Abstract

Introduction: Anorexia nervosa (AN) and atypical AN (defined as weight loss and all the psychological features of AN but BMI>18.5 kg/m2) are serious disorders characterized by undernutrition and complicated by endocrine dysregulation. Predictors of recovery, including serum biomarkers, are lacking. Prior studies have suggested that higher urinary free cortisol (UFC) may predict weight gain in women with AN, but 24-hour urine collections are not feasible in a real-world setting. Like cortisol, the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfated form DHEAS, which has a longer half-life, are stimulated by ACTH. We hypothesized that DHEAS levels would correlate with UFC and be a predictor of weight gain in women with AN.Methods: We prospectively studied 34 women with AN and atypical AN, mean age 27.4 ± 7.7 years (mean ± SD), who received placebo in a randomized trial. AN and atypical AN were diagnosed by SCID. Baseline DHEAS and 24-hour UFC were measured by LC-MS/MS (Endocrine Sciences, Calabasas Hills, CA). Weight and body composition were assessed at baseline and 6 months later by DXA and cross-sectional abdominal CT at L4.Results: At baseline, mean weight was 51.3 ± 4.9 kg. Of the 18 subjects who gained weight (range 0.1–10.3 kg), 28% were eumenorrheic, 39% amenorrheic, and 33% on oral contraceptives at baseline; baseline reproductive status was similar for subjects who did not subsequently gain weight. In the group as a whole, mean baseline DHEAS level was 173 ± 70 µg/dL (0.7 ± 0.3 times the mean normal range for age) and mean baseline UFC for subjects who completed testing (n=15) was 20 ± 18 µg/24h (normal range 0–50 µg/24h). Higher DHEAS levels at baseline predicted weight gain over 6 months (r=0.61, p<0.001), which remained significant after controlling for age, baseline BMI, OCP use, and SSRI/SNRI use (p<0.001); none of these covariates were predictors of weight gain. Baseline DHEAS levels predicted an increase in fat mass (r=0.40, p=0.03) and appendicular lean mass (r=0.38, p=0.04) by DXA, and abdominal fat by CT (r=0.60, p<0.001); the associations remained significant after controlling for the above factors. UFC did not predict change in weight (r=0.37, p=0.17) or body composition. DHEAS levels were positively associated with UFC (r=0.61, p=0.02).Conclusion: In women with AN, higher DHEAS levels are a predictor of weight gain and increases in fat mass, skeletal muscle mass, and abdominal fat. Serum DHEAS correlates with UFC, a predictor of weight gain in prior studies. DHEAS may be a more practical biomarker of recovery, as 24-hour urine collections are challenging. Further studies are needed to determine whether higher DHEAS levels are a marker of global adrenal stress response and a reflection of higher cortisol levels, which may stimulate weight gain, or an independent predictor of weight gain in AN and atypical AN, perhaps through neuromodulation.

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