Growth hormone deficiency in patients with obesity.

Abstract

It is well known that the growth hormone (GH)-insulin-like growth factor type I (IGF-I) axis-in addition to regulating somatic growth exerts important metabolic actions and regulates body composition [1]. GH (like insulin) is essential in adapting the utilization of calories to the amount of ingested food, promoting anabolism when caloric supply exceeds demands, and catabolism in the opposite situation. While insulin is the main metabolic hormone in the fed state, GH assumes a key role as stimulator of lipolysis during prolonged fasting, when it causes preferential oxidation of lipids and protein synthesis [2]. The increase in GH secretion that occurs with fasting may have represented an evolutionary advantage in times of food scarcity. However, GH and IGF-I have opposite effects on glucose homeostasis, with the former reducing insulin sensitivity (mainly acting in the liver) and the latter increasing it in the muscle. The relationships between adipose tissue and GH secretion are complex. Obesity induces hyperinsulinemia, hypo-adiponectinemia, hyper-leptinemia, reduced serum ghrelin, and increased free fatty acid (FFA) levels, thereby suppressing GH secretion from the pituitary [3]. Thus, high prevalent conditions related to insulin resistance, such as visceral obesity, non-alcoholic hepatic disease, and type 2 diabetes, are associated with low GH secretion [3]. Because GH can contribute to insulin resistance that may develop when caloric supply exceeds demand, the reduction in GH secretion that occurs with obesity may be an adaptive phenomenon to prevent insulin resistance [3]. However, the reduction in GH secretion may further increase fat accumulation by reducing lipolysis, and therefore exacerbate obesity, establishing a dangerous vicious circle. Accordingly, truncal adiposity is one of the most important clinical findings of the adult GH deficiency (GHD) syndrome [4]. Despite this association, a reverse causal link between GHD and obesity has not been established. Another important interaction between GH and adipose tissue relates to the activity of the 11b-hydroxy steroid dehydrogenase type 1 (11b-HSD-1) enzyme, which catalyzes the conversion of inactive cortisone to active cortisol. Because GH (and/or IGF-I) inhibits 11b-HSD-1 expression in adipose tissue (and liver), GHD causes increase in 11b-HSD-1 activity, thereby creating a local cortisol excess even when overall cortisol levels are normal [5]. Great attention has been paid in the last 2 decades on studying the consequences of adult onset GHD. This condition results in increased visceral adipose tissue, insulin resistance, and increased cardiovascular risk [4]. Conversely, the GH status of obese subjects is less well characterized. It is well known that the secretion of GH is markedly reduced in obese individuals compared to agematched controls [3]. Indeed, the GH response to a variety of stimuli is significantly blunted in obese subjects. Several mechanisms underlie this condition, including reduction of both frequency and amplitude of GH secretory bursts and increase in GH metabolic clearance [6]. Whether these changes are a simple and adaptive consequence of obesity, or they somehow contribute or worsen the excessive weight accumulation is not yet known. In this issue of Endocrine Lubrano et al. [7] performed pituitary MRI and GH stimulation test (with GHRH ? arginine) in a large number (184) of obese subjects & Roberto Salvatori salvator@jhmi.edu