Patients with
anorexia nervosa (AN) may develop multiple endocrine abnormalities, including
amenorrhea, hyperactivity of the hypothalamus-pituitary-adrenal axis,
hypothyroidism and particular changes in the activity of the
growth hormone (GH)/
insulin-like growth factor I (
IGF-I) axis. Exaggerated GH secretion and reduced
IGF-I levels are usually found in AN, as well as in conditions of
malnutrition and malabsorption,
insulin-dependent diabetes mellitus,
liver cirrhosis and catabolic states. In AN, GH hypersecretion at least partially reflects
malnutrition-induced peripheral GH resistance, which leads to reduced
IGF-I synthesis and release; this implies an impairment of the negative
IGF-I feedback action on GH secretion. On the other hand, primary alterations in the neural control of GH secretion cannot be ruled out. The neuroendocrine alterations include enhanced somatotroph responsiveness to
growth hormone releasing hormone (GHRH) and impaired GH response to most central nervous system-mediated stimuli. Particular resistance to
cholinergic manipulation has also been demonstrated, thus suggesting a somewhat specific alteration in the
somatostatin (SS)-mediated
cholinergic influence on GH secretion. Moreover, paradoxical GH responses to
glucose load,
thyrotropin releasing hormone (TRH) and
luteinizing hormone releasing hormone (
LHRH) have also been reported. The effect of reduced
leptin levels on GH hypersecretion in AN is still unclear, but
ghrelin (the gastric
hormone that is a natural
ligand of the GH
secretagogue receptor and strongly stimulates somatotroph secretion) is thought to play a major role. Regardless of the supposed central and peripheral alterations, it has to be emphasised that the activity of the GH/
IGF-I axis in AN is generally restored by nutritional and stable
weight gain. It therefore reflects an impaired nutritional state and cannot be considered a primary hallmark of the disease.