Carpal tunnel syndrome and gynaecomastia during growth hormone treatment of elderly men with low circulating IGF-I concentrations.

OBJECTIVE: We studied the relationship between plasma level of insulin-like growth hormone I (IGF-I), changes in lean body mass and in adipose mass, and adverse side-effects during human growth hormone (hGH) treatment of elderly men who had low IGF-I levels. DESIGN: The first six months was a period of baseline observation. The subjects were then randomized into two groups so that during months 7-18, men in group I received hGH, and men in group II served as untreated controls. SUBJECTS: Eighty-three overtly healthy elderly men, who were selected because their plasma IGF-I level was less than 0.35 units/ml. The men were randomly assigned in a ratio of three to one into group I (n = 62) or into group II (n = 21). MEASUREMENTS: Plasma IGF-I level was measured monthly. Lean body mass and adipose mass were measured every six months. RESULTS: Fifteen men left the study during the baseline period because of personal reasons or intercurrent medical events. In those who received drug (group I), there were a number of adverse reactions which could have been related to the hGH therapy: carpal tunnel syndrome 10, gynaecomastia 4, and hyperglycaemia 3. In total there were 27 dropouts from group I and two dropouts from group II after the six-month point, for a variety of medical and non-medical reasons, the majority probably not related to hGH therapy. During the hGH treatment of group I, plasma IGF-I increased from the range 0.10-0.35 units/ml into the range 0.5-2.2 units/ml. Among the 18 men who completed 12 months of hGH treatment without experiencing one of the three above-noted presumed hGH side-effects, mean and peak plasma IGF-I during treatment were significantly lower than among the 13 men who experienced carpal tunnel syndrome or gynaecomastia (one subject had both) while on hGH. With one exception, neither carpal tunnel syndrome nor gynaecomastia occurred in any individual with a mean IGF-I level less than 1.0 units/ml during hGH treatment. Twelve months of hGH treatment (group I) caused an increase in lean body mass to 106% of the initial baseline (month one of the protocol), and a reduction in adipose mass to 84% of the baseline. Meanwhile, the lean body mass of the untreated men in group II declined to 97% of the initial baseline. The body composition responses after 12 months of treatment in group I were larger in the men whose mean intra-treatment IGF-I level was 0.5-1.0 units/ml, than in the men whose mean intra-treatment IGF-I level was 1.0-1.5 units/ml. CONCLUSIONS: These observations show that when elderly men with low circulating IGF-I concentrations are treated continuously with hGH, elevation of plasma IGF-I above 1.0 units/ml is associated with a substantial frequency of carpal tunnel syndrome or gynaecomastia. It may be that the effects of the hormone in expanding lean body mass and reducing adipose mass can be achieved, and the side-effects avoided, by maintaining the mean IGF-I level in the range 0.5-1.0 units/ml.

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)

Effects of human growth hormone in men over 60 years old.

BACKGROUND: The declining activity of the growth hormone--insulin-like growth factor I (IGF-I) axis with advancing age may contribute to the decrease in lean body mass and the increase in mass of adipose tissue that occur with aging. METHODS: To test this hypothesis, we studied 21 healthy men from 61 to 81 years old who had plasma IGF-I concentrations of less than 350 U per liter during a six-month base-line period and a six-month treatment period that followed. During the treatment period, 12 men (group 1) received approximately 0.03 mg of biosynthetic human growth hormone per kilogram of body weight subcutaneously three times a week, and 9 men (group 2) received no treatment. Plasma IGF-I levels were measured monthly. At the end of each period we measured lean body mass, the mass of adipose tissue, skin thickness (epidermis plus dermis), and bone density at nine skeletal sites. RESULTS: In group 1, the mean plasma IGF-I level rose into the youthful range of 500 to 1500 U per liter during treatment, whereas in group 2 it remained below 350 U per liter. The administration of human growth hormone for six months in group 1 was accompanied by an 8.8 percent increase in lean body mass, a 14.4 percent decrease in adipose-tissue mass, and a 1.6 percent increase in average lumbar vertebral bone density (P less than 0.05 in each instance). Skin thickness increased 7.1 percent (P = 0.07). There was no significant change in the bone density of the radius or proximal femur. In group 2 there was no significant change in lean body mass, the mass of adipose tissue, skin thickness, or bone density during treatment. CONCLUSIONS: Diminished secretion of growth hormone is responsible in part for the decrease of lean body mass, the expansion of adipose-tissue mass, and the thinning of the skin that occur in old age.

