Dexamethasone-suppressible hyperaldosteronism. Adrenal transition cell hyperplasia?

Abstract

SUMMARY Dexamethasone-suppressible hyperaldosteronism is a rare familial syndrome in which hypokalemia, suppression of plasma renin concentration, and elevated aldosterone secretion are corrected by treatment with glucocorticoids. Regulation of adrenocortical function and body electrolytes was studied in two affected brothers. Both were hypertensive (210/128 and 160/106 mm Hg) with hypokalemia (3.3 and 3.5 mM) and low plasma renin concentrations. Aldosterone was elevated intermittently with levels as high as 45 ng/dl (normal range, 4-16 ng/dl). Cortisol concentrations were normal but were correlated with aldosterone levels (r = 0.9 and 0.7). Concentrations of 11-deoxycorticosterone (19 and 21 ng/dl; normal range, 4-16 ng/dl) and 18-hydroxycortisol (1000 and 950 ng/dl; normal range, 34-150 ng/dl) were elevated, and diurnal changes in both were the same as those seen with aldosterone. Infusion of adrenocorticotropic hormone,_ 24 (ACTH) caused exaggerated increases of aldosterone, 11-deoxycorticosterone, and 18-hydroxycortisol; cortisol response was normal. A 4-week trial of dexamethasone normalized blood pressure and caused a natriuresis, a fall in aldosterone, and a rise in plasma renin. Administration of ACTH after dexamethasone treatment again caused exaggerated increases of aldosterone. Aldosterone did not respond to angiotensin II before dexamethasone therapy (r = 0.01), but it showed a normal response after therapy (r = 0.8, p<0.01). Neither administration of dopamine (1 /xg/kg/min) nor long-term therapy with bromocriptine (2.5 mg t.i.d. for 4 weeks) affected aldosterone biosynthesis. Thus, loss of dopaminergic inhibition of mineralocorticoid biosynthesis does not account for hyperaldosteronism in this condition. The abnormal pattern of steroid secretion in these brothers is consistent with a population of adrenocortical transition-type cells that secrete aldosterone in response to ACTH but not to angiotensin II and have biosynthetic characteristics of both zona glomerulosa and zona fasciculata cell types. These properties would explain the excess synthesis of 18-hydroxycortisol from a cell type that can uniquely hydroxylate steroid at both the 17 and 18 positions. (Hypertension 8: 669-676, 1986) KEY WORDS • hyperaldosteronism • cortisol • 18-hydroxycortisol 11-deoxycorticosterone * corticosterone EXAMETHASONE-suppressible hyperaldo-I I steronism is a familial form of hypertension A.^^ in which features of mineralocorticoid excess (hypokalemia, low plasma renin concentration) and elevated blood pressure remit during glucocorticoid treatment.13 Basal aldosterone secretion is increased 2 and aldosterone response to adrenocorticotropic hormone (ACTH) is exaggerated, 4 but the exact cause of these biochemical abnormalities, and indeed of the Received September 18, 1985; accepted January 28, 1986. hypertension itself, remains a matter for speculation. 56We studied two brothers with this condition and examined the effect of dexamethasone therapy on body sodium and potassium content. We also examined the effe...

Treatment of Familial Hyperaldosteronism Type I: Only Partial Suppression of Adrenocorticotropin Required to Correct Hypertension

“…Expression of the gene is regulated by ACTH by virtue of its 11␤-hydroxylase regulatory sequences, but the gene codes for an enzyme with aldosterone synthase activity, which catalyzes the final steps of aldosterone biosynthesis (1). As a result, aldosterone production in FH-I is regulated by ACTH rather than by angiotensin II (AII), and there is overproduction of aldosterone, which leads to the development of hypertension (2)(3)(4)(5)(6).…”

Combined Primary Aldosteronism and Cushing's Syndrome Due to a Single Adrenocortical Adenoma Complicated by Hashimoto's Thyroiditis.

“…One possibility is that APAmight be differentiated from transitional cells, which are located between the zona glomerulosa and zona fasciculata bearing characteristics of both glomerulosa and fasciculata cells ( 1 5). In normal conditions, this transitional zone exists only during the embryological development period (16). In some pathological conditions, such as glucocorticoidsuppressible aldosteronism, transitional cells have been identified ( 17).…”

Evaluation of the Dexamethasone Suppression Test for the Diagnosis of Glucocorticoid-Remediable Aldosteronism1

“…We believe that DST is best accomplished by administering 0.5 mg dexamethasone, orally, every 6 h for 2 days; concurrent measurement of cortisol with aldosterone is recommended to document adequate suppression of ACTH. Longer duration of DST (Ͼ1 week), as has been performed by some investigators (20,25), is not recommended because this may result in reactivation of the reninangiotensin system in GRA patients, possibly yielding false negative results. Although a cut-off of more than 80% suppression of aldosterone after DST would clearly have misclassified some patients with APA, a post-DST aldosterone level less than 4 ng/dL was seen in less than 7% of APA patients.…”