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Body Composition and Physical Fitness Are Major Determinants of the Growth Hormone-Insulin-Like Growth Factor Axis Aberrations in Adult Turner’s Syndrome, with Important Modulations by Treatment with 17ß-Estradiol¹

Medical Department M (Endocrinology and Diabetes) (C.H.G., S.F., J.S.C.) and Pediatric Department A (R.W.N.), Aarhus University Hospital, Kommunehospitalet, DK-8000 Aarhus C, Denmark

Address all correspondence and requests for reprints to: Dr. Claus Højbjerg Gravholt, Medical Department M (Endocrinology and Diabetes), Kommunehospitalet, DK-8000 Aarhus C, Denmark. E-mail: cg{at}afdm.aau.dk

The objectives of this study were to 1) study the GH-insulin-like growth factor (IGF) axis in adult untreated Turner’s syndrome compared to that in age-matched controls, 2) examine the effects of sex hormone substitution on this axis, 3) study the effects of route of administration of 17ß-estradiol on the measured variables, and 4) examine the effects of sex steroids on hepatic function in Turner patients. Twenty-seven patients with Turner’s syndrome were evaluated before and during sex hormone replacement, and an age-matched control group (n = 24) was evaluated once. Main outcome variables were GH and other measures of the GH-IGF axis, body composition, maximal oxygen uptake, sex hormone-binding globulin, and hepatic enzymes and proteins.

The integrated 24-h GH concentration (IC-GH; micrograms per L/24 h) was reduced in women with Turner’s syndrome (T) compared to controls [C; mean ± SD, 18.3 ± 12.0 (T) vs. 37.2 ± 29.7 (C); P = 0.007]. However, multiple regression revealed that fat-free mass (FFM) and maximal oxygen uptake were significant explanatory variables (joint r = 0.77; P < 0.0005), accounting for 60% of the variance in the 24-h IC-GH. This association was also present in controls. After adjustment for these two variables, any difference in GH concentration between Turner patients and controls disappeared. Serum IGF-I and IGF-II were identical in Turner patients and controls despite the difference in 24-h IC-GH. The level of GH-binding protein (GHBP; nanomoles per L) was higher in Turner women [1.87 ± 0.72 (T) vs. 1.22 ± 0.33 (C); P = 0.0005]; after adjustment for FFM, the difference in GHBP levels disappeared between Turner patients and controls. During sex hormone treatment a significant increase was seen in the 24-h IC-GH (P = 0.02), FFM (percentage of weight; P < 0.0005) and maximal oxygen uptake (milliliters of O₂ per kg/min; P = 0.02). Serum IGF-I was unchanged, whereas serum IGF-II (micrograms per L) decreased significantly [Turner, basal (T_B), vs. Turner, treatment (T_T), 860 ± 135 vs. 823 ± 150; P = 0.04]. Alanine aminotransferase (units per L), -glutamyl transferase (units per L), and alkaline phosphatase (units per L) were significantly elevated during the basal study period, and all decreased during treatment [alanine aminotransferase, 55 ± 55 (T_B) vs. 30 ± 20 (T_T; P = 0.006); -glutamyl transferase, 92 ± 98 (T_B) vs. 43 ± 65 (T_T; P = 0.003); alkaline phosphatase, 211 ± 113 (T_B) vs. 175 ± 54 (T_T); P = 0.06]. The route of administration of 17ß-estradiol did not affect its actions.

In conclusion, we found the GH-IGF axis in Turner’s syndrome to be normal, with body composition and physical fitness exerting the same modifying effects on this axis as seen in the normal population. Sex hormone replacement in Turner’s syndrome is associated with normalizing effects on the GH-IGF axis, body composition, physical fitness, and hepatic function. The lowering of hepatic enzymes is a surprising and hitherto undiscovered action of sex steroids. Finally, the route of administration of 17ß-estradiol is of minor importance in Turner’s syndrome.

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