Jeunemaitre CHL, Schambelan M, Plouin PF, Corvol P
Dexamethasone-sensitive hyperaldosteronism with adrenal adenoma - Clinical, biological, and genetic analysis

Presse Medicale (Sep) 24:1243-1248 1995

This paper in French reports the family history of dexamethasone-sensitive hyperaldosteronism. Five adults (four brothers and sisters and their mother) presented with the complete syndrome, i.e., hypertension, hypokalemia (although variable) and hyperaldosteronism. Low plasma renin levels were found associated with elevated values of plasma aldosterone (221-435 pg/ml, normal being less than 100). Abnormally high urinary excretion of 18-OH components was present (a 10 to 70 fold increase in 18-OH cortisol excretion and a 4 to 8 fold increase in 18-oxocortisol excretion). Diagnosis was established by a positive dexamethasone test (e.g., administration of 1 mg of dexamethasone at 12:00 a.m., then 0.5 mg at 6:00 a.m.), which induces a drop greater than 80% in plasma aldosterone levels and in urine aldosterone excretion.

The underlying genetic abnormality for this syndrome has been recently reported. A chimeric gene (from CYP11B1 and CYP11B2 genes) induces a abnormal 11OHase-aldosterone synthase which is ACTH-sensitive. This mutation cosegregates with the hormonal impairment and appears to be transmitted in an autosomally dominant pattern. The authors present a rapid genetic testing (Southern blotting) performed in 17 subjects from that family. The chimeric gene was present in 6 hypertensive patients (born in 1939, 1959, 1962, 1965, 1968 and 1972) and in 2 nonhypertensive although younger subjects (born in 1983 and 1989) from a common grandmother. Treatement of five patients by 1 mg dexamethasone daily for 8 to 10 weeks resulted in a blood pressure reduction (140/90 to 130/80 mmHg), an increase in serum K+ from 3.8 to 4.3 mmol/l and a decrease in plasma aldosterone from 469 to 259 pg/ml. Of interest, 2 of the 6 patients presented an adrenal adenoma (15 and 13 mm) and two others had small (less than 10 mm) nodules in their adrenal glands, suggesting a continuum between adrenal hyperplasia and adenoma.

Comment:: The diagnosis of DXM-sensitive hyperaldosteronism is based on the abnormal urinary excretion of 18-OH compounds, a technically difficult test to perform. The genetic testing presented here is accurate and may allow an early diagnosis of this syndrome. (Fouque)

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H: Special problems : Endocrine hypertension