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Multiple Endocrine Abnormalities of the Growth Hormone and Insulin-Like Growth Factor Axis in Patients with Anorexia Nervosa: Effect of Short- and Long-Term Weight Recuperation¹

Department of Pediatrics, Autonomous University, Division of Pediatric Endocrinology (J.A., N.C., V.B., M.T.M., J.P., M.H.) and the Division of Pediatric Psychiatry (G.M.), Hospital of Niño Jesús,E-28009 Madrid; and the Laboratory of Molecular and Cellular Neuroendocrinology, Ramón y Cajal Institute, Madrid, Spain

Address all correspondence and requests for reprints to: Jesús Argente, M.D., Ph.D., Division of Pediatric Endocrinology, Department of Pediatrics, Hospital Niño Jesús, Avenida Menéndez Pelayo 65, 28009 Madrid, Spain.

We have studied the GH-insulin-like growth factor (IGF) axis in patients with anorexia nervosa at the time of diagnosis and at two points during weight recuperation. We report their spontaneous GH secretion and IGF-I, free IGF-I (fIGF-I), IGF-II, the IGF-binding proteins (IGFBP-1, IGFBP-2, and IGFBP-3), and GH-binding protein (GHBP) levels at the time of the clinical diagnosis (n = 50) and after recuperation of between 6–8% (n = 42) and 10% or less of the initial weight (n = 20). Two distinct groups were seen, those who significantly hypersecreted GH and those whose GH secretion was reduced significantly. After recuperation of 10% or more of their initial weight, all patients had a normal GH pattern. Independently of GH secretory dynamics, IGF-I, IGFBP-3, and GHBP serum levels were all significantly decreased at diagnosis, and only GHBP returned to normal after weight recuperation. Serum IGFBP-1 and IGFBP-2 levels were significantly increased at the time of diagnosis and decreased after weight recuperation. The body mass index (BMI) correlated positively with fIGF-I levels and negatively with IGFBP-1 and IGFBP-2 levels, but only after weight recuperation in all cases. Contrary to what is seen in normal individuals, no correlation was found between BMI and serum GHBP levels in anorexia nervosa patients. Serum IGFBP-2 levels had a strong negative correlation with fIGF-1, IGF-II, and the sum of IGF-I and IGF-II, but only at the time of diagnosis.

In conclusion, the GH-IGF axis is dramatically altered in patients with anorexia nervosa. Changes in the peripheral IGF system, however, appear to be independent of modifications in GH secretion and, in contrast to current thought, not all of the observed abnormalities are rapidly reversed with weight recuperation.

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