Kaup R. Shetty

Effects of Human Growth Hormone on Body Composition in Elderly Men

Body composition changes progressively in mid and late adulthood. Lean body mass in men over 50 years old contracts at an average rate of -0.6% per year. Body weight tends to remain stable because of a reciprocal expansion of adipose mass. The shrinkage of the lean body mass reflects the atrophy of skeletal muscles, skin and visceral organs. Because growth hormone causes expansion of the lean body mass and contraction of the adipose mass, and because growth hormone secretion tends to diminish in late adulthood, it has been postulated that geriatric hyposomatotropism is a contributory cause to the body composition changes described above. The authors have tested this hypothesis by recruiting 45 independent men over 61 years old with plasma somatomedin C level below 0.35 U/ml, indicating little or no detectable growth hormone secretion. The 21-month protocol was as follows: baseline period 0-6 months, experimental period 6-18 months and post-experimental period 18-21 months. During the experimental period, 26 men (group I) received approximately 0.03 mg/kg of biosynthetic human growth hormone (hGH) subcutaneously 3 times a week, while 19 men (group II) received no treatment. Plasma somatomedin C was measured monthly. The following outcome variables were measured at 0, 6, 12 and 18 months: lean body mass, adipose mass, skin thickness (dermis plus epidermis), sizes of the liver, spleen and kidneys, the cross sectional areas of ten muscle groups, and bone density at 9 skeletal sites. Lean body mass and adipose mass were also measured at 21 months. In group I, hGH treatment raised the plasma somatomedin C level and maintained it in the range 0.5-1.5 U/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma Dehydroepiandrosterone Sulfate in Nursing Home Men

Previous studies have shown the normal range of plasma dehydroepiandrosterone sulfate (DHEAS) for independent community men over 60 years old to be 30–200 μg/dL. In human adults, low levels of plasma DHEAS have been correlated with a high mortality rate. In rodents, dehydroepiandrosterone, the precursor of DHEAS, has exhibited antidiabetic, anticarcinogenic, neurotropic, and memory‐enhancing effects. We have now measured plasma DHEAS in 50 independent community men age 55–94 and in 61 nursing home men age 57–104. Mean DHEAS was significantly lower in the nursing home men than in the community men. Plasma DHEAS was subnormal (less than 30 μg/dL) in 40% of the nursing home residents and in only 6% of the community subjects. In both groups, DHEAS was inversely related to age. In the nursing home men, additionally, plasma DHEAS was inversely related to the presence of an organic brain syndrome and to the degree of dependence in activities of daily living. Plasma DHEAS was subnormal in 80% of the nursing home men who required total care. There was no significant correlation between the plasma concentrations of DHEAS and testosterone, or between plasma DHEAS and one‐year mortality rate.

Hyposomatomedinemia in Quadriplegic Men

Many studies have shown that vigorous exercise acutely stimulates growth hormone (GH) release but the relative contribution of daily physical activity to maintaining the GH/somatomedin C (SmC) axis is not known. It has been reported that basal and post-exercise plasma SmC values are higher in physically conditioned young men than in sedentary men of similar age. To assess the effect of severe inactivity on the plasma SmC level, basal concentrations of this hormone were measured in patients with quadriplegia (QP) resulting from spinal cord injury (SCI). Venous blood samples were obtained after overnight fast in 41 QP men, ages 24-66, and compared with 119 healthy men of similar ages. Nonparametric analysis of variance showed SmC to be significantly lower in QP than in healthy men (p < .007). Plasma SmC below 0.35 U/ml in adults usually indicates little or no GH secretion by the pituitary gland. In QP, 46% of plasma SmC values were < 0.35 U/ml compared to 24% in the healthy group (p < .02). In both groups, an inverse relationship of SmC and increasing age was observed (p < .01). The data suggest that severe inactivity or SCI tend to cause hyposomatomedinemia. The latter endocrine alteration may contribute to the decrease in lean body mass and muscle atrophy of QP patients, and add further functional impairment to the original neurologic deficit. In addition, hyposomatomedinemia could increase the tendency for pressure sore formation and osteoporosis in SCI patients.

Prevalence of Low Plasma IGF-I in Poliomyelitis Survivors

Objective: To compare plasma levels of insulin‐like growth factor‐I (IGF‐I, also termed somatomedin C) in polio survivors and healthy control subjects and to determine their relation to selected clinical characteristics.

Hyposomatomedinemia in Men with Post-Poliomyelitis Syndrome

The age of onset of the post‐poliomyelitis syndrome (PPS) coincides with the tendency for declining activity of the growth hormone/somatomedin C (GH/SmC) axis. The normal plasma SmC range in men before the age of 40 is 0.50 to 1.50 units/mL. After age 40 about 30% of men have a plasma SmC level below 0.35 units/mL, signifying no detectable spontaneous GH secretory pulses. Because the GH/SmC axis stimulates DNA, RNA, and protein synthesis in muscle cells and increases their size and number, a deficiency of the GH/SmC axis could theoretically contribute as a secondary factor to the occurrence or severity of the PPS. Accordingly, the authors measured the plasma SmC level in 10 men with PPS, ages 35 to 63, and in 94 healthy men of similar age. In the PPS men, 100% of the values were ≤0.40 units/mL, and 90% were ≤0.35 units/mL The corresponding proportions in the healthy men were 40% and 27%. Analysis of variance including age as a factor showed SmC to be significantly lower in the PPS men than in the healthy men. In an additional comparison, totally immobile nursing home men did not have lowered SmC values. In fact their SmC values were slightly higher than those of healthy men of similar age. The data revealed a new biochemical feature of PPS, hyposomatomedinemia, which might play a contributory role in the pathogenesis of the syndrome.

