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[A comparative study of 9 cases of adrenal pheochromocytoma and 11 cases of extra-adrenal pheochromocytoma].

Twenty patients with the diagnosis of pheochromocytoma were studied from January 1990 to January 1998. Nineteen patients had a pathologic investigation performed. The mean age of patients was 49 +/- 16 years (range: 24-71 years), 8 males and 12 females. Nine cases corresponded to adrenal and eleven to extra-adrenal (paragangliomas) pheochromocytomas. The anatomic location was similar in both adrenal glands and for paragangliomas the cervical location predominated. The most consistent clinical finding in our patients was maintained arterial hypertension, followed by headache, palpitations and flushing. Biochemically, an increase in urine catecholamine levels or their metabolites was found in 82.2%. The clonidine test was very useful, particularly for cases where biochemical results were discrepant. CT, NMR and gammagraphy with 123I-MIBG have a high sensitivity for locating pheochromocytomas. NMR and gammagraphy with 111In-pentetreotide located cases in which CT or 123I-MIBG were negative. Preoperative treatment with adrenergic alpha-blockers allowed to surgery with no arterial tension complications. Only one patient with multiple abdominal paragangliomas relapsed. No differences regarding clinical manifestations, biochemical parameters or imaging studies were found between pheochromocytomas and paragangliomas, except their location.

3-Iodobenzylguanidine↗

[Bilateral adrenal hemorrhage with adrenal insufficiency in the framework of primary antiphospholipid antibody syndrome].

We report a case of acute adrenal insufficiency in a context of probable bilateral adrenal haemorrhage, as revealed by CT-scan in a 52-year-old woman with a history of spontaneous abortion and repeated ischaemic stroke without symptoms or signs of collagen vascular disease. The symptoms began after the patient had successfully been treated for pneumonia. She had persistently high titres of IgG anticardiolipin antibodies, antibodies against beta 2-glycoprotein I and a lupus anticoagulant. The diagnosis of primary antiphospholipid syndrome with adrenal insufficiency was postulated.

Adrenal Gland Diseases↗

[Adrenal medullary phaeochromocytoma and adrenal medullary hyperplasia].

From 1979 to 1989, 8 cases of adrenal medullary phaeochromocytoma (AMP) and 6 cases of adrenal medullary hyperplasia (AMH) were treated surgically. We reviewed the two groups of patients, and the results suggested that though the patients of AMP are similar to those of AMH in clinical symptoms and signs, AMP and AMH are virtually two different diseases of the adrenal medulla. CT and echography are helpful in distinguishing AMP from AMH, but the determination of the two diseases depends on the histological findings. The diagnostic criterion of pathology for AMP and AMH, as well as the treatment of the two diseases are discussed.

Adolescent↗

Peripheral and adrenal venous levels of steroids in a patient with virilizing adrenal adenoma.

The peripheral levels of 17-hydroxypregnenolone (17delta5P), progesterone (P), 17-hydroxyprogesterone (17P), testosterone (T), 5alpha-dihydrotestosterone (DHT), androstenedione (A), androst-5-ene-3beta,17beta-diol (delts5diol), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), estradiol-17beta (E2), and cortisol (F) were measured in peripheral and right adrenal venous blood of an amenorrheic patient with a right virilizing adrenal adenoma. Urinary 17-ketosteroids were markedly elevated and were not suppressed on a low dose of dexamethasone (Dex) for 7 days. Peripheral T level was 1.2 ng/ml and DHEA-S was 13,500 ng/ml. Calculations of the ratios of adrenal venous gradients for delta5 and delta4 steroids suggest that the predominant pathway of steroid secretion used by the tumor was as follows: pregnenolone (delta5P) leads to 17delta5P leads to DHEA leads to A leads to T. Following removal of the adenoma, T returned to normal levels but DHEA-S was still above normal at 4100 ng/ml. The patient became eumenorrheic with marked improvement at her hirsutism and virilization.

17-Hydroxycorticosteroids↗

[Hypophyseal and adrenal hormones and the immune reactivity of patients with Itsenko-Cushing disease after an adrenal autograft].

The authors employed for the first time the method of heterotopic autotransplantation of the adrenals on a vascular pedicle in patients with Itsenko-Cushing disease. It was established that heterotopic transplantation of the adrenals results early in a significant reduction of the level of cortical hormones and insignificant change as compared with initial state of the immune status. All terms were characterized by humoral and cellular immune deficit. Results indicate the expediency of using this method. Adrenal transplantation prevents the development of hypocorticism.

Adolescent↗

Ovaries and adrenals in murine Schistosomiasis mansoni. III. Morphology and function of the adrenals in acute infection.

