GH/IGF-I axis in anorexia nervosa.
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.
Gianotti
L
L
Division of Endocrinology, Department of Internal Medicine, University of Turin, Italy. laura.gianotti@unito.it
Lanfranco
F
F
Ramunni
J
J
Destefanis
S
S
Ghigo
E
E
Arvat
E
E
D000856:Anorexia Nervosa / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D044342:Malnutrition / Q000209:etiology / Q000378:metabolism; D009490:Neurosecretory Systems / Q000503:physiopathology*; D013002:Somatomedins / Q000378:metabolism*; D052683:Somatotrophs / Q000378:metabolism
D013002:Somatomedins; D013006:Growth Hormone