial medullary infarction (MMI). We studied 46 patients with medullary infarction (37 LMI, 9 MMI). Based on the MRI findings, each LMI was classified rostrocaudally as either a rostral or caudal lesion, and horizontally as either a superficial (lateral + dorsal) or nonsuperficial lesion. Each MMI was assigned to either a deep (lesion extending to the dorsal surface) or superficial lesion group. VFS examination was conducted and an 8-point scale was used for assessing the severity of dysphagia. Based on these results, dysphagia was classified as: 1) problems on timing of hyolaryngeal excursion (PT), and 2) problems on range of hyolaryngeal excursion (PR). Dysphagia was more frequent (p < 0.05) in MMI patients (78%) than in LMI patients (35%). Among the LMI patients, dysphagia was more frequent (p < 0.01) and severe (p < 0.01) in the rostral than in the caudal group and in the nonsuperficial than in the superficial group. In the MMI group, there was no difference in the frequency of dysphagia between the deep and superficial groups. Regarding the characteristics of dysphagia, seven (54%) of the LMI patients had PR, five (38%) had PT, and one (8%) had both. For the MMI patients, PT was frequent (86%) but PR was present in only one patient (14%). Five MMI patients (71%) showed no responses to penetration or aspiration, and silent dysphagia was observed in only four LMI patients (31%). Dysphagia is as frequent and severe in medial medullary infarction (MMI) as in lateral medullary infarction (LMI) patients. The types and characteristics of dysphagia are different between the LMI and MMI patients, implicating the rationale for a different treatment strategy.

  1. Comprehensive characterization of expression patterns of protein 4.1 family members in mouse adrenal gland: implications for functions.

    PubMed

    Wang, Hua; Liu, Congrong; Debnath, Gargi; Baines, Anthony J; Conboy, John G; Mohandas, Narla; An, Xiuli

    2010-10-01

    The members of the protein 4.1 family, 4.1R, 4.1G, 4.1N, and 4.1B, are encoded by four genes, all of which undergo complex alternative splicing. It is well established that 4.1R, the prototypical member of the family, serves as an adapter that links the spectrin-actin based cytoskeleton to the plasma membrane in red cells. It is required for mechanical resilience of the membrane, and it ensures the cell surface accumulation of selected membrane proteins. However, the function of 4.1 proteins outside erythrocytes remains under-explored, especially in endocrine tissues. Transcripts of all 4.1 homologs have previously been documented to be abundantly expressed in adrenal gland. In order to begin to decipher the function of 4.1 proteins in adrenal gland, we performed a detailed characterization of the expression pattern of various 4.1 proteins and their cellular localization. We show that 4.1R (~80 and ~135 kDa) splice forms are expressed on the membrane of all cells, while a ~160 kDa 4.1G splice form is distributed in the cytoplasm and the membrane of zona glomerulosa and of medullary cells. Two 4.1N splice forms, ~135 and ~95 kDa, are present in the peri-nuclear region of both zona glomerulosa and medullary cells, while a single ~130 kDa 4.1B splice form, is detected in all layers of adrenal gland in both the cytoplasm and the membrane. The characterization of distinct splice forms of various 4.1 proteins with diverse cellular and sub-cellular localization indicates multiple functions for this family of proteins in endocrine functions of adrenal gland.

  2. [Medullary thyroid carcinoma and other rare types of thyroid carcinoma].

    PubMed

    Obara, Takao

    2007-11-01

    Among 4 major traditional groups of thyroid carcinoma, papillary and follicular carcinomas are most common, and other forms, anaplastic and medullary carcinomas, are relatively rare. The 2003 WHO histological classification of thyroid tumor separated 7 other malignant thyroid tumors into distinct pathological entities, such as poorly differentiated, squamous cell, mucinous carcinomas, carcinoma showing thymus-like differentiation (CASTLE), etc. Although they are also extremely rare, recognition of their clinicopathologic features are very important. In this review, not only diagnostic and therapeutic strategies for the rare forms of thyroid carcinomas, specifically focussed on medullary carcinoma and CASTLE, but also their histogenetic abnormalities were discussed.

  3. Mixed medullary and follicular carcinoma of the thyroid.

    PubMed

    Pfaltz, M; Hedinger, C E; Mühlethaler, J P

    1983-01-01

    We report a case of medullary carcinoma of the thyroid which on light microscopy showed not only the well known arrangement of cells in sheets and nests but also unequivocal follicular structures. These follicular structures are present both in the primary tumor and in lymph node metastases. Immunohistochemical investigations revealed that the cells lining the follicles produce thyroglobulin, whereas the remaining tumor tissue is positive for calcitonin and carcinoembrionic antigen. This case represents a medullary carcinoma of the thyroid with an atypical pattern consisting of both thyroglobulin and calcitonin producing cells.

  4. Adrenal adrenoceptors in heart failure

    PubMed Central

    de Lucia, Claudio; Femminella, Grazia D.; Gambino, Giuseppina; Pagano, Gennaro; Allocca, Elena; Rengo, Carlo; Silvestri, Candida; Leosco, Dario; Ferrara, Nicola; Rengo, Giuseppe

    2014-01-01

    Heart failure (HF) is a chronic clinical syndrome characterized by the reduction in left ventricular (LV) function and it represents one of the most important causes of morbidity and mortality worldwide. Despite considerable advances in pharmacological treatment, HF represents a severe clinical and social burden. Sympathetic outflow, characterized by increased circulating catecholamines (CA) biosynthesis and secretion, is peculiar in HF and sympatholytic treatments (as β-blockers) are presently being used for the treatment of this disease. Adrenal gland secretes Epinephrine (80%) and Norepinephrine (20%) in response to acetylcholine stimulation of nicotinic cholinergic receptors on the chromaffin cell membranes. This process is regulated by adrenergic receptors (ARs): α2ARs inhibit CA release through coupling to inhibitory Gi-proteins, and β ARs (mainly β2ARs) stimulate CA release through coupling to stimulatory Gs-proteins. All ARs are G-protein-coupled receptors (GPCRs) and GPCR kinases (GRKs) regulate their signaling and function. Adrenal GRK2-mediated α2AR desensitization and downregulation are increased in HF and seem to be a fundamental regulator of CA secretion from the adrenal gland. Consequently, restoration of adrenal α2AR signaling through the inhibition of GRK2 is a fascinating sympatholytic therapeutic strategy for chronic HF. This strategy could have several significant advantages over existing HF pharmacotherapies minimizing side-effects on extra-cardiac tissues and reducing the chronic activation of the renin–angiotensin–aldosterone and endothelin systems. The role of adrenal ARs in regulation of sympathetic hyperactivity opens interesting perspectives in understanding HF pathophysiology and in the identification of new therapeutic targets. PMID:25071591

  5. Posterior retroperitoneoscopic approach to the adrenal arteries.

    PubMed

    Lotti, Marco; Giulii Capponi, Michela

    2016-12-01

    Differently from transperitoneal adrenalectomy, with the posterior retroperitoneoscopic approach adrenal arteries are dissected first [1, 2]. Knowledge of their position is pivotal as they are covered by peri-adrenal fat [3, 4]. Four posterior retroperitoneoscopic adrenalectomies were selected, in which adrenal arteries are dissected to show their path and how they can be localized among peri-adrenal fat. A video is presented herein, which focuses on surgical anatomy of adrenal arteries when approached during a posterior retroperitoneoscopic adrenalectomy. Details about relative positions between adrenal arteries and adjacent structures are considered and shown during their dissection. The posterior retroperitoneoscopic approach offers a direct view of adrenal arteries and allows for their exposure and safe division in the early steps of adrenalectomy.

  6. Brain prostanoid TP receptor-mediated adrenal noradrenaline secretion and EP3 receptor-mediated sympathetic noradrenaline release in rats.

    PubMed

    Yokotani, Keiko; Okada, Shoshiro; Nakamura, Kumiko; Yamaguchi-Shima, Naoko; Shimizu, Takahiro; Arai, Junichi; Wakiguchi, Hiroshi; Yokotani, Kunihiko

    2005-04-04

    Sympathetic nerves release noradrenaline, whereas adrenal medullary chromaffin cells secrete noradrenaline and adrenaline. Therefore, plasma noradrenaline reflects the secretion from adrenal medulla in addition to the release from sympathetic nerves, however the exact mechanisms of adrenal noradrenaline secretion remain to be elucidated. The present study was designated to characterize the source of plasma noradrenaline induced by intracerebroventricularly (i.c.v.) administered bombesin and prostaglandin E2 in urethane-anesthetized rats. Bombesin (1.0 nmol/animal, i.c.v.) elevated plasma noradrenaline and adrenaline, while prostaglandin E2 (0.3 nmol/animal, i.c.v.) elevated only plasma noradrenaline. The bombesin-induced elevations of both catecholamines were attenuated by pretreatments with furegrelate (an inhibitor of thromboxane A2 synthase) [250 and 500 microg (0.9 and 1.8 micromol)/animal, i.c.v.)] and [(+)-S-145] [(+)-(1R,2R,3S,4S)-(5Z)-7-(3-[4-3H]-phenylsulphonyl-aminobicyclo[2.2.1]hept-2-yl)hept-5-enoic acid sodium salt] (an antagonist of prostanoid TP receptors) [100 and 250 microg (250 and 625 nmol)/animal)], and abolished by acute bilateral adrenalectomy. On the other hand, the prostaglandin E2-induced elevation of plasma noradrenaline was not influenced by acute bilateral adrenalectomy. These results suggest that adrenal noradrenaline secretion and sympathetic noradrenaline release are mediated by differential central mechanisms; brain prostanoid TP receptors activated by bombesin are involved in the adrenal noradrenaline secretion, while brain prostanoid EP (probably EP3) receptors activated by prostaglandin E2 are involved in the sympathetic noradrenaline release in rats. Brain prostanoid TP receptors activated by bombesin are also involved in the adrenal adrenaline secretion.

  7. A developmental model of neuroblastoma: differentiating stroma-poor tumors' progress along an extra-adrenal chromaffin lineage.

    PubMed

    Hoehner, J C; Gestblom, C; Hedborg, F; Sandstedt, B; Olsen, L; Påhlman, S

    1996-11-01

    The prognosis of children with neuroblastoma (NB) is dependent upon the patient's age at diagnosis, the location of the primary tumor, and histologic tumor cell differentiation. These characteristics, as well as the presumption that NB results from clonal expansion of primitive cells involved in sympathetic nervous system (SNS) development, predict that a model of tumorigenesis based upon normal fetal SNS histogenesis might indicate tumor progenitor status and define biologic and clinical behavior. Immunohistochemistry and in situ hybridization were used to examine a panel of marker gene products predicted or shown to be expressed during SNS development in the normal human fetal SNS from 8 to 24 weeks' gestational age. A similar analysis was performed in a selection of clinical NB tumors, and the results were compared. In a subset of differentiating, often extra-adrenal NB tumors in patients who frequently had a favorable outcome; advancing morphologic tumor cell differentiation spatially paralleled an advancing fetal extra-adrenal chromaffin marker gene expression phenotype (ie, increasing TrkA, TrkC, TH, IGF-2, and neuron-specific enolase expression but a lack of phenylethanolamine N-methyltransferase expression). In these tumors, expression of gene products associated with normal fetal sympathetic ganglionic differentiation (ie, Bcl-2, HNK-1, and neuropeptide Y) was lost with morphologic tumor cell differentiation. In contrast, undifferentiated tumors, the majority of which were high stage, adrenal in origin, and prognostically unfavorable, displayed marker expression characteristics mirroring that of an early fetal ganglionic lineage. Thus, we show that morphologic differentiation in stroma-poor NB tumors, long held as an important prognostic feature in tumor grading systems, often corresponds to an extra-adrenal chromaffin rather than a ganglion cell or adrenal medullary chromaffin phenotype. Understanding the biology of extra-adrenal chromaffin tissues may

  8. Management of adolescents with congenital adrenal hyperplasia.

    PubMed

    Merke, Deborah P; Poppas, Dix P

    2013-12-01

    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. 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

  10. Addiction and the adrenal cortex

    PubMed Central

    Vinson, Gavin P; Brennan, Caroline H

    2013-01-01

    Substantial evidence shows that the hypophyseal–pituitary–adrenal (HPA) axis and corticosteroids are involved in the process of addiction to a variety of agents, and the adrenal cortex has a key role. In general, plasma concentrations of cortisol (or corticosterone in rats or mice) increase on drug withdrawal in a manner that suggests correlation with the behavioural and symptomatic sequelae both in man and in experimental animals. Corticosteroid levels fall back to normal values in resumption of drug intake. The possible interactions between brain corticotrophin releasing hormone (CRH) and proopiomelanocortin (POMC) products and the systemic HPA, and additionally with the local CRH–POMC system in the adrenal gland itself, are complex. Nevertheless, the evidence increasingly suggests that all may be interlinked and that CRH in the brain and brain POMC products interact with the blood-borne HPA directly or indirectly. Corticosteroids themselves are known to affect mood profoundly and may themselves be addictive. Additionally, there is a heightened susceptibility for addicted subjects to relapse in conditions that are associated with change in HPA activity, such as in stress, or at different times of the day. Recent studies give compelling evidence that a significant part of the array of addictive symptoms is directly attributable to the secretory activity of the adrenal cortex and the actions of corticosteroids. Additionally, sex differences in addiction may also be attributable to adrenocortical function: in humans, males may be protected through higher secretion of DHEA (and DHEAS), and in rats, females may be more susceptible because of higher corticosterone secretion. PMID:23825159

  11. Medullary serotonin neurons are CO2 sensitive in situ

    PubMed Central

    Richerson, George B.; Harris, Michael B.

    2013-01-01

    Brainstem central chemoreceptors are critical to the hypercapnic ventilatory response, but their location and identity are poorly understood. When studied in vitro, serotonin-synthesizing (5-HT) neurons within the rat medullary raphé are intrinsically stimulated by CO2/acidosis. The contributions of these neurons to central chemosensitivity in vivo, however, are controversial. Lacking is documentation of CO2-sensitive 5-HT neurons in intact experimental preparations and understanding of their spatial and proportional distribution. Here we test the hypothesis that 5-HT neurons in the rat medullary raphé are sensitive to arterial hypercapnia. We use extracellular recording and hypercapnic challenge of spontaneously active medullary raphé neurons in the unanesthetized in situ perfused decerebrate brainstem preparation to assess chemosensitivity of individual cells. Juxtacellular labeling of a subset of recorded neurons and subsequent immunohistochemistry for the 5-HT-synthesizing enzyme tryptophan hydroxylase (TPH) identify or exclude this neurotransmitter phenotype in electrophysiologically characterized chemosensitive and insensitive cells. We show that the medullary raphé houses a heterogeneous population, including chemosensitive and insensitive 5-HT neurons. Of 124 recorded cells, 16 cells were juxtacellularly filled, visualized, and immunohistochemically identified as 5-HT synthesizing, based on TPH-immunoreactivity. Forty-four percent of 5-HT cells were CO2 stimulated (increased firing rate with hypercapnia), while 56% were unstimulated. Our results demonstrate that medullary raphé neurons are heterogeneous and clearly include a subset of 5-HT neurons that are excited by arterial hypercapnia. Together with data identifying intrinsically CO2-sensitive 5-HT neurons in vitro, these results support a role for such cells as central chemoreceptors in the intact system. PMID:24047906

  12. [Is immediate prophylactic thyroidectomy indispensable in familiar medullary thyroid carcinoma?].

    PubMed

    Cañizo, A; Fanjul, M; Cerdá, J; Menárguez, J; Parente, A; Laín, A; Carrera, N; Rodríguez-Arnao, M D; Rodríguez-Sánchez, A; Polo, J R; Vázquez, J

    2008-04-01

    To emphasize the importance of genetic studies in family members and early prophylactic thyroidectomy in oncogene mutation carriers in the management of familiar medullary thyroid carcinoma. A retrospective review of families with familiar medullary thyroid carcinoma treated at our center in the last 7 years was performed. We identified a total of 7 families who has isolated prevalences with thyroid malignancies. Forty members of the 7 families were screened for gene RET mutations. Prophylactic total thyroidectomy was performed in every RET mutation gene carriers. In all families the index case were patients with medullary thyroid carcinoma presenting at a mean age of 37.25 years (range 23-42). The RET oncogen mutation was in codon 634 in exon 11 (multiple endocrine neoplasia type 2A) in all these patients. Fourteen gene carriers were identified with a mean age of 20 years (range 7-37), eleven of whom had medullary thyroid carcinoma at the time of surgery. Five of the gene carriers were children, with a mean age of 11 years (range 7-16), four of whom had microcarcinoma and one had metastatic carcinoma at the time of surgery. After surgery no hypoparathyroidism or recurrent nerve paralysis were documented. No pediatric patient has presented with phaeochromocytoma or hypoparathyroidism to date Four of the five children have normal calcitonin levels (< 2 pg/ml) and they are free of disease. The one who presented metastatic carcinoma has recurrent disease and is awaiting surgical treatment. Genetic studies of family members related to patients with familiar medullary thyroid carcinoma and RET mutations is indispensable. The RET mutation in codon 634 exon 11 was found to be the most frequent association. Prophylactic thyroidectomy is the only curative treatment and has minimal complications when performed by expert surgeons. Early thyroidectomy is recommended since distant metastatic spread can occur at early age.

  13. Primitive neuroectodermal adrenal gland tumour.

    PubMed

    Tsang, Y P; Lang, Brian H H; Tam, S C; Wong, K P

    2014-10-01

    Ewing's sarcoma, also called primitive neuroectodermal tumour of the adrenal gland, is extremely rare. Only a few cases have been reported in the literature. We report on a woman with adult-onset primitive neuroectodermal tumour of the adrenal gland presenting with progressive flank pain. Computed tomography confirmed an adrenal tumour with invasion of the left diaphragm and kidney. Radical surgery was performed and the pain completely resolved; histology confirmed the presence of primitive neuroectodermal tumour, for which she was given chemotherapy. The clinical presentation of this condition is non-specific, and a definitive diagnosis is based on a combination of histology, as well as immunohistochemical and cytogenic analysis. According to the literature, these tumours demonstrate rapid growth and aggressive behaviour but there are no well-established guidelines or treatment strategies. Nevertheless, surgery remains the mainstay of local disease control; curative surgery can be performed in most patients. Adjuvant chemoirradiation has been advocated yet no consensus is available. The prognosis of patients with primitive neuroectodermal tumours remains poor.

  14. Rare adrenal tumors in children.

    PubMed

    Mihai, Radu

    2014-04-01

    Apart from neuroblastomas, adrenal tumors are exceedingly rare in children and young adults. In this age group, the vast majority of patients present with clinical signs associated with excess hormone production. The most common tumor to arise from the adrenal cortex is an adrenocortical carcinoma (ACC). Similar to the situation in adults, this tumor is frequently diagnosed at a late stage and carries a very poor prognosis. ACCs require extensive/aggressive local resection followed by mitotane chemotherapy. A multidisciplinary approach is essential, and these children should be referred to units that have previous experience in managing ACCs. International registries are an invaluable source for evidence-based care, and such collaborations should be further developed in the future. Pheochromocytomas are derived from the adrenal medulla and present with symptoms caused by high secretion of catecholamines. At least one-third of these children will be found to carry genetic mutations, most commonly the RET gene (MEN2 syndrome) or the VHL gene. Open radical adrenalectomy should be offered to children with adrenocortical cancers. For all other cases, laparoscopic adrenalectomy is the treatment of choice. It is possible that the retroperitoneoscopic approach will gain increasing favor. The role of robotic adrenalectomy remains controversial.

  15. Occult adrenal insufficiency in surgical patients.

    PubMed Central

    Hubay, C A; Weckesser, E C; Levy, R P

    1975-01-01

    Eight patients admitted to a University hospital with acute surgical problems and related adrenal insufficiency were reviewed and three are presented in detail. Surgical stress and continued sepsis played major roles in the lack of responsiveness to usual modes of therapy until the adrenal insufficiency was corrected. The patients fell into three major clinical categories of adrenal insufficiency. Chronic illness and sepsis are shown to affect steroid production and metabolism, as well as adrenal responsiveness to ACTH. Pharmacologic amounts of steroids are often needed in patients with shock, gram negative sepsis and prolonged illnesses, even if normal or elevated serum cortisols are present. Therapeutic trials of cortisol administration are shown to be confusing when not accompanied by easily performed diagnostic tests of adrenal function. It is emphasized that a pretreatment serum cortisol should be obtained whenever possible. The evaluation of adrenal function is of lifelong importance to the patient. PMID:165792

  16. Laparoscopic Resection of an Adrenal Schwannoma

    PubMed Central

    Konstantinos, Toutouzas G.; Panagiotis, Kekis B.; Nikolaos, Michalopoulos V.; Ioannis, Flessas; Andreas, Manouras; Geogrios, Zografos

    2012-01-01

    Background and Objectives: Schwannomas are tumors originating from Schwann cells of the peripheral nerve sheath (neurilemma) of the neuroectoderm. Rarely, schwannomas can arise from the retroperitoneum and adrenal medulla. We describe a case of a 71-y-old woman who presented with an incidentally discovered adrenal tumor. Methods: Ultrasound and computed tomography scans revealed a lesion with solid and cystic areas originating from the left adrenal gland. The patient underwent complete laparoscopic resection of the tumor and the left adrenal gland. Results: Histopathological examination and immunohistochemical staining of the excised specimen revealed a benign schwannoma measuring 5.5×5×3.7 cm. To our knowledge, few other cases of laparoscopic resection of adrenal schwannomas have been reported. Conclusion: Because preoperative diagnosis of adrenal tumors is inconclusive, complete laparoscopic excision allows for definitive diagnosis with histological evaluation and represents the treatment of choice. PMID:23484583

  17. [Virilizing adrenal ganglioneuroma : A rare differential diagnosis in testosterone secreting adrenal tumours].

    PubMed

    Gaisa, N T; Klöppel, G; Brehmer, B; Neulen, J; Stephan, P; Knüchel, R; Donner, A

    2009-09-01

    Testosterone secreting tumours of the adrenal glands are usually adrenal carcinomas or adenomas. Here we report the rare case of an adrenal ganglioneuroma with ectopic Leydig cells, a so-called virilizing adrenal ganglioneuroma. Clinically it is characterized by symptoms of virilization, histologically by the occurrence of a population of eosinophilic cells. In the absence of crystalloids of Reinke this cell population can be identified as Leydig cells based on positive immunohistochemical staining of inhibin and calretinin.

  18. Adrenal glands of slaughtered bulls, heifers and cows: a histological study.

    PubMed

    Jelinek, F; Konecny, R

    2011-02-01

    The study involved histological and immunohistochemical examinations of the adrenal glands of healthy slaughtered cattle. Glands of 13 bulls, 10 heifers and 10 cows were examined. The following histological findings were observed: Unequal thickness of connective capsule and nodular formations of the zona glomerulosa (ZG), eosinophilic granules in cells of the ZG, globoid arrangement of the zona fasciculata, nodules or pegs of cortical tissue in the medulla, mutual interlacing of superficial and deep zones of the medulla, proliferation of cortical or medullary cells into the blood vessels wall situated in the medulla and focal inflammatory infiltrates. Cortical cells and noradrenalin-secreting (N) cells in the medulla expressed cytoplasmic positivity of S100 protein. Both adrenalin (A) cells and N cells were positive in synaptophysin. The majority of the cells in the cortex and in the medulla displayed were positive for chromogranin A. Electron microscopy showed structureless, electrondense particles of varying size and shape, mostly displaying the having mostly character of secretory granules.

  19. [Development of the human adrenal glands].

    PubMed

    Folligan, K; Bouvier, R; Targe, F; Morel, Y; Trouillas, J

    2005-09-01

    The human adrenal is an endocrine gland located at the superior part of the kidney. Composed of the adrenal cortex of mesoblastic origin and the adrenal medulla of neuroectoblastic origin, the human fetal adrenal grows considerably during the first three months of development. From 12 to 18 weeks of development (WD), the weight of the adrenals increases seven-fold. The gland's weight doubles from 18 to 28 WD and from 28 to 36 WD. At birth, the two adrenals weigh on average 10 g. At the 8th week, two zones are individualized in the adrenal cortex: the definitive zone and the fetal inner zone. At the second trimester, according to ultrastructural and biochemical studies, a third zone, called the transition zone, is individualized between the definitive zone and the fetal inner zone. The definitive zone persists, but the origin of the three zones (glomerular, fascicular and reticular) of adult adrenal cortex is not known. The fetal inner zone regresses from the 5th month of gestation and disappears totally one year after birth. At the 8th week, the immature neuroblasts migrate to the definitive zone, then to the fetal inner zone to compose the adrenal medulla, which develops essentially after birth and during the first year. Before the 10th week, the human fetal adrenal is able to produce steroid hormones, in particular dehydroepiandrosterone sulfate (DHEA-S); the secretion of cortisol remains discussed. The development of the human fetal adrenal is complex and is under the control of hormones (ACTH, LH and betaHCG), growth factors (ACTH essentially) and transcription factors (essentially SF1 and DAX-1). Knowledge of morphological and molecular phenomena of this development permits to understand the pathophisiology of congenital adrenal deficiencies.

  20. Metabolism of adrenal cholesterol in man

    PubMed Central

    Borkowski, Abraham; Delcroix, Claude; Levin, Sam

    1972-01-01

    The kinetics of plasma and adrenal cholesteral equilibration were analyzed in patients undergoing bilateral adrenalectomy for generalized mammary carcinoma. A biological model is proposed to help in the understanding of adrenal cholesterol physiology. It comprises two intracellular compartments: (1) A compartment of free adrenal cholesterol which is small (of the order of 17 mg) but turns over very fast; it is renewed approximately 8 times per day: 3 times by the inflow of free plasma cholesterol, and 5 times by the hydrolysis of esterified adrenal cholesterol, the contribution of adrenal cholesterol synthesis appearing to be relatively small. (2) A compartment of esterified adrenal cholesterol which is 20 times larger; it is constantly renewed by in situ esterification and hydrolysis with a daily fractional turnover rate of the order of 0.25. The direct and selective accumulation of plasma cholesteryl esters is practically absent. Only free adrenal cholesterol returns to plasma, mostly after conversion into steroid “hormones.” However small the synthesis of adrenal cholesterol may be, it seems more important in the zona “reticularis.” On the other hand, the inflow of plasma cholesterol and the turnover of the free adrenal compartment tend to be faster in the zona “fasciculata.” The equilibration of plasma and adrenal cholesterol can proceed unmodified under conditions of ACTH suppression. In one patient with Cushing's disease the size of the two adrenal compartments was clearly increased but their equilibration with plasma cholesterol proceeded normally. In another patient the kinetics of hydrocortisone corresponded to those of free adrenal cholesterol in the control studies. PMID:4338119

  1. The variable pathologic presentations of medullary and micro-medullary thyroid carcinoma: an institutional experience.

    PubMed

    Samulski, T Danielle; Livolsi, Virginia A; Montone, Kathleen; Baloch, Zubair

    2014-03-01

    Medullary thyroid carcinoma (MTC) is a rare tumor; its pathologic diagnosis can be difficult due to variability in its clinical presentation, size, morphology, and follow-up. We report our institutional experience with 45 cases of MTC diagnosed at University of Pennsylvania Medical Center between 2000 and 2007. The collected data points included patient's age, sex, family history, tumor size, method of diagnosis, calcitonin and CEA levels, presence of concomitant follicular derived thyroid carcinoma (FDTC), lymph node (LN) status, and clinical follow-up. The cohort included 17 males and 28 females (average age 53 years); 6 had a history of multiple endocrine neoplasia II (MENII). Pre-operative FNA was performed in 33/45 cases (33%); 23/33 were diagnosed as MTC or suspicious for MTC. Of 45 cases 20 were micro-MTC; 15 occurred with other thyroid malignancies. LN metastases were present at primary resection in 18/45 cases. Calcitonin levels rose or remained elevated postoperatively in 4 cases; of these, 2 had regional LN recurrence and 1 developed distant metastases and subsequently died of disease. MTC is a heterogeneous disease. Sporadic micro-MTC carcinoma is an indolent tumor and can occur with other malignant tumors of the thyroid gland. Copyright © 2013 Elsevier GmbH. All rights reserved.

  2. Imaging of adrenal and renal hemorrhage.

    PubMed

    Hammond, Nancy A; Lostumbo, Antonella; Adam, Sharon Z; Remer, Erick M; Nikolaidis, Paul; Yaghmai, Vahid; Berggruen, Senta M; Miller, Frank H

    2015-10-01

    Hemorrhage of the kidneys and adrenal glands has many etiologies. In the adrenal glands, trauma, anticoagulation, stress, sepsis, surgery, and neoplasms are common causes of hemorrhage. In the kidneys, reasons for hemorrhage include trauma, bleeding diathesis, vascular diseases, infection, infarction, hemorrhagic cyst rupture, the Antopol-Goldman lesion, and neoplasms. Angiomyolipoma and renal cell carcinoma are the neoplasms most commonly associated with hemorrhage in the kidneys and adrenal cortical carcinoma, metastases, and pheochromocytoma are associated with hemorrhage in the adrenal glands. Understanding the computed tomography and magnetic resonance imaging features, and causes of hemorrhage in the kidneys and adrenal glands is critical. It is also important to keep in mind that mimickers of hemorrhage exist, including lymphoma in both the kidneys and adrenal glands, and melanoma metastases in the adrenal glands. Appropriate imaging follow-up of renal and adrenal hemorrhage should occur to exclude an underlying malignancy as the cause. If there is suspicion for malignancy that cannot be definitively diagnosed on imaging, surgery or biopsy may be warranted. Angiography may be indicated when there is a suspected underlying vascular disease. Unnecessary intervention, such as nephrectomy, may be avoided in patients with benign causes or no underlying disease. Appropriate management is dependent on accurate diagnosis of the cause of renal or adrenal hemorrhage and it is incumbent upon the radiologist to determine the etiology.

