DEXAMETRASONE-SENSITIVE HYPERALDOSTERONIS M WITH ADRENAL ADENOMA - CLINICAL, BIOLOGICAL AND GENETIC-ANALYSIS

Objectives: Dexamethasone-sensitive hyperaldosteronism is associated w ith early onset hypertension and primary hyperaldosteronism, Diagnosis is difficult but can be improved by genetic testing for the mutant ge ne. Methods: We collected the clinical, biological and genetic element s observed in a family with dexamethasone-sensible hyperaldosteronism. Complete data were obtained in 5 adult subjects with the disease, Deg ree of hypertension varied, more so in the second generations as did h ypokaliaemia and hyperaldosteronism, In affected patients, there was a 10 to 50 fold increase in urinary 18-OH components and 18 oxocortisol . Results: Single dose (1.5 mg) dexamethasone led to a greater than 80 % drop in aldosterone levels in the blood and urine, confirming the ab normal effect of ACTH on mineralocorticoid secretion, At the dose of 1 mg/d for 10 weeks, dexamethasone lowered mean 24-H ambulatory arteria l pressure (11.8/9.6 mmHg) and corrected for the hypokaliaemia (+ 0.54 mmol/l) and the hyperaldosteronism (mean decrease -36% and -75% in bl ood and urine respectively), An adrenal tumour was identified in hyper plasic glands in two subjects and a micronodular formation was identif ied in two others, The specific molecular diagnosis of the disease was done with Southern blotting, Among the 18 families in 3 generations, 8 carried a 11 beta OHase-aldosterone synthetase chimeric gene, This m utation cosegregates with hormonal abnormalities and confirms the auto somal dominant inheritance of the disease. Conclusion: The simplicity and rapidity of genetic testing allows early diagnosis of this disease among families with early onset hypertension and associated hyperaldo steronism with or without adrenal hyperplasia and/or a tumoral formati on.