In mice with acute Schistosoma mansoni infection lipoid depletion was found in the zona fasciculata of the adrenal cortex without any other major histological alterations of the adrenals. Schistosomiasis did not influence the weight of the adrenals, or the cortisol level of the blood serum as determined by radioimmunoassay. The changes in morphology and function of the ovaries in the same infected animals reported earlier point to the vulnerability of the gonads in schistosomiasis mansoni, which may be a consequence of partial hypopituitarism.

Adrenal Cortex↗

[Adrenal scintigraphy-value and indications in adrenal disease].

Adrenal scintillation scanning is a very useful method in the diagnosis of steroid producing diseases of the adrenal glands. The diagnosis of bilateral hyperplasia and primary adenoma of the adrenal cortex in Cushing's syndrome and Conn's syndrome is possible by this non-invasive procedure. Morphological questions (e.g. the localization of a phaeochromocytoma) cannot be answered. It is not a screening examination.

Adenoma↗

Childhood primary aldosteronism due to an adrenal adenoma: preoperative localization by adrenal vein catheterization.

Primary aldosteronism resulting from an adrenal adenoma is rare in children. An 8 1/2-year-old girl was found to have hypertension and spontaneous hypokalemia, both detected as incidental findings. Subsequent investigations revealed inappropriately elevated levels of plasma and urinary aldosterone with suppressed plasma renin activity. Adrenal vein blood sampling and venography suggested the presence of left adrenal adenoma which was confirmed at surgical exploration and pathologic examination. All the clinical and biochemical abnormalities were corrected by the adrenalectomy. The differential diagnoses of various types of hyperaldosteronism and/or hypokalemia in such a clinical setting are discussed.

Adenoma↗

Immunohistochemical analysis of adrenal proliferation and corticosterone expression in experimental adrenal regeneration.

The proliferative activity, the organization and the corticosterone expression of adrenocortical cells in an experimental adrenal regeneration process after the transplantation of neonatal adrenal glands to adult hosts was investigated. Three days after transplantation, the medullar and the innermost adrenocortical cells of the neonatal adrenal glands showed degenerative and necrotic changes due to the lack of vascular supply. The remaining outermost adrenocortical cells did not display any PCNA immunoreaction. The first PCNA expression, pointing out the beginning of the proliferative cycle, was observed in a 45.4% of the adrenocortical cells, one week after transplantation. After three weeks, several regenerated adrenocortical nodules with a bigger size than the one observed in the previous periods were seen. In these nodules, while the outermost adrenocortical cells were disposed in parallel to the capsule or in rounded groups, the bulk of the regenerated mass width was composed of cells forming longitudinal cords. PCNA immunoreaction was almost exclusively restricted to subcapsular cells (62.5%) and to cells of the outermost portion of the cords (32.5%), the global percentage of PCNA immunopositive cells being 18.4%. Twelve weeks after transplantation, regenerated adrenocortical cells were arranged in three layers: glomerulosa, fasciculata and reticularis. Only 1.85% of the adrenocortical cells were PCNA immunopositive. Although in the early stages of the regeneration process, all the adrenocortical cells, both proliferating and non proliferating cells expressed corticosterone, a restriction of this immunoreactivity to the zonae fasciculata and reticularis was observed when cell zonation was apparent.

Adrenal Cortex↗

[Endothelin-1 receptors of the normal adrenal gland and adrenal tumors in human].

Endothelin-1 (ET-1) receptors of normal adrenal gland (ADR, 6 cases), aldosterone-producing adenoma (APA, 5 cases), idiopathic hyperaldosteronism (IHA, 4 cases) and pheochromocytoma (PHE, 6 cases) in human were measured by radioligand binding assay (RBA) of receptors. Binding studies using 125I-ET-1 as a radio ligand showed the presence of a single class of high-affinity binding sites for ET-1 in all of the above tissues. The values of dissociation constant (Kd) of ET-1 for its receptor were similar in ADR, APA and IHA (28.3 +/- 2.5, 27.9 +/- 6.1, 27.7 +/- 1.9 pmol/L, respectively), but the maximal binding capacity (Bmax) of ET receptor tended to be lower in APA tissue (107.2 +/- 13.2 fmol/mg protein) in comparison with ADR (P < 0.01) and IHA (P < 0.05, 274.9 +/- 40.8, 247.0 +/- 19.8 fmol/mg protein, respectively). Both the Kd (50.8 +/- 5.1 pmol/L) and Bmax (675.3 +/- 93.7 fmol/mg protein) in PHE were higher than those in ADR (P < 0.01), APA (P < 0.01) or IHA (P < 0.05 for Kd, P < 0.01 for Bmax). Our data may suggest that there is the down-regulation for ET-1 receptor in APA and support the concept of an important role of ET-1 in the paracrine-autocrine regulation of aldosterone and catecholamine secretion in the adrenal and adrenal tumors.

