Appropriate use of stimulation tests and insulin-like growth factor-I in obesity.

Obesity is characterized by abnormal GH secretion, with GH levels reduced up to levels that are comparable to those found in adult patients with organic GH deficiency (GHD). Despite the marked GH insufficiency, obese patients with no evidence of pituitary disease have generally normal levels of total IGF-I but increased levels of free IGF-I. Although the mechanism of the low GH in obesity is not completely understood nor is it clear whether its relationship with visceral adiposity is causal, it is widely accepted that the low GH secretory state in obesity is reversible since it is completely reversed by the normalization of body weight. Since overweight and obesity might affect the GH response to all provocative stimuli, particular attention has been recently paid to the confounding effect of body weight on the interpretation of GH stimulating tests and appropriate cut-offs for lean, overweight, and obese subjects must be used in order to avoid false-positive diagnoses of severe GHD in obese adults. As the definition of appropriate criteria for the correct diagnosis of GHD in obesity is still debated, and the beneficial effects of chronic recombinant human GH replacement on obese individuals have not been definitely proved yet, further studies are therefore mandatory to confirm the real effectiveness of GH supplementation in conditions associated with a blunted GH secretion without organic hypopituitarism and to understand the physiological relevance of "functional" GHD on the pathogenesis of the multiple maladaptative endocrine changes involved in the pathogenesis of obesity.