CARPAL-TUNNEL SYNDROME AND GYNECOMASTIA 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 adipos e mass, and adverse side-effects during human growth hormone (hGH) tre atment of elderly men who had low IGF-I levels. DESIGN The first six m onths was a period of baseline observation. The subjects were then ran domized into two groups so that during months 7-18, men in group I rec eived hGH, and men in group II served as untreated controls. SUBJECTS Eighty-three overtly healthy elderly men, who were selected because th eir plasma IGF-I level was less than 0.35 units/ml. The men were rando mly 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 monthl y. Lean body mass and adipose mass were measured every six months. RES ULTS Fifteen men left the study during the baseline period because of personal reasons or intercurrent medical events. In those who received drug (group 1), there were a number of adverse reactions which could have been related to the hGH therapy: carpal tunnel syndrome 10, gynae comastia 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 n ot 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 treatmen t without experiencing one of the three above-noted presumed hGH side- effects, mean and peak plasma IGF-I during treatment were significantl y lower than among the 13 men who experienced carpal tunnel syndrome o r gynaecomastia (one subject had both) while on hGH. With one exceptio n, neither carpal tunnel syndrome nor gynaecomastia occurred in any in dividual with a mean IGF-I level less than 1.0 units/ml during hGH tre atment. Twelve months of hGH treatment (group I) caused an increase in lean body mass to 106% of the initial baseline (month one of the prot ocol), and a reduction in adipose mass to 84% of the baseline. Meanwhi le, the lean body mass of the untreated men in group II declined to 97 % of the initial baseline. The body composition responses after 12 mon ths of treatment in group I were larger in the men whose mean intra-tr eatment IGF-I level was 0.5-1.0 units/ml, than in the men whose mean i ntra-treatment IGF-I level was 1.0-1.5 units/ml. CONCLUSIONS These obs ervations show that when elderly men with low circulating IGF-I concen trations are treated continuously with hGH, elevation of plasma IGF-I above 1.0 units/ml is associated with a substantial frequency of carpa l tunnel syndrome or gynaecomastia. It may be that the effects of the hormone in expanding lean body mass and reducing adipose mass can be a chieved, and the side-effects avoided, by maintaining the mean IGF-I l evel in the range 0.5-1.0 units/ml.