Adenoma↗

Differentiation and transdifferentiation of adrenal chromaffin cells of the guinea pig. II. Adrenal medullary explants grown in tissue culture.

Explants of adrenal medullary tissue taken from newborn guinea pigs were grown in culture for up to two weeks. The explants exhibited sparse outgrowth of neurite-like processes, in contrast to adrenal medullae taken from young postnatal rats or adults guinea pigs that were (i) grown under identical conditions (Unsicker and Chamley 1977) or (ii) transplanted to the anterior chamber of the eye (Unsicker et al. 1981), respectively. Nerve growth factor (10-100 ng/ml, 2.5 S NGF) did not enhance formation of processes. However, electron-microscopic investigations revealed the presence of numerous processes within the explants, which extended from chromaffin cells and were characterized by longitudinally oriented cytoskeletal structures, various population of clear and dense-cored vesicles, varicosities and growth cones. Chromaffin cell bodies largely resembled their in situ-counterparts, but had fewer and smaller storage vesicles than controls. The results are discussed in light of recent findings regarding the potency of NGF and NGF-like growth factors to induce neuronal transdifferentiation of adrenal chromaffin cells.

Adrenal Medulla↗

Metorphamide, a novel endogenous adrenal opioid peptide, inhibits nicotine-induced secretion from bovine adrenal chromaffin cells.

Opioid peptides are found in high concentrations in the adrenal medulla. Recently, a novel opioid octapeptide, metorphamide, possessing an amidated C-terminal, was characterized and also found to be present in adrenal tissue. We have studied the ability of this novel peptide to modify nicotine-induced secretion from isolated bovine adrenal chromaffin cells. Exocytosis was monitored by measuring adenosine triphosphate (ATP) release on-line by the luciferin-luciferase bioluminescence method, or by measuring endogenous catecholamine release by high-performance liquid chromatography (HPLC) with electrochemical detection. Metorphamide inhibited 5 microM nicotine-induced ATP release from fresh chromaffin cells by almost 50% at 5 microM. Metorphamide at concentrations less than 1 microM had no effect on 5 microM nicotine-induced adrenaline and noradrenaline release from cultured cells, but at higher concentrations inhibited their release equally, with an IC50 of approximately 10 microM. By contrast, Met5-enkephalin inhibited the release of both catecholamines equally with an IC50 of greater than 1 mM, making metorphamide greater than 100-fold more potent than Met5-enkephalin in this system. Naloxone (10 microM) and diprenorphine (1 microM) failed to antagonise the inhibitory action of metorphamide on nicotine-induced catecholamine release. Metorphamide inhibited the nicotinic response in a non-competitive manner, and failed to affect either adrenaline or noradrenaline release induced by elevated potassium ion concentrations. The results suggest metorphamide acts on naloxone- and diprenorphine-resistant receptors to inhibit chromaffin cell nicotinic secretion and that the novel amidated C-terminal of the peptide is important for this action.

Adenosine Triphosphate↗

Adrenal 11-hydroxylase activity in a hypercortisolemic New World primate: adaptive intra-adrenal changes.

The squirrel monkey, a representative New World primate, has high plasma cortisol and aldosterone concentrations when compared to Old World primates. We measured adrenal mitochondrial 11-hydroxylase (11-OHase) activity in squirrel monkeys and in two representative Old World species (cynomolgus and rhesus macaques) in an effort to explain these elevated plasma glucocorticoid and mineralocorticoid levels. The activity of 11-OHase was 5-fold higher in the squirrel monkey than in the Old World species tested. Calculated 11-OHase Vmax was different in the squirrel monkey and the cynomolgus. However, the Km values were similar in the New World primate when compared to cynomolgus. The ability of metyrapone to block 11-OHase was less in the former than in the latter. The data are consistent with the hypothesis that the squirrel monkey adrenal cortex possesses an increased number of 11-hydroxylase enzyme units compared to that of Old World primate species, and is therefore more efficient in producing cortisol. This difference in 11-OHase activity in the squirrel monkey, in addition to other previously reported adrenal steroidogenic enzyme alterations, may be adaptive in nature, favoring increased cortisol and aldosterone production in this and possibly other New World primate species.

Adaptation, Physiological↗

The role of neuropeptides in the regulation of adrenal zona fasciculata/reticularis function. Effects of vasoactive intestinal polypeptide, substance P, neuropeptide Y, Met- and Leu-enkephalin and neurotensin on corticosterone secretion in the intact perfused rat adrenal gland in situ.

