We have studied a family (12 members) with 3 patients (2 adult females and 1 pubertal-aged genotypic male) affected by congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency, all of whom presented as phenotypically female subjects with lack of sexual development and with hypokalemic hypertension. The baseline hormonal pattern revealed low glucocorticoid levels (17-hydroxyprogesterone, plasma and urinary cortisol, cortisol secretion rate), as well as androgen (testosterone and dehydroepiandrosterone sulfate) and estrogen (17-beta-estradiol) levels, since the defect is present at both adrenal and gonadal levels. As a consequence ACTH, LH, and FSH concentrations were high. Otherwise steroids not requiring 17-alpha-hydroxylation, such as deoxycorticosterone, corticosterone and their 18-hydroxylated compounds, were secreted in excess with the exception of aldosterone whose levels were undetectable; baseline plasma renin activity levels were suppressed. Short-term dexamethasone treatment normalized potassium and reduced blood pressure and the abnormal mineralocorticoid levels. During chronic ACTH suppression with low doses of glucocorticoids (8 years), electrolyte disturbances were corrected, blood pressure was normalized in 2 cases but only reduced in the third; plasma renin activity returned to normal range within four years in all the patients, while urinary aldosterone was normalized only after 8 years of therapy and became partially responsive to posture, ACTH, angiotensin II, and furosemide. The other mineralocorticoids were reduced but remained above the normal range. The HLA-genotyping in all the family members revealed that the gene responsible for 17-alpha-hydroxylase deficiency was not linked to the HLA system. Measurement of plasma steroids (deoxycorticosterone, corticosterone, aldosterone) in this family revealed that the heterozygotes were different from the control population only in their ACTH-stimulated corticosterone levels.
Since calcium entry blocker drugs can interfere with aldosterone secretion in vitro, a similar effect in vivo, in man, has been suggested and partially confirmed. The data available in primary aldosteronism are more controversial. Therefore, we have studied the acute and chronic effect of nifedipine in 7 patients with idiopathic hyperaldosteronism (IHA) and 8 with aldosterone producing adenoma (APA). On 2 different days, 10 mg of nifedipine or placebo were given sublingually to the patients and blood pressure and heart rate were recorded every 5 min. for 60 min. Plasma aldosterone, cortisol, PRA and serum K+ were measured at 0, 30 and 60 min. 5 patients with IHA and 6 with APA received nifedipine 20 mg per os bid for 3 months; the same parameters were evaluated on days 0, 30, 60 and 90; urinary aldosterone was measured on days 0, 30, 60 and 90. BP decreased in both groups both after acute and chronic administration of nifedipine. Plasma aldosterone showed a similar trend either after acute nifedipine or placebo; however, during chronic treatment it was slightly decreased in IHA patients. Cortisol, PRA, urinary aldosterone and K+ remained unchanged. In conclusion, nifedipine is an effective antihypertensive agent also in primary aldosteronism; its aldosterone inhibiting properties are minimal and seem to be present only during long-term therapy in IHA.
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