  3. Unilateral adrenal enlargement due to Histoplasma capsulatum.

    PubMed

    Swartz, M A; Scofield, R H; Dickey, W D; Kirk, J L; Wilson, D A; Pitha, J V; Muchmore, H G

    1996-10-01

    Human infection with Histoplasma capsulatum runs the gamut from asymptomatic to disseminated disease. CT-directed fine-needle aspiration of bilaterally enlarged adrenal glands has been used in diagnosing serious infections with this ubiquitous organism. Three cases have previously been reported in which H. capsulatum infection caused unilateral adrenal enlargement; this enlargement was diagnosed post-mortem. We describe three patients with unilateral adrenal enlargement due to H. capsulatum whose conditions were diagnosed antemortem. We encourage clinicians to include infection with H. capsulatum as well as other granulomatous diseases and tumors in the differential diagnosis of unilateral adrenal enlargement.

  4. Adrenal scan in 17-alpha-hydroxylase deficiency: false indication of adrenal adenoma

    SciTech Connect

    Shore, R.M.; Lieberman, L.M.; Newman, T.J.; Friedman, A.; Bargman, G.J.

    1981-07-01

    A patient who was thought to have testicular feminization syndrome and primary aldosteronism had an adrenal scan that suggested an adrenal adenoma. After later diagnosis of 17-alpha-hydroxylase deficiency, she was treated with glucocorticoids rather than surgery. Her clinical course and a repeat adrenal scan confirmed she did not have a tumor.

  5. Simultaneous monitoring of monoamines, amino acids, nucleotides and neuropeptides by liquid chromatography-tandem mass spectrometry and its application to neurosecretion in bovine chromaffin cells.

    PubMed

    Wojnicz, Aneta; Avendaño-Ortiz, José; de Pascual, Ricardo; Ruiz-Pascual, Lucía; García, Antonio G; Ruiz-Nuño, Ana

    2016-08-01

    The primary functions of adrenal medullary chromaffin cells are the synthesis and storage in their chromaffin vesicles of the catecholamines noradrenaline (NA) and adrenaline (AD), and their subsequent release into the bloodstream by Ca(2+) -dependent exocytosis under conditions of fear or stress (fight or flight response). Several monoamines, nucleotides and opiates, such as leucine-enkephalin (LENK) and methionine-enkephalin (MENK), are also co-stored and co-released with the catecholamines. However, other neurotransmitters have not been studied in depth. Here, we present a novel high-resolution liquid chromatography-tandem mass spectrometry approach for the simultaneous monitoring of 14 compounds stored and released in bovine chromaffin cells (BCCs). We validated the analytical method according to the recommendations of the EMA and FDA by testing matrix effect, selectivity, sensitivity, precision, accuracy, stability and carry-over. After testing on six batches of BCCs from different cultures, the method enabled simultaneous quantitative determination of monoamines (AD, NA, dopamine, serotonin, 5-hydroxyindoleacetic acid, histamine and metanephrine), amino acids (L-glutamic acid, γ-aminobutyric acid), nucleotides (adenosine 5'-diphosphate, adenosine 5'-monophosphate, cyclic adenosine 5'-monophosphate) and neuropeptides (LENK and MENK) in the intracellular content, basal secretion and acetylcholine induced secretion of BBCs. The high-resolution approach used here enabled us to determine the levels of 14 compounds in the same BCC batch in only 16 min. This novel approach will make it possible to study the regulatory mechanisms of Ca(2+) signaling, exocytosis and endocytosis using different neurotrophic factors and/or secretagogues as stimuli in primary BCC cultures. Our method is actually being applied to human plasma samples of different therapeutic areas where sympathoadrenal axis is involved in stress situations such as Alzheimer's disease, migraine or

  6. Is There Such a Thing as Adrenal Fatigue?

    MedlinePlus

    ... adrenal insufficiency caused by chronic stress. The unproven theory behind adrenal fatigue is that your adrenal glands ... feel good. Existing blood tests, according to this theory, aren't sensitive enough to detect such a ...

  7. Microsurgical anatomy of the arterial basket of the conus medullaris.

    PubMed

    Martirosyan, Nikolay L; Kalani, M Yashar S; Lemole, G Michael; Spetzler, Robert F; Preul, Mark C; Theodore, Nicholas

    2015-06-01

    OBJECT The arterial basket of the conus medullaris (ABCM) consists of 1 or 2 arteries arising from the anterior spinal artery (ASA) and circumferentially connecting the ASA and the posterior spinal arteries (PSAs). The arterial basket can be involved in arteriovenous fistulas and arteriovenous malformations of the conus. In this article, the authors describe the microsurgical anatomy of the ABCM with emphasis on its morphometric parameters and important role in the intrinsic blood supply of the conus medullaris. METHODS The authors performed microsurgical dissections on 16 formalin-fixed human spinal cords harvested within 24 hours of death. The course, diameter, and branching angles of the arteries comprising the ABCM were then identified and measured. In addition, histological sections were obtained to identify perforating vessels arising from the ABCM. RESULTS The ASA tapers as it nears the conus medullaris (mean preconus diameter 0.7 ± 0.12 mm vs mean conus diameter 0.38 ± 0.08 mm). The ASA forms an anastomotic basket with the posterior spinal artery (PSA) via anastomotic branches. In most of the specimens (n= 13, 81.3%), bilateral arteries formed connections between the ASA and PSA. However, in the remaining specimens (n= 3, 18.7%), a unilateral right-sided anastomotic artery was identified. The mean diameter of the right ABCM branch was 0.49 ± 0.13 mm, and the mean diameter of the left branch was 0.53 ± 0.14 mm. The mean branching angles of the arteries forming the anastomotic basket were 95.9° ± 36.6° and 90° ± 34.3° for the right- and left-sided arteries, respectively. In cases of bilateral arterial anastomoses between the ASA and PSA, the mean distance between the origins of the arteries was 4.5 ± 3.3 mm. Histological analysis revealed numerous perforating vessels supplying tissue of the conus medullaris. CONCLUSIONS The ABCM is a critical anastomotic connection between the ASA and PSA, which play an important role in the intrinsic blood supply

  8. Effect of angiotensin II, ATP, and ionophore A23187 on potassium efflux in adrenal glomerulosa cells

    SciTech Connect

    Lobo, M.V.; Marusic, E.T.

    1986-02-01

    Angiotensin II stimulus on perifused bovine adrenal glomerulosa cells elicited an increase in 86Rb efflux from cells previously equilibrated with the radioisotope. When 45Ca fluxes were measured under similar conditions, it was observed that Ca and Rb effluxes occurred within the first 30 s of the addition of the hormone and were independent of the presence of external Ca. The 86Rb efflux due to angiotensin II was inhibited by quinine and apamin. The hypothesis that the angiotensin II response is a consequence of an increase in the K permeability of the glomerulosa cell membrane triggered by an increase in cytosolic Ca is supported by the finding that the divalent cation ionophore A23187 also initiated 86Rb or K loss (as measured by an external K electrode). This increased K conductance was also seen with 10(-4) M ATP. Quinine and apamin greatly reduced the effect of ATP or A23187 on 86Rb or K release in adrenal glomerulosa cells. The results suggest that Ca-dependent K channels or carriers are present in the membranes of bovine adrenal glomerulosa cells and are sensitive to hormonal stimulus.

  9. 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

  10. Isolation, Characterization, and Differentiation of Progenitor Cells from Human Adult Adrenal Medulla

    PubMed Central

    Santana, Magda M.; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Karl; Bastos, Carlos A.; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R.; Cavadas, Cláudia

    2012-01-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10–12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)+/β-3-tubulin+ cells and TH−/β-3-tubulin+ cells, and into chromaffin cells (TH+/PNMT+). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  11. Isolation, characterization, and differentiation of progenitor cells from human adult adrenal medulla.

    PubMed

    Santana, Magda M; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Klaus; Bastos, Carlos A; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R; Cavadas, Cláudia; Ehrhart-Bornstein, Monika

    2012-11-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10-12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)(+)/β-3-tubulin(+) cells and TH(-)/β-3-tubulin(+) cells, and into chromaffin cells (TH(+)/PNMT(+)). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases.

  12. Medullary Sponge Kidney and Testicular Dysgenesis Syndrome: A Rare Association

    PubMed Central

    Masciovecchio, Stefano; Saldutto, Pietro; Paradiso Galatioto, Giuseppe; Vicentini, Carlo

    2014-01-01

    The medullary sponge kidney is also known as Lenarduzzi's kidney or Cacchi and Ricci's disease from the first Italian authors who described its main features. A review of the scientific literature underlines particular rarity of the association of MSK with developmental abnormalities of the lower urinary tract and genital tract such as hypospadias and bilateral cryptorchidism. The work presented is the only one in the scientific literature that shows the association between the medullary sponge kidney and the testicular dysgenesis syndrome. A question still remains unanswered: are the MSK and TDS completely independent malformation syndromes occurring, in this case, simultaneously for a rare event or are they different phenotypic expressions of a common malformative mechanism? In the future we hope that these questions will be clarified. PMID:24716085

  13. Russell-Silver syndrome associated with low conus medullaris.

    PubMed

    Gabor, Larisa; Canaz, Huseyin; Canaz, Gokhan; Kara, Nursu; Alatas, Ibrahim; Bozkus, Hakan

    2016-01-01

    Russell-Silver syndrome is a rare heterogeneous disorder mainly characterized by intrauterine and postnatal growth retardation, craniofacial disproportion, clinodactyly, variation in urogenital development, and skeletal asymmetry. It is rare to come across tethered cord-associated Russell-Silver syndrome. We report a rare case of Russell-Silver syndrome associated with low conus medullaris in a 2-year-old patient with demonstrative phenotype. Magnetic resonance imaging indicated a low conus medullaris at the inferior border of the L3 vertebral body. Urodynamic study revealed detrusor-sphincter dyssynergia and detrusor overactivity. A decision to follow-up the patient was made because of the suspicion of tethered cord syndrome. Even though tethered cord syndrome is not a common finding in Russell-Silver syndrome, it is important to consider tethered cord syndrome to avoid scoliosis and other long-term complications.

  14. Medullary sponge kidney and testicular dysgenesis syndrome: a rare association.

    PubMed

    Masciovecchio, Stefano; Saldutto, Pietro; Paradiso Galatioto, Giuseppe; Vicentini, Carlo

    2014-01-01

    The medullary sponge kidney is also known as Lenarduzzi's kidney or Cacchi and Ricci's disease from the first Italian authors who described its main features. A review of the scientific literature underlines particular rarity of the association of MSK with developmental abnormalities of the lower urinary tract and genital tract such as hypospadias and bilateral cryptorchidism. The work presented is the only one in the scientific literature that shows the association between the medullary sponge kidney and the testicular dysgenesis syndrome. A question still remains unanswered: are the MSK and TDS completely independent malformation syndromes occurring, in this case, simultaneously for a rare event or are they different phenotypic expressions of a common malformative mechanism? In the future we hope that these questions will be clarified.

  15. Mixed Medullary-follicular-derived carcinomas of the thyroid gland.

    PubMed

    Sadow, Peter M; Hunt, Jennifer L

    2010-07-01

    Tumors of the thyroid are subclassified based on the cell of origin and commonly include follicular-derived tumors and C-cell-derived tumors. The most common follicular-derived tumors are papillary carcinoma and follicular carcinoma, whereas the malignant C-cell-derived tumor is medullary thyroid carcinoma. Rare cases in the literature describe patients who have follicular-derived and C-cell-derived tumors in the same thyroid gland. These can be synchronous but anatomically separate carcinomas, or they can show some mixing of the 2 components. The mixture may be at an interface, as in collision tumors, or can be throughout the entire lesion, as in true mixed medullary-follicular-derived carcinomas. The clinical, histologic, and molecular features of these mixed tumors and the classification guidelines are reviewed.

  16. [A case of medial medullary infarction without Dejerine syndrome].

    PubMed

    Kobayashi, Y; Shimada, A; Takabatake, M

    1999-12-01

    A 67-year-old man with right hemiparesis and dysarthria was admitted with right hemiparesis involving the face, hyperpathia, numbness and pain of the right body and limb except the face, and had hyperreflexia and pathological reflex in the right limb. Brain MRI on the day after admission disclosed no lesion which might explain the symptoms. Short latency somatosensory evoked potential showed a low amplitude after P14 when the right side was stimulated. Cerebral angiography revealed occlusion of the left vertebral artery. Brain MRI on the 18th hospital day disclosed left medial medullary infarction, so we diagnosed medial medullary syndrome. This case was hard to diagnose, because of the atypical features and the absence of an abnormal lesion on the initial MRI.

  17. A Case Report of Bilateral Sarcomatoid Carcinoma of Adrenal Glands With Adrenal Insufficiency.

    PubMed

    Ishikawa, Noriyoshi; Nagase, Mamiko; Takami, Saki; Araki, Asuka; Ishikawa, Nahoko; Koike, Chiaki; Shiina, Hiroaki; Maruyama, Riruke

    2016-12-01

    Adrenocortical carcinomas are relatively rare, but they are considered to be highly aggressive malignant tumors. Sarcomatoid carcinomas represent an even more aggressive type. Bilateral malignant adrenal tumors are extraordinary rare, except for those that represent metastatic spread from a primary neoplasm. Here we report a case of a 69-year-old woman who presented symptoms that raised strong suspicions of adrenal insufficiency. Bilateral adrenal masses, identified in the imaging study, were responsible for the clinical manifestation and surgically resected. Surgical specimens of the bilateral adrenal tumors shared histological features compatible with sarcomatoid carcinoma. It was very difficult to confirm that the sarcomatoid carcinomas were derived from the cortex of the adrenal glands, but careful morphological observation and the panel of antibodies used for immunohistochemistry made the diagnosis possible. This is the first report of sarcomatoid carcinomas involving both adrenal glands. It should be emphasized that sarcomatoid carcinoma can arise bilaterally from even functionally impaired adrenal glands. © The Author(s) 2016.

  18. Delayed Diagnosis of Graves’ Thyrotoxicoisis Presenting as Recurrent Adrenal Crisis in Primary Adrenal Insufficiency

    PubMed Central

    Naik, Dukhabandhu; Jebasingh, K Felix

    2016-01-01

    Adrenal crisis is a potential life threatening complication. The common causes of adrenal crisis are infections, surgical stress and abrupt cessation of steroid medications. Endocrine causes like Graves’ disease with thyrotoxicosis is one of the less common causes of an adrenal crisis. We report a 42-year-old female who presented with recurrent episodes of adrenal crisis due to delayed diagnosis of thyrotoxicosis. She was initially treated with Carbimazole followed by Radio-iodine ablation and currently she is euthyroid. Her adrenal insufficiency was initially treated with hydrocortisone during the time of adrenal crisis followed by Prednisolone 5 mg once daily in the morning along with fludrocortisone 50 mcg once daily. This case highlights the need for high index of suspicion and less common causes like thyrotoxicosis should be ruled out in patients with adrenal crisis. PMID:27190873

  19. Medullary thyroid carcinoma: The third most common thyroid cancer reviewed

    PubMed Central

    STAMATAKOS, MICHAEL; PARASKEVA, PANORAIA; STEFANAKI, CHARIKLEIA; KATSARONIS, PARASKEVAS; LAZARIS, ANDREAS; SAFIOLEAS, KONSTANTINOS; KONTZOGLOU, KONSTANTINOS

    2011-01-01

    Medullary thyroid cancer is a type of thyroid cancer of neuroendocrine origin. It occurs in hereditary and sporadic forms, and its aggressive behavior is associated with the clinical presentation and type of RET mutation. Total thyroidectomy remains the ideal choice of treatment. Early diagnosis and treatment are the fundamental for a 100% cure rate. In this study, we present our experience of 3 cases, along with a complete review of the literature derived from a Pubmed Database search. PMID:22870127

  20. Unilateral adrenal hemorrhagic infarction in essential thrombocythemia.

    PubMed

    Burnet, G; Lambert, M; Annet, L; Lefebvre, C

    2015-12-01

    Adrenal hemorrhage is a rare disease associated with various conditions. We report a case of a 68-year-old woman with abdominal and back pain. The diagnostic work-up showed a left adrenal gland infarction associated with essential thrombocythemia. Treatment consisted in painkillers and treating the underlying condition in order to prevent further thrombotic events.

  1. Computed tomographic findings in bilateral adrenal tuberculosis

    SciTech Connect

    Wilms, G.E.; Baert, A.L.; Kint, E.J.; Pringot, J.H.; Goddeeris, P.G.

    1983-03-01

    The computed tomographic (CT) features of bilateral adrenal tuberculosis are reported in two cases that demonstrate two typical different clinical and morphological manifestations of the disease. The incidence and CT appearance of adrenal tuberculosis are discussed, with emphasis on differential diagnosis.

  2. Somatostatin receptors and somatostatin content in medullary thyroid carcinomas

    SciTech Connect

    Reubi, J.C.; Chayvialle, J.A.; Franc, B.; Cohen, R.; Calmettes, C.; Modigliani, E. )

    1991-04-01

    Human medullary thyroid carcinomas from 19 patients were analyzed for their content in somatostatin (SRIF) receptors using receptor autoradiography with a SRIF-28 analogue and the SRIF octapeptide (Tyr3)-SMS 201-995 as iodinated radioligands. Four out of 19 cases were SRIF receptor positive with the SRIF octapeptide radioligand. These cases as well as four additional tumors were also positive with the SRIF-28 radioligand 125I-(Leu8, D-Trp22, Tyr25)-SRIF-28. High affinity binding sites pharmacologically specific for bioactive SRIF analogues, specifically located on tumor tissue, were identified. In some cases the SRIF receptors were distributed in a non-homogeneous pattern, with labelling occurring preferentially in highly differentiated tumor regions. Numerous cases were shown to have a high tumoral SRIF content measured by radioimmunoassay or immunohistochemical technique. However, there was no correlation between SRIF receptor status and tumor levels of endogenous SRIF. No correlation was seen between the clinical outcome or the survival of the patients and their tumoral SRIF receptor content. Whereas some medullary thyroid carcinomas seem to be a target for SRIF, the SRIF function in these tumors remains unclear. SRIF receptors in a group of medullary thyroid carcinomas may be useful morphological marker of these tumors and of potential interest for their in vivo localization.

  3. Advances in chemotherapy of differentiated epithelial and medullary thyroid cancers.

    PubMed

    Sherman, Steven I

    2009-05-01

    Systemic chemotherapies for advanced or metastatic thyroid carcinomas have been of only limited effectiveness. For patients with differentiated or medullary carcinomas unresponsive to conventional treatments, novel therapies are needed to improve disease outcomes. The PubMed and Google Scholar search engines were used to identify publications and peer-reviewed meeting presentations addressing chemotherapy and targeted therapy for differentiated or medullary carcinoma. Multiple novel therapies primarily targeting angiogenesis have entered clinical trials for metastatic thyroid carcinoma. Partial response rates up to 30% have been reported in single agent studies, but prolonged disease stabilization is more commonly seen. The most successful agents target the vascular endothelial growth factor receptors, with potential targets including the mutant kinases associated with papillary and medullary oncogenesis. Two drugs approved for other malignancies, sorafenib and sunitinib, have had promising preliminary results reported, and are being used selectively for patients who do not qualify for clinical trials. Randomized trials for several agents are underway that may lead to eventual drug approval for thyroid cancer. Treatment for patients with metastatic or advanced thyroid carcinoma now emphasizes clinical trial opportunities for novel agents with considerable promise. Alternative options now exist for use of tyrosine kinase inhibitors that are well tolerated and may prove worthy of regulatory approval for this disease.

  4. Biochemical results of reoperations for medullary thyroid carcinoma.

    PubMed

    Fernandez Vila, Juan Manuel; Peix, Jean L; Mandry, Alexandra C; Mezzadri, Norberto A; Lifante, Jean C

    2007-05-01

    The calcitonin is a sensitive marker for the presence of medullary thyroid carcinoma, therefore, invaluable in the follow-up of patients who have been treated. Biological cure of the medullary thyroid cancer refers to a basal plasma calcitonin of less than 10 ng/l without elevation after stimulation tests. Biochemical results of reoperations for medullary thyroid carcinoma were reviewed from a series of 35 patients who underwent 47 reinterventions. The indications for reoperation were: hypercalcitoninemia with clinical evidence of the disease (32 cases); hypercalcitoninemia after an inadequate primary surgery (6 cases); persistent hypercalcitoninemia with biochemical evidence of the disease (2 cases); liver metastases (1 case); and palliative surgery for relieving symptoms (1 case). Only three patients of the series had biochemical cure after reoperation (patients with an inadequate primary surgery). This study is consistent with the bibliographic reviews supporting that the cervical reoperation, eventually mediastinal, for residual hypercalcitoninemia after primary surgical treatment is indicated when the initial intervention did not follow the French Calcitonin Tumour Study Group (GETC) recommendations or when a specific lesion is evidenced by imaging studies without systemic dissemination.

  5. Medullary carcinoma of the colon: can the undifferentiated be differentiated?

    PubMed

    Fiehn, Anne-Marie Kanstrup; Grauslund, Morten; Glenthøj, Anders; Melchior, Linea Cecilie; Vainer, Ben; Willemoe, Gro Linno

    2015-01-01

    Medullary carcinoma of the colon is a rare variant of colorectal cancer claimed to have a more favorable prognosis than conventional adenocarcinomas. The histopathologic appearance may be difficult to distinguish from poorly differentiated adenocarcinoma. The study aimed to evaluate the diagnostic interobserver agreement and to characterize the immunohistochemical and molecular differences between these two subgroups. Fifteen cases initially classified as medullary carcinoma and 30 cases of poorly differentiated adenocarcinomas were included. Two pathologists reviewed the slides independently without knowledge of the original diagnosis and subgrouped the tumors into the two entities. Agreement was reached in 31 of 45 cases (69 %) with kappa = 0.32. An extensive immunohistochemical panel was performed, and KRAS, NRAS, and BRAF mutational status was assessed. Of the 31 cases with diagnostic agreement, the expression of only MLH-1 along with corresponding expression of PMS-2 differed significantly (p = 0.04). A high rate of BRAF mutations was detected in both subgroups without significant differences. Expression of MLH-1 was superior in dividing the tumors into two separate entities with significant differences in CK20 (p = 0.005) expression and in the rate of BRAF mutations (p = 0.0035). In conclusion, medullary carcinomas of the colon are difficult to discriminate from poorly differentiated adenocarcinoma even with the help of immunohistochemical and molecular analyses. This raises the question whether these morphological subtypes should be maintained or whether an alternative classification of poorly differentiated colorectal adenocarcinomas based on MLH-1 status rather than morphology should be suggested.

  6. 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.

  7. Effect of chronic renal medullary nitric oxide inhibition on blood pressure.

    PubMed

    Mattson, D L; Lu, S; Nakanishi, K; Papanek, P E; Cowley, A W

    1994-05-01

    The effects of chronic nitric oxide inhibition in the renal medulla on renal cortical and medullary blood flow, sodium balance, and blood pressure were evaluated in conscious uninephrectomized Sprague-Dawley rats. During a 5-day renal medullary interstitial infusion of the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 120 micrograms/h) in saline (0.5 ml/min), renal medullary blood flow was selectively decreased by 30% after 2 h and was maintained at that level for the entire infusion. The decrease in medullary blood flow was associated with sodium retention and increased blood pressure. After the cessation of L-NAME infusion, medullary blood flow returned to control, and the sodium balance became negative as blood pressure returned to baseline. These data indicate that renal medullary nitric oxide plays an important role in the regulation of renal blood flow, sodium excretion, and blood pressure.

  8. Extensive expertise in endocrinology. Adrenal crisis.

    PubMed

    Allolio, Bruno

    2015-03-01

    Adrenal crisis is a life-threatening emergency contributing to the excess mortality of patients with adrenal insufficiency. Studies in patients on chronic replacement therapy for adrenal insufficiency have revealed an incidence of 5-10 adrenal crises/100 patient years and suggested a mortality rate from adrenal crisis of 0.5/100 patient years. Patients with adrenal crisis typically present with profoundly impaired well-being, hypotension, nausea and vomiting, and fever responding well to parenteral hydrocortisone administration. Infections are the major precipitating causes of adrenal crisis. Lack of increased cortisol concentrations during infection enhances pro-inflammatory cytokine release and sensitivity to the toxic effects of these cytokines (e.g. tumour necrosis factor alpha). Furthermore, pro-inflammatory cytokines may impair glucocorticoid receptor function aggravating glucocorticoid deficiency. Treatment of adrenal crisis is simple and highly effective consisting of i.v. hydrocortisone (initial bolus of 100  mg followed by 200  mg over 24  h as continuous infusion) and 0.9% saline (1000  ml within the first hour). Prevention of adrenal crisis requires appropriate hydrocortisone dose adjustments to stressful medical procedures (e.g. major surgery) and other stressful events (e.g. infection). Patient education is a key for such dose adjustments but current education concepts are not sufficiently effective. Thus, improved education strategies are needed. Every patient should carry an emergency card and should be provided with an emergency kit for parenteral hydrocortisone self-administration. A hydrocortisone pen would hold a great potential to lower the current barriers to hydrocortisone self-injection. Improved patient education and measures to facilitate parenteral hydrocortisone self-administration in impending crisis are expected to significantly reduce morbidity and mortality from adrenal crisis. © 2015 European Society of Endocrinology.

  9. Synthesis of adrenal peptide E and some of its biological activities.

    PubMed

    Heimer, E P; Lambros, T J; Felix, A M; Fleminger, G; Li, C H; Westphal, M; Meienhofer, J

    1983-09-01

    A synthesis of peptide E, a highly potent, 25-amino acid adrenal opioid peptide containing both a [Met]enkephalin at the NH2-terminus and [Leu]enkephalin sequence at the COOH-terminus, originally isolated from bovine adrenal medulla [D. L. Kilpatrick, T. Taniguchi, B. N. Jones, A. S. Stern, J. E. Shively, J. Hullihan, S. Kimura, S. Stein, and S. Udenfriend (1981) Proc. Natl. Acad. Sci. USA 78, 3265-3268], is reported. The synthesis was accomplished by the solid-phase method employing the 4-(aminoacyloxymethyl)phenylacetamidomethyl(Pam)-copoly(styrene-1% divinylbenzene) resin. Two synthetic strategies (N-indole formyl protected vs unprotected tryptophan) were followed and results compared and evaluated. It was determined that peptide E prepared with protection of tryptophan (residues 13 and 14) was preferred and gave final product that was readily purified by HPLC. The biological activity of the synthetic material was found to be equivalent to the reported activity of the natural compound.

  10. Peptide F (pro-enkephalin fragment): radioimmunoassay, and stress-induced changes in adrenal

    SciTech Connect

    Alessi, N.; Taylor, L.; Akil, H.

    1982-10-18

    Utilizing a nine amino-acid (Asp-Glu-Leu-Tyr-Pro-Leu-Glu-Val-Glu) non-enkephalin containing fragment of Peptide F from the pro-enkephalin molecule, a radioimmunoassay was developed. Extraction of bovine, rat, and guinea pig adrenomedullary preparations demonstrated this fragment to be present and apparently partially conserved across species. In rats, acute inescapable foot-shock stress led to a significant decrease of the immunoreactive material in the adrenal medulla. Chronic daily stress for two weeks resulted in an inability of the adrenals to alter F levels upon subsequent stress. The existence of F-like immunoreactivity and its alteration by environmental manipulation, suggest that it may play a unique physiological role.

  11. Reducing radiation exposure in intra-medullary nailing procedures: intra-medullary endo-transilluminating (iMET).

    PubMed

    Chu, William; Wang, Jyhpyng; Young, Shuenn-Tsong; Chu, Woei Chyn

    2009-10-01

    The purpose of the study was to reduce the level of radiation exposure during intra-medullary nailing procedures. A visible light source was inserted into the medullary bone cavity in order to detect the distal interlocking screw holes. The light penetrates out of the bone surface, revealing the position of the screw hole, and this allows the subsequent drilling and placing of the interlocking screw to be free of fluoroscopy. Among the 19 consecutive tibia-fracture patients recruited for this study, no repetition of the drilling procedure or insertion of a transverse interlocking screw was needed. The average time to finish the insertion of one distal interlocking screw was 4.1+/-1.8 min. It was extrapolated that 13-41% of previous radiation exposure levels could be saved. The non-fluoroscopic approach thus decreases the health hazards that the patients are experiencing as well as those of the surgical team who need to perform such intra-medullary nailing operations on a routine basis.

  12. 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.

  13. Quantitation of iodine-123 MIBG uptake by normal adrenal medulla in hypertensive patients

    SciTech Connect

    Bomanji, J.; Flatman, W.D.; Horne, T.; Fettich, J.; Britton, K.E.; Ross, G.; Besser, G.M.

    1987-03-01

    Eighteen hypertensive patients with a clinical suspicion of pheochromocytoma and raised or borderline raised plasma catecholamine and urinary vanillyl mandelic acid (VMA) levels were studied by scintigraphy using /sup 123/I-labeled metaiodobenzylguanidine (MIBG). None of these patients had any scintigraphic evidence of pheochromocytoma at the time of study or on subsequent clinical follow-up. A quantitative approach was taken to calculate the adrenal medullary uptake of (/sup 123/I)MIBG in these patients. Three different methods of quantitation were evaluated using data acquired from an anthropomorphic phantom and analysed by three independent observers. In the patient studies 34 out of 35 adrenal medullas were visualized with uptake in the range of 0.01-0.22% of the administered dose 22 hr postinjection which was calculated using the preferred quantitation method. This is an appropriate control group range for comparison with patients who have proven norepinephrine and epinephrine secreting tumors. A quantitative approach to (/sup 123/I)MIBG imaging provides an important tool for studying adrenomedullary pathophysiology.

