Atypical anorexia nervosa is a new formal diagnosis within Other Specified Feeding or Eating Disorder (OSFED) for individuals who meet anorexia nervosa psychological criteria but are not low weight183. Much less is known about anorexia nervosa in adolescent boys and men than girls and women, and should be an active area of investigation. Further research is also needed to understand the interplay between appetite-regulating hormones and brain food motivation circuitry, specifically in anorexia nervosa. Data on the efficacy of testosterone replacement on BMD in adolescent boys or men with anorexia nervosa are not available. The sex-specific effects of anorexia nervosa on BMD suggest that not all data from women can be extrapolated to the male population. Men with anorexia nervosa have a higher percentage trunk fat and a higher trunk-to-extremity fat ratio than healthy men after controlling for weight174. Although 5–15% of those affected by anorexia nervosa are men, very limited data exists regarding the endocrine impact of the disease in this population. AN also has dramatic effects on normal growth, bone turnover, nutrient metabolism, and appetite regulation. Appetite is modulated by the neuroendocrine system, and characteristic patterns of leptin and ghrelin concentrations have been observed in anorexia nervosa. We performed a PubMed search of the English-language literature related to the pathophysiology of the endocrine disorders observed in anorexia nervosa, and we describe a case to illustrate these findings. Decreased DHEA-S levels could reflect changes in DHEA sulfotransferase and/or PAPSS2 activities.51 Whether the relatively higher DHEA levels are due in part to activation of the hypothalamic–pituitary–adrenal axis and ACTH stimulation, for example, is not known, and further study is needed to better understand this divergence between DHEA and DHEA-S levels in AN. Therefore, it is critical for clinicians to keep AN in the differential diagnosis of patients with cortisol excess, as not doing so may result in patients undergoing unnecessary evaluations/procedures and possible treatment, which potentially may result in more harm than benefit. First, cortisol assessments in patients with AN are elevated, and therefore, the biochemical assessment will be similar to that in patients with Cushing's syndrome. Whether this relative hyperleptinaemia of weight recovery contributes to resistance to weight gain or recurrent weight loss is unknown. Leptin stimulates secretion of GnRH and hypoleptinaemia might contribute to hypothalamic amenorrhea in anorexia nervosa18. In anorexia nervosa, basal and pulsatile secretion of leptin is reduced in association with reductions in fat mass88. Other electrolyte abnormalities that might occur in anorexia nervosa include hypokalaemia, hypomagnesaemia and hypophosphataemia. There were no significant differences in DHEAS levels among the other groups, including women with anorexia nervosa not receiving oral contraceptives and healthy controls. In addition, mean free testosterone levels were lower in women with anorexia nervosa receiving oral contraceptives than in women with anorexia nervosa not receiving oral contraceptives. However, it is not known whether similar reductions occur in women with anorexia nervosa or whether estrogeninduced hypoandrogenemia is one of the mechanisms underlying the ineffectiveness of oral contraceptives to either prevent or reverse bone loss in women with anorexia nervosa. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. Pituitary growth hormone (GH) pulsatility and secretion are higher in states of chronic starvation such as AN , which may be mediated in part by increased levels of ghrelin, a GH secretagogue . In addition, T4 and/or T3 supplements have the potential to be abused by patients with AN since they increase basal metabolic rate and can cause weight loss. In more severe disease, levels of thyroid stimulating hormone (TSH) from the anterior pituitary and free T4 from the thyroid may fall into the low-normal range due to general suppression of the hypothalamic-pituitary-thyroid axis. The 24-hour pooled serum cortisol measurement is a highly accurate measurement, as it provides a comprehensive measurement of total cortisol over the 24-hour period, but it is also challenging and time-consuming to implement. As this study only involved the analysis of data from previously published studies, ethics approval was not required. As different studies used varying units of measurement, these were standardized for each hormone.8,9 Extracted data included the name of the study, name of the first author, year(s) of study, year of publication, recruitment of cases and comparators, diagnostic criteria, baseline characteristics (age and BMI) of cases and comparators, method of hormone measurement, and means and SDs for each reported adrenal hormone. This finding is important to consider when evaluating low-weight women for disorders involving the adrenal axis, especially Cushing's syndrome. Means and standard deviations for each hormone were extracted from the studies to calculate a mean difference (MD). Regarding the comparison of CT and AN, hormone levels can help to distinguish between these two conditions if in doubt. The average BMI was 14 kg/m2 with an average weight loss of 16.48 pounds per month. Three of the 4 patients had no previous diagnosis of AN or other eating disorder; therefore, it was not initially considered in the differential diagnosis. Weight loss and increased stress may have led to hypothalamic dysfunction, with further adaptive mechanisms causing organ dysfunction. These men had an average BMI of 13.85 kg/m2 (range, 12 to 18 kg/m2), weight loss of 87.75 pounds (range, 35 to 141 pounds), temperature of 35.2°C (range, 33.9 to 36.4°C), heart rate of 39.75 beats per minute (range, 30 to 60 beats per minute), and blood pressure 87/57 mm Hg (range, 74/48 to 94/68 mm Hg). An upper endoscopy was performed to further evaluate weight loss and persistent nausea and vomiting, which revealed chronic gastritis and Helicobacter pylori, without evidence of malabsorption. Total testosterone was 614 ng/dL (normal, 249 to 836 ng/dL), and free testosterone was 5.4 pg/mL (normal, 9.3 to 26.5 pg/mL), with FSH 1.9 IU/L (normal, 4.7 to 21.5 IU/L) and LH 6.3 IU/L (normal, 2.4 to 12.6 IU/L).
