Endocrinologic Sequelae of Anorexia Nervosa and Obesity

Anorexia nervosa (AN) is a severe psychiatric and medical condition characterized by restricted eating. Eighty-five percent of patients with AN present between the ages of 13 and 20 years during a critical period for growth, pubertal development, and maximal bone accretion that culminates in peak bone mass. The disorder can result in a compromise in each of these important endocrinologic events, with lifelong sequelae. Recent trends demonstrate an earlier age of onset of AN, and it is recognized that onset at a young age is associated with poor growth and bone health outcomes. More boys (i.e., assigned male at birth) are also presenting with restricted eating, with accompanying testosterone deficiency and other endocrine alterations. The prevalence has also increased dramatically since the onset of the COVID-19 pandemic. Patients with AN have a characteristic clinical picture of endocrine dysfunction, including amenorrhea in girls (i.e., assigned female at birth), abnormal temperature regulation, elevated growth hormone (GH) levels, hypercortisolemia, and abnormal eating suggestive of hypothalamic or pituitary dysfunction. Therefore, endocrine function has been studied extensively in these patients. The multiple endocrine abnormalities appear to represent an adaptation to the starvation state. Obesity, defined by weight above the 95th percentile for age and gender based on standardized growth curves (Centers for Disease Control and Prevention (CDC) (2000)), is a growing public health crisis in the United States and worldwide. Like AN, pediatric obesity has also increased as a result of the COVID-19 pandemic. Almost 20% of children and adolescents have obesity, and the prevalence does not appear to be plateauing. The accumulation of adiposity during puberty contributes to the development of multiple metabolic and endocrinologic abnormalities. Adolescents are growing rapidly and progressing through pubertal changes and, therefore, teleologically are programmed for efficiency in fuel utilization in preparation for the reproductive phase in life. Therefore, when adolescents gain excess weight and develop obesity, the physiologic insulin resistance and high levels of growth hormone, estrogens and androgens, lead to pathologic insulin resistance and resultant abnormalities in glycemia, lipids, liver function, musculoskeletal functioning, and reproductive function. In addition, adolescents with obesity demonstrate an endocrine profile that, in some aspects, is the polar opposite from anorexia nervosa, but with some overlapping features including amenorrhea, abnormal growth hormone secretion, hypercortisolemia, and altered appetite and metabolic rate due to central signalling pathway disturbances. Obesity clearly represents a pathologic state, with excess adiposity resulting in the activation of other compensatory mechanisms.