Low-renin ("primary") hyperaldosteronism. Differential diagnosis and distinction of sub-groups within the syndrome.
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Two patient with primary aldosteronism, one with a solitary adrenal adenoma and the other with bilateral nodular hyperplasia, are described. Both patients showed the classic features of primary aldosteronism in electrolyte and hormone patterns, but there were important differences in the biochemistry of their excised adrenal tissue. In addition, the injection of plasma from the patient with bilateral adrenal hyperplasia into the sheep's transplanted adrenal gland elicited a definite aldosterone secretory response, but there was no aldosterone response to the injection of plasma from the patient with a solitary adrenal adenoma. The findings support the hypothesis that an extra-adrenal stimulus may contribute to the pathogenesis of bilateral adrenal hyperplasia.
A 51-year-old woman with a virilizing adenoma and underlying undetected and untreated congenital adrenocortical hyperplasia is described. The 10 instances of the combination of these two pathologic lesions are reviewed with particular attention to the steroid abnormalities encountered.
A 15-year-old girl with primary amenorrhea, hirsutism, and enlargement of the clitoris was found to have an increased titer of the urinary neutral 17-ketosteroids which failed to decrease after the administration of dexamethasone and an adrenal tumor was demonstrable on venography. Analysis of the adrenal venous effluent revealed gradients on the side of the tumor for testosterone, androstenedione, estradiol, and dehydroepiandrosterone sulfate. Following removal of the tumor, the hirsutism improved markedly, the menses returned, and sexual maturation progressed.
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The cholesterol side-chain cleavage enzyme system of rat adrenal mitochondria and rat adrenocortical carcinoma cells was found to metabolize three halogenated side-chain cholesterol analogues to pregnenolone. The analogues were 26-bromocholesterol, 26-nor-25(RS)-bromocholesterol and 26-iodocholesterol. The addition of Ca2+ to rat adrenal mitochondria did not produce an increase in the rate of metabolism of the halogenated sterol to pregnenolone. The brominated sterols suppressed the de novo sterol biosynthesis of rat adrenocortical carcinoma cells. The experimental findings are supportive of the notion that a halogen atom at such a position in a sterol is analogous to a hydroxyl group but unlike a proton. ACTH, therefore, may not be a requirement for the uptake and utilization of such sterols. The halogenated sterols may have a use as probes in the study of sterol transfer into and within cells.
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We studied whether specific receptors for endothelin (ET) isopeptide exist in human aldosterone-producing adenoma and normal adrenal cortex, and whether ET isopeptides are produced by human adrenal gland. Competitive binding studies using [125I]ET-1 as a radioligand revealed the presence of a single class of high-affinity binding sites for ET-1 with the apparent KD of 70 +/- 31 pM and Bmax of 226 +/- 139 fmol/mg protein in adenoma membranes almost comparable to those in adjacent normal cortex. The apparent Ki for ET-2 and ET-3 were 89 +/- 33 pM and 82 +/- 16 pM, respectively. Northern blot analysis of poly(A)+ RNA of adenoma and adjacent normal cortex using cDNAs for ET receptor subtype (ETA, ETB) and ET isopeptide (ET-1, ET-3) as probes revealed that ETA and ETB receptors as well as ET isopeptides (preproET-1, preproET-3) are concomitantly expressed in both tissues. Our data demonstrate for the first time that ET receptor subtype (ETA and ETB) and ET isopeptide (ET-1 and ET-3) are concomitantly expressed by human adrenal cortex, suggesting the potential role of ETs as a local mediator in human adrenal gland.
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The synthesis of [6-3H]-25-hydroxycholesterol from 26-norcholest-5-en-3 beta-ol-25-one is described. The metabolism of the radiolabeled hydroxysterol in rat adrenocortical carcinoma cells and in mitochondria-enriched preparations of rat adrenal tissue was investigated. We found that [6-3H]-25-hydroxycholesterol was metabolized efficiently to [3H]-pregnenolone in both preparations of rat adrenal tissue.
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We have used specific radioimmunoassays to measure urinary free deoxycorticosterone (DOC) and total aldosterone excretion in 15 patients with Cushing's syndrome. Free DOC excretion was increased in 6 of 8 patients with pituitary-dependent adrenal hyperplasia, in 2 of 3 patients with adrenal adenoma, and in all 4 cases with adrenal carcinoma. The most marked increase was noted in the adrenal carcinoma cases. Aldosterone excretion was high, normal, or low in each of the three types of Cushing's syndrome. The free DOC response to metyrapone in Cushing's syndrome due to adrenal adenoma was markedly different from that in patients with adrenal hyperplasia (pituitary-dependent) and may serve as a test to ascertain the etiology of the disorder. Correlations of free DOC and aldosterone excretion with free cortisol excretion, and their responses to the administration of metyrapone and dexamethasone were compatible with ACTH dependency in adrenal hyperplasia, autonomous production of steroids in adrenal adenomas and a chaotic steroidogenesis in adrenal carcinoma.