Effects of three liquid diets on nutrition-sensitive plasma proteins of tube-fed elderly men.

The effects on three nutrition-sensitive plasma proteins of isocaloric feedings with three enteral formulas were compared in 10 tube-fed male nursing home residents. The enteral products were Isocal (based on whole protein), Peptamen (based on a mixture of oligopeptides), and Vivonex T.E.N. (based on free amino acids). The nutrition-sensitive plasma proteins were albumin, transferrin, and retinol-binding protein. After observation during four weeks of feeding with Isocal, each subject was then monitored during four weeks of Peptamen and four weeks of Vivonex T.E.N. The latter two products were alternated in a crossover design. The shift of Isocal to Peptamen did not significantly (P greater than .05) influence the serum level of albumin, transferrin, or retinol-binding protein. In contrast, the shift of Isocal to Vivonex T.E.N. or of Peptamen to Vivonex caused a significant (P less than .05) decline in all three plasma proteins, the kinetics of their reductions corresponding to their known half-lives. The behavior of the three nutrition-sensitive plasma proteins suggests that in elderly nursing home men without gastrointestinal disease the nutritional value of the protein component of the three formulas follows the order Isocal = Peptamen greater than Vivonex T.E.N. However, this conclusion will require confirmation by nitrogen balance studies.

Serum fatty acid profile of elderly tube-fed men in a nursing home.

Severely dependent tube-fed elderly men with dementia in this VA nursing home are nourished exclusively with Isocal, which provides only four fatty acids in amounts over 1% of the total (palmitic, oleic, linoleic, and alpha-linolenic). It has not been proven that the frail elderly can efficiently convert linoleic to arachidonic acid, and alpha-linolenic to eicosapentanoic and docosahexaenoic acids. Therefore, we compared the serum profile of fatty acids in six of the tube-fed elderly men with the profile of six healthy young men eating mixed foods ad lib. Expressed as percent of total fatty acids, arachidonic, eicosapentanoic and docosahexaenoic acids did not differ significantly between the two groups. The data show that linoleic and alpha-linolenic acids satisfy the requirements for omega 6 and omega 3 fatty acids, respectively, in severely impaired elderly men.

A mortality risk index for men in a Veterans Administration extended care facility.

the purpose of this study was to develop (phase I) and validate (phase II) a mortality prognostic index, based on the annual clinical data base, for the men of this Veterans Administration extended care facility. The study population during phase I consisted of 123 men who were residing in three of the seven wards of the facility in August 1984. Sixty-six of these individuals were institutionalized because of a chronic neurologic (50) or medical (15) disorder ("nonpsychiatric group"). In 57 men, the reason for institutionalization was a chronic psychosis (schizophrenia, 53; manic depressive illness, 4) ("psychiatric group"). During August to October 1984, a comprehensive clinical data base comprising 70 attributes (including diagnoses and drugs) was collected. Deaths were recorded during the next 14 months. Death rate during the 14 months of observation was 33.3% in the nonpsychiatric group, and only 1.7% in the psychiatric group. In the nonpsychiatric men, univariate analysis yielded six attributes significantly correlated with death rate: serum cholesterol level, hematocrit, hemoglobin, midarm muscle circumference, triceps skinfold, and number of morbidity episodes. After serum cholesterol and hematocrit had been entered into a multivariate analysis model, none of the other four attributes contributed significant information about death rate. The multivariate analysis led to a mortality risk index (MRI) for nonpsychiatric patients, MRI = [hematocrit in %] + 10% [serum cholesterol in mg/dl]. As MRI varied from less than 50 to greater than 65, death rate in the nonpsychiatric group varied in parallel from 86-11%.(ABSTRACT TRUNCATED AT 250 WORDS)

Fasting plasma amino acids in elderly men.

The fasting amino acid profile in 22 healthy young men aged 25-35 y (group A) was compared with the fasting profile in 21 healthy independent men aged 65-85 y (group B), in 23 orally-fed nursing home men with dementia aged 65-92 y (group C), and in 17 tube-fed nursing home men with dementia aged 65-88 y (group D). Groups B, C, and D had significantly (p less than 0.05) lower levels of methionine and branched-chain amino acids than group A. Methionine was significantly lower in groups C and D than in group B. The ratio of essential to nonessential amino acids was significantly lower in groups B, C, and D than in group A. The data suggest that the intake of essential amino acids may often be suboptimal in both independent and institutionalized elderly men.

