Endocrine consequences of anorexia nervosa

Abstract

Anorexia nervosa is prevalent in adolescents and young adults, and endocrine changes include hypothalamic amenorrhoea; a nutritionally acquired growth-hormone resistance leading to low concentrations of insulin-like growth factor-1 (IGF-1); relative hypercortisolaemia; decreases in leptin, insulin, amylin, and incretins; and increases in ghrelin, peptide YY, and adiponectin. These changes in turn have harmful effects on bone and might affect neurocognition, anxiety, depression, and the psychopathology of anorexia nervosa. Low bone-mineral density (BMD) is particularly concerning, because it is associated with changes in bone microarchitecture, strength, and clinical fractures. Recovery leads to improvements in many--but not all--hormonal changes, and deficits in bone accrual can persist. Oestrogen-replacement therapy, primarily via the transdermal route, increases BMD in adolescents, although catch-up is incomplete. In adults, oral oestrogen--combined with recombinant human IGF-1 in one study and bisphosphonates in another--increased BMD, but not to the normal range. More studies are necessary to investigate the optimum therapeutic approach in patients with, or recovering from, anorexia nervosa.

Figure 1. Impact of anorexia nervosa (AN) on growth hormone (GH) and IGF-1

A. Representative overnight GH secretory characteristics in a teenage girl with AN (left) and a normal-weight control (right) showing increased GH secretion in the girl with AN. B. Mean overnight GH concentrations (left) and fasting IGF-1 levels (right) in adolescent girls with AN and controls. Adolescent girls with AN have lower IGF-1 levels than controls despite higher GH concentrations, suggestive of a nutritionally acquired resistance to GH effects. Adapted from Misra et al. J Clin Endocrinol Metab 88: 5615–5623; 2003. Copyright © by The Endocrine Society 2003.

Figure 2. Impact of anorexia nervosa (AN) on cortisol secretion

A. Representative overnight cortisol secretory characteristics in a teenage girl with AN (left) and a normal-weight control (right), showing greater cortisol secretion in the girl with AN. B. 24-h urinary free cortisol levels in adolescent girls with AN and controls. Adolescent girls with AN have higher 24-h urinary free cortisol compared with controls. Adapted from Misra et al. J Clin Endocrinol Metab 89: 4972–4980; 2004. Copyright © by The Endocrine Society 2004.

Figure 3. The proportion of body fat is an important determinant of menstrual function

A. Percent body fat in girls with anorexia nervosa (AN) who did or did not resume menses: Girls with AN who recovered menstrual function over a year of follow-up had greater percent body fat at the end of the follow-up period than those who did not. All girls with body fat greater than 24% resumed menses, whereas none of those with body fat less than 18% had menstrual recovery. From Misra et al. Pediatr Res 59: 598–603; 2006. Copyright © by International Pediatric Research Foundation, Inc., 2006. B. Percent body fat in low weight adult women who were amenorrheic (mean BMI 16.8±0.2 kg/m²) vs. those who were eumenorrheic (mean BMI 17.1±0.2 kg/m²). Despite similarly low BMI status, eumenorrheic women had greater percent body fat than amenorrheic women. Adapted from Miller et al. J Clin Endocrinol Metab 89: 4434–38; 2004. Copyright © by The Endocrine Society 2004.

Figure 4. Impact of weight and/or menstrual recovery on bone density parameters in adult women with anorexia nervosa not receiving oral contraceptives

A. Women who both improved weight and resumed menses increased BMD at the PA spine and hip, compared with those who neither improved weight nor resumed menses. B. Women who resumed menses increased PA spine BMD (but not hip BMD), compared with those who did not improve menstrual function. C. Women who improved weight increased hip BMD (but not PA spine BMD), compared with those who did not improve weight. Black bars, PA spine BMD; white bars, hip BMD. *, P < 0.05. From Miller et al. J Clin Endocrinol Metab 91: 2931–7; 2006. Copyright © by The Endocrine Society 2006.

Figure 5. Impact of physiologic estrogen replacement on bone density in adolescent girls with anorexia nervosa (AN). Girls with AN randomized to physiologic estrogen administration (ANE+) had significant increases in bone density at the lumbar spine over 6, 12 and 18 months compared with those randomized to placebo (AN-E−), to approximate bone accrual rates observed in controls (C) (adjusted for baseline age and weight)

From Misra et al. J Bone Mineral Metab. 26; 2430–2438; 2011. Copyright © by The American Society for Bone and Mineral Research, 2011.

Figure 6. Endocrine changes in anorexia nervosa that maintain euglycemia and preserve energy for vital functions, and also contribute to impaired bone metabolism

CRH: corticotrophin releasing hormone; ACTH: adrenocorticotropic hormone GH-IGF-1 axis: growth hormone- insulin like growth factor-1 axis GHBP: GH binding protein GLP-1: glucagon like peptide-1; GIP: glucose-dependent insulinotropic peptide HPG axis: hypothalamic-pituitary-gonadal axis HPA axis: hypothalamic-pituitary-adrenal axis HPT axis: hypothalamic-pituitary-thyroid axis LH: luteinizing hormone PYY: peptide YY T3: tri-iodothyronine; T4: tetra-iodothyronine; TSH: thyroid stimulating hormone