Lipid and Lipoprotein Abnormalities in Young Quadriplegic Men

To assess the effect of severe inactivity on the serum lipid and lipoprotein profile, 21 quadriplegic men between the ages of 24 and 47 were compared with 20 age-matched healthy control men. The group of quadriplegic men had significantly lower levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), HDL2-C and HDL3-C. The current recommendation for desirable TC is less than 200 mg/dl, whereas HDL-C of less than 35 mg/dl is considered a risk factor for coronary heart disease. Of the 50% (10/20) of the men in the normal control group who had a desirable TC, only 10% (1/10) had a low or undesirable HDL-C value. In comparison, although 81% (17/21) of the group of quadriplegic men had a desirable TC, 53% (9/17) of these individuals had a low HDL-C level. It is concluded that although the presence of lower TC could be beneficial in QM, the decreased values of HDL-C and HDL2-C and the increased ratio of TC/HDL-C suggest a higher risk of coronary heart disease. The findings are consistent with recent reports of an increased prevalence of coronary heart disease in spinal cord injury patients, which could be due to an abnormal lipoprotein profile related to diet, inactivity, changes in body composition, and life style. Moreover, the present data suggest that HDL-C should be measured in quadriplegic men with modifiable risk factors, even if they have desirable TC, to avoid missing an increased coronary heart disease risk status.

Human growth hormone effect on serum IGF-I and muscle function in poliomyelitis survivors.

Previous work showed low insulin-like growth factor I (IGF-I) in polio survivors compared with age-matched controls and it was hypothesized that the low IGF-I was caused by the lack of growth hormone (GH) secretion. The present study asked: Is the nocturnal release of GH subnormal in polio survivors? Can the low IGF-I level be raised to the range of healthy young men (240 to 460 ng/mL) by human growth hormone (hGH) treatment? If so, what dose of hGH is required? Does the hormone treatment affect muscle function? Eleven polio survivors with evidence of postpoliomyelitis syndrome, aged 50 to 65 years, and low IGF-I levels (average IGF-I value of 170 ng/mL) were studied. The serum level of GH was measured in the first 4 hours of sleep. The serum IGF-I level was determined before and during hGH treatment at 0.0075, 0.015 or 0.03 mg/kg of ideal body weight (IBW), three times a week for successive periods of 1 month. Before and after hGH treatment, strength was determined in knee extensor and flexor muscles and the elbow flexor and elbow extensor muscles. Nocturnal GH was low in the polio survivors compared with healthy young men. Serum IGF-I was raised into the target range by either 0.0075 or 0.015 mg hGH/kg three times a week. After 3 months of hGH treatment, no consistent changes in muscle strength were observed in the study group.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies of growth hormone/insulin-like growth factor-I in polio survivors.

In the later years of life, many polio survivors develop post-polio syndrome manifested by progressive muscular weakness. Previous work by the authors showed low IGF-I level in polio survivors compared to age-matched controls. IGF-I concentration tended to be lower in polio survivors who were older, male, obese, and also in persons experiencing difficulty in the activities of daily living which were independent of other factors. IGF-I levels did not correlate with the subjective report of recent decline in functional status. Further studies of nocturnal GH secretion indicated that low IGF-I level was secondary to impaired growth hormone secretion. Low IGF-I levels in subjects with post-polio syndrome were corrected by physiologic doses of hGH and the response was dose dependent. Lesser dosage was required to normalize IGF-I level compared to standard dosages previously used in younger persons. Inasmuch as low IGF-I level resulting from GH deficiency is known to be associated with weakness, muscle atrophy, and decrease in aerobic work capacity, it is postulated that low IGF-I levels that occur in aging polio survivors may have an adverse effect on their neuromuscular function, and that hGH replacement may improve their functional status. Moreover, the new dose-response data may decrease the frequency of side effects in future hGH treatment of older adults.

Chapter 4 Growth Hormone and Body Composition in Aging

Publisher Summary This chapter describes the components and organization of the hypothalamic-growth hormone (GH)-insulin like growth factor (IGF)-I axis, the regulation of the axis in healthy young people, its effects on the various organ systems, the diminished activity of the axis in old age, and the implications of this endocrine decline for the physiology and treatment of the elderly. Two hypothalamic peptides, growth hormone-releasing hormone (GHRH) and somatostatin, are released into the portal venous system under neuroregulatory control and exert opposing actions on the secretion of GH. IGF-I, produced in the liver and other peripheral tissues in response to GH, is a useful measure of integrated GH secretion and appears to be the major mediator of GH actions. After the age of 40 years, there is a progressive decline in the integrated serum GH secretion and circulating IGF-I concentrations. Currently available evidence indicates that the decline in endogenous GH production with age results from diminished hypothalamic secretion of GHRH and augmented release of somatostatin; and these in turn could be related to the depletion of hypothalamic dopamine and norepinephrine. It is well known that the composition of the human body changes with advancing age. Lean body mass decreases and adiposity increases. Simultaneously, the functional capacity of most organs declines. Because these body compositional changes seen in the elderly are similar to those of children and adults with GH deficiency, it is speculated that dwindling activity of the GW-IGF-I axis may provide a partial explanation for the pathogenesis of these age-related changes. Recent clinical trials of human GH in the elderly tend to support this hypothesis.

Potential Benefits and Risks in Treating the Hyposomatomedinemia and Hypogonadism of Elderly Men

When a deficiency of growth hormone (GH) or testosterone occurs in men during early or mid-adulthood, hormone replacement is an important consideration. Because of its favorable anabolic, hematopoietic, androgenic, and antiosteopenic effects, there is usually little question that testosterone should be prescribed. Treatment with human GH (hGH), a more expensive and only recently available medication, is now also being advocated by some endocrinologists because of its beneficial actions on body composition, work capacity, and quality of life (1-5).