Adrenal insufficiency in Smith-Lemli-Opitz syndrome

We describe three unrelated patients with adrenal insufficiency and RSH or Smith-Lemli-Opitz syndrome (SLOS), a disorder due to deficient synthesis of cholesterol, These patients presented with hyponatremia, hyperkalemia, and decreased aldosterone-to-renin ratio, which is a sensitive measure of the renin-aldosterone axis. All patients had profound serum total cholesterol d eficiency (14-31 mg/dl) and marked elevation of 7-dehydrocholesterol (10-45 mg/dl), Two patients were newborn infants with 46, XY karyotypes and compl ete failure to masculinize; one of these patients also had cortisol deficie ncy. Both patients died within 10 days of birth of cardiopulmonary complica tions while on adrenal replacement therapy. The third patient diagnosed wit h SLOS at birth presented at age 7months with fever and diarrhea and was no ted to have profound hyponatremia, This patient is maintaining normal serum electrolytes on mineralocorticoid replacement. We conclude that adrenal in sufficiency may be a previously undetected and treatable manifestation in S LOS, We hypothesize that deficiency of cholesterol, an adrenal hormone prec ursor, may lead to insufficient synthesis of adrenal steroid hormones. (C) 1999 Wiley-Liss, Inc.