  14. Testicular Adrenal Rest Tumors in Patients with Congenital Adrenal Hyperplasia

    PubMed Central

    Şentürk Mutlu, Fatma; Eren, Erdal; Paşa, Aliye Özlem; Sağlam, Halil; Tarım, Ömer

    2012-01-01

    Objective: Early diagnosis and treatment of testicular adrenal rest tumors (TART) is important for gonadal functions and fertility protection in boys with congenital adrenal hyperplasia (CAH). In this descriptive study, we investigated the prevalence of TART in boys with 21-hydroxylase deficient (21OHD) CAH followed in our pediatric endocrine clinic. Methods: The study group consisted of 14 male patients with a mean age of 9.6±5.1 (range: 0.8-18.3) years. Six (42.9%) of the 14 patients were diagnosed as having salt-wasting type (SW) and eight (57.1%) patients - as having the simple virilizing (SV) form of 21OHD. Mean age at diagnosis was 2.9±2.7 (range: 0.03-6.3) years. Two different radiologists performed scrotal ultrasonography. Chronological age, bone age, and anthropometric measurements were evaluated. Serum adrenocorticotropic hormone (ACTH), 17-alpha-hydroxyprogesterone (17OHP) and androstenedione levels were also evaluated in all patients during the follow-up period. Results: Scrotal ultrasonography revealed bilateral TART in two patients (14.3%) and testicular microlithiasis (TM) in four patients (28.6%). One patient had both TART and TM bilaterally. During the follow-up period, the mean serum adrenocorticotropic hormone, 17OHP and androstenedione levels in the total group of patients were 130.0±179.1 pg/mL (21.7-726.5), 5.8±3.3 ng/mL (0.8-11.4) and 4.3±4.1 (0.2-11.0) ng/mL, respectively. Conclusions: Microlithiasis or TART may be frequently encountered during the follow-up of patients with CAH. In order to prevent late complications including infertility, we suggest that ultrasonographic evaluations be performed yearly in all male CAH patients. Conflict of interest:None declared. PMID:22672867

  15. Natural course of benign adrenal incidentalomas in subjects with extra-adrenal malignancy.

    PubMed

    Yener, Serkan; Ertilav, Senem; Secil, Mustafa; Akinci, Baris; Demir, Tevfik; Comlekci, Abdurrahman; Yesil, Sena

    2009-08-01

    Patients with extra-adrenal malignancies are diagnosed increasingly with benign adrenal tumors, as well as non-oncology subjects. We aimed to demonstrate the natural course of adrenal adenomas in terms of mass size and hormonal status in oncology and non-oncology subjects. We also compared the characteristics and behavior of adrenal adenomas with adrenal malignancies. In our registry of adrenal tumors (n = 335), we prospectively evaluated 29 oncology subjects (EAM+) and age, gender, and follow-up duration matched 110 non-oncology subjects (EAM-) with adrenal adenomas. Median follow-up was 24 months. We also included 16 subjects with adrenal malignancies (primary; 3 and metastasis; 13). Tumor size was followed-up with CT or MRI at 6th and 12th months and annually in subsequent visits. Hormonal assessment was repeated at the 6th month after the initial visit and annually in subsequent visits. Initial tumor size, mean increase in tumor size, and number of subjects who showed mass enlargement or developed subclinical Cushing Syndrome were comparable (P > 0.05) between EAM+ and EAM- groups. Subjects with malignant adrenal tumors were older (P = 0.06), had larger tumors at presentation (P < 0.001), and showed mass enlargement during a shorter follow-up duration (P < 0.001). Oncology subjects with adrenal adenomas featured similar baseline and follow-up parameters in terms of mass enlargement and development of subclinical Cushing Syndrome when compared with non-oncology subjects. Malignant adrenal tumors were characterized with large, rapidly growing tumors of older ages. Conservative approach can be suggested to oncology subjects for adrenal adenomas unless clinical and radiological suspicion of adrenal malignancy is present.

  16. Association of filtered sodium load with medullary volumes and medullary hypoxia in hypertensive African Americans as compared with whites.

    PubMed

    Textor, Stephen C; Gloviczki, Monika L; Flessner, Michael F; Calhoun, David A; Glockner, James; Grande, Joseph P; McKusick, Michael A; Cha, Stephen S; Lerman, Lilach O

    2012-02-01

    African Americans develop hypertension earlier with more target manifestations than whites despite having a higher glomerular filtration rate (GFR) for any level of serum creatinine. STUDY DESIGN & PARTICIPANTS: This study tested the hypothesis that increased GFR and sodium reabsorption in African Americans is associated with increased metabolic work and medullary hypoxia in 49 nondiabetic patients with essential hypertension (29 whites and 20 African Americans) following a constant-sodium diet (150 mEq/d) and renin-angiotensin system blockade. Ethnicity, age, measured GFR, sodium excretion, and body mass index. We examined cortical and medullary volumes and blood flows using multidetector computed tomography and intrarenal deoxyhemoglobin (R2*) using blood oxygen level-dependent magnetic resonance. Blood pressure and sodium excretion were similar, whereas African Americans were more obese and had higher iothalamate GFRs. Renal cortical volumes did not differ, but medullary volumes adjusted for body size and age were higher in African Americans (32.3 ± 11.2 vs 25.1 ± 7.4 cm(3)/m(2) body surface area; P < 0.001). Sodium reabsorption and blood flows were higher in African Americans. Basal cortical deoxyhemoglobin values were similar between ethnic groups, whereas medullary R2* was higher in African Americans (39.7 ± 5.1 vs 36.3 ± 6.5/s; P = 0.02), but decreased to levels similar to whites after furosemide treatment. Levels of the circulating isoprostane prostaglandin F(2α) were higher in African Americans and daily urinary prostaglandin F(2α) excretion in African Americans correlated directly with renal blood flow (R = 0.71; P < 0.01). Studies were limited to treated volunteers with normal kidney function without knowledge of prior nutrient intake. These data show for the first time that increased sodium reabsorption in obese African American patients with hypertension was associated with enlarged medullary volumes, functional hypoxia related to solute

  17. Corticomedullary mixed tumor of the adrenal gland.

    PubMed

    Wieneke, J A; Thompson, L D; Heffess, C S

    2001-10-01

    Corticomedullary mixed tumors of the adrenal gland are quite rare, with only five well-documented cases reported in the literature.(1-4) Herein, we report the light microscopic and immunohistochemical features of two cases of this rare tumor. Patient 1 is a 34-year-old woman who presented with hypertension, hair loss, and amenorrhea of 1-year duration. Patient 2 is a 52-year-old woman who presented with flank pain and what appeared to be a renal mass on arteriogram with no history of hypertension, Cushing's syndrome, or other endocrine abnormalities. At surgery, the tumor was noted to arise from the adrenal gland rather than the kidney and adrenalectomy was performed. In both cases, the surgically resected specimens consisted of a well-circumscribed, single adrenal mass surrounded by a rim of uninvolved adrenal cortical tissue. The tumors were composed of adrenal cortical cells intimately admixed with pheochromocytes. Immunohistochemical studies highlighted these two cellular components. The pheochromocytes were strongly reactive with chromogranin and the sustentacular cells with S-100 protein, whereas the adrenal cortical cells reacted specifically with inhibin. Thus, we report two additional cases of mixed corticomedullary tumor of the adrenal gland. Ann Diagn Pathol 5:304-308, 2001. This is a US government work. There are no restrictions on its use.

  18. 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.

  19. Sonography of the adrenal glands in the adult.

    PubMed

    Kim, Kyoung Won; Kim, Jeong Kon; Choi, Hyuck Jae; Kim, Mi-hyun; Lee, Jeongjin; Cho, Kyoung-Sik

    2012-01-01

    Although its capability has been overlooked, sonography can be a useful screening tool for adrenal lesion in adults. In this article, we discuss scan technique, patient positioning, and anatomic consideration for adrenal sonography in adults and illustrate sonographic appearance of normal adrenal gland as well as adrenal tumors and tumor-like lesions. Copyright © 2012 Wiley Periodicals, Inc.

  20. Severe hyponatremia caused by hypothalamic adrenal insufficiency.

    PubMed

    Shibata, T; Oeda, T; Saito, Y

    1999-05-01

    A 60-year-old woman was admitted with severe hyponatremia. Basal values of adrenocorticotropic hormone (ACTH), thyroid hormone and cortisol were normal on admission. Impairment of water diuresis was observed by water loading test. Initially, we diagnosed her condition as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). By provocation test, we finally confirmed that the hyponatremia was caused by hypothalamic adrenal insufficiency. The basal values of ACTH and cortisol might not be sufficient to exclude the possibility of adrenal insufficiency. Therefore, it is necessary to evaluate adrenal function by provocation test or to re-evaluate it after recovery from hyponatremia.

  1. Spontaneous Unilateral Adrenal Hemorrhage in Pregnancy

    PubMed Central

    Ebrahem, Rawaa; Munguti, Cyrus; Mortada, Rami

    2017-01-01

    Spontaneous adrenal hemorrhage (SAH) is a serious medical condition associated with variable clinical presentation depending on the extent of the hemorrhage. Pregnancy-induced adrenal hemorrhage is poorly understood. A low cortisol level in the peripartum period with radiological findings is sufficient to establish the diagnosis. Prompt hormone replacement and supportive care to ensure good clinical outcomes is crucial. Due to the potentially life-threatening complications, physicians should have a high suspicion for adrenal hemorrhage when they evaluate patients with hypotension, fatigue, and abdominal pain during the peripartum period. PMID:28191381

  2. 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.

  3. Adrenal Collision Tumor: Coexistence of Pigmented Adrenal Cortical Oncocytoma and Ganglioneuroma

    PubMed Central

    Kim, Chungyeul

    2016-01-01

    Background. Adrenal collision tumors (ACTs), in which distinct tumors coexist without intermingling in the same adrenal gland, are rare and their actual prevalence is unknown. ACTs commonly consist of adrenal cortical adenoma, pheochromocytoma, or metastatic malignant tumor. Case Report. A 32-year-old woman who had been experiencing gastric discomfort for one month was referred to our hospital with abnormal imaging findings. The physical examination and the laboratory data including endocrine studies were unremarkable. Abdomen computed tomography (CT) and magnetic resonance imaging (MRI) showed two adjacent masses in the left suprarenal fossa, and a laparoscopic left adrenalectomy was done. Histological and immunohistochemical (IHC) examinations revealed two distinct tumors: a pigmented adrenal cortical oncocytoma (ACO) and a ganglioneuroma, respectively. Conclusion. Both tumors are rare in the adrenal gland and exist as ACTs only exceptionally rarely. This is the first reported case of coexisting oncocytoma and ganglioneuroma in the same adrenal gland to our knowledge. PMID:28053800

  4. A case of adrenal Cushing’s syndrome with bilateral adrenal masses

    PubMed Central

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

    2016-01-01

    Summary 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 131I-6β-iodomethyl-19-norcholesterol (131I-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 131I-NP-59 scintigraphy are good diagnostic methods for Cushing’s syndrome presenting with bilateral adrenal masses. Learning points 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 131I-NP-59 scintigraphy are good methods to use in these patients with Cushing’s syndrome presenting with bilateral adrenal masses. PMID:27252858

  5. Presence of kisspeptin-like immunoreactivity in human adrenal glands and adrenal tumors.

    PubMed

    Takahashi, Kazuhiro; Shoji, Itaru; Shibasaki, Akiko; Kato, Ichiro; Hiraishi, Keisuke; Yamamoto, Hajime; Kaneko, Kiriko; Murakami, Osamu; Morimoto, Ryo; Satoh, Fumitoshi; Ito, Sadayoshi; Totsune, Kazuhito

    2010-05-01

    Kisspeptins are neuropeptides which activate the hypothalamo-pituitary gonadal axis and are considered to play important physiological roles in the reproduction. Kisspeptins have also been reported to stimulate the aldosterone secretion from the adrenal cortex. However, the expression of kisspeptins in human adrenal glands and adrenal tumors has not been clarified yet. We, therefore, studied the presence of kisspeptin-like immunoreactivity (LI) in human adrenal glands and adrenal tumors (adrenocortical adenomas, adrenocortical carcinomas, and pheochromocytomas) by radioimmunoassay and immunocytochemistry. Kisspeptin-LI was detected in all the tissues examined; normal portions of adrenal glands (3.0 +/- 2.3 pmol/g wet weight, n = 21, mean +/- SD), aldosterone-producing adenomas (4.6 +/- 3.3 pmol/g wet weight, n = 10), cortisol-producing adenomas (2.7 +/- 1.4 pmol/g wet weight, n = 14), adrenocortical carcinomas (1.7 +/- 0.2 pmol/g wet weight, n = 4), and pheochromocytomas (1.8 +/- 0.8 pmol/g wet weight, n = 6). There was no significant difference in kisspeptin-LI levels among them. Immunocytochemistry showed positive kisspeptin-immunostaining in normal adrenal glands, with stronger immunostaining found in the medulla. Furthermore, positive kisspeptin-immunostaining was found in all types of adrenal tumors examined; adrenocortical adenomas, adrenocortical carcinomas, and pheochromocytomas. The intensity of kisspeptin-immunostaining in these adrenal tumors was, however, not so strong as that in normal adrenal medulla. The present study has shown for the first time the presence of kisspeptin-LI in adrenal glands and adrenal tumors.

  6. Non-Hodgkin's lymphoma involving a femur bone and bilateral adrenal glands alone with adrenal insufficiency.

    PubMed

    Iwahara, Yoshihito; Shinohara, Tsutomu; Naruse, Keishi; Komatsu, Yukihisa

    2017-01-31

    Primary bone lymphoma and primary adrenal lymphoma are rare clinicopathological entities of non-Hodgkin's lymphoma (NHL). We present the first case of diffuse large B-cell lymphoma with the involvement of a single bone and both adrenal glands alone with adrenal insufficiency. As primary extranodal NHL may have other unusual extranodal lesions, which may present unexplained clinical findings, patients with primary extranodal NHL require careful systemic examination, even when lymphadenopathy is absent. 2017 BMJ Publishing Group Ltd.

  7. Radiology of the adrenals with sonography and CT

    SciTech Connect

    Mitty, H.A.; Yeh, H.C.

    1982-01-01

    The basic science and application of clinical adrenal imaging is presented. The initial chapters deal with anatomic review and methods of adrenal imaging. The bulk of the book consists of individual chapters describing pathologic entities and syndromes of adrenal disease. The final chapter deals with differentiation of adrenal lesions from masses arising in adjacent organs. There is no other single source available which so concisely presents adrenal imaging. (KRM)

  8. [Neonatal adrenal hemorrhage revealed by jaundice: a case report].

    PubMed

    Oulmaati, A; Hays, S; Mory-Thomas, N; Bretones, P; Bensaid, M; Jordan, I; Bonfils, M; Godbert, I; Picaud, J-C

    2012-04-01

    The clinical presentation of adrenal hemorrhage varies, depending on the extent of hemorrhage as well as the amount of adrenal cortex involved by the hemorrhage. We report here a case of neonatal adrenal hemorrhage revealed by late onset of neonatal jaundice. This adrenal hemorrhage most probably resulted from shoulder dystocia. The aim of this work was to focus on the fact that jaundice can be caused by adrenal hemorrhage and to emphasize the crucial importance of abdominal ultrasound in cases of persistent jaundice.

  9. Neural differentiation potential of sympathoadrenal progenitors derived from fresh and cryopreserved neonatal porcine adrenal glands.

    PubMed

    Bozhok, G A; Sidorenko, O S; Plaksina, E M; Gurina, T M; Sukach, A N; Kholodnyy, V S; Ustichenko, V D; Bilyavskaya, S B; Bondarenko, T P; Legach, E I

    2016-10-01

    Stem/progenitor cells are thought to have the potential in the treatment of severe neurodegenerative diseases. Recently, sympathoadrenal progenitors expressing specific markers of neural crest derivatives and capable to differentiate into neurons were discovered in adult bovine and human adrenal glands, but there was no reported data on cryopreservation of sympathoadrenal progenitors. The aim of the present study was to examine the neural differentiation potential of sympathoadrenal progenitors derived from fresh and cryopreserved neonatal porcine adrenal glands. Considering impact of various initial state of frozen biomaterial on cell recovery, we carried out a comparative estimation of cryopreservation outcome both for adrenal tissue fragments and isolated primary cells. The estimation consisted of determining cell yield, viability, ability to adhere, proliferate and differentiate in vitro. Cells isolated from the fresh adrenal glands were cultured until confluence. A formation of sympathoadrenal progenitors-embedded spherical cell colonies, whose cells are differentiated then into βIII-tubulin-positive cells with neuron-like morphology, was observed on the monolayer. The colonies were well preserved after cryopreservation of cell culture with a cooling rate of 1 °C/min in the cryoprotectant media containing 5-15% of dimethylsulfoxide. Adrenal tissue fragments were cryopreserved in the presence of 10% dimethylsulfoxide at the cooling rates of 0.3; 1: 5; 40 and > 100 °C/min. Sympathoadrenal progenitors were recovered after cryopreservation with 0.3 °C/min cooling rate but not higher. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. alpha1H T-type Ca2+ channel is the predominant subtype expressed in bovine and rat zona glomerulosa.

    PubMed

    Schrier, A D; Wang, H; Talley, E M; Perez-Reyes, E; Barrett, P Q

    2001-02-01

    The low voltage-activated (T-type) Ca2+ channel has been implicated in the regulation of aldosterone secretion from the adrenal zona glomerulosa by extracellular K+ levels, angiotensin II, and ACTH. However, the identity of the specific subtype mediating this regulation has not been determined. We utilized in situ hybridization to examine the distribution of three newly cloned members of the T-type Ca2+ channel family, alpha1G, alpha1H, and alpha1I, in the rat and bovine adrenal gland. Substantial expression of only the mRNA transcript for the alpha1H-subunit was detected in the zona glomerulosa of both rat and bovine. A much weaker expression signal was detected for the alpha1H transcript in the zona fasciculata of bovine. Whole cell recordings of isolated bovine adrenal zona glomerulosa cells showed the native low voltage-activated current to be inhibited by NiCl2 with an IC50 of 6.4 +/- 0.2 microM. Because the alpha1H subtype exhibits similar NiCl2 sensitivity, we propose that the alpha1H subtype is the predominant T-type Ca2+ channel present in the adrenal zona glomerulosa.

  11. Ependymoma of conus medullaris presenting as subarachnoid haemorrhage.

    PubMed

    Ulrich, C T; Beck, J; Seifert, V; Marquardt, G

    2008-02-01

    Subarachnoid haemorrhage (SAH) due to spinal ependymoma is very rare. We report a 37 year old man who presented with typical clinical signs of SAH. Lumbar puncture confirmed SAH but cerebral angiography was negative, and further diagnostic work-up revealed an ependymoma of the conus medullaris as the source of the haemorrhage. A comprehensive review of the literature was conducted. Only 17 patients with spontaneous SAH due to a spinal ependymoma have been reported since 1958. However, in cases of SAH and negative diagnostic findings for cerebral aneurysms or malformations, this aetiology should be considered and work-up of the spinal axis completed.

  12. Involvement of medullary serotonergic groups in multiple system atrophy.

    PubMed

    Benarroch, Eduardo E; Schmeichel, Ann M; Low, Phillip A; Parisi, Joseph E

    2004-03-01

    We sought to determine whether medullary serotonergic neurons were affected in multiple system atrophy (MSA). Immunostaining for tryptophan hydroxylase was performed on serial 50 microm sections of the medulla of brains obtained at autopsy from six control subjects, eight subjects with clinical diagnosis of MSA, and four with Parkinson's disease. There was a severe depletion of serotonergic neurons in the nucleus raphe magnus, raphe obscurus, raphe pallidus, and ventrolateral medulla in MSA. Depletion of serotonergic neurons may contribute to impaired control of sympathetic outflow and other abnormalities in MSA.

  13. 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

  14. Advanced glycosylation end products in adrenal lipofuscin.

    PubMed

    Shimokawa, I; Higami, Y; Horiuchi, S; Iwasaki, M; Ikeda, T

    1998-01-01

    The present study examined the presence of advanced glycosylation end products (AGEs) in lipofuscin present in the brain and adrenal gland of aging rats by immunohistochemistry using antibodies raised against AGEs. Lipofuscin identified as yellow to brown granules emitting bright yellow to orange autofluorescence with ultraviolet light were detected in cortical neurons, cerebellar Purkinje cells, and adrenal cells in the inner part of the zona reticularis. However, none of the antibodies visualized lipofuscin in these areas. The outer part of the zona reticularis contained yellow granules emitting a faint orange autofluorescence. These granules were immunostained by an antibody that reacted with AGEs structures unrelated to the carboxymethyllysine moiety. Newly formed adrenal cortical cells are thought to migrate from the outer layer to the inner layer of the zona reticularis. Therefore, our results suggest that glycosylation-related processes are involved in lipofuscinogenesis, at least in its early stage, in the adrenal zona reticularis.

  15. Genetics Home Reference: primary macronodular adrenal hyperplasia

    MedlinePlus

    ... produced from the GNAS gene helps stimulate the activity of an enzyme called adenylate cyclase. This enzyme is involved in controlling the production of several hormones that help regulate the activity of certain endocrine glands, including the adrenal glands. ...

  16. Ancient history of congenital adrenal hyperplasia.

    PubMed

    New, Maria I

    2011-01-01

    Although there are many erudite reports on the history of endocrinology and endocrine disorders, the history of congenital adrenal hyperplasia has not been published. I have tried to review ancient as well as modern history of CAH.

  17. Effect of nicotine on the renal microcirculation in anesthetized rats: a potential for medullary hypoxic injury?

    PubMed

    Heyman, Samuel N; Goldfarb, Marina; Rosenberger, Christian; Shina, Ahuva; Rosen, Seymour

    2005-01-01

    Cigarette smoking has been associated with accelerated renal dysfunction among patients with chronic renal disease. Conceivably, repeated parenchymal hypoxic injury, induced by nicotine-related vasomotor changes, might contribute to the progression of renal failure in smokers. Renal blood flow and selective cortical and outer medullary blood flows were determined in anesthetized rats. Changes in total renal, cortical and medullary vascular resistance were calculated. Nicotine was repeatedly infused at rising doses (50-200 microg/kg) to intact (CTR) animals and to rats chronically administered with nicotine in their drinking water (NIC). In a complementary study, nicotine-treated and control rats were subjected to medullary hypoxic stress, induced by radiocontrast and indomethacin. Chronic nicotine exposure led to lower baseline renal blood flow and creatinine clearance. Nicotine infusion induced a transient dose-dependent rise in blood pressure, renal blood flow and cortical flow, with a corresponding decline in renal vascular resistance and cortical resistance in both experimental groups. However, while medullary flow increased in CTR by up to 16 +/- 6%, it remained unchanged or even somewhat declined in the NIC group. Calculated medullary resistance reciprocally declined in CTR while it rose in the NIC group (p < 0.001). In animals subjected to radiocontrast and indomethacin, nicotine intensified renal dysfunction, associated with focal medullary hypoxic damage. Chronic exposure to nicotine selectively compromises the outer medullary microcirculation, blunting a local vasodilatory response to acute nicotine administration. Repeated acute-on-chronic exposure to nicotine may predispose to hypoxic medullary injury.

  18. Primary hydatid cyst in the adrenal gland.

    PubMed

    Mohammadi, Afshin; Ghasemi-Rad, Mohammad; Oklu, Rahmi

    2014-10-23

    An elderly man presented with a 2-year history of refractory hypertension. His medical history, physical examination and laboratory findings were unremarkable. On subsequent ultrasound study for the evaluation of renal artery stenosis, a large mass obliterating the adrenal gland containing internal cystic structures was identified. A CT study confirmed the diagnosis of primary adrenal gland hydatid cyst. Following surgical resection, the patient's hypertension resolved and medications to control blood pressure were discontinued.

  19. Metabolism of adrenal cholesterol in man

    PubMed Central

    Borkowski, Abraham; Delcroix, Claude; Levin, Sam

    1972-01-01

    The synthesis of adrenal cholesterol, its esterification and the synthesis of the glucocorticosteroid hormones were studied in vitro on human adrenal tissue. It was found that the synthesis of adrenal cholesterol may normally be small in the zona “fasciculata,” particularly when compared with the synthesis of the glucocorticosteroid hormones, that it is several times higher in the zona “reticularis” where esterified cholesterol is less abundant, and that under ACTH stimulation it increases strikingly and proportionally to the degree of esterified adrenal cholesterol depletion. On the other hand, the relative rate of esterification as well as the concentration of free adrenal cholesterol are remarkably stable: they do not differ according to the adrenal zonation and are unaffected by ACTH. Furthermore, from a qualitative point of view, the relative proportions of Δ1 and Δ2 cholesteryl esters formed in situ are similar to those anticipated from their relative concentrations, suggesting that the characteristic fatty acid distribution of the adrenal cholesteryl esters results from an in situ esterification rather than from a selective uptake of the plasma cholesteryl esters. Besides, the in vitro esterification reveals a propensity to the formation of the most unsaturated cholesteryl esters. Regarding hydrocortisone and corticosterone, their synthesis tends to be more elevated in the zona “fasciculata.” Despite its higher cholesterol concentration the zona “fasciculata” should not therefore be viewed as a quiescent functional complement to the zona “reticularis” and the cortical distribution of glucocorticosteroid hormone synthesis is quite distinct from that of adrenal cholesterol synthesis. PMID:4338120

  20. Coexistence of pheochromocytoma, adrenal adenoma and hypokalemia.

    PubMed Central

    Wilkins, G. E.; Schmidt, N.; Lee-Son, L.

    1977-01-01

    A 56-year-old woman had a 22-year history of hypertension. Investigation showed hypokalemia and kaliuresis without pronounced suppression of plasma renin activity or elevation of urinary aldosterone excretion. There was biochemical evidence of catecholamine metabolite excess but the usual clinical features of pheochromocytoma were absent. Laparotomy revealed a pheochromocytoma and adrenal adenoma in the right adrenal gland. Excision of the tumours was followed by resolution of the hypertension and metabolic abnormalities. Images FIG. 2 FIG. 3 PMID:844017

  1. Black adrenal adenoma causing preclinical Cushing's syndrome.

    PubMed

    Inomoto, Chie; Sato, Haruhiro; Kanai, Genta; Hirukawa, Takashi; Shoji, Sunao; Terachi, Toshiro; Kajiwara, Hiroshi; Osamura, Robert Yoshiyuki

    2010-07-20

    Functioning black adrenal adenoma (BAA) rarely causes preclinical Cushing's syndrome (CS). In the present case, a 46-year-old Japanese Peruvian woman presented with left flank pain and hypertension. Abdominal computed tomography showed that she had a 15-mm in diameter, round, left adrenal adenoma. She had no physical features of CS, such as moon face, buffalo hump, truncal obesity, or purple striae. Endocrinological examination showed that the plasma adrenocorticotropic hormone (ACTH) level was below the detectable level, despite a serum cortisol level within the normal range. A normal cortisol circadian rhythm was not present. Dexamethasone (1 mg and 8 mg) suppression testing did not decrease serum cortisol levels to the reference levels. These findings were compatible with preclinical CS. The left adrenal adenoma was laparoscopically removed. Examination of the surgical specimen revealed unilateral double adrenal adenomas of the left adrenal gland, one of which was a BAA. The BAA measured 20 × 11 × 10 mm. Microscopically, the BAA showed proliferation of compact cells containing numerous brown-pigmented granules. There were also foci of myelolipomatous degenerative changes in the tumor. The compact cell zones remained in the adrenal cortex adjacent to the BAA showed atrophic change. These findings indicated that BAA appeared to have caused preclinical CS in this patient.

  2. [Adrenal gland insufficiency secondary to paracoccidioidomycosis].

    PubMed

    Oñate, José M; Tobón, Angela María; Restrepo, Angela

    2002-09-01

    Paracoccidioidomycosis is regularly associated with adrenal insufficiency in 10-15% of symptomatic cases, and in some instances, diagnosis of the mycosis precedes the adrenal manifestation. To establish the frequency of this association, records were reviewed of 207 cases diagnosed with mycosis at the Mycology Service of the Corporación para Investigaciones Biológicas. Six cases (2.9%) were found to have adrenal insufficiency. Patients were all males with a mean age of 67.2 years (range 48-75) and most worked in agriculture. The duration of the symptoms of adrenal damage was 4.1 months (range 2-6). All patients experienced weight loss and malaise; all had abnormal lung X-rays. Major clinical improvement was recorded after initiation of the specific treatments consisting of itraconazole, prednisolone and fluorcortisone. Diminished antibody titers against Paracoccidioides brasiliensis were also recorded after treatment. Prompt treatment re-established adrenal function and effected recovery of normal gland morphology. Consequently, early detection of hypoadrenalism in patients living in the endemic areas is necessary to avoid further adrenal damage and permits a shorter hormonal treatment period in patients afflicted by the mycosis.

  3. 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.