Prognostic significance of serum cholesterol in nursing home men.

Serum cholesterol was measured in 129 men (average age 70.6; range 41-96) of a Veterans Administration Nursing Home, and was correlated with other items in an extensive clinical data base. Serum cholesterol was less than 150 mg/dl in 13% of the subjects, and was less than 160 mg/dl in 18%. Cholesterol greater than 280 mg/dl occurred in 8%. Serum cholesterol varied directly (p less than 0.02) with: body weight, serum albumin, serum total protein, serum sodium, ability to walk, and ability to feed oneself; and indirectly (p less than 0.02) with death rate, degree of functional dependence, and serum SGOT and LDH. Nursing home men with cholesterol less than 150 mg/dl had a death rate of 63% during the 14 months after the cholesterol analysis, compared to a death rate of 9% in men with cholesterol greater than 150 mg/dl (p less than 0.05). Death rate during the year after the analysis was 52% if cholesterol was below 160 mg/dl, compared to 7% if it was above this threshold (p less than 0.05).

Plasma testosterone in nursing home men.

Plasma testosterone (T) was measured at 8-9 a.m. in 44 men chronically institutionalized in a Veterans Administration Nursing Home, and correlated with an extensive clinical data base (including age, diagnoses, drugs, laboratory tests, anthropometric measurements, and mortality during the year after the T analysis). Age averaged 76.4 years (range 60-95). Plasma T was below the lower limit of the normal range for healthy young men (i.e. less than 300 ng/dl) in 46% of the men studied. Samples containing low T (less than 300 ng/dl) also contained subnormal unbound T, but normal concentrations of thyroxine and cortisol. Of the low T samples, 45% contained elevated LH, FSH or both (over 20 mU/ml), and the remaining 55% contained LH and FSH levels below this threshold, these two subgroups representing peripheral and central hypogonadism respectively. Plasma T was significantly (p less than 0.02) correlated in a direct relationship with hemoglobin, serum cholesterol, and the occurrence of seizures.

Relation of serum albumin concentration to death rate in nursing home men.

Serum albumin was measured in 126 men (average age 70.6; range 40 to 96) of a Veterans Administration Nursing Home, and was correlated with other items in an extensive clinical data base, including death or survival during the year after the analysis. The reason for institutionalization was chronic neurologic disease or other disabling physical condition in 63 men (group A), and psychiatric disorder in 63 men (group B). In group A, the proportions of men with albumin less than 3.5, 3.5-4.0, and greater than 4.0 g/dl were 6%, 37%, and 57%, respectively. In this group, the serum albumin level was significantly (p less than 0.05) correlated with death rate, hemoglobin, hematocrit, serum cholesterol, and serum lactic dehydrogenase. The death rate in group A during the year after the albumin analysis was 25%. For the patients with albumin level less than 3.5, 3.5-4.0, and greater than 4.0 g/dl, the death rates were 50%, 43%, and 11% respectively (p less than 0.01 for comparison of the former two groups with the latter). The subgroup with albumin 3.5-4.0 g/dl represented only 37% of the men in group A, but accounted for 63% of the group's deaths. In group B, serum albumin level was not significantly correlated with any other clinical variable. Death rate during the year after the albumin analysis was only 2% in group B, and did not correlate with the albumin level. These data indicate that, in nonpsychiatric Nursing Home men, the desirable level for the serum albumin concentration is higher than 3.5 g/dl.

Subnormal concentrations of serum selenium and plasma carnitine in chronically tube-fed patients.

Forty-seven tube-fed nursing home patients were investigated with regard to serum or plasma selenium (Se), carnitine, and red blood cell (RBC) glutathione peroxidase (GSH-Px). Thirty-six patients were tube fed with Isocal, and 11 were tube fed with Compleat B, an L-carnitine-containing formula. Eighteen elderly nursing home patients and 10 young adults served as controls. Serum Se and plasma carnitine were lowest (p less than 0.05) in the Isocal patients. In all 36 Isocal subjects, Se was below normal, and in 26% of Isocal patients RBC GSH-Px was also below normal. Free and total carnitine were below normal in most Isocal subjects. All 11 Compleat B patients had subnormal serum Se, but most had normal carnitine concentrations. These data suggest that enteral formulae in nursing homes should contain greater than 100 micrograms Se and on the order of a mmol carnitine/1600 kcal.