Subnormal Plasma Dehydroisoandrosterone to Cortisol Ratio in Anorexia Nervosa: A Second Hormonal Parameter of Ontogenic Regression

Twenty-four-hour mean plasma concentrations of cortisol, dehydroisoandrosterone (DHA), and dehydroisoandrosterone sulfate (DHAS) were measured in 14 young women (aged 19-29 yr) with anorexia nervosa (AN) in relapse and 10 age-matched healthy control women. Six of the AN patients were restudied after 5-35 months, when they were in partial remission. The AN patients in relapse showed significantly elevated plasma cortisol levels (11.3 vs. 7.3 μg/dl; P < 0.0001), as previously reported, but had subnormal adrenal androgen levels; DHA averaged 375 ng/dl (vs. 540 ng/dl in controls; P < 0.05), and DHAS averaged 64 μg/dl (vs.86 μg/dl in controls; P = NS). The DHA to cortisol ratio, which reflects the relative activities of the 17-hydroxypregnenolone → DHA and 17-hydroxypregnenolone → cortisol pathways, averaged less than half of normal (32 vs. 74;P < 0.001). Each of the 6 patients restudied while in partial remission showed an increase in the DHA to cortisol ratio, and the group as a whole showed a significant increase (P < 0.001), from a mean of 36 to a nearly normal value of 62. The failure of DHA levels to rise in AN patients in response to increased ACTH levels that result in elevated cortisol production and plasma cortisol levels resembles the picture seen in normal preadrenarcheal children; presumably, it is due to low activity of 17, 20-lyase (the enzyme that converts 17-hydroxypregnenolone to DHA), physiological in preadrenarcheal children and pathological in AN. The subnormal DHA to cortisol ratio in AN, therefore, constitutes a second hormonal parameter of ontogenic regression, regression of the 24-h plasma LH profile being the first.