  4. Outcome of congenital adrenal hyperplasia.

    PubMed

    Kuhnle, U; Bullinger, M

    1997-09-01

    In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, affected girls are born with ambiguous genitalia due to increased secretion of androgens in utero by the defective adrenal gland. Even though it is generally accepted that there are differences between male and female brain development, determining factors have been difficult to identify. Girls with CAH have frequently been studied to evaluate the impact of prenatal androgen exposure on psychological, psychosocial, and psychosexual development, and impairments in various areas have been identified. However, there is no comprehensive study available regarding the outcome of this chronic disorder in adult life. We studied the quality of life in women with CAH, with particular emphasis on how they cope with genital malformations, genital operations, and chronic disease as well as lifelong medication. The patients filled out questionnaires covering their physical state, psychological well-being, social relationships, and functional capacity, as well as questionnaires on psychosexual identification and psychosocial integration. The results were evaluated using a computerized statistical program for social studies. Out of a total of 94 patients above 18 years of age, 45 agreed to participate and were compared to 46 healthy, age-matched controls. Age at diagnosis was 2. 31 +/- 1.55 years and 38% suffered from the simple-virilizing, 45% from the salt-wasting, and 17.0% from the late-onset form of CAH. About one-third of patients had Prader stage 3 or 4 genital virilization. While the overall quality of life did not differ significantly, CAH patients were more often single (47.8% vs. 66.7%) and fewer of them had children (22.2% vs. 38.6%) compared to controls. Significant impairments were found in regard to body image and attitudes toward sexuality, but there was no increased homosexual preference. The women were successful in adjusting to illness and receiving social support. It is speculated that

  5. Protective effect of angiotensin II-induced increase in nitric oxide in the renal medullary circulation.

    PubMed

    Zou, A P; Wu, F; Cowley, A W

    1998-01-01

    This study examined the effect of intravenous infusion of subpressor doses of angiotensin (Ang II) on renal medullary blood flow (MBF), medullary partial oxygen pressure (PO2), and nitric oxide (NO) concentration under normal conditions and during reduction of the medullary nitric oxide synthase (NOS) activity in anesthetized rats. With laser Doppler flowmetry and polarographic measurement of PO2 with microelectrodes, Ang II (5 ng/kg per minute) did not alter renal cortical and medullary blood flows or medullary PO2. N(omega)-nitro-L-arginine methyl ester (L-NAME) was infused into the renal medullary interstitial space at a dose of 1.4 microg/kg per minute, a dose that did not significantly alter basal levels of MBF or PO2. Intravenous infusion of Ang II at the same dose in the presence of L-NAME decreased MBF by 23% and medullary PO2 by 28%, but it had no effect on cortical blood flow or arterial blood pressure. An in vivo microdialysis-oxyhemoglobin NO trapping technique was used in other rats to determine tissue NO concentrations using the same protocol. Ang II infusion increased tissue NO concentrations by 85% in the renal cortex and 150% in the renal medulla. Renal medullary interstitial infusion of L-NAME (1.4 microg/kg per minute) reduced medullary NO concentrations and substantially blocked Ang II-induced increases in NO concentrations in the renal medulla, but not in the renal cortex. Tissue slices of the renal cortex and medulla were studied to determine the effects of Ang II and L-NAME on the nitrite/nitrate production. Ang II stimulated the nitrite/nitrate production predominately in the renal medulla, which was significantly attenuated by L-NAME. We conclude that small elevations of circulating Ang II levels increase medullary NO production and concentrations, which plays an important role in buffering the vasoconstrictor effects of this peptide and in maintaining a constancy of MBF.

  6. Estrogen levels influence medullary bone quantity and density in female house finches and pine siskins.

    PubMed

    Squire, Maria E; Veglia, Megan K; Drucker, Kevin A; Brazeal, Kathleen R; Hahn, Thomas P; Watts, Heather E

    2017-05-15

    Medullary bone, a non-structural osseous tissue, serves as a temporary storage site for calcium that is needed for eggshell production in a number of avian species. Previous research focusing primarily on domesticated species belonging to the Anseriformes, Galliformes, and Columbiformes has indicated that rising estrogen levels are a key signal stimulating medullary bone formation; Passeriformes (which constitute over half of extant bird species and are generally small) have received little attention. In the current study, we examined the influence of estrogen on medullary bone and cortical bone in two species of Passeriformes: the Pine Siskin (Spinus pinus) and the House Finch (Haemorhous mexicanus). Females of these species received either an estradiol implant or were untreated as a control. After 4.5-5months, reproductive condition was assessed and leg (femora) and wing (humeri) bones were collected for analysis using high-resolution (10μm) micro-computed tomography scanning. We found that in both species estradiol-treated females had significantly greater medullary bone quantity in comparison to untreated females, but we found no differences in cortical bone quantity or microarchitecture. We were also able to examine medullary bone density in the pine siskins and found that estradiol treatment significantly increased medullary bone density. Furthermore, beyond the effect of the estradiol treatment, we observed a relationship between medullary bone quantity and ovarian condition that suggests that the timing of medullary bone formation may be related to the onset of yolk deposition in these species. Further research is needed to better understand the precise timing and endocrine regulation of medullary bone formation in Passerines and to determine the extent to which female Passerines rely on medullary bone calcium during the formation of calcified eggshells. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Cytological aspects of melanotic variant of medullary thyroid carcinoma.

    PubMed

    de Lima, M A; Dias Medeiros, J; Rodrigues Da Cunha, L; de Cássia Caldas Pessôa, R; Silveira Tavares, F; de Fátima Borges, M; Marinho, E O

    2001-03-01

    We had the opportunity to examine a case of fine-needle aspiration (FNA) of a melanotic variant of medullary thyroid carcinoma (MTC) in a 20-yr-old man. The patient presented a single node, hardened and mobile upon deglutition, in the right lobe of the thyroid, for 9 mo, without symptoms of glandular dysfunction. Calcitonin (138 pg/ml), urinary calcium (177 mg/dl), and the carcinoembryonic antigen (341 ng/ml) were increased. The nodular aspirate, drawn by FNA, was represented by pleomorphic cells, with frequent intranuclear cytoplasmic inclusions, sometimes bi- or multinucleated, with abundant, finely granular cytoplasm, sometimes containing a brown pigment resembling melanin. An immunohistochemical study using monoclonal antibodies (Dako Corp., Carpinteria, CA) showed that the neoplastic cells were intensely and diffusely positive for calcitonin and chromogranin, and focally positive for HMB45. In view of these findings, the case was characterized as a melanotic variant of medullary carcinoma, a rare type of neoplasia, but having a prognosis similar to the classical variant of MTC.

  8. Medullary infarcts may cause ipsilateral masseter reflex abnormalities.

    PubMed

    Thömke, Frank; Marx, Jürgen J; Cruccu, Giorgio; Stoeter, Peter; Hopf, Hanns C

    2007-10-01

    There is a suprasegmental influence on the masseter reflex (MassR) in animals, which is mediated via the fifth nerve spinal nucleus (5SpN). Corresponding data in humans are lacking. Out of 268 prospectively recruited patients with clinical signs of acute brainstem infarctions, we identified 38 with magnetic resonance imaging (MRI)-documented unilateral infarcts caudal to the levels of the fifth nerve motor and main sensory nuclei. All had biplanar T2- and echo planar diffusion-weighted MRI and MassR testing. Five patients (13%) had ipsilateral MassR abnormalities. In all, the infarcts involved the region of the 5SpN. Patients with medullary infarcts involving the region of the 5SpN may thus have ipsilateral MassR abnormalities. This possibly represents an interruption of an excitatory projection mediated via the 5SpN to masseter motoneurons in the fifth nerve motor nucleus. MassR abnormalities with medullary lesions restrict the topodiagnostic value of the MassR.

  9. Secretion of Parathyroid Hormone in Patients with Medullary Thyroid Carcinoma

    PubMed Central

    Deftos, Leonard J.; Parthemore, Jacqueline G.

    1974-01-01

    The secretion of parathyroid hormone (PTH) and calcitonin (CT) was studied in 30 patients with medullary thyroid carcinoma. Most patients with elevated levels of CT were normocalcemic and also had normal basal levels of PTH. Five of six patients with associated hyperparathyroidism were hypercalcemic and had elevated basal PTH levels. Hormone secretion was also studied during infusions with standard and low doses of calcium. PTH unexpectedly increased during 12 of 18 calcium infusions. Such a paradoxical increase in PTH was seen in those patients with the greatest increase in CT and the least increase in calcium during the calcium infusion. Accordingly, increases in PTH concentration during the calcium infusions could be correlated directly with increases in CT and correlated inversely with increases in calcium. These observations suggest that, in some patients with medullary thyroid carcinoma, a further increase in the abnormally elevated CT levels may stimulate PTH secretion. Therefore, at least in acute studies, there may be a functional, as well as a genetic, relationship between the secretion of these two hormones in patients with this thyroid tumor. PMID:4847251

  10. Putative BRAF activating fusion in a medullary thyroid cancer.

    PubMed

    Kasaian, Katayoon; Wiseman, Sam M; Walker, Blair A; Schein, Jacqueline E; Hirst, Martin; Moore, Richard A; Mungall, Andrew J; Marra, Marco A; Jones, Steven J M

    2016-03-01

    Medullary thyroid cancer (MTC) is a malignancy of the calcitonin-producing parafollicular cells of the thyroid gland. Surgery is the only curative treatment for this cancer. External beam radiation therapy is reserved for adjuvant treatment of MTC with aggressive features. Targeted therapeutics vandetanib and cabozantinib are approved for the treatment of aggressive and metastatic tumors that are not amenable to surgery. The use of these multikinase inhibitors are supported by the observed overactivation of the RET oncoprotein in a large subpopulation of MTCs. However, not all patients carry oncogenic alterations of this kinase. Hence, there is still a need for comprehensive molecular characterization of MTC utilizing whole-genome and transcriptome-sequencing methodologies with the aim of identifying targetable mutations. Here, we describe the genomic profiles of two medullary thyroid cancers and report the presence of a putative oncogenic BRAF fusion in one. Such alterations, previously observed in other malignancies and known targets of available drugs, can benefit patients who currently have no treatment options.

  11. Adrenal Imaging: Magnetic Resonance Imaging and Computed Tomography.

    PubMed

    McCarthy, Colin J; McDermott, Shaunagh; Blake, Michael A

    2016-01-01

    The adrenal glands are located superior to the kidneys and play an important role in the endocrine system. Each adrenal gland contains an outer cortex, responsible mainly for the secretion of androgens and corticosteroids, and an inner medulla, which secretes epinephrine and norepinephrine. Here, we review the anatomy of the adrenal glands and explain the current imaging modalities that are most useful for the assessment of the various conditions--both benign and malignant--that can affect these glands. As adrenal lesions are often identified incidentally on cross-sectional imaging performed for other reasons, the management of such adrenal 'incidentalomas' is also discussed. In many cases, adrenal lesions have distinctive imaging features that allow for a full characterization with noninvasive techniques. In some cases, invasive studies such as adrenal vein sampling or adrenal biopsy become necessary. This review should give the reader a wide overview of how various imaging techniques can be useful in the assessment of adrenal pathology.

  12. Bovine coronavirus associated syndromes.

    PubMed

    Boileau, Mélanie J; Kapil, Sanjay

    2010-03-01

    Bovine coronaviruses, like other animal coronaviruses, have a predilection for intestinal and respiratory tracts. The viruses responsible for enteric and respiratory symptoms are closely related antigenically and genetically. Only 4 bovine coronavirus isolates have been completely sequenced and thus, the information about the genetics of the virus is still limited. This article reviews the clinical syndromes associated with bovine coronavirus, including pneumonia in calves and adult cattle, calf diarrhea, and winter dysentery; diagnostic methods; prevention using vaccination; and treatment, with adjunctive immunotherapy.

  13. The agonistic adrenal: melatonin elicits female aggression via regulation of adrenal androgens.

    PubMed

    Rendon, Nikki M; Rudolph, Lauren M; Sengelaub, Dale R; Demas, Gregory E

    2015-11-22

    Classic findings have demonstrated an important role for sex steroids as regulators of aggression, but this relationship is lacking within some environmental contexts. In mammals and birds, the adrenal androgen dehydroepiandrosterone (DHEA), a non-gonadal precursor of biologically active steroids, has been linked to aggression. Although females, like males, use aggression when competing for limited resources, the mechanisms underlying female aggression remain understudied. Here, we propose a previously undescribed endocrine mechanism regulating female aggression via direct action of the pineal hormone melatonin on adrenal androgens. We examined this in a solitary hamster species, Phodopus sungorus, in which both sexes are highly territorial across the seasons, and display increased aggression concomitant with decreased serum levels of sex steroids in short 'winter-like' days. Short- but not long-day females had increased adrenal DHEA responsiveness co-occurring with morphological changes in the adrenal gland. Further, serum DHEA and total adrenal DHEA content were elevated in short days. Lastly, melatonin increased DHEA and aggression and stimulated DHEA release from cultured adrenals. Collectively, these findings demonstrate that DHEA is a key peripheral regulator of aggression and that melatonin coordinates a 'seasonal switch' from gonadal to adrenal regulation of aggression by direct action on the adrenal glands.

  14. The agonistic adrenal: melatonin elicits female aggression via regulation of adrenal androgens

    PubMed Central

    Rudolph, Lauren M.; Sengelaub, Dale R.; Demas, Gregory E.

    2015-01-01

    Classic findings have demonstrated an important role for sex steroids as regulators of aggression, but this relationship is lacking within some environmental contexts. In mammals and birds, the adrenal androgen dehydroepiandrosterone (DHEA), a non-gonadal precursor of biologically active steroids, has been linked to aggression. Although females, like males, use aggression when competing for limited resources, the mechanisms underlying female aggression remain understudied. Here, we propose a previously undescribed endocrine mechanism regulating female aggression via direct action of the pineal hormone melatonin on adrenal androgens. We examined this in a solitary hamster species, Phodopus sungorus, in which both sexes are highly territorial across the seasons, and display increased aggression concomitant with decreased serum levels of sex steroids in short ‘winter-like' days. Short- but not long-day females had increased adrenal DHEA responsiveness co-occurring with morphological changes in the adrenal gland. Further, serum DHEA and total adrenal DHEA content were elevated in short days. Lastly, melatonin increased DHEA and aggression and stimulated DHEA release from cultured adrenals. Collectively, these findings demonstrate that DHEA is a key peripheral regulator of aggression and that melatonin coordinates a ‘seasonal switch’ from gonadal to adrenal regulation of aggression by direct action on the adrenal glands. PMID:26582025

  15. Failure to visualize adrenal glands in a patient with bilateral adrenal hyperplasia. [/sup 131/I

    SciTech Connect

    Gordon, L.; Mayfield, R.K.; Levine, J.H.; Lopes-Virella, M.F.; Sagel, J.; Buse, M.G.

    1980-01-01

    A patient with clinical and biochemical evidence of Cushing's disease and severe hyperlipidemia underwent an adrenal imaging procedure with NP-59 (6..beta..-(/sup 131/I)iodomethyl-19-norcholesterol), without visualization of either gland. Correction of the hyperlipidemia followed by repeated adrenal imaging resulted in bilateral visualization. A pituitary tumor was removed at surgery, confirming the diagnosis of Cushing's disease.

  16. [Adrenal insufficiency in cirrhotic patients].

    PubMed

    Orozco, Federico; Anders, María; Mella, José; Antinucci, Florencia; Pagano, Patricia; Esteban, Paula; Cartier, Mariano; Romero, Gustavo; Francini, Bettina; Mastai, Ricardo

    Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 υg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh = 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with = 8 (3/13, p < 0.05). A correlation between salivary cortisol and basal plasma cortisol (r = 0.6, p < 0.0004) was observed. Finally, survival at 1 year (97%) and 3 years (91%) was significantly higher without RAI than those who developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality.

  17. Role of renal medullary adenosine in the control of blood flow and sodium excretion.

    PubMed

    Zou, A P; Nithipatikom, K; Li, P L; Cowley, A W

    1999-03-01

    This study determined the levels of adenosine in the renal medullary interstitium using microdialysis and fluorescence HPLC techniques and examined the role of endogenous adenosine in the control of medullary blood flow and sodium excretion by infusing the specific adenosine receptor antagonists or agonists into the renal medulla of anesthetized Sprague-Dawley rats. Renal cortical and medullary blood flows were measured using laser-Doppler flowmetry. Analysis of microdialyzed samples showed that the adenosine concentration in the renal medullary interstitial dialysate averaged 212 +/- 5.2 nM, which was significantly higher than 55.6 +/- 5.3 nM in the renal cortex (n = 9). Renal medullary interstitial infusion of a selective A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 300 pmol. kg-1. min-1, n = 8), did not alter renal blood flows, but increased urine flow by 37% and sodium excretion by 42%. In contrast, renal medullary infusion of the selective A2 receptor blocker 3, 7-dimethyl-1-propargylxanthine (DMPX; 150 pmol. kg-1. min-1, n = 9) decreased outer medullary blood flow (OMBF) by 28%, inner medullary blood flows (IMBF) by 21%, and sodium excretion by 35%. Renal medullary interstitial infusion of adenosine produced a dose-dependent increase in OMBF, IMBF, urine flow, and sodium excretion at doses from 3 to 300 pmol. kg-1. min-1 (n = 7). These effects of adenosine were markedly attenuated by the pretreatment of DMPX, but unaltered by DPCPX. Infusion of a selective A3 receptor agonist, N6-benzyl-5'-(N-ethylcarbonxamido)adenosine (300 pmol. kg-1. min-1, n = 6) into the renal medulla had no effect on medullary blood flows or renal function. Glomerular filtration rate and arterial pressure were not changed by medullary infusion of any drugs. Our results indicate that endogenous medullary adenosine at physiological concentrations serves to dilate medullary vessels via A2 receptors, resulting in a natriuretic response that overrides the tubular A1 receptor

  18. Adrenal diseases during pregnancy: pathophysiology, diagnosis and management strategies.

    PubMed

    Kamoun, Mahdi; Mnif, Mouna F; Charfi, Nadia; Kacem, Faten H; Naceur, Basma B; Mnif, Fatma; Dammak, Mohamed; Rekik, Nabila; Abid, Mohamed

    2014-01-01

    : Adrenal diseases--including disorders such as Cushing's syndrome, Addison's disease, pheochromocytoma, primary hyperaldosteronism and congenital adrenal hyperplasia--are relatively rare in pregnancy, but a timely diagnosis and proper treatment are critical because these disorders can cause maternal and fetal morbidity and mortality. Making the diagnosis of adrenal disorders in pregnancy is challenging as symptoms associated with pregnancy are also seen in adrenal diseases. In addition, pregnancy is marked by several endocrine changes, including activation of the renin-angiotensin-aldosterone system and the hypothalamic-pituitary-adrenal axis. The aim of this article was to review the pathophysiology, clinical manifestation, diagnosis and management of various adrenal disorders during pregnancy.

  19. A Case Report of Bilateral Adrenal Sarcomatoid Carcinoma

    PubMed Central

    Cerit, Ethem Turgay; Özkan, Çiğdem; Altınova, Eroğlu; Çimen, Ali Rıza; Sözen, Sinan; Kerem, Mustafa; Aktürk, Müjde; Memiş, Leyla; Törüner, Baloş; Çakır, Nuri; Arslan, Metin

    2016-01-01

    Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Sarcomatoid adrenal carcinoma is even more aggressive type of ACC. Bilateral malignant adrenal tumors are extremely rare except for those that represent metastasis from an extra-adrenal organ. Here we report a 53-year-old woman who presented with abdominal pain and weight loss. Abdominal computed tomography revealed bilateral adrenal masses and a mass in her liver. Surgical specimens showed pleomorphic tumor cells with epithelial and spindle cell morphology and immunohistochemical staining was compatible with sarcomatoid carcinoma. Sarcomatoid adrenal carcinoma should be kept in mind during the management of bilateral adrenal masses. PMID:28097033

  20. Papillary thyroid cancer with bilateral adrenal metastases.

    PubMed

    Batawil, Nadia

    2013-12-01

    Papillary thyroid cancer is the most common type of thyroid malignancy and has an excellent prognosis. Distant organ metastasis is rare. Bilateral adrenal metastases with iodine uptake has not been described before. A 47-year-old woman presented for evaluation because of severe right upper arm pain and weakness. Magnetic resonance imaging of the thoracic spine showed a compression fracture at the third thoracic vertebra associated with a soft tissue mass. Computed tomography (CT)-guided biopsy of the mass showed metastatic papillary thyroid carcinoma. Ultrasonography of the neck showed an enlarged right thyroid lobe with cervical lymphadenopathy. A high-resolution CT scan of the chest showed multiple bilateral pulmonary nodules. Treatment included total thyroidectomy and lymph node dissection, external beam radiation to the thoracic spine, and (131)I therapy. Initial whole body (131)I scintigraphy showed faint uptake in the right upper abdomen, interpreted as a sign of physiologic bowel activity; however, repeat whole body (131)I scintigraphy showed increased uptake in both adrenal glands, consistent with metastatic disease. Serial abdominal CT scans showed progressively enlarging bilateral adrenal masses. Despite additional treatment with (131)I, the patient's disease progressed at all metastatic sites. This patient had bilateral adrenal metastases from advanced papillary thyroid cancer with distant metastasis to lung and bone at initial presentation and poor response to repeated (131)I therapy. Unilateral adrenal metastasis from thyroid cancer has been described previously in six cases; this is the first case report of bilateral adrenal metastases. Bilateral adrenal metastasis is rare in papillary thyroid cancer. Elevated abdominal uptake of (131)I in a high-risk patient may be a sign of abdominal metastatic disease.

  1. Differential distribution of synaptotagmin-1, -4, -7, and -9 in rat adrenal chromaffin cells.

    PubMed

    Matsuoka, Hidetada; Harada, Keita; Nakamura, Jun; Fukuda, Mitsunori; Inoue, Masumi

    2011-04-01

    Neurons and certain kinds of endocrine cells, such as adrenal chromaffin cells, have large dense-core vesicles (LDCVs) and synaptic vesicles or synaptic-like microvesicles (SLMVs). These secretory vesicles exhibit differences in Ca(2+) sensitivity and contain diverse signaling substances. The present work was undertaken to identify the synaptotagmin (Syt) isoforms present in secretory vesicles. Fractionation analysis of lysates of the bovine adrenal medulla and immunocytochemistry in rat chromaffin cells indicated that Syt 1 was localized in LDCVs and SLMVs, whereas Syt 7 was the predominant isoform present in LDCVs. In contrast to PC12 cells and the pancreatic β cell line INS-1, Syt 9 was not immunodetected in LDCVs in rat chromaffin cells. Double-staining revealed that Syt 9-like immunoreactivity was nearly identical with fluorescent thapsigargin binding, suggesting the presence of Syt 9 in the endoplasmic reticulum (ER).The exogenous expression of Syt 1-GFP in INS-1 cells, which had a negligible level of endogenous Syt 1, resulted in an increase in the amount of Syt 9 in the ER, suggesting that Syt 9 competes with Syt 1 for trafficking from the ER to the Golgi complex. We conclude that LDCVs mainly contain Syt 7, whereas SLMVs contain Syt 1, but not Syt 7, in rat and bovine chromaffin cells.

  2. Isolation of neural crest derived chromaffin progenitors from adult adrenal medulla.

    PubMed

    Chung, Kuei-Fang; Sicard, Flavie; Vukicevic, Vladimir; Hermann, Andreas; Storch, Alexander; Huttner, Wieland B; Bornstein, Stefan R; Ehrhart-Bornstein, Monika

    2009-10-01

    Chromaffin cells of the adrenal medulla are neural crest-derived cells of the sympathoadrenal lineage. Unlike the closely-related sympathetic neurons, a subpopulation of proliferation-competent cells exists even in the adult. Here, we describe the isolation, expansion, and in vitro characterization of proliferation-competent progenitor cells from the bovine adrenal medulla. Similar to neurospheres, these cells, when prevented from adherence to the culture dish, grew in spheres, which we named chromospheres. These chromospheres were devoid of mRNA specific for smooth muscle cells (MYH11) or endothelial cells (PECAM1). During sphere formation, markers for differentiated chromaffin cells, such as phenylethanolamine-N-methyl transferase, were downregulated while neural progenitor markers nestin, vimentin, musashi 1, and nerve growth factor receptor, as well as markers of neural crest progenitor cells such as Sox1 and Sox9, were upregulated. Clonal analysis and bromo-2'-deoxyuridine-incorporation analysis demonstrated the self-renewing capacity of chromosphere cells. Differentiation protocols using NGF and BMP4 or dexamethasone induced neuronal or endocrine differentiation, respectively. Electrophysiological analyses of neural cells derived from chromospheres revealed functional properties of mature nerve cells, such as tetrodotoxin-sensitive sodium channels and action potentials. Our study provides evidence that proliferation and differentiation competent chromaffin progenitor cells can be isolated from adult adrenal medulla and that these cells might harbor the potential for the treatment of neurodegenerative diseases, such as Parkinson's disease.

  3. 78 FR 73993 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-10

    ... Health Inspection Service 9 CFR Parts 92, 93, 94, 95, 96, and 98 RIN 0579-AC68 Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products Corrections In rule document 2013-28228 appearing on...

  4. 77 FR 20319 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-04

    ...; ] DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service 9 CFR Part 93 RIN 0579-AC68 Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products Correction In proposed rule document...

  5. Genetics Home Reference: congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency

    MedlinePlus

    ... collectively called congenital adrenal hyperplasia) that affect the adrenal glands . The adrenal glands are located on top of the kidneys and ... CAH due to 11-beta-hydroxylase deficiency, the adrenal glands produce excess androgens, which are male sex hormones. ...

  6. Intracerebral adrenal medulla grafts: a review.

    PubMed

    Freed, W J; Poltorak, M; Becker, J B

    1990-11-01

    This review summarizes basic and clinical research on intracerebral adrenal medulla grafts, emphasizing potential applications to Parkinson's disease. Properties of intraventricular and intraparenchymal grafts are described, and cell survival and functional effects are compared. It is clear that adrenal medulla allografts survive poorly in the parenchyma of the corpus striatum and better in the lateral ventricle. Nerve growth factor (NGF) may improve the survival of adrenal medulla grafts. In the absence of added NGF even adrenal medulla grafts in the ventricle survive irregularly, and the factors required for graft survival in the ventricle are not well understood. In the 6-hydroxydopamine-lesioned rat model most evidence suggests, not surprisingly, that adrenal medulla grafts produce functional effects only when they survive. These effects may be related to production of catecholamines by the transplanted cells. In addition, adrenal medulla grafts may produce trophic effects on host brain. These effects are most evident in animals with MPTP-induced damage to dopaminergic systems and may be nonspecific, possibly related in part to the brain injury that is induced by graft implantation. Trophic effects may contribute to the functional effects of adrenal medulla grafts: For intraparenchymal grafts, trophic effects that do not require cell survival may contribute small functional changes, while additional behavioral effects may require substantial chromaffin cell survival. The evidence for direct dopamine-mediated effects as compared to trophic mechanisms of action for these grafts in animal models for Parkinson's disease is presented. Clinical studies of adrenal medulla grafts in human patients are examined and compared in detail. When inspected closely, the various clinical studies are in general agreement on most points, although there are differences in the degree of improvement found, both across different studies and individual patients. It is concluded that

  7. [Cervical lymph node metastasis in medullary thyroid carcinoma].

    PubMed

    Yan, Dangui; Zhang, Bin; Li, Zhengjiang; Wu, Yuehuang; Liu, Shaoyan; Liu, Wensheng; Xu, Zhengang; Tang, Pingzhang

    2015-04-01

    To study the patterns of cervical lymph node metastasis of medullary thyroid carcinoma. Ninety-one patients with medullary thyroid carcinoma first treated between January 1999 and October 2014 were analyzed retrospectively. Of 91 patients, 39 cases presented with clinical negative node (cN0) and 52 cases with clinical positive node (cN+). Central compartment dissection was performed in all cases. Lateral neck dissection was performed in 52 cN+ cases (71 sides). All neck dissection specimens were obtained and analyzed for lymph node (LN) involvement with respect to neck levels. The distribution of LN with metastasis was studied in cN+ patients and the following factors were used to study the predictive value of central compartment LN metastasis: sex, age, family history, tumor size, bilateral tumor, multifocality of the tumor, extracapsular spread, and remote metastasis. Univariate analysis with the χ(2) test was used to analyze the statistical correlation between central compartment LN metastasis and other clinical factors. Multiple logistic regression analysis was used to identify the factors related to central compartment metastasis. Neck and bilateral neck metastasis rates were 73.6%, 19.8% respectively. Metastasis rates in central compartment and superior mediastinal region were 68.1% and 27.5% respectively. The central compartment metastasis rate was 33.3% in cN0 patients and 94.2% in cN+ patients. The superior mediastinal metastasis rate was 2.6% in cN0 patients and 46.2% in cN+ patients. Extracapsular spread was an independent predictive factor for central compartment metastasis (χ(2)=15.592, P=0.000, OR=12.876). The incidences of LN metastases at level II, III, IV, V were 62.9%,84.5%,83.1%,50.0% in cN+ patient, respectively. Multi-sites were involved. The possibility of lateral neck metastasis was higher when preoperative value of calcitonin was higher than 300 ng/L (66.7% vs 28.6%, χ(2)=5.771, P=0.016). Cervical lymph node metastasis of medullary

  8. Adrenal toxicology: a strategy for assessment of functional toxicity to the adrenal cortex and steroidogenesis.

    PubMed

    Harvey, Philip W; Everett, David J; Springall, Christopher J

    2007-01-01

    The adrenal is the most common toxicological target organ in the endocrine system in vivo and yet it is neglected in regulatory endocrine disruption screening and testing. There has been a recent marked increase in interest in adrenal toxicity, but there are no standardised approaches for assessment. Consequently, a strategy is proposed to evaluate adrenocortical toxicity. Human adrenal conditions are reviewed and adrenocortical suppression, known to have been iatrogenically induced leading to Addisonian crisis and death, is identified as the toxicological hazard of most concern. The consequences of inhibition of key steroidogenic enzymes and the possible toxicological modulation of other adrenal conditions are also highlighted. The proposed strategy involves an in vivo rodent adrenal competency test based on ACTH challenge to specifically examine adrenocortical suppression. The H295R human adrenocortical carcinoma cell line is also proposed to identify molecular targets, and is useful for measuring steroids, enzymes or gene expression. Hypothalamo-pituitary-adrenal endocrinology relevant to rodent and human toxicology is reviewed (with an emphasis on multi-endocrine axis effects on the adrenal and also how the adrenal affects a variety of other hormones) and the endocrinology of the H295R cell line is also described. Chemicals known to induce adrenocortical toxicity are reviewed and over 60 examples of compounds and their confirmed steroidogenic targets are presented, with much of this work published very recently using H295R cell systems. In proposing a strategy for adrenocortical toxicity assessment, the outlined techniques will provide hazard assessment data but it will be regulatory agencies that must consider the significance of such data in risk extrapolation models. The cases of etomindate and aminoglutethimide induced adrenal suppression are clearly documented examples of iatrogenic adrenal toxicity in humans. Environmentally, sentinel species, such as

  9. Role of adrenal imaging in surgical management

    SciTech Connect

    Lamki, L.M.; Haynie, T.P. )

    1990-03-01

    Adrenal imaging using radiopharmaceuticals is a functional test that can contribute significantly to surgical management and follow-up of patients with either benign or malignant conditions of the adrenal cortex and medulla. Imaging of the cortex is achieved by iodine-131-labeled iodomethyl nor-cholesterol (NP-59), while adrenal medulla imaging can be successfully accomplished by 131I-metaiodobenzylguanidine (MIBG), which localizes in the adrenergic nerve terminal with norepinephrine. Both tests carry high sensitivity and specificity for functional tumors and hyperplasia, and often better than CT scanning. This article reviews the current status and clinical utility of nuclear imaging of the adrenal cortex in congenital hyperplasia, low renin hypertension and aldosteronism, and Cushing's syndrome. Adrenal medulla imaging is reviewed in light of our experience at the University of Texas M.D. Anderson Cancer Center in pheochromocytoma, neuroblastoma, and other neuroectodermal tumors. Investigation of {sup 131}I-MIBG therapy of metastatic tumors of neuroectodermal origin potentially offers a means of at least controlling symptoms of hormonal secretion in these patients. 40 references.

