[Hyperaldosteronism sensitive to dexamethasone with adrenal adenoma. Clinical, biological and genetic study].

OBJECTIVES

Dexamethasone-sensitive hyperaldosteronism is associated with early onset hypertension and primary hyperaldosteronism. Diagnosis is difficult but can be improved by genetic testing for the mutant gene.

METHODS

We collected the clinical, biological and genetic elements observed in a family with dexamethasone-sensible hyperaldosteronism. Complete data were obtained in 5 adult subjects with the disease. Degree of hypertension varied, more so in the second generations as did hypokaliaemia 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 abnormal effect of ACTH on mineralocorticoid secretion. At the dose of 1 mg/d for 10 weeks, dexamethasone lowered mean 24-H ambulatory arterial pressure (11.8/9.6 mmHg) and corrected for the hypokaliaemia (+0.54 mmol/l) and the hyperaldosteronism (mean decrease -36% and -75% in blood and urine respectively). An adrenal tumour was identified in hyperplasic glands in two subjects and a micronodular formation was identified 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 mutation cosegregates with hormonal abnormalities and confirms the autosomal 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 hyperaldosteronism with or without adrenal hyperplasia and/or a tumoral formation.