Neuroendocrine consequences of anorexia nervosa in adolescents

Abstract

Anorexia nervosa (AN) is a condition of severe undernutrition characterized by alterations in multiple neuroendocrine axes and peptides that signal or regulate energy intake. These alterations include a state of hypogonadotropic hypogonadism, a nutritionally acquired resistance to growth hormone (GH) with low IGF-1 levels, relative hypercortisolemia, low total T3 despite normal TSH, low levels of leptin and insulin, and elevated levels of ghrelin, peptide YY (PYY) and possibly adiponectin. Although many of these changes are adaptive to low weight, they can impact bone metabolism, body composition, reproductive function and statural growth. Low bone mass is characteristic of AN in both adolescent boys and girls. In girls, sites of trabecular bone are more likely to be affected than sites of cortical bone, whereas in boys with AN, sites of cortical bone are more commonly affected. Bone microarchitecture is also affected in adolescent girls with AN, with a decrease in trabecular thickness and bone trabecular volume, and an increase in trabecular separation. Important predictors of low bone density include nutritional factors, body composition, hypogonadism, low IGF-1, elevated cortisol and PYY levels, with possible contributions of low insulin. Weight gain is associated with a stabilization of bone density, although residual deficits persist in the short term, and in some cases, long term.

Fig. 1

Changes in fat mass in AN girls who recovered menses (n = 19) (gray bar), AN girls who did not recover menses (n = 14) (black bar) and controls (n = 33) (white). ANOVA demonstrated a significant difference between the groups (p < 0.0001). AN girls who recovered menses had greater increases in fat mass than AN girls who did not resume menses and controls (p < 0.05 for both). Reprinted with permission from Misra et al. [8].

Fig. 2

Cluster and deconvolutional analyses in AN patients and controls. a Cluster analysis in 2 girls with AN (two left panels) and 2 healthy adolescent girls (two right panels). The mean and nadir GH concentrations and the total AUC were greater in girls with AN than in controls. b Deconvolutional analysis in the 2 girls with AN and the 2 healthy controls analyzed by cluster in a. The upper panels show GH concentrations over the sampling period; the lower panels show the individual secretory bursts. Girls with AN had higher basal GH secretion and a greater number of secretory episodes than healthy adolescents of comparable chronological and bone ages. Reprinted with permission from Misra et al. [11].

Fig. 3

Cluster analysis of cortisol concentration and deconvolutional analysis of cortisol secretion AN and healthy adolescents. a Cluster analysis in 2 girls with AN (two left panels) and 2 healthy adolescent girls (two right panels). Mean, nadir, valley mean, peak mass, peak amplitude of cortisol concentration, and total AUC were greater in girls with AN than in controls. b Deconvolutional analysis in the 2 girls with AN and the 2 healthy controls analyzed by cluster in a. The upper panels show cortisol concentrations over the sampling period, whereas the lower panels show the individual secretory bursts. Girls with AN had a greater number of secretory episodes than healthy adolescents of comparable CA and BA and higher pulsatile and total cortisol secretion. Reprinted with permission from Misra et al. [11].

Fig. 4

Bone density Z-scores in adolescent girls with AN and controls. Z-scores for lumbar spine bone mineral density (BMD), lumbar spine bone mineral apparent density (BMAD), hip bone density, whole body bone density and whole body bone mineral content/height (BMC/Ht) were lower in girls with AN (black bars) than in healthy controls (white bars). * p < 0.05.

Fig. 5

Bone density Z-scores in adolescent boys with anorexia nervosa and controls. Z-scores of the lumbar spine, total hip and its sub-regions (femoral neck, trochanter, intertrochanteric region) and the whole body were significantly lower in boys with anorexia nervosa than in controls. * p < 0.05. Reprinted with permission from Misra et al. [7].

Fig. 6

Change in lumbar BMAD and WB BMC/Ht measures in AN-not recovered (black bar), AN-recovered (gray bar), and healthy adolescents (white bar). AN-not recovered continued to lose bone mass over the 1-year follow-up period, and change in bone density measures was significantly lower in this group, compared with controls (Tukey-Kramer test for multiple comparisons). AN-recovered did not differ from controls for change in bone density parameters and differed significantly from AN-not recovered for change in whole body bone density Z-scores. * p < 0.05. Reprinted with permission from Misra et al. [41].