  10. Thymus and adrenal glands in elder abuse.

    PubMed

    Hayashi, Takahito; Bunai, Yasuo; Ago, Kazutoshi; Ago, Mihoko; Ogata, Mamoru

    2011-12-01

    Endogenous glucocorticoid-induced thymic involution is generally considered to be an important finding for determining child abuse. The present study investigated the weight of the thymus and the adrenal glands in elder abuse cases to identify a potential marker for elder abuse. There was no significant difference in the thymus and the adrenal weight between elder abuse and control cases. However, the elder abuse cases in which the duration of abuse was less than 3 months showed a significant increase in the adrenal weight in comparison to control cases. In such cases, histopathological findings showed a loss of intracellular light granules from the zona fasciculata, which might indicate a loss of cholesterol due to the overproduction of glucocorticoid. These results might imply that the elderly, who were maltreated for less than 3 months, were in the early phase of a long-term stress state during which stress-induced overproduction of glucocorticoid was observed in adrenal glands as indicated by Selye. Our results suggest that an increase in adrenal weight may be a potential marker for elder abuse of relatively short periods, especially less than a few months.

  11. Prevalence and natural history of adrenal incidentalomas.

    PubMed

    Barzon, Luisa; Sonino, Nicoletta; Fallo, Francesco; Palu, Giorgio; Boscaro, Marco

    2003-10-01

    Clinically silent adrenal masses discovered by imaging studies performed for unrelated reasons, i.e. adrenal incidentalomas, have become a rather common finding in clinical practice. However, only limited studies of incidence, prevalence, and natural history of adrenal incidentalomas are available. A comprehensive review of the literature shows the prevalence of adrenal incidentalomas to be 2.3% at autopsy and 0.5-2% at abdominal computed tomography scan. Most lesions are adrenocortical adenomas at histology, whereas the prevalence of adrenocortical carcinomas is relatively low. The risk of malignancy over time for masses defined as benign at diagnosis is estimated at about 1/1000, even though 5-25% of masses increase in size during follow-up. Hyperfunction develops in about 1.7% of cases and the risk is higher in patients with lesions larger than 3 cm. Cortisol hypersecretion is the most likely disorder that may ensue, and it remains subclinical in about two-thirds of cases. The lack of controlled studies precludes making specific management recommendations. Large perspective controlled studies to define the epidemiology, natural history, and possible associated morbidity of adrenal incidentalomas and their impact on the quality of life of patients are needed.

  12. Sonographic features of medullary thyroid carcinomas according to tumor size: comparison with papillary thyroid carcinomas.

    PubMed

    Zhou, Liguang; Chen, Bo; Zhao, Miaoqing; Zhang, Huawei; Liang, Bo

    2015-06-01

    The aim of this study was to evaluate the differences in sonographic features of medullary thyroid carcinomas according to nodule size and compared with findings for papillary thyroid carcinomas. This study included 38 medullary thyroid carcinoma nodules and 91 papillary thyroid carcinoma nodules, which were confirmed by pathologic examination between May 2008 and September 2013. Nodules were divided into those that were greater than 10 mm (large nodules) and 10 mm or less (small nodules). The differences in sonographic features (composition, echogenicity, margin, calcifications, and shape) between groups were analyzed with a χ(2) test. Large medullary thyroid carcinomas more frequently showed an ovoid-to-round shape and a smooth margin; small medullary thyroid carcinomas more frequently showed a taller-than-wide shape and a spiculated margin; the differences were statistically significant between the groups (P < .05). Compared with papillary thyroid carcinomas, large medullary thyroid carcinomas tended to have an ovoid-to-round shape, a smooth margin, and macrocalcifications and were more frequently diagnosed as indeterminate nodules (P < .05); however, there were no significant differences in the internal composition, calcifications, echogenicity, margin, and shape between small medullary thyroid carcinomas and small papillary thyroid carcinomas (P > .05). Our data indicate that the sonographic features of medullary thyroid carcinomas are associated with tumor size; furthermore, the sonographic features of medullary thyroid carcinomas are similar to those of small papillary thyroid carcinomas but greatly different from those of large papillary thyroid carcinomas. Large medullary thyroid carcinomas are more commonly diagnosed as indeterminate nodules by sonography than large papillary thyroid carcinomas, and fine-needle aspiration biopsy or serum calcitonin measurement may be helpful. © 2015 by the American Institute of Ultrasound in Medicine.

  13. Unlocking the bovine genome

    USDA-ARS?s Scientific Manuscript database

    The draft genome sequence of cattle (Bos taurus) has now been analyzed by the Bovine Genome Sequencing and Analysis Consortium and the Bovine HapMap Consortium, which together represent an extensive collaboration involving more than 300 scientists from 25 different countries. ...

  14. 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.

  15. Angiotensin effects on calcium and steroidogenesis in adrenal glomerulosa cells

    SciTech Connect

    Elliott, M.E.; Siegel, F.L.; Hadjokas, N.E.; Goodfriend, T.L.

    1985-03-01

    We investigated the role of cellular calcium pools in angiotensin II-stimulated aldosterone synthesis in bovine adrenal glomerulosa cells. Angiotensin II decreased the size of the exchangeable cell calcium pool by 34%, consistent with previous observations that angiotensin II causes decreased uptake of /sup 45/Ca+2 into cells and increased efflux of /sup 45/Ca+2 from preloaded cells. Atomic absorption spectroscopy showed that angiotension II caused a decrease of 21% in total cellular calcium. Angiotensin II caused efflux of /sup 45/Ca+2 in the presence of EGTA and retarded uptake of /sup 45/Ca+2 when choline was substituted for sodium, suggesting that hormone effects on calcium pools do not involve influx of trigger calcium or sodium. Cells incubated in calcium-free buffer and 0.1 mM or 0.5 mM EGTA synthesized reduced (but still significant) amounts of the steroid in response to hormone. Cells incubated in increasing concentrations of extracellular calcium contained increasing amounts of intracellular calcium and synthesized increasing amounts of aldosterone in response to angiotensin II. These results point to the participation of intracellular calcium pools in angiotensin II-stimulated steroidogenesis and the importance of extracellular calcium in maintaining these pools.

  16. [Biomechanical analysis of the medullary bone nail and its locking].

    PubMed

    Teubner, E

    1985-07-01

    By mechanical definition an intramedullary nail is not a nail but rather a bendable feather, subject to longitudinal tension and to a lesser degree to transverse pressure. Reaming the medullary canal is necessary for centralization of the nail as well as to increase the area of contact with the bone. However, this procedure is detrimental to the bone metabolism and reduces its elasticity against torsional forces. The dynamic locking nail-system is more biologic than conventional nailing and it reduces rotatory instability with the help of additional components, such as transverse screws. Only static locking allows true static weight bearing with crutches, but not dynamic mobilisation. Nails with conventional strength and in leaf of trefoil formation are superior to other designs. However, an improved angle in the proximal locking is suggested, as this would allow for a three to four times greater weight bearing.

  17. Treating medullary thyroid cancer in the age of targeted therapy

    PubMed Central

    Cabanillas, Maria E; Hu, Mimi I; Jimenez, Camilo; Grubbs, Elizabeth G; Cote, Gilbert J

    2015-01-01

    Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor deriving from the thyroid parafollicular cell. Thyroidectomy continues to serve as the primary initial treatment for this cancer. Because standard cytotoxic chemotherapy has proven ineffective, reoperation and external beam radiation therapy had been the only tools to treat recurrences or distant disease. The discovery that aberrant activation of RET, a receptor tyrosine kinase, is a primary driver of MTC tumorigenesis led to clinical trials using RET-targeting tyrosine kinase inhibitors. The successes of those trials led to the approval of vandetanib and cabozantinib for treating patients with progressive or symptomatic MTC. The availability of these drugs, along with additional targeted therapies in development, requires a thoughtful reconsideration of the approach to treating patients with unresectable locally advanced and/or metastatic progressive MTC. PMID:25908961

  18. Pain and neuroma formation in Wallenberg's lateral medullary syndrome.

    PubMed

    Moffie, D; Hamburger, H L

    1986-01-01

    We report a patient with a Wallenberg's lateral medullary syndrome in which pain was a prominent feature. This led to substitution of the original and correct diagnosis by that of a thalamic syndrome for which a prefrontal leucotomy was performed. The patient died some years later from a myocardial infarction and autopsy was performed. In the dorsolateral part of the medulla oblongata a cavity was found in which aberrant nerve fibres with neuroma-like formations could be seen. These fibres coursed along blood vessels, and penetrated from the surface of the medulla oblongata. On the base of the clinico-pathological correlations, it is conjectured that destruction of the lateral reticular formation cannot be the sole cause of the severe pain.

  19. Thyroid cancers. II. Medullary, anaplastic, lymphoma, sarcoma, squamous cell.

    PubMed

    Austin, J R; el-Naggar, A K; Goepfert, H

    1996-08-01

    Medullary thyroid carcinoma in both sporadic and familial forms is a curable disease if detected early and treated by the proper surgery. The advent of genetic screening for the RET protooncogene portends great promise in the earlier diagnosis and treatment of familial forms of MTC. New chemotherapy protocols have produced some tumor regression in patients with metastatic MTC. Improved use of Adriamycin and hyper-fractionated radiotherapy combined with debulking procedures has prolonged survival in anaplastic thyroid cancer. Thyroid gland lymphoma, if diagnosed early and treated by combined chemoradiotherapy, carries a good prognosis for survival. The best treatment for thyroid sarcomas and SCC of the thyroid is early diagnosis and aggressive surgery combined with radiotherapy.

  20. Genetic alterations in medullary thyroid cancer: diagnostic and prognostic markers.

    PubMed

    A, Taccaliti; F, Silvetti; G, Palmonella; M, Boscaro

    2011-12-01

    Medullary thyroid carcinoma (MTC) is a rare calcitonin producing neuroendocrine tumour that originates from the parafollicular C-cells of the thyroid gland. The RET proto-oncogene encodes the RET receptor tyrosine kinase, with consequently essential roles in cell survival, differentiation and proliferation. Somatic or germline mutations of the RET gene play an important role in this neoplasm in development of sporadic and familial forms, respectively. Genetic diagnosis has an important role in differentiating sporadic from familiar MTC. Furthermore, depending on the location of the mutation, patients can be classified into risk classes. Therefore, genetic screening of the RET gene plays a critical role not only in diagnosis but also in assessing the prognosis and course of MTC.

  1. Medullary Sponge Kidney and Urinary Calculi Aeromedical Concerns

    NASA Technical Reports Server (NTRS)

    Jones, Jeffrey A.; Cherian, Sebastian F.; Barr, Yael R.; Stocco, Amber

    2008-01-01

    Medullary Sponge Kidney (MSK) is a benign disorder associated with renal stones in 60% of patients. Patients frequently have episodic painless hematuria but are otherwise asymptomatic unless renal calculi or infections complicate the disease. Nephrolithiasis is a relative, but frequently enforced, contraindication to space or other high performance flight. Two case reports of asymptomatic NASA flight crew with MSK and three cases of military aviators diagnosed with MSK are reviewed, all cases resulted in waiver and return to flight status after treatment and a vigorous follow up and prophylaxis protocol. MSK in aviation and space flight necessitates a highly case-by-case dependent evaluation and treatment process to rule out other potential confounding factors that might also contribute to stone formation and in order to re-qualify the aviator for flight duties.

  2. [Calcitonin determination for early diagnosis of medullary thyroid cancer].

    PubMed

    Karges, W

    2010-07-01

    Calcitonin is considered to be a sensitive marker for medullary thyroid cancer (MTC) therefore early detection and surgical treatment may help to improve the clinical prognosis of MTC. Routine calcitonin measurement has therefore been recommended in the diagnostic evaluation of patients with nodular thyroid disease. In the case of elevated serum calcitonin (>20 pg/ml) stimulation testing is recommended to improve the predictive power for MTC particularly in patients with small nodules. Serum calcitonin measurement cannot reliably discriminate between micro-MTC (<10 mm) and C cell hyperplasia. In patients with stimulated calcitonin levels exceeding 100 pg/ml thyroidectomy is recommended because of a high inherent risk of MTC. Highly elevated basal and stimulated serum calcitonin levels are strongly suggestive of MTC with practical implications for surgical management.

  3. 2012 European Thyroid Association Guidelines for Metastatic Medullary Thyroid Cancer

    PubMed Central

    Schlumberger, M.; Bastholt, L.; Dralle, H.; Jarzab, B.; Pacini, F.; Smit, J.W.A.

    2012-01-01

    Distant metastases are the main cause of death in patients with medullary thyroid cancer (MTC). These 21 recommendations focus on MTC patients with distant metastases and a detailed follow-up protocol of patients with biochemical or imaging evidence of disease, selection criteria for treatment, and treatment modalities, including local and systemic treatments based on the results of recent trials. Asymptomatic patients with low tumor burden and stable disease may benefit from local treatment modalities and can be followed up at regular intervals of time. Imaging is usually performed every 6–12 months, or at longer intervals of time depending on the doubling times of serum calcitonin and carcinoembryonic antigen levels. Patients with symptoms, large tumor burden and progression on imaging should receive systemic treatment. Indeed, major progress has recently been achieved with novel targeted therapies using kinase inhibitors directed against RET and VEGFR, but further research is needed to improve the outcome of these patients. PMID:24782992

  4. Genetic Alterations in Medullary Thyroid Cancer: Diagnostic and Prognostic Markers

    PubMed Central

    A, Taccaliti; F, Silvetti; G, Palmonella; M, Boscaro

    2011-01-01

    Medullary thyroid carcinoma (MTC) is a rare calcitonin producing neuroendocrine tumour that originates from the parafollicular C-cells of the thyroid gland. The RET proto-oncogene encodes the RET receptor tyrosine kinase, with consequently essential roles in cell survival, differentiation and proliferation. Somatic or germline mutations of the RET gene play an important role in this neoplasm in development of sporadic and familial forms, respectively. Genetic diagnosis has an important role in differentiating sporadic from familiar MTC. Furthermore, depending on the location of the mutation, patients can be classified into risk classes. Therefore, genetic screening of the RET gene plays a critical role not only in diagnosis but also in assessing the prognosis and course of MTC. PMID:22654561

  5. Medullary thyroid carcinoma with ectopic adrenocorticotropic hormone syndrome.

    PubMed

    Choi, Hong Seok; Kim, Min Joo; Moon, Chae Ho; Yoon, Jong Ho; Ku, Ha Ra; Kang, Geon Wook; Na, Im Il; Lee, Seung-Sook; Lee, Byung-Chul; Park, Young Joo; Kim, Hong Il; Ku, Yun Hyi

    2014-03-01

    Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.

  6. [Difficulties in diagnosis and localization of recurrent medullary thyroid carcinoma].

    PubMed

    Biterman, Arie; Bloch, Boaz; Wolf, Tamir; Baron, Ela; Lephel, Oleg; Cohen, Oded

    2002-02-01

    Recurrent and residual medullary thyroid carcinoma (MTC) are common in patients following primary surgical resection. Difficulty arises in performing precise localization of the tumor because of anatomical distortion of the neck structures following surgery. To date, no modality has been shown superior to others in the diagnosis of recurrent or residual MTC, and the issue is currently under debate in the literature. We report a case in which secondary recurrence of MTC was detected and localized using a novel combination of preoperative and intraoperative radionuclide imaging, and a method of preventing intraoperative damage to the recurrent laryngeal nerve in the anatomically disrupted neck. To our knowledge, this is the first report of a combination of these three modalities in detection and localization of recurrent MTC, while minimizing the possibility for nerve injury during the operative procedure. Such a therapeutic strategy may prove useful in the management of patients who have previously undergone neck surgery and suffer from anatomical distortion of normal neck structures.

  7. Lateral medullary stroke in patient with granulomatous polyangiitis.

    PubMed

    Taraschenko, Olga D; Amory, Colum F; Waldman, Jonathan; Hanspal, Era K; Bernardini, Gary L

    2014-01-01

    Granulomatous polyangiitis (GPA), also known as Wegener granulomatosis, is a systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis that infrequently affects the central nervous system. We report a 41-year-old man with lateral medullary infarction who developed rapidly progressive renal failure. He was diagnosed with GPA based on positive serum c-ANCA and antiproteinase 3 antibodies and demonstration of pauci-immune crescentic glomerulonephritis on kidney biopsy. He was treated with Coumadin, pulse steroids, cyclophosphamide, and plasmapheresis. He had resolution of his neurologic deficits and improvement in renal function. This case report highlights the importance to consider GPA vasculitis in the differential diagnosis of stroke in patients with development of acute kidney injury.

  8. 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

  9. Testicular adrenal rest tissue in congenital adrenal hyperplasia: comparison of MR imaging and sonographic findings.

    PubMed

    Avila, N A; Premkumar, A; Merke, D P

    1999-04-01

    The purpose of our study was to describe the MR features of testicular adrenal rest tissue in patients with congenital adrenal hyperplasia and to compare the usefulness of MR imaging with that of sonography for the detection of testicular adrenal rest tissue. Nineteen patients with congenital adrenal hyperplasia underwent MR imaging and gray-scale and color Doppler sonography of the testicles during the same visit to our institution. Findings were compared. MR features of testicular adrenal rest tissue included the following: isointensity (71% of the masses) and slight hyperintensity (29% of the masses) relative to normal testicular tissue on T1-weighted images; hypointensity relative to normal testicular tissue on T2-weighted images (100% of the masses); and diffuse enhancement on contrast-enhanced T1-weighted images (85% of the masses). MR imaging and sonography revealed the testicular lesions equally well. Eleven (58%) of 19 patients had normal findings on MR imaging and sonography. Eight (42%) of 19 patients had 14 intratesticular masses detected by both imaging techniques. MR imaging and sonography are equally useful in the detection of testicular adrenal rest tissue. Because sonography is more accessible to most institutions and is less expensive, it is the imaging technique of choice for the detection of testicular adrenal rest tissue.

  10. Neurologic complications of disorders of the adrenal glands.

    PubMed

    Bertorini, Tulio E; Perez, Angel

    2014-01-01

    Disorders of the adrenal glands frequently have secondary neurological manifestations, while some diseases that involve the central nervous system are accompanied by adrenal gland dysfunction. Excessive corticosteroid secretions in primary or secondary Cushing's syndrome causes muscle weakness and behavioral disturbances, such as emotional lability and sometimes depression, while adrenal insufficiency may cause fatigue, weakness, and depression. Adrenoleukodystrophy and adrenoneuromyelopathy are X-linked recessive disorders of the metabolism of very long chain fatty acids that manifest with white matter abnormalities of the brain, myelopathy and/or neuropathy, as well as adrenal insufficiency. Other disorders of the adrenal glands include hyperaldosteroidism, which may cause weakness from hypokalemia. Dysfunction of the adrenal medulla causes excessive or deficient secretion of catecholamines, primarily causing cardiovascular symptoms. This chapter reviews the clinical manifestations and diagnostic aspects and treatment of the various disorders of the adrenal glands. Some of the congenital adrenal diseases are also discussed. © 2014 Elsevier B.V. All rights reserved.

  11. How Do Health Care Providers Diagnose Adrenal Gland Disorders?

    MedlinePlus

    ... Gland Disorders > About > Diagnosis Page Content ​ ​How do health care providers diagnose adrenal gland disorders? Methods for diagnosing ... Tumors To diagnose an adrenal gland tumor, a health care provider may order one or more tests. 3 ...

  12. Vandetanib for the treatment of medullary thyroid carcinoma.

    PubMed

    Cooper, Maryann R; Yi, Soo Yun; Alghamdi, Wael; Shaheen, Daniel J; Steinberg, Michael

    2014-03-01

    To review the place in therapy of vandetanib for medullary thyroid carcinoma (MTC). Literature searches were performed in Ovid MEDLINE, EMBASE, and Google Scholar using the search terms ZD6474 OR vandetanib OR Caprelsa combined with medullary thyroid carcinoma. Two phase 2 trials and 1 phase 3 trial were identified. Vandetanib is approved for the treatment of unresectable, locally advanced or metastatic MTC in patients with symptomatic or progressive disease. In the phase 3 randomized, double-blind, placebo-controlled trial, vandetanib 300 mg daily (n = 231) was compared with placebo (n = 100). Vandetanib-treated patients experienced a significant improvement in progression-free survival (PFS; hazard ratio [HR] = 0.46; 95% CI = 0.31-0.69; P < .001). No difference in overall survival (OS) was seen at the time of publication. Most adverse effects were grade 1 or 2 and managed by dose interruptions or reductions. The most common grade 3/4 adverse effects were diarrhea, hypertension, QT prolongation, fatigue, and rash. Because of the potential for QT prolongation, torsades de pointes, and sudden death, vandetanib is restricted via a Risk Evaluations and Mitigation Strategy program. Vandetanib prolongs PFS but has not been shown to improve OS. Vandetanib can be considered for patients with unresectable locoregional disease. It is a first-line option for patients with unresectable symptomatic distant metastases as well as an option for advanced disseminated symptomatic metastatic disease. Vandetanib is expected to be an important addition to the formulary of health plans that provide prescription drug benefits.

  13. Imaging of the adrenal gland lesions.

    PubMed

    Herr, Keith; Muglia, Valdair F; Koff, Walter José; Westphalen, Antonio Carlos

    2014-01-01

    With the steep increase in the use of cross-sectional imaging in recent years, the incidentally detected adrenal lesion, or "incidentaloma", has become an increasingly common diagnostic problem for the radiologist, and a need for an approach to classifying these lesions as benign, malignant or indeterminate with imaging has spurred an explosion of research. While most incidentalomas represent benign disease, typically an adenoma, the possibility of malignant involvement of the adrenal gland necessitates a reliance on imaging to inform management decisions. In this article, we review the literature on adrenal gland imaging, with particular emphasis on computed tomography, magnetic resonance imaging, and photon-emission tomography, and discuss how these findings relate to clinical practice. Emerging technologies, such as contrast-enhanced ultrasonography, dual-energy computed tomography, and magnetic resonance spectroscopic imaging will also be briefly addressed.

  14. Bilateral adrenal hemorrhage in polycythemia vera

    PubMed Central

    Agito, Katrina; Krug, Esther I.

    2016-01-01

    Bilateral adrenal hemorrhage (BAH) is a rare complication typically seen in critically ill patients, which can lead to acute adrenal insufficiency and death unless it is recognized promptly and treated appropriately. We describe the case of a 64-year-old man with polycythemia vera found to be unresponsive with fever, hypotension, tachycardia, and hypoglycemia. Electrocardiogram showed ST-elevation with elevated troponin, hemoglobin, prothrombin time, and partial thromboplastin time. He required aggressive ventilator and vasopressor support. Despite primary coronary intervention, he remained hypotensive. Random cortisol level was low. He received stress dose hydrocortisone with immediate hemodynamic stability. BAH was highly suspected and was confirmed by non-contrast abdominal computed tomography. Prompt recognition and timely initiated treatment remain crucial to impact the mortality associated with acute adrenal insufficiency. PMID:27609733

  15. Principles and management of adrenal cancer

    SciTech Connect

    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; imaging techniques; adrenal disorders in childhood; primary aldosteronism; Cushing's syndrome; carcinoma; pheochromocytoma; neuroblastoma; metastatic disease; surgical management; and subject index.

  16. Imaging of the adrenal gland lesions*

    PubMed Central

    Herr, Keith; Muglia, Valdair F.; Koff, Walter José; Westphalen, Antonio Carlos

    2014-01-01

    With the steep increase in the use of cross-sectional imaging in recent years, the incidentally detected adrenal lesion, or "incidentaloma", has become an increasingly common diagnostic problem for the radiologist, and a need for an approach to classifying these lesions as benign, malignant or indeterminate with imaging has spurred an explosion of research. While most incidentalomas represent benign disease, typically an adenoma, the possibility of malignant involvement of the adrenal gland necessitates a reliance on imaging to inform management decisions. In this article, we review the literature on adrenal gland imaging, with particular emphasis on computed tomography, magnetic resonance imaging, and photon-emission tomography, and discuss how these findings relate to clinical practice. Emerging technologies, such as contrast-enhanced ultrasonography, dual-energy computed tomography, and magnetic resonance spectroscopic imaging will also be briefly addressed. PMID:25741090

  17. Adrenal Hemorrhage in Neonates: Unusual Presentation.

    PubMed

    Alabsi, Samir Y; Layland, Teresa

    2015-01-01

    Adrenal hemorrhage (AH) is a relatively uncommon condition in newborns. It may be asymptomatic or may present with flank abdominal mass, anemia, jaundice, or rarely as scrotal bruising or hematoma. We report two cases of AH in neonates; the first presented with scrotal hematoma and the second with adrenal mass associated with hypertension and oliguria, primarily secondary to coincidental renal vein thrombosis. Diagnosis was confirmed by abdominal ultrasound. Patients were managed conservatively with clinical observation and by following hemoglobin and bilirubin levels closely. Both infants were discharged without surgical intervention after several days in the hospital. Clinicians should consider AH when a newborn presents with scrotal bruising or hematoma, unexplained anemia, unexplained jaundice, or flank abdominal mass. Timely ultrasonographic evaluation of both adrenal glands and testes in neonates with scrotal hematoma may spare infants from unnecessary surgical intervention because scrotal hematoma often raises the suspicion of testicular torsion.

  18. Laparoscopic Operative Technique for Adrenal Tumors

    PubMed Central

    Szostek, Grzegorz; Nazarewski, Slawomir; Borkowski, Tomasz; Chudzinski, Witold; Tolloczko, Tadeusz

    2000-01-01

    Background and Objectives: Laparoscopy has acquired an unquestionable position in surgical practice as a diagnostic and operative tool. Recently, the laparoscopic approach has become a valuable option for adrenalectomy. This paper reports, in detail, our experience of laparoscopic adrenalectomy performed for adrenal tumors. Methods: We performed 12 laparoscopic adrenalectomies from October 29, 1997 to October 31, 1998. The technique of laparoscopic adrenalectomy is described thoroughly in all relevant details for either left or right-sided adrenal lesions. Results: The presented technique of laparoscopic adrenalectomy in all 12 cases provided good and relatively simple exposure of the immediate operative area. All relevant vascular elements were safely controlled, adrenal tumors could be successfully removed, and adequate hemostasis was achieved. No intraoperative or postoperative complications were observed. Conclusions: Laparoscopic adrenalectomy is a safe alternative to open surgery and is preferred for most patients because of shorter postoperative hospital stay and less postoperative discomfort. PMID:10917119

  19. Addison, pernicious anemia and adrenal insufficiency

    PubMed Central

    Graner, John L.

    1985-01-01

    In 1849 Thomas Addison described the clinical entity now known as pernicious anemia. In 1855 he reported several cases of adrenal insufficiency, or Addison's disease. Considering the importance of these works, there remains a great deal of confusion about them. Contrary to what many historians have written, a review of Addison's original publications demonstrates a firm appreciation of the distinction between pernicious anemia and adrenal insufficiency, based particularly on the discoloration of the skin in these conditions. Three major sources of possible confusion for historians who are attempting to understand Addison's views include Addison's early attempts to link pernicious anemia with disease of the supra-renal capsules, Addison's redefinition of pernicious anemia in his monograph on adrenal disease, and several confusing statements made by Wilks and Daldy in the first reprint of Addison's monograph. ImagesFig. 1 PMID:3902186

  20. Image-Guided Adrenal and Renal Biopsy

    PubMed Central

    Sharma, Karun V.; Venkatesan, Aradhana M.; Swerdlow, Daniel; DaSilva, Daniel; Beck, Avi; Jain, Nidhi; Wood, Bradford J.

    2010-01-01

    Image-guided biopsy is a safe and well-established technique that is familiar to most interventional radiologists (IRs). Improvements in image-guidance, biopsy tools and biopsy techniques now routinely allow for safe biopsy of renal and adrenal lesions which traditionally were considered difficult to reach or technically challenging. Image-guided biopsy is used to establish the definitive tissue diagnosis in adrenal mass lesions that can not be fully characterized with imaging or laboratory tests alone. It is also used to establish definitive diagnosis in some cases of renal parenchymal disease and has an expanding role in diagnosis and characterization of renal masses prior to treatment. Although basic principles and techniques for image-guided needle biopsy are similar regardless of organ, this paper will highlight some technical considerations, indications and complications which are unique to the adrenal gland and kidney because of their anatomic location and physiologic features. PMID:20540919

  1. 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.

  2. Adrenal glands in patients with cogenital renal anomalies: CT appearance

    SciTech Connect

    Kenney, P.J.; Robbins, G.L.; Ellis, D.A.; Spirt, B.A.

    1985-04-01

    The CT appearance of the adrenal glands was investigated in 30 patients with congenital renal anomalies. The ipsilateral adrenal was clearly identified in 83% of these patients; in all of them, the adrenal was a paraspinal disk-shaped organ, which appeared linear on CT. Conversely, the adrenals retained their normal shape in a control group of 20 patients with acquired renal atrophy or prior simple nephrectomy.

