Lavin Chapter 12

138   Section 2 • Hypothalamic-Pituitary Dysfunction

GH treatment might promote the development of growth of tumors, but this has not been observed to be the case with GH therapy. J. Elderly. Normal age-related GH and serum IGF-1 reductions are associated with age-related changes that are similar to the signs and symptoms seen in GHD adults. Reports of effects of GH on BMD in non-GHD normal aging are conflict- ing. Thus, the use of GH to counter some of the effects of normal aging is still controversial. K. Diabetes. Because GH antagonizes the action of insulin, it may tend to raise blood glucose values, although this has not proven to be a significant problem in children. Despite widely demonstrated benefits of GH replacement treatment in adult GHD, an increase in the risk of developing diabetes should be considered. L. Ecuadorian dwarves. GH receptor deficiency (GHRD) in Ecuadorian adults is associated with obesity and enhanced insulin sensitivity. In a group of Ecuadorian dwarves, GHRD is associated with insulin efficiency and obesity. Studies state that these patients did not develop diabetes because they lack the counterregulatory effect of GH, thereby inducing a state of enhanced insulin sensitivity to compare to control relatives without diabetes and despite less insulin secretion. They said that there was a sixfold increase in the development of type II diabetes with GH therapy, which did not resolve when GH therapy was stopped. They suggest that the obesity of GHRD can best be attributed to unopposed insulin action associated with leptin resistance and that the elevated adiponectin concentrations are an accompaniment rather than a cause of their enhanced insulin sensitivity. They conclude, therefore, that the absence of GH is to the benefit of these patients and that GH therapy should not be given, at least to this subgroup of patients. M. Athletics: GH has been touted to achieve faster recovery from injury and enhanced ergogenicity, although there is no evidence that GH or IGF-1 actually improves competitive performance in young, healthy adults. 1. GH therapy offers significant clinical benefits in body composition, exercise capacity, skeletal integrity, and quality of life. GH reduces visceral fat and increases muscle mass and cardiac performance. Total cholesterol and LDL levels decrease, and CRP declines. CRP is a good indicator of cardiovascular risk because it accelerates vascular inflammation by interacting with endothelial receptors. Most patients with GHD have elevated CRP levels. Most, but not all, studies demonstrate a significant decrease of CRP levels with GH replacement. 2. An improvement in the lipid profile is often seen after GH treatment. A meta-analysis of several studies documented the effects on total cholesterol, with significant changes more prominent in elderly patients than in the young. Apoprotein B-100 is a known independent risk factor for cardiovascular disease that has been shown to decrease after GH therapy. LDL concentrations also decrease. Arterial distensibility and plaque formation are improved with GH treatment. GH is also a cytokine, and its receptor belongs to the family of cytokine recep- tors. Intracellular activation occurs through the signal-transducing activator of transcription protein 4, a well-known pathway for cytokines. One could speculate that by interfering with the action of proinflammatory cytokines, GH reduces or even reverses intima-media thickness and plaque formation. There is improved peripheral vasodilatation and production of nitric oxide. Systolic and diastolic blood pressure measurements decrease slightly but signifi- cantly in hypertensive patients. B. Acquired immune deficiency syndrome (AIDS): GH in adults has been approved by the Food and Drug Administration for people whose bodies are under stress or wasting because of the effects of AIDS, burns, or traumatic injuries. In AIDS, the wasting syndrome is characterized by significant unintended weight loss. GH may help with weight gain. C. Crohn disease: Crohn disease is a chronic inflammatory disorder of the bowel. In one study, researchers evaluated whether the administration of GH would improve

XXII. ARGUMENTS FOR GH TREATMENT A. Cardiovascular