Endocrine disturbances associated with myotonic dystrophy (MD) include testicular atrophy, hyperinsulinemic glucose intolerance, thyroid abnormalities, and low or low normal urinary 17-ketosteroid (17-KS) excretion. Since the major circulating precursors of urinary 17-KS are dehydroepiandrosterone sulfate (DHAS) and dehydroepiandrosterone (DHA), a decrease in adrenal androgen production has been suggested. This possibility was studied in 19 MD patients and 19 age- and sex-matched normal subjects. Each patient had a 24-h urine collection for 17-KS and cortisol determinations, a 4-h iv infusion of 25 micrograms tetracosactrin with serial measurements of serum DHAS, DHA, and cortisol, and an insulin-induced hypoglycemia test. Sixteen patients had 0800 and 2400 h serum collections for cortisol estimations. Serum DHAS [1.0 +/- 0.5 (+/- SD) vs. 3.9 +/- 1.9 mumol/liter; P less than 0.0005] and DHA (5.9 +/- 2.7 vs. 11.0 +/- 7.1 nmol/liter; P less than 0.005) levels were significantly lower in MD patients than in normal subjects; cortisol levels were higher (540 +/- 222 vs. 394 +/- 128 nmol/liter; P less than 0.01), almost certainly a reflection of stress. A normal diurnal cortisol rhythm was found in all 16 subjects. Cortisol responses to insulin-induced hypoglycemia were normal, increasing from 345 +/- 243 nmol/liter to a maximum of 831 +/- 282 nmol/liter. Urinary 17-KS excretion was low or low normal, while urinary cortisol levels were normal in 18 and mildly elevated in 1 patient. There was a significant correlation between 17-KS and DHAS levels (r = 0.46; P less than 0.05). DHAS, DHA, and cortisol responses to tetracosactrin infusion were similar in patients and normal subjects. It is concluded that 1) in MD patients, serum DHAS and DHA concentrations are significantly lower than those in normal subjects, explaining the frequent reports of low or low normal 17-KS excretion; 2) the reduced DHAS and DHA concentrations are most likely due to decreased production rather than increased clearance; and 3) glucocorticoid production is normal.