  3. Localization of metastatic adrenal cortical carcinoma with Ga-67

    SciTech Connect

    Ward, F.T.; Anderson, J.H.; Jelinek, J.; Anderson, D.W. )

    1991-02-01

    Data are limited on the localization of Ga-67 in primary or metastatic adrenal cortical carcinoma. We report the localization of Ga-67 to pathologically confirmed adrenal cortical carcinoma metastatic to the lung. A review of the literature revealed four patients have previously been reported to have metastatic adrenal cortical carcinoma detected on Ga-67 scan. Gallium imaging may be useful in the evaluation of patients with adrenal cortical carcinoma. SPECT imaging should further improve lesion resolution and localization.

  4. Two cases of neonatal adrenal hemorrhage presenting with persistent jaundice.

    PubMed

    Ruffini, E; De Petris, L; Zorzi, G; Paoletti, P; Mambelli, G; Carlucci, A

    2013-01-01

    The adrenal hemorrhage is a relatively rare event in newborns but must be considered in the presence of a persistent unexplained jaundice, especially in presence of predisposing factors. Serial ultrasonography is the modality of choice for initial diagnosis and follow-up of neonatal adrenal hemorrhage. We report two cases of neonatal adrenal hemorrhage presenting with persistent jaundice. The causes of the neonatal adrenal hemorrhages were a difficult vaginal delivery in macrosomic infant and a neonatal infection.

  5. Noncholinergic control of adrenal catecholamine secretion.

    PubMed Central

    Livett, B G; Marley, P D

    1993-01-01

    It has been known for over 70 years that adrenal catecholamine secretion can be modulated or elicited by noncholinergic neurotransmitters and hormones. However, our understanding of the cellular mechanisms by which these agents produce their effects and the physiological conditions under which they act are not well characterised. Here we briefly review the mechanisms by which one such agent (the neuropeptide substance P) modulates the cholinergic secretory response of adrenal chromaffin cells, and another agent (angiotensin II) elicits catecholamine secretion independently of the cholinergic innervation. PMID:7507911

  6. 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.

  7. [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.

  8. 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.

  9. Cystic Pheochromocytoma Presenting as Adrenal Cyst

    PubMed Central

    Abdulsalam, Mohammed Shafi; Satish, Priyanka; Janakiraman, Raghunath Keddy; Singh, Shivshankar

    2016-01-01

    Pheochromocytomas are usually solid tumours. But it can present as cystic lesions in the adrenal gland. Cystic lesions in adrenal gland with hypertension needs attention to rule out pheochromocytoma. If ignored, it may lead to hypertensive emergency, multisystem crisis and death. Early diagnosis with biochemistry, Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) of abdomen, proper functional imaging like Meta Iodo Benzyl Guanidine (MIBG) scan is essential. Proper preoperative preparation is important to prevent hypertensive crisis during and after surgery. We are reporting a case of cystic pheochromocytoma in a young male. PMID:28050427

  10. Steroid 21 hydroxylase deficiency congenital adrenal hyperplasia.

    PubMed

    Nimkarn, Saroj; Lin-Su, Karen; New, Maria I

    2011-10-01

    Steroid 21 hydroxylase deficiency is the most common form of congenital adrenal hyperplasia (CAH). The severity of this disorder depends on the extent of impaired enzymatic activity, which is caused by various mutations of the 21 hydroxylase gene. This article reviews adrenal steroidogenesis and the pathophysiology of 21 hydroxylase deficiency. The three forms of CAH are then discussed in terms of clinical presentation, diagnosis and treatment, and genetic basis. Prenatal diagnosis and treatment are also reviewed. The goal of therapy is to correct the deficiency in cortisol secretion and suppress androgen overproduction. Glucocorticoid replacement has been the mainstay of treatment for CAH, but new treatment strategies continue to be developed and studied.

  11. Cystic Pheochromocytoma Presenting as Adrenal Cyst.

    PubMed

    Abdulsalam, Mohammed Shafi; Ganapathy, Vijaya; Satish, Priyanka; Janakiraman, Raghunath Keddy; Singh, Shivshankar

    2016-11-01

    Pheochromocytomas are usually solid tumours. But it can present as cystic lesions in the adrenal gland. Cystic lesions in adrenal gland with hypertension needs attention to rule out pheochromocytoma. If ignored, it may lead to hypertensive emergency, multisystem crisis and death. Early diagnosis with biochemistry, Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) of abdomen, proper functional imaging like Meta Iodo Benzyl Guanidine (MIBG) scan is essential. Proper preoperative preparation is important to prevent hypertensive crisis during and after surgery. We are reporting a case of cystic pheochromocytoma in a young male.

  12. 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.

  13. Imaging of an adrenal cortical carcinoma and its skeletal metastasis

    SciTech Connect

    Drane, W.E.; Graham, M.M.; Nelp, W.B.

    1983-08-01

    Though the typical scintigraphic appearance in adrenal cortical carcinoma is bilateral nonvisualization of the adrenal glands, a case with simultaneous visualization of both an adrenal cortical carcinoma and its skeletal metastasis using 6-..beta..-(/sup 131/I)iodomethyl-19-norcholesterol is reported.

  14. Adrenal pseudotumors on CT due to dilated portosystemic veins

    SciTech Connect

    Mitty, H.M.; Cohen, B.A.; Sprayregen, S.; Schwartz, K.

    1983-10-01

    The adrenal and periadrenal venous systems are part of the portosystemic collateral pathways that may enlarge in portal hypertension. The cross-sectional image of the resulting enlarged venous channels may simulate an adrenal msss. Three examples of such computed tomographic (CT) scans are presented with selective venographic correlation. Patients with portal hypertension and suspected adrenal pathology may require enhanced or dynamic CT scans.

  15. Biopsy of the right adrenal gland by the transhepatic approach

    SciTech Connect

    Price, R.B.; Bernardino, M.E.; Berkman, W.A.; Sones, P.J. Jr.; Torres, W.E.

    1983-08-01

    A transhepatic computed-tomographic-guided biopsy of a right adrenal mass is described. This method is simpler to perform than the usual posterior biopsy carried out with the patient prone and is less likely to cause a complicating pneumothorax. In seven of eight patients with right adrenal masses, adrenal tissue was obtained and an accurate diagnosis was possible. No complications resulted.

  16. Ultrasonographic appearance of adrenal glands in healthy and sick cats.

    PubMed

    Combes, Anaïs; Pey, Pascaline; Paepe, Dominique; Rosenberg, Dan; Daminet, Sylvie; Putcuyps, Ingrid; Bedu, Anne-Sophie; Duchateau, Luc; de Fornel-Thibaud, Pauline; Benchekroun, Ghita; Saunders, Jimmy H

    2013-06-01

    The first part of the study aimed to describe prospectively the ultrasonographic features of the adrenal glands in 94 healthy cats and 51 chronically sick cats. It confirmed the feasibility of ultrasonography of adrenal glands in healthy and chronically sick cats, which were not statistically different. The typical hypoechoic appearance of the gland surrounded by hyperechoic fat made it recognisable. A sagittal plane of the gland, not in line with the aorta, may be necessary to obtain the largest adrenal measurements. The reference intervals of adrenal measurements were inferred from the values obtained in the healthy and chronically sick cats (mean ± 0.96 SD): adrenal length was 8.9-12.5 mm; cranial height was 3.0-4.8 mm; caudal height was 3.0-4.5 mm. The second part of the study consisted of a retrospective analysis of the ultrasonographic examination of the adrenal glands in cats with adrenal diseases (six had hyperaldosteronism and four had pituitary-dependent hyperadrenocorticism) and a descriptive comparison with the reference features obtained in the control groups from the prospective study. Cats with hyperaldosteronism presented with unilateral severely enlarged adrenal glands. However, a normal contralateral gland did not preclude a contralateral infiltration in benign or malignant adrenal neoplasms. The ultrasonographic appearance of the adrenal glands could not differentiate benign and malignant lesions. The ultrasonographic appearance of pituitary-dependent hyperadrenocorticism was mainly a symmetrical adrenal enlargement; however, a substantial number of cases were within the reference intervals of adrenal size.

  17. Imaging of an adrenal cortical carcinoma and its skeletal metastasis

    SciTech Connect

    Drane, W.E.; Graham, M.M.; Nelp, W.B.

    1983-08-01

    Though the typical scintigraphic appearance in adrenal cortical carcinoma is bilateral nonvisualization of the adrenal glands, we report a case with simultaneous visualization of both an adrenal cortical carcinoma and its skeletal metastasis using 6-beta-(/sup 131/I)iodomethyl-19-norcholesterol.

  18. Histopathology and immunohistochemistry of tissues outside central nervous system in bovine rabies.

    PubMed

    Abreu, Camila C; Nakayama, Priscilla A; Nogueira, Clayton I; Mesquita, Leonardo P; Lopes, Priscila F R; Wouters, Flademir; Varaschin, Mary S; Bezerra, Pedro S

    2014-08-01

    We performed a histopathological and immunohistochemical study of tissues outside the central nervous system in 48 cases of bovine rabies confirmed by direct immunofluorescence and/or immunohistochemistry (IHC) of the central nervous system. In the bovines of this study, mononuclear inflammation in all ganglia (trigeminal, spinal, stellate, and celiac) and adrenal medulla was observed. This injury also occurred in 85 % of neuro-pituitaries in 55 % of pars intermediate and 15 % of the pars distalis of pituitary evaluated. IHC was positive in 92.31 % of lumbar spinal ganglia, 90.9 % of trigeminal ganglia, stellate ganglia of 41.67 and 16.67 % of the celiac ganglia. One of the evaluated adrenal (1/17) showed strong immunohistochemical labeling in the cytoplasm of pheochromocytes. The pituitary IHC was positive in one case in the neurohypophysis (1/20) and in one case in the pars intermedia of the adenohypophysis (1/20). Data from this study indicate that in suspected cases of rabies, besides the complex pituitary rete mirabile and trigeminal ganglion, the evaluation of other ganglia, particularly the lumbar spinal, and adrenal may also contribute to the diagnosis and understanding of the clinical presentation and pathogenesis of the disease in bovines.

  19. 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

  20. A case of mixed medullary and follicular cell carcinoma of the thyroid.

    PubMed

    Ueki, Ikuko; Ando, Takao; Haraguchi, Ai; Horie, Ichiro; Imaizumi, Misa; Hayashi, Tomayoshi; Uga, Tatsuya; Usa, Toshiro; Kawakami, Atsushi

    2011-01-01

    A medullary thyroid carcinoma is a malignant tumor derived from the C-cells of the thyroid. Despite their distinct embryological origin, medullary thyroid carcinomas are exceptionally accompanied by a tumor derived from the follicular cells; this is defined as mixed medullary and follicular cell carcinoma. There have been controversies regarding the origin of this rare mixed thyroid carcinoma questioning whether or not a mixed carcinoma originates from a common cancer stem cell. We present a case of mixed medullary and follicular cell carcinoma in which two thyroid carcinomas were found intermingled in the thyroid as well as in the metastatic cervical lymph nodes. We examined the tumor by immunostaining with thyroglobulin, calcitonin, and thyroid transcription factor-1, and also reviewed the literature and discuss the origin of this rare mixed thyroid carcinoma.

  1. Peri-implant medullary cisternae at the interface of bone-smooth surface titanium endosseous implant.

    PubMed

    Ruggeri, A; Strocchi, R; Franchi, M; Martini, D; Raspanti, M; Congiu, T; Ruggeri, A

    1999-01-01

    A histological and ultrastructural study was carried out on the spongy bone response to smooth titanium oral implant surfaces. The samples obtained both from monkeys and from patients at various times from the implant insertion revealed that the bone-implant integration developed through different morphological aspects. The implant surface appeared in contact with medullary lacunae, as well as with osteoid tissue or directly with bone matrix. The complementary ultrastructural techniques employed have shown that the medullary lacunae appeared as wide and flattened cisternae delimited by a continuous single layer of flattened cells forming a thin lamina adhering to the implant and an endosteal lamina facing the bone surface. For their position and flattened shape we named them peri-implant medullary cisternae. The presence of blood vessels, reticular cells and myeloid cells in their lumen suggested that these peri-implant medullary cisternae were functional sites of new bone formation.

  2. The medullary pyramid index: an objective assessment of prominence in renal transplant rejection.

    PubMed

    Fried, A M; Woodring, J H; Loh, F K; Lucas, B A; Kryscio, R J

    1983-12-01

    Prominence of the medullary pyramids at sonography has been considered a sign of renal transplant rejection. A search of the literature reveals no previously published objective assessment of this phenomenon. Medullary pyramids of 67 normal kidneys, 53 nonrejecting transplanted kidneys, and 71 transplanted kidneys in rejection were measured. The area of the pyramid was related to the thickness of the overlying renal cortex by a "medullary pyramid index" (MPI): MPI (formula; see text) The median MPI was 4.17 for normal kidneys, 6.0 for nonrejecting transplanted kidneys, and 7.50 for transplanted kidneys in rejection. The results are significantly different (P = 0.0001) for all possible pairs. Overlap between rejection and nonrejection distributions is, however, considerable, rendering the discriminatory value of an individual observation quite low (0.69). Prominence of the medullary pyramids is therefore of very limited predictive value in the determination of transplant rejection in an individual patient.

  3. [An expert system for differential diagnosis of medullary and oxyphilic cell thyroid carcinoma].

    PubMed

    Kirillov, V A; Emel'ianova, O A; Gladyshev, A O

    2014-01-01

    To reveal the quantitative regularities of pathological changes in the nuclei and aggregates of C and B cells and to build an expert system on their basis for the differential diagnosis of medullary and oxyphilic cell thyroid carcinoma. Puncture smears with histologically verified medullary (C cell) carcinoma and oxyphilic cell (B cell) carcinoma were investigated. The nuclei and aggregates of C cells and B cells (Hürthle cells, oncocytes) were morphometrically examined with a computer color image analyzer on the basis of a light microscope and a digital photo camera. The quantitative regularities of the degree of C and B cell aggregation in medullary and oxyphilic cell thyroid carcinoma were found by morphometry. The threshold values for the aggregates in the comparison groups and their weight coefficients formed the basis for the expert system to differentially diagnose medullary and oxyphilic cell carcinoma at the initial stages of patient examination. The clinical trials showed the high efficiency of the developed expert system.

  4. Kidney Involvement in Systemic Calcitonin Amyloidosis Associated With Medullary Thyroid Carcinoma.

    PubMed

    Koopman, Timco; Niedlich-den Herder, Cindy; Stegeman, Coen A; Links, Thera P; Bijzet, Johan; Hazenberg, Bouke P C; Diepstra, Arjan

    2017-04-01

    A 52-year-old woman with widely disseminated medullary thyroid carcinoma developed nephrotic syndrome and slowly decreasing kidney function. A kidney biopsy was performed to differentiate between malignancy-associated membranous glomerulopathy and tyrosine kinase inhibitor-induced focal segmental glomerulosclerosis. Surprisingly, the biopsy specimen revealed diffuse glomerular deposition of amyloid that was proved to be derived from the calcitonin hormone (Acal), produced by the medullary thyroid carcinoma. This amyloid was also present in an abdominal fat pad biopsy. Although local ACal deposition is a characteristic feature of medullary thyroid carcinoma, the systemic amyloidosis involving the kidney that is presented in this case report has not to our knowledge been described previously and may be the result of long-term high plasma calcitonin levels. Our case illustrates that systemic calcitonin amyloidosis should be considered in the differential diagnosis of proteinuria in patients with medullary thyroid carcinoma.

  5. Fenestration of the superior medullary velum as treatment for a trapped fourth ventricle: a feasibility study.

    PubMed

    Tubbs, R Shane; Wellons, John C; Salter, George; Oakes, W Jerry

    2004-03-01

    We developed a novel approach for fenestration of the trapped fourth ventricle utilizing the superior medullary velum (valve of Vieussens). Trapped fourth ventricles, which are seen often in the pediatric hydrocephalic population, are troublesome entities surgically. A right burr hole was carried out in 10 adult cadavers with no gross intracranial pathology and the superior medullary velum was fenestrated to the quadrigeminal cistern with the aid of an endoscope. This technique was carried out easily in all cadaveric specimens. With endoscopy, no vascular insult was appreciated either before or after fenestration of the superior medullary velum. These preliminary findings demonstrate that fenestration of the superior medullary velum may provide a good alternative to the present therapy of shunting trapped fourth ventricles, a therapy wrought with complications.

  6. Total lymphoid irradiation leads to transient depletion of the mouse thymic medulla and persistent abnormalities among medullary stromal cells

    SciTech Connect

    Adkins, B.; Gandour, D.; Strober, S.; Weissman, I.

    1988-05-15

    Mice given multiple doses of sublethal irradiation to both the thymus and the peripheral lymphoid tissues showed major transient, and some persistent disruptions in general thymic architecture and in thymic stromal components. At 2 wk after total lymphoid irradiation (TLI), the thymus lacked identifiable medullary regions by immunohistochemical analyses. Medullary stromal cells expression MHC Ag or a medullary epithelial cell Ag, as well as medullary macrophages, were undetectable. Instead, the processes of cortical epithelial cells were observed throughout the entire thymus. Strikingly, thymocyte subsets with mature phenotypes (CD4+CD8- and CD4-CD8+) were present in the apparent absence of a medulla. This early, gross effect was rapidly reversed such that by 1 to 2 mo after TLI, medullary areas with MHC Ag-positive cells were evident. However, abnormalities in a subset of medullary stromal cells appeared to be more persistent. Medullary epithelial cells, identified by the MD1 mAb, were greatly reduced in number and abnormally organized for at least 4 mo after TLI. In addition, macrophages containing endogenous peroxidase activity, normally abundant in medullary regions, were undetectable at all times examined after TLI. Therefore, this irradiation regimen induced both transient and long term effects in the thymus, primarily in medullary regions. These results suggest that TLI may be used as an experimental tool for studying the impact of selective depletion of medullary stromal cells on the development of specific T cell functions.

  7. Bilateral adrenal myelolipoma in Cushing's disease: a relook into the role of corticotropin in adrenal tumourigenesis.

    PubMed

    Chakraborty, Partha Pratim; Bhattacharjee, Rana; Mukhopadhyay, Pradip; Chowdhury, Subhankar

    2016-06-15

    Adrenal myelolipomas are infrequently encountered benign tumours of unknown aetiology. In the majority of cases they are unilateral, and clinically and hormonally silent, only requiring periodic follow-up. However, bilateral adrenal myelolipomas are sometimes associated with endocrine disorders and warrant appropriate evaluation. Though the understanding of the pathophysiology of adrenal myelolipomas has long been elusive, adrenocorticotropic hormone (ACTH) has been proposed as the main tropic factor in a number of studies. Cushing's disease is rarely associated with bilateral and sometimes giant myelolipomas. In this article, the association of bilateral adrenal myelolipomas with Cushing's disease has been discussed and the role of ACTH in the tumourigenesis has been reviewed. 2016 BMJ Publishing Group Ltd.

  8. Medullary thyroid carcinoma metastatic to the pituitary gland: an unusual site of metastasis.

    PubMed

    Williams, Michelle D; Asa, Sylvia L; Fuller, Gregory N

    2008-06-01

    We present a case of metastatic medullary thyroid carcinoma involving the pituitary gland of a 23-year-old woman with multiple endocrine neoplasia type 2b who presented with diabetes insipidus and visual loss. The diagnostic features, including cytomorphology and immunohistochemistry, used to differentiate pituitary adenoma from metastatic medullary carcinoma are discussed. Pituitary metastases and tumor-to-tumor metastases in this region are also highlighted.

  9. Anatomy of the clavicle and its medullary canal: a computed tomography study.

    PubMed

    King, P R; Scheepers, S; Ikram, A

    2014-01-01

    With recent literature indicating certain clavicle shaft fracture types are best treated surgically, there is renewed interest in the anatomy of the clavicle. Intramedullary fixation of clavicle fractures requires an adequate medullary canal to accommodate the fixation device used. This computed tomography anatomical study of the clavicle and its medullary canal describes its general anatomy and determines the suitability of its medullary canal to intramedullary fixation. Four hundred and eighteen clavicles in 209 patients were examined using computed tomography imaging. The length and curvatures as well as the height and width of the clavicle and its canal at various predetermined points were measured. The start and end of the medullary canal from the sternal and acromial ends of the clavicle were determined. The data was grouped according to age, gender and lateralization. The average length of the clavicle was 151.15 mm with the average sternal and acromial curvature being 146° and 133°, respectively. The medullary canal starts on average 6.59 mm from the sternal end and ends 19.56 mm from the acromial end with the average height and width of the canal at the middle third being 5.61 and 6.63 mm, respectively. The medullary canal of the clavicle is large enough to accommodate commonly used intramedullary devices in the majority of cases. The medullary canal extends far enough medially and laterally for an intramedullary device to adequately bridge most middle third clavicle fractures. An alternative surgical option should be available in theatre when treating females as the medullary canal is too small to pass an intramedullary device past the fracture site on rare occasions.

  10. Renal medullary and urinary oxygen tension during cardiopulmonary bypass in the rat.

    PubMed

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

    2017-09-01

    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 P$_{\\rm O2}$, which is an indicator of renal hypoxia, is predicted near the thick ascending limbs. Interstitial tissue P$_{\\rm O2}$ exhibits a general decrease along the inner medullary axis, but urine P$_{\\rm O2}$ increases significantly along the ureter. Thus, bladder urinary P$_{\\rm O2}$ is predicted to be substantially higher than medullary P$_{\\rm O2}$. 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. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  11. Failure of pentagastrin-stimulated calcitonin testing in early manifestation of familial medullary thyroid cancer.

    PubMed

    Pirich, Christian; Rendl, Gundula; Hauser-Kronberger, Cornelia; Häusler, Ingrid

    2012-10-01

    This case report describes three generations of a family with familial medullary thyroid cancer (RET gene mutation L790F). One of the three siblings-all of them carrier of the respective mutation-exhibited the absence of pathological basal and pentagastrin-stimulated calcitonin levels in spite of multifocal medullary thyroid microcancer. This case illustrates the challenge to consider the biological diversity of RET gene mutations in the clinical management of affected gene carriers.

  12. [Autograft of the adrenal medulla to caudate nucleus as Parkinson disease treatment: long-term clinical evaluation].

    PubMed

    Madrazo, I; Franco-Bourland, R; Ostrosky-Solis, F; Aguilera Riestra, M C; Madrazo, M; Zarate, A

    1989-01-01

    This work presents the long-term evolution (12-27 months) of the patients with adrenomedullary autotransplants to the caudate nucleus for the treatment of Parkinson's disease. Sixteen men and 6 women, mean age of 49.9 years, received brain implants of their own adrenal medulla using the procedure of Madrazo et al. (1). Nineteen of the transplanted patients suffered idiopathic Parkinson's disease and 3 of them parkinsonism. Before surgery 20 patients were on L-dopa and suffered collateral signs due to the drug. The degree of severity of their disease was evaluated pre and postoperatively, with and without medication, in their "on" and "off" periods, using the international scales of Schwab and England, Hoehn and Yahr, Madrazo, and the UPRS, and was documented by videotape. Biochemical analyses were made of lumbar and ventricular cerebrospinal fluid, and neuropsychological and neurophysiological evaluations were performed before and after surgery. In some patients, the location and viability of the adrenal medullary implants were demonstrated by brain scintigraphy using 131-I-metaiodobenzylguanidine, a chromaffin specific radiopharmaceutical. The clinical evaluations of 18 autotransplanted patients (4 died) showed their significant functional recovery both in their "on" and "off" periods, that for the first patients operated has remained stable for 27 months. Also, their response to L-dopa improved allowing the reduction of their postoperative doses of medication to 30% of their preoperative requirements, with the disappearance of the collateral effects of the drug.

  13. Recovery of Adrenal Function in Patients with Glucocorticoids Induced Secondary Adrenal Insufficiency

    PubMed Central

    Baek, Jong Ha; Kim, Soo Kyoung; Jung, Jung Hwa; Hahm, Jong Ryeal

    2016-01-01

    Background The chronic use of glucocorticoids (GC) suppresses function of the hypothalamic-pituitary-adrenal axis and often results in secondary adrenal insufficiency (AI). The present study aimed to determine the recovery rate of adrenal function in patients with secondary AI within 1 to 2 years and to assess the factors predictive of adrenal function recovery. Methods This was a retrospective observational study that enrolled patients diagnosed with GC-induced secondary AI between 2007 and 2013. AI was defined by peak serum cortisol levels <18 µg/dL during a standard-dose short synacthen test (SST). A follow-up SST was performed after 1 to 2 years, and responders were defined as those with adrenocorticotropic hormone (ACTH)-stimulated peak serum cortisol levels ≥18 µg/dL. Results Of the total 34 patients diagnosed with GC-induced secondary AI at first, 20 patients (58.8%) recovered normal adrenal function by the time of the follow-up SST (median follow-up period, 16.5 months). Although the baseline serum ACTH and cortisol levels at the first SST did not differ between responders and non-responders, the incremental cortisol response during the first SST was higher in responders than that of non-responders (7.88 vs. 3.56, P<0.01). Additionally, higher cortisol increments during the first SST were an independent predictive factor of the adrenal function recovery (odds ratio, 1.58; 95% confidence interval, 1.02 to 2.46; P<0.05). Conclusion In the present study, adrenal function recovery was achieved frequently in patients with GC-induced secondary AI within 1 to 2 years. Additionally, an incremental cortisol response at the first SST may be an important predictive factor of adrenal function recovery. PMID:26676337

  14. Decreased GABAA receptor binding in the medullary serotonergic system in the sudden infant death syndrome.

    PubMed

    Broadbelt, Kevin G; Paterson, David S; Belliveau, Richard A; Trachtenberg, Felicia L; Haas, Elisabeth A; Stanley, Christina; Krous, Henry F; Kinney, Hannah C

    2011-09-01

    γ-Aminobutyric acid (GABA) neurons in the medulla oblongata help regulate homeostasis, in part through interactions with the medullary serotonergic (5-HT) system. Previously, we reported abnormalities in multiple 5-HT markers in the medullary 5-HT system of infants dying from sudden infant death syndrome (SIDS), suggesting that 5-HT dysfunction is involved in its pathogenesis. Here, we tested the hypothesis that markers of GABAA receptors are decreased in the medullary 5-HT system in SIDS cases compared with controls. Using tissue receptor autoradiography with the radioligand H-GABA, we found 25% to 52% reductions in GABAA receptor binding density in 7 of 10 key nuclei sampled of the medullary 5-HT system in the SIDS cases (postconceptional age [PCA] = 51.7 ± 8.3, n = 28) versus age-adjusted controls (PCA = 55.3 ± 13.5, n = 8) (p ≤ 0.04). By Western blotting, there was 46.2% reduction in GABAAα3 subunit levels in the gigantocellularis (component of the medullary 5-HT system) of SIDS cases (PCA = 53.9 ± 8.4, n = 24) versus controls (PCA = 55.3 ± 8.3, n = 8) (56.8% standard in SIDS cases vs 99.35% in controls; p = 0.026). These data suggest that medullary GABAA receptors are abnormal in SIDS infants and that SIDS is a complex disorder of a homeostatic network in the medulla that involves deficits of the GABAergic and 5-HT systems.

  15. 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.

  16. Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

    PubMed Central

    Abe, Michiaki; Mori, Takefumi; O'Connor, Paul M.; Ohsaki, Yusuke; Zheleznova, Nadezhda N.

    2014-01-01

    The physiological evidence linking the production of superoxide, hydrogen peroxide, and nitric oxide in the renal medullary thick ascending limb of Henle (mTAL) to regulation of medullary blood flow, sodium homeostasis, and long-term control of blood pressure is summarized in this review. Data obtained largely from rats indicate that experimentally induced elevations of either superoxide or hydrogen peroxide in the renal medulla result in reduction of medullary blood flow, enhanced Na+ reabsorption, and hypertension. A shift in the redox balance between nitric oxide and reactive oxygen species (ROS) is found to occur naturally in the Dahl salt-sensitive (SS) rat model, where selective reduction of ROS production in the renal medulla reduces salt-induced hypertension. Excess medullary production of ROS in SS rats emanates from the medullary thick ascending limbs of Henle [from both the mitochondria and membrane NAD(P)H oxidases] in response to increased delivery and reabsorption of excess sodium and water. There is evidence that ROS and perhaps other mediators such as ATP diffuse from the mTAL to surrounding vasa recta capillaries, resulting in medullary ischemia, which thereby contributes to hypertension. PMID:25354941

  17. Two-dimensional Fourier analysis of the spongy medullary keratin of structurally coloured feather barbs

    PubMed Central

    Prum, R. O.; Torres, R.; Williamson, S.; Dyck, J.

    1999-01-01

    We conducted two-dimensional (2D) discrete Fourier analyses of the spatial variation in refractive index of the spongy medullary keratin from four different colours of structurally coloured feather barbs from three species of bird: the rose-faced lovebird, Agapornis roseicollis (Psittacidae), the budgerigar, Melopsittacus undulatus (Psittacidae), and the Gouldian finch, Poephila guttata (Estrildidae). These results indicate that the spongy medullary keratin is a nanostructured tissue that functions as an array of coherent scatterers. The nanostructure of the medullary keratin is nearly uniform in all directions. The largest Fourier components of spatial variation in refractive index in the tissue are of the appropriate size to produce the observed colours by constructive interference alone. The peaks of the predicted reflectance spectra calculated from the 2D Fourier power spectra are congruent with the reflectance spectra measured by using microspectrophotometry. The alternative physical models for the production of these colours, the Rayleigh and Mie theories, hypothesize that medullary keratin is an incoherent array and that scattered waves are independent in phase. This assumption is falsified by the ring-like Fourier power spectra of these feathers, and the spacing of the scattering air vacuoles in the medullary keratin. Structural colours of avian feather barbs are produced by constructive interference of coherently scattered light waves from the optically heterogeneous matrix of keratin and air in the spongy medullary layer.

