Lavin Chapter 12

136   Section 2 • Hypothalamic-Pituitary Dysfunction

correlates with the severity of osteopenia. There is an increase in the volume of tra- becular bone, increased reabsorption, and increased osteolite thickness, suggesting delayed mineralization. Fracture rates up to two to five times greater than normal have been reported in GH-deficient patients. One study showed that GH induced an increase in BMD. The mean initial dose of GH was 0.98 mg/day, which was gradually lowered, so that at the end of the study the mean dose was 0.47 mg/day. GH replacement induced a sustained increase in total lumbar and femur neck BMD and bone mineral content as measured by DEXA scan. The authors concluded that 10 years of GH replacement in patients with GHD induced a sustained and, in some cases, a progressive increase in bone mass and bone density. B. GH stimulates both bone formation and reabsorption, but with < 12 months of treatment, the BMD by DEXA scanning may not increase, but after 18 to 24 months of treatment, most studies have shown increases in BMD. C. Ten years after it was administered, GH continued to reduce the risk of fractures and helped maintain bone density in postmenopausal women who had osteoporosis, according to a new study published in the JCEM . D. 15-Year GH replacement in GHD adults induced a sustained increase in total body and lumbar (L2–L4) spine bone mineral concentration and BMD. This meta-analysis suggests a beneficial effect of human growth hormone (HGH) replacement on BMD in adults with GHD. When compared with non-GHD control populations, adults with GHD and hypopituitarism have been shown to have twofold to fivefold higher fracture rates. It is interesting that GH replacement initially decreases the bone den- sity, which is followed by a subsequent increase after at least 1 year of replacement. The results of short-term (12 months or less) randomized controlled trials of GH replacement were indeed mostly negative, revealing a decrease or no change within a short period of time, but long-term usage shows significant improvement in BMD. This biphasic effect of HGH replacement observed in randomized studies has been previously described in the literature and is consistent with the hypothesis that GH stimulates both bone formation and bone resorption as evidenced by changes in bone markers, which results in increased bone turnover. The Endocrine Society recommends GH for this abnormality using a fixed starting replacement dose of 0.2 to 0.3 mg/day in adults aged 30 to 60. Women require higher replacement GH doses as compared with men because oral estrogen inhibits GH-induced IGF-1 synthesis . XIX. ADOLESCENTS A. After discontinuation of GH therapy in children 15 to 17 years of age, there may be a reduced acquisition of bone mineral content. An important issue, therefore, is whether therapy should be maintained or reinstituted, at least until the subjects reach peak bone mass. B. There is some evidence that BMD is greater in those who continue GH therapy for an additional 2 years after cessation of growth. C. When GH therapy is stopped at a young age, the GH-deficient adult may gain weight and become relatively obese. They may be more predisposed to atherosclerosis, perhaps secondary to high levels of cholesterol and triglycerides. D. Young adults who were GHD during childhood and not provided with GH during adulthood may have signs and symptoms of impaired psychological well-being, including feelings of depressed mood, emotional instability, social isolation, anxiety, and reduced vitality. One of the striking effects of GH therapy in GHD adults is the improvement in psychological well-being. XX. QUALITY OF LIFE Quality of life is assessed by means of a self-administered survey. Energy and vitality are diminished in GH-deficient patients. Many studies showed definite benefit after patients received GH, whereas in others, improvements were more limited or no im- provement was seen. XXI. ARGUMENTS AGAINST GH TREATMENT A. Safety concerns. Although treatment appears to be safe overall, certain areas require long-term surveillance, such as risks of glucose intolerance and pituitary