Lavin Chapter 12

140   Section 2 • Hypothalamic-Pituitary Dysfunction

Muscle strength and aerobic capacity are impaired in GHD and restored by GH replacement over a period of a few months. A study of physical performance by Meinhardt observed that GH induced a significant and selective improvement in sprinting, a measure of performance dependent on anaerobic capacity. This study was undertaken in GH-sufficient healthy adults using a superphysiologic dose of GH. J. Aerobic capacity: A recent study confirms previous findings that aerobic capacity is impaired in GH-deficient adults. Adults with GHD have impaired cardiac func- tion, diminished lung capacity, and reduced red cell mass, factors that collectively reduce oxygen delivery to exercising muscles. These defects lead to a decrease in oxygen supply to a reduced muscle mass, explaining impaired aerobic capacity in adults with GHD. K. Anaerobic and aerobic capacity: In summary, anaerobic and aerobic capacities are reduced in adults with GHD. GH status is an independent determinate of anaerobic and aerobic capacities.We conclude that GH regulates the anaerobic energy system, and GH treatment helps reverse these concerns. L. Sleep: Low energy and fatigue are frequent complaints in subjects with GHD. Because interrelations between sleep and GH regulation are well documented, these complaints could partly reflect GHD. GHD is associated with sleep disorders that may cause poor subjective sleep quality and daytime sleepiness. Disturbed sleep is likely to be partly responsible for increased tiredness, a component of quality of life in GHD. GH treatment may reverse these concerns. M. Traumatic brain injury and GHD (see Chapter 6): Head injuries can cause cog- nitive impairments and reduce GH levels. Human GH can improve quality of life in traumatic brain injuries. N. GH reverses nonalcoholic steatohepatitis (NASH) in patients with human GHD: NASH is an emerging progressive hepatic disease and demonstrates steatosis, inflammation, and fibrosis. Insulin resistance is a common feature in the develop- ment of NASH. Six months of GH replacement therapy in a few patients ameliorated NASH and the abnormal lipid profile concomitant with a marked reduction in oxidative stress. These results suggest that GH plays an essential role in the metabolic and redox regulation in the liver. XXIII. TREATMENT A. GH dose requirements should be lower in older patients. Higher GH doses are needed to achieve the same IGF-1 levels in women receiving oral estrogen replacement. For ages 30 to 60 years, a starting dose of 300 m g/day is recommended. Daily dosing should be increased from 100 to 200 m g every 1 to 2 months—the goals being an appropriate clinical response, no side effects, and an IGF-1 level in the age-adjusted reference range. Clinical benefits may not become apparent for up to 6 months of treatment. Patients > 60 years of age should be started on an even lower dose, such as 100 to 200 m g/day, with slower incremental increases. B. After maintenance doses have been achieved, monitoring usually occurs at 3- to 6-month intervals. In addition to a normal IGF-1 level for age, monitoring should include a clinical evaluation, assessment of side effects, a lipid profile, a fasting glu- cose, a free T 4 and thyroid-stimulating hormone, a cortisol level, and, if indicated, a BMD scan. Assessment of quality of life provides another modality for monitoring response to therapy. C. It is not clear how long one should administer GH therapy. If benefits are being achieved, I would continue the therapy, but begin tapering the dose unless clinical goals decline. On the other hand, if there are no apparent or objective benefits after at least 1 year of treatment, discontinuing GH therapy should be considered. D. Recommendations: 1. GH dosing regimens should be individualized rather than weight based. 2. GH treatment should start with low doses and be titrated according to clinical response, side effects, and IGF-1 levels.