  18. Liver X receptors regulate adrenal cholesterol balance

    PubMed Central

    Cummins, Carolyn L.; Volle, David H.; Zhang, Yuan; McDonald, Jeffrey G.; Sion, Benoît; Lefrançois-Martinez, Anne-Marie; Caira, Françoise; Veyssière, Georges; Mangelsdorf, David J.; Lobaccaro, Jean-Marc A.

    2006-01-01

    Cholesterol is the obligate precursor to adrenal steroids but is cytotoxic at high concentrations. Here, we show the role of the liver X receptors (LXRα and LXRβ) in preventing accumulation of free cholesterol in mouse adrenal glands by controlling expression of genes involved in all aspects of cholesterol utilization, including the steroidogenic acute regulatory protein, StAR, a novel LXR target. Under chronic dietary stress, adrenal glands from Lxrαβ–/– mice accumulated free cholesterol. In contrast, wild-type animals maintained cholesterol homeostasis through basal expression of genes involved in cholesterol efflux and storage (ABC transporter A1 [ABCA1], apoE, SREBP-1c) while preventing steroidogenic gene (StAR) expression. Upon treatment with an LXR agonist that mimics activation by oxysterols, expression of these target genes was increased. Basally, Lxrαβ–/– mice exhibited a marked decrease in ABCA1 and a derepression of StAR expression, causing a net decrease in cholesterol efflux and an increase in steroidogenesis. These changes occurred under conditions that prevented the acute stress response and resulted in a phenotype more specific to the loss of LXRα, including hypercorticosteronemia, cholesterol ester accumulation, and adrenomegaly. These results imply LXRα provides a safety valve to limit free cholesterol levels as a basal protective mechanism in the adrenal gland, where cholesterol is under constant flux. PMID:16823488

  19. Giant cavernous hemangioma of the adrenal gland

    PubMed Central

    Quildrian, Sergio Damián; Silberman, Ezequiel Aníbal; Vigovich, Felix Alberto; Porto, Eduardo Agustín

    2012-01-01

    INTRODUCTION Cavernous hemangioma of the adrenal gland is a rare non-functioning benign neoplasm. PRESENTATION OF CASE A 62-year-old woman with chronic obstructive pulmonary disease was diagnosed as having an incidental non-functioning adrenal tumor. Because of the impossibility of ruling out the presence of malignancy, conventional surgical resection was carried out. The histopathology revealed a 12.5 cm × 11.5 cm × 8 cm adrenal mass with large and lacunae vascular spaces lined with mature endothelial cells. These findings were compatible with cavernous hemangioma. DISCUSSION The majority of patients in the literature underwent surgical resection due to the impossibility of excluding malignancy, because of related symptoms in patients with large masses, or because of the risk of spontaneous tumoral rupture. CONCLUSION These tumors are quite infrequent. Due to the low frequency and the lack of specific symptoms, most adrenal hemangiomas are diagnosed postoperatively. PMID:23287064

  20. Imaging features of benign adrenal cysts.

    PubMed

    Sanal, Hatice Tuba; Kocaoglu, Murat; Yildirim, Duzgun; Bulakbasi, Nail; Guvenc, Inanc; Tayfun, Cem; Ucoz, Taner

    2006-12-01

    Benign adrenal gland cysts (BACs) are rare lesions with a variable histological spectrum and may mimic not only each other but also malignant ones. We aimed to review imaging features of BACs which can be helpful in distinguishing each entity and determining the subsequent appropriate management.

  1. Korsakoff's Syndrome Associated with Adrenal Virilism

    PubMed Central

    Cookson, B. A.

    1964-01-01

    Korsakoff's syndrome of obscure etiology was observed in a 34-year-old single woman with an 11-year history of hirsutism and mood swings, and previous hospitalizations for mania three years ago and depression 11 years ago. Recently the virilism had intensified with increased muscularity and coarsening of facial features. The 24-hour urinary 17-ketosteroids ranged between 14.4 mg. and 21.5 mg. and were suppressed by dexamethasone. The 17-hydroxycorticosteroid excretion was normal. These and other findings suggested a diagnosis of adrenal virilism due to adrenocortical hyperplasia. In the absence of other discernible causes it appeared that the adrenal pathology was responsible for the Korsakoff's syndrome. Both conditions responded well to glucocorticoid therapy although low doses were necessary to avoid mania. It is speculated that the encephalopathy was due to an associated adrenal insufficiency. Although hypoadrenalism is accepted as a complication of only the infant form of adrenal virilism, it is noteworthy that this patient had pathological pigmentation of her skin. PMID:14158554

  2. CT manifestations of adrenal trauma: experience with 73 cases.

    PubMed

    Sinelnikov, Alex O; Abujudeh, Hani H; Chan, David; Novelline, Robert A

    2007-03-01

    Adrenal injuries, although an uncommon consequence of abdominal trauma, are important to recognize. If bilateral, adrenal trauma could result in life-threatening adrenal insufficiency. Furthermore, in the setting of trauma, adrenal injury can point to other concomitant injuries and has been associated with overall increased morbidity and mortality. In the past, before the advent of computed tomography (CT), detection was difficult, and the diagnosis was often made only at surgery or postmortem. Today, the diagnosis of adrenal injuries can be quickly and accurately made with CT. This retrospective review was carried out to identify, describe, and analyze different CT appearances of adrenal injuries and correlated with associated injuries and observed clinical context and outcomes. A patient cohort of CT-detected adrenal injuries was identified through a radiology software research tool by searching for keywords in radiology reports. The identified CT scans were reviewed and correlated with the patients' available clinical chart data and follow-up. Between April 1995 and October 2004, 73 cases of CT-detected adrenal injuries were identified, including 48 men and 25 women, with an age range 6 to 90 years and a mean age of 42.7 years. Of the cases, 77% were right-sided, 15% were left-sided, and 8% were bilateral. The causes of injuries were motor vehicle collisions (75%), falls (14%), sports related (4%), and miscellaneous causes (7%). Associated trauma included injuries of the liver (43%), spleen (23%), lung (19%), and kidney (18%), as well as pneumothoraces/hemothoraces (22%). Skeletal injuries included fractures of the ribs, clavicles, and/or scapulae (39%), pelvis and hips (30%), and the spine (23%). Isolated adrenal trauma was seen in only 4% of the cases. The CT findings of adrenal trauma were focal hematoma (30%), indistinct (27%) or enlarged (18%) adrenal gland, gross (15%) or focal (7%) adrenal hemorrhage, and adrenal mass (11%). Associated CT findings

  3. Adrenal venous sampling using Dyna-CT--a practical guide.

    PubMed

    Plank, Christina; Wolf, Florian; Langenberger, Herbert; Loewe, Christian; Schoder, Maria; Lammer, Johannes

    2012-09-01

    Primary hyperaldosteronism due to aldosterone secreting adrenal adenomas is an important and potentially curable cause for hypertension. The differentiation between unilateral or bilateral adrenal adenomas is crucial, as unilateral adenomas can easily be cured by surgery whereas bilateral adenomas have to be treated conservatively. Exact diagnosis can be made when unilateral or bilateral hormone production is proven with adrenal vein sampling. We present an effective step-by-step technique how to perform an adrenal vein sampling with a special emphasis on how to reliably catheterize the right adrenal vein using Dyna CT.

  4. 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.

  5. Delay in Diagnosis of Adrenal Insufficiency Is a Frequent Cause of Adrenal Crisis

    PubMed Central

    Rabijewski, Michał

    2013-01-01

    Delay of diagnosis of primary adrenal insufficiency (PAI) leads to adrenal crisis which is potentially lethal complication. The objective of our work was an assessment whether the establishment of diagnosis of adrenocortical insufficiency in Poland is so much delayed as assessed in the past. We have analysed data from 60 patients with diagnosis of PAI established in our department during the past 12 years and who are still under our care. We found that the time to diagnosis of primary adrenal insufficiency in Poland exceeds 3 months in every patient and 6 months in patients admitted with symptoms of adrenal crisis. Forty-four percent of patients were diagnosed only just after the hospitalisation due to crisis, despite the evident signs and symptoms of PAI. Lack of appetite and loss of body weight occurred in all patients and for that reason a diagnosis of chronic gastric and duodenal ulcer disease was the most often incorrect diagnosis. After the proper diagnosis and treatment, in the course of 1–11 years of observation, there was only 6 imminent adrenal crises in 5 patients. Our results indicated that training of primary care physicians in the field of recognising and treatment of adrenal insufficiency is still essential. PMID:23864857

  6. Human adrenal chromaffin cell calcium channels: drastic current facilitation in cell clusters, but not in isolated cells.

    PubMed

    Gandía, L; Mayorgas, I; Michelena, P; Cuchillo, I; de Pascual, R; Abad, F; Novalbos, J M; Larrañaga, E; García, A G

    1998-10-01

    Human adrenal medullary chromaffin cells were prepared and cultured from a cystic tumoral adrenal gland whose medullary tissue was unaffected. Adrenaline-containing and noradrenaline-containing cells were identified using a confocal fluorescence microscope and antibodies against dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). Current/voltage (I/V) curves performed with the voltage-clamped cells bathed in 10 mM Ba2+ (holding potential, Vh=-80 mV) revealed the presence of only high-threshold voltage-dependent Ca2+ channels; T-type Ca2+ channels were not seen. By using supramaximal concentrations of selective Ca2+ channel blockers, the whole-cell IBa could be fractionated into various subcomponents. Thus, IBa had a 25% fraction sensitive to 1 microM nifedipine (L-type channels), 21% sensitive to 1 microM omega-conotoxin GVIA (N-type channels), and 60% sensitive to 2 microM omega-agatoxin IVA (P/Q-type channels). The activation of IBa was considerably slowed down, and the peak current was inhibited upon superfusion with 10 microM ATP. The slow activation and peak current blockade were reversed by strong depolarizing pre-pulses to +100 mV (facilitation). A drastic facilitation of IBa was also observed in voltage-clamped human chromaffin cell surrounded by other unclamped cells; in contrast, in voltage-clamped cells not immersed in a cell cluster, facilitation was scarce. So, facilitation of Ca2+ channels in a voltage-clamped cell seems to depend upon the exocytotic activity of neighbouring unclamped cells, which is markedly increased by Ba2+. It is concluded that human adrenal chromaffin cells mostly express P/Q-types of voltage-dependent Ca2+ channels (60%). L-Type channels and N-type channels are also expressed, but to a considerably minor extent (around 20% each). This dominance of P/Q-type channels in human chromaffin cells clearly contrasts with the relative proportion of each channel type expressed by chromaffin cells of five

  7. Endosonography of the adrenal glands: normal size--pathological findings.

    PubMed

    Kann, P; Hengstermann, C; Heussel, C P; Bittinger, F; Engelbach, M; Beyer, J

    1998-01-01

    Transabdominal sonography of the adrenal glands frequently is non-successful. It was the aim of this project to improve the imaging of the adrenal glands using high resolution sonography in order to obtain information about even small changes in these organs. Therefore, endosonographic imaging was investigated using an endosonoscope PENTAX FG32UA. The correct identification of the adrenal glands was examined in five human cadavers. A total of 58 patients with 113 adrenal glands (in 3 cases history of unilateral adrenalectomy) were investigated. 109 adrenal glands (97%) were identified and evaluated. Healthy adrenal glands are slightly hyperechoich and regarding their echogeneity comparable to other endocrine organs such as the testes or the thyroid. Adrenal size can be determined as largest cross sectional area and was found to be 216 +/- 93 mm2 right and 231 +/- 98 mm2 left. In the adrenal glands which could be imaged by endosonography, all findings detected by CT (n = 33) or MRI (n = 19) could also be demonstrated endosonographically. Additional information as compared to CT/MRI was obtained in 7 out of 33 and in 6 out of 19 patients. This concerns in particular differentiation between tumor and hyperplasia and detection of small adrenal adenomas. High resolution endosonography of the adrenal glands can provide information about adrenal gland morphology which cannot be obtained by any other diagnostic approach.

  8. Adrenal myelolipoma: Controversies in its management

    PubMed Central

    Shenoy, Vasanth G.; Thota, Anuroop; Shankar, Ravi; Desai, Mallikarjun G.

    2015-01-01

    Adrenal myelolipomas (AMLs) are rare, benign neoplasms of the adrenal gland with varied clinical presentations. The rarity of these tumors precludes any case-controlled or randomized study into their management. The available literature is limited to case reports and short series from referral centers. This review is an effort to put the available literature into perspective such that clinical decision making can be done with some clarity. The PubMed and Cochrane databases were searched with key words Adrenal Myelolipoma, Adrenal Incidentaloma (AI) and Adrenal Collision Tumor (ACT). From over 1300 search results, 547 relevant publications dating from 1954 to 2014 were reviewed. Details of about 1231 AMLs in the indexed literature were analyzed. Increasing usage of imaging studies has significantly increased the discovery of AMLs. Although AMLs are benign tumors, those measuring larger than 6 cm are prone to rupture and hemorrhage. Thorough endocrine work-up may benefit a selected group of patients, especially those who are hypertensive, diabetic/pre-diabetic, young patients (<50 years) and those with bilateral AML. Regular observation is needed for AML patients who are being treated non-operatively, as many of them may require surgery during follow-up. Although the AACE/AAES guidelines for AI (2009) exclude AML from mandatory metabolic work-up for a newly discovered AI, we feel that a significant number of patients with AML would benefit from metabolic work-up. In the literature, endocrine dysfunction in AML is 7% as compared with 11% in AI. Endocrine dysfunction in AML is probably underdiagnosed. PMID:25878407

  9. Laparoscope resection of ectopic corticosteroid-secreting adrenal adenoma.

    PubMed

    Wang, Xian-Ling; Dou, Jing-Tao; Gao, Jiang-Ping; Zhong, Wen-Wen; Jin, Du; Hui, Lüzhao; Lu, Ju-Ming; Mu, Yi-Ming

    2012-01-01

    Tumors originating from ectopic adrenal tissue are relatively rare. In this article, we describe a case with Cushing's syndrome caused by an ectopic adrenal adenoma. A 38 year-old male patient presenting with cushingoid appearance for 2 years was diagnosed to have ACTH-independent Cushing's syndrome based on endocrinological evaluation. Mutiple radiological examinations detected bilateral adrenal atrophy. When the images were investigated in a more expanded scope, a 3.0×3.5×5.3 cm mass was detected in the anterior of left renal hilum and left renal vein. The mass was successfully resected with intraoperative endoscopy and pathological evaluation revealed an ectopic adrenal tumor. It is suggested that when the endocrinlogically confirmed adrenal neoplasm could not be well and definitely localized, the possibility of ectopic adrenal should be presumed and further radiography examinations should extend to the field where ectopic adrenal usually presents.

  10. Histoplasmosis of the adrenal glands studied by CT

    SciTech Connect

    Wilson, D.A.; Muchmore, H.G.; Tisdal, R.G.; Fahmy, A.; Pitha, J.V.

    1984-03-01

    Computed tomography (CT) of the adrenal glands was performed on seven patients who had histologically proved disseminated histoplasmosis. All seven patients showed some degree of adrenal gland abnormality. The range of CT findings included minimal enlargement with faint flecks of calcium, moderate enlargement with focal low attenuation nodules, and massive enlargement with large areas of necrosis or dense calcification. The changes in each patient were bilateral and symmetrical. Adrenal gland shape was usually preserved. Finding of percutaneous adrenal biopsy, which was performed under CT guidance, made the diagnosis in one patient. Five of seven patients had adrenal insufficiency. It is concluded that the diagnosis of disseminated histoplasmosis should be considered in any patient who has bilateral adrenal gland enlargement and who resides in an endemic area, especially if there is evidence of adrenal insufficiency.

  11. Three uncommon adrenal incidentalomas: a 13-year surgical pathology review

    PubMed Central

    2012-01-01

    Background The discovery of adrenal incidentalomas due to the widespread use of sophisticated abdominal imaging techniques has resulted in an increasing trend of adrenal gland specimens being received in the pathology laboratory. In this context, we encountered three uncommon adrenal incidentalomas. The aim of this manuscript is to report in detail the three index cases of adrenal incidentalomas in the context of a 13-year retrospective surgical pathology review. Methods The three index cases were investigated and analyzed in detail with relevant review of the English literature as available in PubMed and Medline. A 13-year retrospective computer-based histopathological surgical review was conducted in our laboratory and the results were analyzed in the context of evidence-based literature on adrenal incidentalomas. Results A total of 94 adrenal specimens from incidentalomas were identified, accounting for 0.025% of all surgical pathology cases. In all 76.6% were benign and 23.4% were malignant. A total of 53 females (56.4%) and 41 males (43.6%) aged 4 to 85 years were identified. The benign lesions included cortical adenoma (43.1%), pheochromocytoma (29.3%) and inflammation/fibrosis/hemorrhage (8.3%). Metastatic neoplasms were the most common malignant lesions (50%) followed by primary adrenocortical carcinomas (31.8%) and neuroblastoma (13.6%). These cases were discovered as adrenal incidentalomas that led to surgical exploration. The three index cases of adrenal incidentalomas with unusual pathologies were encountered that included (a) adrenal ganglioneuroma, (b) periadrenal schwannoma and (c) primary adrenal pleomorphic leiomyosarcoma. These cases are discussed, with a literature and clinicopathological review. Conclusions Adrenal lesions are uncommon surgical specimens in the pathology laboratory. However, higher detection rates of adrenal incidentalomas aided by the ease of laparoscopic adrenalectomy has resulted in increased adrenal surgical specimens

  12. Sectional anatomy of the adrenal gland in the coronal plane.

    PubMed

    Ma, Gang; Liu, Shu Wei; Zhao, Zhen Mei; Lin, Xiang Tao; Lou, Li; Li, Zhen Ping; Tang, Yu Chun; Zhong, Shi Zhen

    2008-05-01

    To provide practical anatomic data for the imaging diagnosis and surgical treatment of adrenal disease, we investigated the anatomy of the adrenal gland and its relationships to regional structures using 31 sets of serial coronal sections of upper abdomen of Chinese adult cadavers and correlated coronal magnetic resonance (MR) images of ten upper abdomens of adult healthy volunteers and coronal reconstructed multislice spiral computed tomography (MSCT) images of five patients without lesions in the adrenal gland. The adrenal glands were visualized mainly on the successive coronal sections between 18 mm anterior to the posterior margin of inferior vena cava and 24 mm posterior to the posterior margin of inferior vena cava. In general, the left adrenal gland was visualized two sections earlier than the right adrenal gland. On the plane through the anterior parts of bilateral renal hili (A18), the appearance rate of bilateral adrenal glands was 100%, and the maximal measurements of bilateral adrenal glands were visualized. The length, width, thickness of right adrenal body, thickness of medial limb and lateral limb were, respectively, 34.02 +/- 2.12 mm, 10.91 +/- 0.89 mm, 5.82 +/- 0.26 mm, 2.78 +/- 0.08 mm, 2.62 +/- 0.06 mm, whereas the measurements of left adrenal gland were 28.31 +/- 2.46 mm, 18.40 +/- 1.06 mm, 6.84 +/- 0.24 mm, 3.02 +/- 0.08 mm, 2.86 +/- 0.07 mm, respectively. The coronal plane has superior advantage in showing the bilateral adrenal glands. The shapes of adrenal glands are various, whereas the range of adrenal thickness is quite narrow. The thickness of adrenal medial and lateral limbs, especially the thickness of lateral limb are useful for the diagnosis of the bilateral adrenocortical disease.

  13. Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation.

    PubMed

    Winn, Brody; Tavares, Rosemarie; Fanion, Jacqueline; Noble, Lelia; Gao, John; Sabo, Edmond; Resnick, Murray B

    2009-03-01

    Undifferentiated or medullary carcinoma is characterized by its distinct histologic appearance and relatively better prognosis compared to poorly differentiated colonic carcinoma. These 2 entities may be difficult to differentiate by light microscopy alone. Only limited immunohistochemical studies investigating medullary carcinoma have been reported. These studies suggest a loss of intestinal differentiation, exemplified by a high percentage of CDX2 negativity. Our aim was to further characterize the immunohistochemical profile of medullary carcinoma, with particular emphasis on intestinal markers. Paraffin blocks from 16 cases of medullary carcinoma and 33 cases of poorly differentiated colonic carcinoma were retrieved, and tissue microarrays were constructed and stained with an immunohistochemical panel including CDX2, CK7, CK20, p53, intestinal trefoil factor 3, chromogranin, synaptophysin, MLH-1, MUC-1, MUC-2, and calretinin. A significantly higher proportion of medullary carcinomas, as opposed to poorly differentiated colonic carcinomas, showed loss of staining for MLH-1 and for the intestinal transcription factor CDX2, in accordance with previous studies. MLH-1 staining was present in only 21% of medullary carcinoma cases compared with 60% of the poorly differentiated colonic carcinoma cases (P = .02), whereas CDX2 was positive in 19% of medullary carcinomas and 55% of poorly differentiated colonic carcinomas (P = .03). Interestingly, calretinin staining was strongly positive in 73% of medullary carcinomas compared to only 12% of poorly differentiated colonic carcinomas (P < .0001). Evidence of intestinal differentiation by MUC-1, MUC-2, and TFF-3 staining was seen in 67%, 60%, and 53% of the medullary carcinomas, respectively. These 3 markers were frequently positive in many of the CDX2-negative medullary carcinoma cases. Medullary carcinoma of the colon retains a significant degree of intestinal differentiation as evidenced by its high percentage of

  14. Morphological changes and parasite load of the adrenal from dogs with visceral leishmaniasis.

    PubMed

    Momo, Claudia; Rocha, Nathália Alves de Souza; Moreira, Pamela Rodrigues Reina; Munari, Danísio Prado; Bomfim, Suely Regina Mogami; Rozza, Daniela Bernadete; Vasconcelos, Rosemeri de Oliveira

    2014-03-01

    The objective of this study was to analyze morphological changes and parasite loads in the adrenal gland from 45 dogs with visceral leishmaniasis (VL). The animals were from the Zoonosis Control Center of Araçatuba, state of São Paulo, which is an endemic region for the disease. These animals were euthanized due to positive diagnoses of VL. The dogs were classified into asymptomatic, oligosymptomatic and symptomatic groups. The parasite load was determined by immunohistochemistry, using VL-positive dog hyperimmune serum. Nine dogs showed an inflammatory infiltrate composed, predominantly, of plasma cells and macrophages. However, only eight dogs showed macrophages with amastigote forms of the parasite, immunolabeled in the cytoplasm. The medullary and reticular layers were the most affected areas, possibly due to a favorable microenvironment created by hormones in these regions. The density of parasites in the glandular tissue was not associated with clinical signs of VL (P > 0.05). However, the presence of the parasite was always associated with the presence of a granulomatous inflammatory infiltrate. This gland may not be an ideal place for the parasite's multiplication, but the presence of injuries to the glandular tissue could influence the dog's immune system, thus favoring the parasite's survival in the host's different organs.

  15. Preliminary report on adrenal-brain transplantation for parkinsonism in man.

    PubMed

    Bakay, R A; Watts, R L; Freeman, A; Iuvone, P M; Watts, N; Graham, S D

    1990-01-01

    The attempt to restore lost neurological function through grafting of catecholaminergic tissue into the striatum is a dramatic new experimental treatment approach for parkinsonism. We have grafted autologous adrenal medullary tissue into the right caudate nucleus in 12 patients with advanced Parkinson's disease (10 males, 2 females, mean age 53 years, mean Hoehn and Yahr stage 'off' medications 4.2) applying a transcortical technique similar to that of Madrazo as modified by Allen using right adrenalectomy performed via a flank approach. There have been no deaths, surgical complications, or serious postoperative morbidity. Modified Columbia Parkinson's disease ratings of patients off all dopaminergic agents for 72 h revealed 22% improvement (p less than 0.01) 3-6 months postoperatively (n = 10) and 22% improvement (p less than 0.01) 7-12 months later (n = 9). Postoperative dyskinesias necessitated reduction of L-dopa by 11% and of carbidopa by 29%. Analysis of lumbar cerebrospinal fluid biogenic amine metabolites following a 4-day 'drug holiday' revealed that homovanillic acid increased to 159% of preoperative levels (p less than 0.01) 3-6 months (n = 9) and to 197% of preoperative levels (p less than 0.02) 7-12 months postoperatively (n = 5). We have observed a mild to moderate improvement persisting up to 1 year with this therapeutic approach, but further study is needed.

  16. Influence of hemorrhage on adrenal secretion, blood glucose and serum insulin in the awake pig.

    PubMed Central

    Carey, L C; Curtin, R; Sapira, J D

    1976-01-01

    A study was performed to quantitate the adrenal medullary and cortical response to hemorrhage in awake animals bled at different rates and to relate these responses to simultaneous changes in blood glucose and serum insulin. A series of awake pigs were bled either slowly or rapidly of 30% of their calculated blood volume. Infusions of exogenous epinephrine were performed in an additional series of unbled animals and infusions of epinephrine plus hydrocortisone were similarly performed in an additonal series. Increase in blood glucose and epinephrine secretion rate following hemorrhage were found to be significantly dependent upon the rate of initial hemorrhage. Cortisol secretion was found to rise significantly during and following hemorrhage in both rapidly and slowly bled animals. Serum insulin levels remained at baseline levels during shock, despite the presence of significant hyperglycemia. In unbled animals infused with epinephrine at rates comparable to those measured in shock, elevations in blood glucose were markedly lower, shifting to the right of the dose-response curve during hemorrhage. Simultaneous infusions of cortisol and epinephrine resulted in a dose-response curve which did not differ significantly from that following infusion of epinephrine alone. Images Fig. 2. PMID:1247317

  17. Diffuse large B-cell lymphoma of the adrenal gland: a rare cause of primary adrenal insufficiency.

    PubMed

    de Sousa Lages, Adriana; Bastos, Margarida; Oliveira, Patrícia; Carrilho, Francisco

    2016-03-18

    Although it is a rare entity, primary lymphoma of the adrenal gland should be considered in the differential diagnosis of bilateral nodular adrenal lesions, particularly when there is evidence of associated adrenal insufficiency. We describe the case of an 83-year-old woman admitted to the emergency department due to a month's history of asthenia, weight loss, anorexia and nausea. Abdominopelvic CT showed bilateral nodular lesions of adrenal glands and a stimulation test with tetracosactide was compatible with primary adrenal insufficiency. CT-guided biopsy of the left adrenal gland was performed, and histopathological results were consistent with diffuse large B-cell lymphoma. Positron emission tomography (18)F-fluorodeoxyglucose detected two intensely hypermetabolic lesions limited to both adrenal glands. Replacement therapy with hydrocortisone 15 mg/day and fludrocortisone 0.1 mg/day was promptly started and chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone was initiated after haematology-oncology consultation.

  18. Renal inner medullary choline dehydrogenase activity: characterization and modulation.

    PubMed

    Grossman, E B; Hebert, S C

    1989-01-01

    Betaine belongs to the trimethylamine class of osmolytes (osmotically active substances believed to play an important role in cell volume homeostasis) and has recently been identified in the inner medulla of the mammalian kidney. Trimethylamines accumulate in the renal inner medulla during hypertonic stress, and betaine content in the inner medulla has been shown recently to increase during hypernatremia, yet the mechanisms governing the modulation of trimethylamine content and, in particular, of betaine content are not well understood. In this study, we demonstrate the presence of choline dehydrogenase activity in the renal inner medullas of three separate rat strains. Choline dehydrogenase is the enzyme that catalyzes the first of two successive oxidation steps in the biosynthetic conversion of choline to betaine. The presence of choline dehydrogenase activity in the inner medulla suggests that betaine accumulation in the inner medulla may result, at least in part, through in situ synthesis. The Km and Vmax of the reaction in the inner medullas of Long-Evans rats are 4.7 +/- 0.5 mM and 36.9 +/- 5.0 nmol.mg protein-1.min-1, respectively. These values are similar to the characteristics of choline dehydrogenase in mammalian liver. During hypernatremia, when betaine content of the inner medulla has been shown to increase 1.5-fold, choline dehydrogenase activity remains unchanged (or slightly increased), whereas enzyme activity in the cortex increases approximately 50%. Possible mechanisms of inner medullary betaine accumulation are discussed.