There is much evidence to suggest that glucocorticoid secretion may be influenced by the splanchnic innervation to the adrenal gland, and that this effect may be mediated by neuropeptides. The present studies investigated the effects of several neuropeptides on corticosterone secretion by the intact perfused rat adrenal gland in situ. Both vasoactive intestinal polypeptide and Met-enkephalin caused a dose-dependent increase in corticosterone secretion, with a maximum response of 450% and 370% increment in corticosterone respectively. Of the other peptides tested, Leu-enkephalin, substance P and neurotensin all stimulated corticosterone secretion, with a maximum response of around 160% increase in each case. Neuropeptide Y on the other hand, had only a minor effect, which was only apparent over a small dose range. These results support the theory that adrenal neuropeptides may have a role in the regulation of glucocorticoid secretion.

Adrenal Glands↗

Neural regulation of adrenal chromaffin cell function in the mouse: fate and distribution of [3H]dopamine in denervated adrenal medulla.

The distribution and time course of appearance and decline of radioactivity in denervated adrenal medulla of mice injected with [3H]dopamine was examined by autoradiography. Radioactivity irradiated from [3H]dopamine was increased from 7.5 min to 30 min, then decreased rapidly in both adrenaline-storing (A) cells and noradrenaline-storing (NA) cells of either intact or denervated adrenals. In subcortical A cells, the incorporation of radioactivity was increased by denervation while in NA cells and in A cells in the center of the medulla, the increment was not significant. In the denervated adrenals, the decline of [3H]dopamine-derived radioactivity was slower than that in the intact gland. The denervation increased the gradient in radioactivity from the surface to the center of the medulla. The present results suggest that the sensitivity to neuronal suppression of dopamine uptake in subcortical A cells is different from that in A and NA cells in the rest of the gland. The results also indicate a functional heterogeneity within a single type of chromaffin cells.

Adrenal Medulla↗

Cytochrome P-450 from mitochondria of bovine adrenal cortex: comparison of cholesterol side-chain cleavage P-450 with steroid 11beta-hydroxylation P-450 and immunochemical cross-reactivity between adrenal mitochondrial and liver microsomal cytochromes P-450.

Adrenocortical mitochondrial cytochrome P-450 specific to the cholesterol side-chain cleavage (desmolase) reaction differs from that for the 11beta-hydroxylation reaction of deoxycorticosterone. The former cytochrome appears to be more loosely bound to the inner membrane than the latter. Upon ageing at 0 degrees C or by aerobic treatment with ferrous ions, the desmolase P-450 was more stable than the 11beta-hydroxylase P-450. By utilizing artificial hydroxylating agents such as cumene hydroperoxide, H2O2, and sodium periodate, the hydroxylation reaction of deoxycorticosterone to corticosterone in the absence of NADPH was observed to a comparable extent with the reaction in the presence of adrenodoxin reductase, adrenodoxin and NADPH. However, the hydroxylation reaction of cholesterol to pregnenolone was not supported by these artificial agents. Immunochemical cross-reactivity of bovine adrenal desmolase P-450 with rabbit liver microsomal P-450LM4 was also investigated. We found a weak but significant cross-reactivity between the adrenal mitochondrial P-450 and liver microsomal P-450LM4, indicating to some extent a homology between adrenal and liver cytochromes P-450.

Adrenal Cortex↗

Prevalence of 3beta-hydroxysteroid dehydrogenase-deficient nonclassic adrenal hyperplasia in hyperandrogenic women with adrenal androgen excess.

OBJECTIVE: We sought to determine the prevalence of 3beta-hydroxysteroid dehydrogenase-deficient nonclassic adrenal hyperplasia among adult hyperandrogenic women with dehydroepiandrosterone sulfate excess. STUDY DESIGN: Thirty consecutive hyperandrogenic women with hirsutism, oligomenorrhea, or both and dehydroepiandrosterone sulfate levels of >8.5 micromol/L and 24 control subjects were studied. Basal sex hormone binding globulin, total and free testosterone, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, and basal and 60-minute corticotropin-stimulated 17-hydroxypregnenolone and dehydroepiandrosterone were measured, and the increment (change from basal to 60-minute value) was calculated. RESULTS: Twenty-six (87%) and 25 (83%) of the 30 hyperandrogenic patients studied had 60-minute dehydroepiandrosterone and change in 0- to 60-minute dehydroepiandrosterone levels greater than the mean + 2 SD of control subjects, respectively. Six (20%) and 6 (20%) of the 30 hyperandrogenic patients had 60-minute 17-hydroxypregnenolone and 0- to 60-minute change in 17-hydroxypregnenolone levels greater than the mean + 2 SD of control subjects, respectively. However, none of the subjects had either 60-minute 17-hydroxypregnenolone levels or 60-minute dehydroepiandrosterone levels or both associated with the diagnosis of genetically proved 3beta-hydroxysteroid dehydrogenase deficiency (>5-fold of the control mean value). CONCLUSION: 3beta-Hydroxysteroid dehydrogenase-deficient nonclassic adrenal hyperplasia is rare even among adult hyperandrogenic patients with adrenal androgen excess.

17-alpha-Hydroxyprogesterone↗