  19. Hormone receptor status and survival of medullary breast cancer patients

    PubMed Central

    Aksoy, Asude; Odabas, Hatice; Kaya, Serap; Bozkurt, Oktay; Degirmenci, Mustafa; Topcu, Turkan O.; Aytekin, Aydın; Arpaci, Erkan; Avci, Nilufer; Pilanci, Kezban N.; Cinkir, Havva Y.; Bozkaya, Yakup; Cirak, Yalcin; Gumus, Mahmut

    2017-01-01

    Objectives: To analyze the relationship between clinical features, hormonal receptor status, and survival in patients who were diagnosed with medullary breast cancer (MBC). Methods: Demographic characteristics, histopathological features, and survival statuses of 201 patients diagnosed with MBC between 1995 and 2015 were retrospectively recorded. Survival analyses were conducted with uni- and multivariate cox regression analysis. Results: Median follow-up time was 54 (4-272) months. Median patient age at the time of diagnosis was 47 years old (26-90). Of the patients, 91.5% were triple negative. Five-year recurrence free survival time (RFS) rate was 87.4% and overalll survival (OS) rate 95.7%. For RFS, progesterone receptor (PR) negativity, atypical histopathological evaluation, absence of lymphovascular invasion, smaller tumor, lower nodal involvement were found to be favourable prognostic factors by univariate analysis (p<0.05). The PR negativity and smaller tumor were found to be favourable factors by univariate analysis (p<0.05). However, none of these factors were determined as significant independent prognostic factors for OS (p>0.05). Conclusion: Turkish MBC patients exhibited good prognosis, which was comparable with survival outcomes achieved in the literature. The PR negativity was related to a better RFS and OS rates. PMID:28133688

  20. Recent Updates on the Management of Medullary Thyroid Carcinoma

    PubMed Central

    2016-01-01

    Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor derived from the thyroid C cells producing calcitonin. MTC accounts for 0.6% of all thyroid cancers and incidence of MTC increased steadily between 1997 and 2011 in Korea. It occurs either sporadically or in a hereditary form based on germline rearranged during transfection (RET) mutations. MTC can be cured only by complete resection of the thyroid tumor and any loco-regional metastases. The most appropriate treatment is still less clear in patients with residual or recurrent disease after initial surgery or those with distant metastases because most patients even with metastatic disease have indolent courses with slow progression for several years and MTC is not responsive to either radioactive iodine therapy or thyroid-stimulating hormone suppression. Recently, two tyrosine kinase inhibitors (TKIs), vandetanib and cabozantinib, are approved for use in patients with advanced, metastatic or progressive MTC. In this review, we summarize the current approach according to revised American Thyroid Association guidelines and recent advances in systemic treatment such as TKIs for patients with persistent or recurrent MTC after surgery. PMID:27586449

  1. Paroxysmal kinesigenic dystonia associated with a medullary lesion.

    PubMed

    Riley, D E

    1996-11-01

    A 67-year-old man experienced the abrupt onset of intermittent spasms of tightening of his throat muscles and elevation of his tongue to the roof of his mouth. These were precipitated by initiating movements, either of his mouth (eating, drinking, speaking, yawning) or of his whole body (arising from bed or a chair, lifting heavy weights). Episodes occurred six to 20 times per day, lasted 10-30 s, then resolved spontaneously. Two years later, results of his general neurological examination, including speech, were normal. Several spasms were provoked by arising from a seated or supine position or by drinking. Objectively, there was a strained dysphonia accompanied by palpable hardening of the supralaryngeal muscles. Each episode resolved within 15 s. Magnetic resonance imaging (MRI) showed evidence of a remote hemorrhage in the medulla. No abnormal blood vessels were seen. Phenytoin 300 mg/day abolished the spasms within days. Decreasing the dose to 200 mg/day months later led to a partial return of symptoms. Relief has persisted for 3 years. This patient has paroxysmal kinesigenic dystonia (PKD) of structures (pharynx, larynx, tongue) innervated by lower cranial motor nerves and a medullary lesion on MRI. PKD has been associated with focal lesions at all levels of the central nervous system (CNS), although never before in the medulla. PKD seems to be a nonspecific phenomenon of the CNS in reaction to injury.

  2. Medullary thyroid cancer: RET testing of an archival material.

    PubMed

    Godballe, Christian; Jørgensen, Gita; Gerdes, Anne-Marie; Krogdahl, Annelise S; Tybjaerg-Hansen, Anne; Nielsen, Finn C

    2010-04-01

    Medullary thyroid carcinoma (MTC) might be sporadic (75%) or hereditary (25%). Until the mid nineties the diagnosis of hereditary MTC was based on family history, clinical evaluation, histological detection of C-cell hyperplasia and tumor multifocality. Patients and families with hereditary MTC might be missed? Today mutation analysis of the RET proto-oncogene is routinely performed on DNA. Departments of pathology often store tissue specimens from performed surgical procedures. The purpose of this study was to examine if analysis of DNA extracted from formalin fixed archival tissue might be a possible method to identify not previously known cases of hereditary MTC. In 23 cases, tissue analysis was performed, and in 2 patients (9%) a mutation was identified, but in both cases the most likely explanation was contamination with tumor tissue. The ability to detect RET mutations was confirmed by testing of non-tumor tissue from patients with known hereditary MTC. This study shows that genetic testing of archival MTC material is technically possible and might be a way of identifying patients with previously not recognized hereditary MTC.

  3. Pretargeted immunoscintigraphy in patients with medullary thyroid carcinoma.

    PubMed Central

    Magnani, P.; Paganelli, G.; Songini, C.; Samuel, A.; Sudati, F.; Siccardi, A. G.; Fazio, F.

    1996-01-01

    To evaluate the use of pretargeted immunoscintigraphy (ISG) in the diagnosis and follow-up of patients with medullary thyroid carcinoma (MTC), we studied 25 patients with histologically proven disease; ISG was repeated after surgery in two patients. The antibody, either an anticarcinoembryonic antigen (CEA) or an antichromogranin A (CgA) biotinylated monoclonal antibody (MAb) or a cocktail of the two biotinylated MAbs was first injected. After 24 h, avidin was administrated i.v., followed by 111In-labelled biotin 24 h later. Fifty-two lesions were visualised. Six primary tumours, diagnosed by increased calcitonin levels, were all correctly diagnosed; 47 recurrences, also suspected by blood tumour markers, were detected and confirmed by cytology or histology. In one case, single photon emission tomography allowed the detection of small lymph nodes with a diameter of 4-7 mm. These lesions, not judged neoplastic by ultrasound, were confirmed to be neoplastic by fine needle aspiration. Pretargeted ISG correctly localises primary tumours and recurrences in MTC patients, when the only marker of relapse is serum elevation of calcitonin. With this three-step pretargeting method, cocktails of potentially useful MAbs can be used, avoiding false-negative studies that may occur when CEA or CgA are not expressed. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8795589

  4. Hormonal regulation of medullary bone metabolism in the laying hen

    SciTech Connect

    Harrison, J.R.

    1987-01-01

    A new organ culture system for the study of bone formation has been developed using medullary bone, a non-structural, metabolically active form of bone which is found in the marrow cavities of egg-laying birds. In the presence of fetal calf serum, bone explants were viable in culture by morphological criteria, and retained large numbers of osteoblasts and osteoclasts. Incorporation of /sup 3/H-proline into collagenase-digestible protein (CDP) and non-collagen protein (NCP) was determined using purified bacterial collagenase. Collagen accounted for over 10% of the total protein labeled. The calcium-regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), caused a dose-dependent inhibition of /sup 3/H-proline incorporation into CDP. The effective dose range of 1,25(OH)2D3 was 0.1 nM to 100 nM, while that of PTH was 1.0 nM to 100 nM. The effect of both hormones was specific for collagen, since /sup 3/H-proline incorporation into NCP was unaffected. Hydroxyproline analysis of bone explants and culture medium revealed that both hormones decreased the total hydroxyroline content of the cultures, suggesting that the inhibition of /sup 3/H-proline incorporation into DCP is due to inhibition of collagen synthesis.

  5. Histochemical carbonic anhydrase in rat inner medullary collecting duct

    NASA Technical Reports Server (NTRS)

    Kleinman, J. G.; Bain, J. L.; Fritsche, C.; Riley, D. A.

    1992-01-01

    Rat inner medullary collecting duct (IMCD) secretes substantial amounts of H+. However, carbonic anhydrase (CA), a concomitant of H+ secretion, has been generally reported absent in this segment. To reexamine this problem, we investigated CA and the morphological phenotypes of cells comprising the IMCD by CA histochemistry, using a modified Hansson technique with light and electron microscopy. Throughout the medulla, tubule cells exhibit histochemical CA activity. In the initial third of the inner medulla, a small proportion have features of intercalated cells and demonstrate some degree of CA activity. However, the majority population in the early portions of the IMCD appears to consist of principal cells. These also show CA staining of widely variable intensity, both among and within cells. A third cell type, previously called "IMCD cells", appears in the middle portion of the IMCD and is the only cell type present near the papilla tip. In contrast to previous reports, these "IMCD cells" have histochemical CA staining, also of highly variable intensity. These results demonstrate that stainable carbonic anhydrase to support acidification is present throughout the rat IMCD, both in intercalated cells and in some cells clearly not of this type. Therefore, the presence of CA is not specific for the intercalated cell type and suggests that other cell types may participate in acid secretion in IMCD.

  6. Epigenetics in Medullary Thyroid Cancer: From Pathogenesis to Targeted Therapy.

    PubMed

    Vitale, Giovanni; Dicitore, Alessandra; Messina, Erika; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

    2016-01-01

    Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC. Germline activating mutations of this gene have been reported in about 88-98% of familial MTCs, while somatic mutations of RET gene have been detected in about 23-70% of sporadic forms. Although these genetic events are well characterized, much less is known about the role of epigenetic abnormalities in MTC. The present review reports a detailed description of epigenetic abnormalities (DNA methylation, histone modifications and miRNA profile), probably involved in the pathogenesis and progression of MTC. A systematic review was performed using Pubmed and Google patents databases. We report the current understanding of epigenetic patterns in MTC and discuss the potential use of current knowledge in designing novel therapeutic strategies through epigenetic drugs, focusing on recent patents in this field. Taking into account the reversibility of epigenetic alterations and the recent development in this field, epigenetic therapy may emerge for clinical use in the near future for patients with advanced MTC.

  7. Histopathology of C Cells and Medullary Thyroid Carcinoma.

    PubMed

    Schmid, Kurt Werner

    2015-01-01

    The human thyroid gland contains less than 0.01-0.1% calcitonin producing and secreting C cells, which in men are almost exclusively situated in an intrafollicular location; the vast majority of C cells are embryologically derived of remnants of the ultimobranchial body and ultimately of the neural crest, a small subset, however, is presumed to originate from endodermal stem cells. Thyroid tumours with C cell differentiation have been named medullary thyroid carcinoma (MTC); calcitonin is also produced and secreted by MTC which makes this peptide hormone a very useful serum marker both for early detection and clinical follow-up of patients with MTC. About 70-80% of MTC are sporadic tumours, whereas 20-30% are familial MTC which are autosomal-dominant inherited and caused by germline mutations of the RET proto-oncogene located on chromosome 10. This article summarizes the histological, immunhistochemical and molecular genetic features of C cells, C-cell hyperplasia (CCH) and MTC, emphasizing the role of diagnostic pathology.

  8. [Clinico-prognostic analysis of course of thyroid medullary carcinoma].

    PubMed

    Kravcheniuk, A M; Reĭzin, D B; Pilets'kyĭ, A M; Reĭzin, V I

    2013-07-01

    Analysis of localization, character of development, sizes and metastatic potential of tumors in patients, suffering various forms of thyroid medullary carcinoma (THMC), was accomplished, permitting to establish a certain dependence of these characteristics from the recurrence occurrence frequency and lethality in groups of patients, owing different gender. The tumor diameter more than 2 cm and presence of metastases in time with diagnosis establishing have constituted the unfavorable factors, causing lethality enhancement in sporadic form of THMC. In women patients more frequent multifocal development coincide with lesser frequent metastasizing and lesser lethality in comparison with such in men. Lethality in men in sporadic form of THMC is twice as more, than in women patients, and it is explained by tumor diagnosis in them in later stages, although their postoperative life span is longer, taking into account the unfavorable impact of intraoperative age (bigger, than in men) on the results of treatment and prognosis. Lethality in inherited forms of THMC is significantly lesser, than in sporadic form, independently from impact of such existing factors, as more frequent multifocal tumor development, bilateral thyroid affection and similar frequency of metastasizing. In men the metastasizing is occurring more frequently, as it take place in cases of a sporadic form of the disease, causing higher lethality in them, comparing with such in women, suffering inherited forms of THMC.

  9. Leflunomide suppresses growth in human medullary thyroid cancer cells.

    PubMed

    Alhefdhi, Amal; Burke, Jocelyn F; Redlich, Aaron; Kunnimalaiyaan, Muthusamy; Chen, Herbert

    2013-11-01

    Medullary thyroid cancer (MTC) is a neuroendocrine tumor that arises from the calcitonin-secreting parafollicular cells of the thyroid gland. Leflunomide (LFN) is a disease-modifying antirheumatic drug approved for the treatment of rheumatoid arthritis, and its active metabolite teriflunomide has been identified as a potential anticancer drug. In this study we investigated the ability of LFN to similarly act as an anticancer drug by examining the effects of LFN treatment on MTC cells. Human MTC-TT cells were treated with LFN (25-150 μmol/L) and Western blotting was performed to measure levels of neuroendocrine markers. MTT assays were used to assess the effect of LFN treatment on cellular proliferation. LFN treatment downregulated neuroendocrine markers ASCL1 and chromogranin A. Importantly, LFN significantly inhibited the growth of MTC cells in a dose-dependent manner. Treatment with LFN decreased neuroendocrine tumor marker expression and reduced the cell proliferation in MTC cells. As the safety of LFN in human beings is well established, a clinical trial using this drug to treat patients with advanced MTC may be warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Calcitonin precursor levels in human medullary thyroid carcinoma.

    PubMed

    Bihan, H; Becker, K L; Snider, R H; Nylen, E; Vittaz, L; Lauret, C; Modigliani, E; Moretti, J L; Cohen, R

    2003-08-01

    The hormonal serum marker for the presence and course of patients with medullary thyroid cancer (MTC) is the mature calcitonin (CT) peptide. Other CALC-1 gene products such as the 116-amino acid polypeptide prohormone, procalcitonin, as well as its component calcitonin precursors (CTpr) may also be increased in their sera. We performed a study to evaluate the clinical utility of serum levels CTpr in these patients. Twenty-one patients with MTC (9 males, 12 females; 23-76 years of age) were evaluated. The diagnosis was confirmed by histologic examination, except for 2 (a proven RET mutation plus an abnormal pentagastrin-stimulated CT level). Nine patients had postoperative hypercalcitoninemia and 3 of these died. The specific assay for mature CT was a commercial immunoradiometric assay (hCT-IRMA); the immunoluminometric assay for CTpr (B.R.A.H.M.S Diagnostica, Berlin, Germany) detects intact procalcitonin and the free CT:CT carboxypeptide-1. All patients had detectable serum CTpr. These levels considerably exceeded those of mature CT, averaging 7.6-fold greater. CTpr levels correlated positively with mature CT (r = 0.61; p < 0.001). After pentagastrin administration, there was a parallelism of response between the two assays. Whenever there were known metastases, CTpr increased markedly. This study demonstrates the universal presence of CTpr in the blood of patients with MTC. The measurement of these peptides may offer a new dimension to the clinical evaluation of this malignancy.

  11. [Hypercalcitoninemia in conditions other than medullary cancers of the thyroid].

    PubMed

    Niccoli, P; Conte-Devolx, B; Lejeune, P J; Carayon, P; Henry, J F; Roux, F; Wion-Barbot, N; Bigorgne, J C

    1996-01-01

    Serum calcitonin (CT) assays are the most useful tumoral marker for the diagnosis and follow up of medullary thyroid carcinoma (MTC). Since 1988 the sensitivity and specificity of CT assays have been considerably improved. Normal basal and pentagastrin (Pg) stimulated CT ranges remain to be established and it appears necessary to determine the pathological circumstances which may be responsible for hypercalcitoninemia in addition to MCT. By reviewing literature and data from the "Groupe d'Etude des Tumeurs à Calcitonine": a/we compared basal and Pg stimulated CT values obtained with two commercially available immunometric CT assays and we observed that CT values measured by the CT-EASIA MEDGE-NIX kit were three fold the values obtained by suing the hGH ELSA CIS BIOINDUSTRIE Kit; b/we determined that hypercalcitoninemia may be observed in isolated C Cell Hyperplasia (HCC) surrounding either lymphocytic thyroiditis or follicular thyroid carcinoma loci, in chronic renal failure on maintenance hemodialysis, and in various neuroendocrine tumors. Surprisingly, the hypercalcitoninemia related to HCC has been found in genetically unaffected members (without any identified gene RET mutation) of both a Multiple Endocrine Neoplasia type 2A and isolated familial hereditary MTC.

  12. DNA analysis and persistent hypercalcitoninemia in medullary thyroid carcinoma.

    PubMed

    Jeng, T K; Lee, C H; Wang, H C; Chiu, J W; Lui, W Y

    1993-05-01

    The clinical data of 20 patients with medullary thyroid carcinoma (MTC) treated in Veterans General Hospital (VGH)-Taipei from 1970 to 1991 were reviewed. DNA content of the MTC and postoperative serum calcitonin (CT) were compared to evaluate patients' survival. All three patients with stage IV disease had aneuploid DNA and died within 7 months. The average survival was 4 months. The other 17 patients were all alive at the time of study and the mean follow up was 86 months. Three (3/7) patients had less than total thyroidectomy while only 2 (2/13) of the total thyoidectomized patients needed reoperation because of tumor recurrence. Of the 15 patients with available calcitonin data 11 had persistent post-operative hypercalcitoninemia. Among these 11 patients 5 out of the 6 patients with demonstrable lesions received reoperation; the other five (5/11) without demonstrable lesions were not operated and lived well in spite of persistent hypercalcitoninemia. One in 4 diploid patients and 9 in 12 aneuploid patients had metastatic lesions. No statistical significant correlation was found between the DNA content and survival, metastases or hypercalcitoninemia, although aneuploid MTC tended to be more advanced. We therefore concluded that total thyroidectomy is the treatment of choice for MTC. Persistent postoperative hypercalcitoninemia without clinical demonstrable lesions can be treated conservatively and DNA aneuploidy cannot be used as a reliable indicator of the grade of malignancy for MTC.

  13. Culturing primary rat inner medullary collecting duct cells.

    PubMed

    Faust, Dörte; Geelhaar, Andrea; Eisermann, Beate; Eichhorst, Jenny; Wiesner, Burkhard; Rosenthal, Walter; Klussmann, Enno; Klussman, Enno

    2013-06-21

    Arginine-vasopressin (AVP) facilitates water reabsorption by renal collecting duct principal cells and thereby fine-tunes body water homeostasis. AVP binds to vasopressin V2 receptors (V2R) on the surface of the cells and thereby induces synthesis of cAMP. This stimulates cellular signaling processes leading to changes in the phosphorylation of the water channel aquaporin-2 (AQP2). Protein kinase A phoshorylates AQP2 and thereby triggers the translocation of AQP2 from intracellular vesicles into the plasma membrane facilitating water reabsorption from primary urine. Aberrations of AVP release from the pituitary or AVP-activated signaling in principal cells can cause central or nephrogenic diabetes insipidus, respectively; an elevated blood plasma AVP level is associated with cardiovascular diseases such as chronic heart failure and the syndrome of inappropriate antidiuretic hormone secretion. Here, we present a protocol for cultivation of primary rat inner medullary collecting duct (IMCD) cells, which express V2R and AQP2 endogenously. The cells are suitable for elucidating molecular mechanisms underlying the control of AQP2 and thus to discover novel drug targets for the treatment of diseases associated with dysregulation of AVP-mediated water reabsorption. IMCD cells are obtained from rat renal inner medullae and are used for experiments six to eight days after seeding. IMCD cells can be cultured in regular cell culture dishes, flasks and micro-titer plates of different formats, the procedure only requires a few hours, and is appropriate for standard cell culture laboratories.

  14. Culturing Primary Rat Inner Medullary Collecting Duct Cells

    PubMed Central

    Faust, Dörte; Geelhaar, Andrea; Eisermann, Beate; Eichhorst, Jenny; Wiesner, Burkhard; Rosenthal, Walter; Klussman, Enno

    2013-01-01

    Arginine-vasopressin (AVP) facilitates water reabsorption by renal collecting duct principal cells and thereby fine-tunes body water homeostasis. AVP binds to vasopressin V2 receptors (V2R) on the surface of the cells and thereby induces synthesis of cAMP. This stimulates cellular signaling processes leading to changes in the phosphorylation of the water channel aquaporin-2 (AQP2). Protein kinase A phoshorylates AQP2 and thereby triggers the translocation of AQP2 from intracellular vesicles into the plasma membrane facilitating water reabsorption from primary urine. Aberrations of AVP release from the pituitary or AVP-activated signaling in principal cells can cause central or nephrogenic diabetes insipidus, respectively; an elevated blood plasma AVP level is associated with cardiovascular diseases such as chronic heart failure and the syndrome of inappropriate antidiuretic hormone secretion. Here, we present a protocol for cultivation of primary rat inner medullary collecting duct (IMCD) cells, which express V2R and AQP2 endogenously. The cells are suitable for elucidating molecular mechanisms underlying the control of AQP2 and thus to discover novel drug targets for the treatment of diseases associated with dysregulation of AVP-mediated water reabsorption. IMCD cells are obtained from rat renal inner medullae and are used for experiments six to eight days after seeding. IMCD cells can be cultured in regular cell culture dishes, flasks and micro-titer plates of different formats, the procedure only requires a few hours, and is appropriate for standard cell culture laboratories. PMID:23852264

  15. Diethyl pyrocarbonate inhibits rostral ventrolateral medullary H+ sensitivity.

    PubMed

    Nattie, E E

    1988-04-01

    Diethyl pyrocarbonate (DEPC), an acylating agent that reacts with imidazole-histidine in vitro, inhibits CO2 sensitivity when applied by pledget to the rostral chemosensitive area on the ventrolateral medullary (VLM) surface in glomectomized, chloralose-urethan-anesthetized cats. In this study similar application of DEPC inhibits the phrenic nerve response to CO2 expressed as a function of VLM [H+] measured by surface pH electrode. Attempts to evaluate direct chemoreceptor stimulation by HCL-soaked surface pledgets proved difficult, but rostral DEPC did inhibit the response to intravenous infusion of HCl. As previously reported, the CO2 and intravenous H+ responses are not a unique function of the VLM [H+]. DEPC had similar inhibitory effects on both the CO2 and the intravenous H+ responses, suggesting that the difference between them may reflect more the orientation or accessibility of the central chemoreceptor than a different mechanism for sensing CO2 vs. H+. DEPC did not alter the phrenic nerve response to hypoxia, indicating that DEPC effects on central chemoreception are not the result of a generalized inhibitory process. The results support the hypothesis that imidazolehistidine is involved at the rostral area with chemoreception of both CO2 and H+.

  16. Four patients with cutaneous metastases from medullary thyroid cancer.

    PubMed

    Santarpia, Libero; El-Naggar, Adel K; Sherman, Steven I; Hymes, Sharon R; Gagel, Robert F; Shaw, Stephanie; Sarlis, Nicholas J

    2008-08-01

    Cutaneous metastasis from thyroid cancer, especially medullary thyroid cancer (MTC) is rare. We report four patients with cutaneous metastases from sporadic MTC, three women and one man, aged 50 to 69 years. They presented different cutaneous lesions phenotypes. The first patient had a remote history of MTC and initial presentation of the recurrence was a rapidly progressing cutaneous lesion; on subsequent disease staging, widely metastatic disease was discovered. The other three patients developed cutaneous metastases in the presence of known distant metastases, indicating systemic spread of thyroid cancer. Definitive diagnosis of cutaneous metastases of MTC was made on biopsy of the lesions with cells that stained positive for neuroendocrine markers. Accurate diagnosis of cutaneous metastasis from MTC is important because it is a negative prognostic factor indicative of multisystemic disease. Thus, MTC metastases should be included in the differential diagnosis of erythematous maculopapular eruptions and nodular lesions of the skin, especially when these metastases occur in the upper part of the body and if the patient has a history of MTC. The appearing of cutaneous metastasis is a negative prognostic factor since all the patients here described died within one year from the diagnosis of cutaneous metastases.

  17. Histochemical carbonic anhydrase in rat inner medullary collecting duct

    NASA Technical Reports Server (NTRS)

    Kleinman, J. G.; Bain, J. L.; Fritsche, C.; Riley, D. A.

    1992-01-01

    Rat inner medullary collecting duct (IMCD) secretes substantial amounts of H+. However, carbonic anhydrase (CA), a concomitant of H+ secretion, has been generally reported absent in this segment. To reexamine this problem, we investigated CA and the morphological phenotypes of cells comprising the IMCD by CA histochemistry, using a modified Hansson technique with light and electron microscopy. Throughout the medulla, tubule cells exhibit histochemical CA activity. In the initial third of the inner medulla, a small proportion have features of intercalated cells and demonstrate some degree of CA activity. However, the majority population in the early portions of the IMCD appears to consist of principal cells. These also show CA staining of widely variable intensity, both among and within cells. A third cell type, previously called "IMCD cells", appears in the middle portion of the IMCD and is the only cell type present near the papilla tip. In contrast to previous reports, these "IMCD cells" have histochemical CA staining, also of highly variable intensity. These results demonstrate that stainable carbonic anhydrase to support acidification is present throughout the rat IMCD, both in intercalated cells and in some cells clearly not of this type. Therefore, the presence of CA is not specific for the intercalated cell type and suggests that other cell types may participate in acid secretion in IMCD.

  18. Unusual gastric mucosal infiltration by a medullary thyroid carcinoma: a case report.

    PubMed

    Karrasch, T; Doppl, W; Roller, F C; Schäffler, A; Schäffer, R; Gattenlöhner, S

    2016-07-27

    Medullary thyroid carcinoma accounts for approximately 1 to 2 % of all thyroid carcinoma cases. The most common route of dissemination is to locoregional lymph nodes. Distant metastases commonly affect bones, lungs, and liver. We present a case of a white woman with a 25-year history of medullary thyroid carcinoma on multiple medications including tyrosine kinase inhibitor therapy for the last 11 months, who exhibited unusual diffuse infiltration of advanced stage medullary thyroid carcinoma to her gastric mucosa. A 53-year-old white woman presented with increasing fatigue, loss of appetite, and severe epigastric pain radiating to her back. She had a history of medullary thyroid carcinoma (pT2pN1b), diagnosed 25 years ago and treated by complete thyroidectomy and repeated bilateral cervical lymph node dissection. Medical therapy included octreotide 20 mg every 4 weeks, which was switched to the tyrosine kinase inhibitor vandetanib 300 mg/day 11 months ago when computed tomography scanning revealed progressive mediastinal lymph node and diffuse and symptomatic pulmonary metastases. Of note, she demonstrated macroscopically stable pulmonary and mediastinal lymph node metastases; however, her calcitonin serum levels dramatically increased. Computed tomography scanning revealed a single new intrahepatic lesion (4 mm) as well as multiple (>10) new supraclavicular lesions suggestive of medullary thyroid carcinoma progress. As proven by gastric biopsy and immunohistochemical evaluation, her epigastric pain was explained by a diffuse infiltration of her gastric mucosa by metastatic medullary thyroid carcinoma. Subsequently, she rapidly deteriorated and died. The current case report shows for the first time an unusual metastatic infiltration of the gastric mucosa by medullary thyroid carcinoma. When treating these patients, it is important to include this differential diagnosis during follow-up.

  19. Effects of renal perfusion pressure on renal medullary hydrogen peroxide and nitric oxide production.

    PubMed

    Jin, Chunhua; Hu, Chunyan; Polichnowski, Aaron; Mori, Takefumi; Skelton, Meredith; Ito, Sadayoshi; Cowley, Allen W

    2009-06-01

    Studies were designed to determine the effects of increases of renal perfusion pressure on the production of hydrogen peroxide (H(2)O(2)) and NO(2)(-)+NO(3)(-) within the renal outer medulla. Sprague-Dawley rats were studied with either the renal capsule intact or removed to ascertain the contribution of changes of medullary blood flow and renal interstitial hydrostatic pressure on H(2)O(2) and NO(2)(-)+NO(3)(-) production. Responses to three 30-minute step changes of renal perfusion pressure (from approximately 85 to approximately 115 to approximately 145 mm Hg) were studied using adjustable aortic occluders proximal and distal to the left renal artery. Medullary interstitial H(2)O(2) determined by microdialysis increased at each level of renal perfusion pressure from 640 to 874 to 1593 nmol/L, as did H(2)O(2) urinary excretion rates, and these responses were significantly attenuated by decapsulation. Medullary interstitial NO(2)(-)+NO(3)(-) increased from 9.2 to 13.8 to 16.1 mumol/L, with parallel changes in urine NO(2)(-)+NO(3)(-), but decapsulation did not significantly blunt these responses. Over the range of renal perfusion pressure, medullary blood flow (laser-Doppler flowmetry) rose approximately 30% and renal interstitial hydrostatic pressure rose from 7.8 to 19.7 cm H(2)O. Renal interstitial hydrostatic pressure and the natriuretic and diuretic responses were significantly attenuated with decapsulation, but medullary blood flow was not affected. The data indicate that pressure-induced increases of H(2)O(2) emanated largely from increased tubular flow rates to the medullary thick-ascending limbs of Henle and NO largely from increased medullary blood flow to the vasa recta. The parallel pressure-induced increases of H(2)O(2) and NO indicate a participation in shaping the "normal" pressure-natriuresis relationship and explain why an imbalance in either would affect the blood pressure salt sensitivity.

  20. Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer.

    PubMed

    Machens, Andreas; Hoffmann, Florian; Sekulla, Carsten; Dralle, Henning

    2009-12-01

    Men and women differ in thyroidal C-cell mass and calcitonin secretion. This difference may have implications for the definition of calcitonin thresholds to distinguish sporadic C-cell hyperplasia from occult medullary thyroid cancer. This retrospective study examined the hypothesis that gender-specific calcitonin thresholds predict occult medullary thyroid cancer more accurately among patients with increased basal calcitonin levels than unisex thresholds. A total of 100 consecutive patients were evaluated with occult sporadic C-cell disease no larger than 10 mm who were referred for increased basal calcitonin levels and underwent pentagastrin stimulation preoperatively at this institution. Altogether, gender-specific calcitonin thresholds predicted medullary thyroid cancer better than unisex thresholds. At lower (medullary thyroid cancer four to eight times more often than men. Most discriminatory between C-cell hyperplasia and medullary thyroid cancer was a basal calcitonin threshold of 15 pg/ml (corrected 20 pg/ml) for women and 80 pg/ml (corrected 100 pg/ml) for men, based on the greatest accuracy at the lowest possible calcitonin level. The respective gender-specific stimulated peak calcitonin thresholds were 80 pg/ml (corrected 100 pg/ml) and 500 pg/ml. Corresponding positive predictive values for medullary thyroid cancer at these calcitonin thresholds were 89 and 90% for women, as opposed to 100% for men. To increase the positive predictive value for women to 100%, the respective calcitonin thresholds would have to be raised to 40 pg/ml (corrected 50 pg/ml) and 250 pg/ml. These findings indicate that gender-specific calcitonin thresholds predict sporadic occult medullary thyroid cancer better than unisex thresholds.