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Adults with Partial Growth Hormone Deficiency Have an Adverse Body Composition

Department of Endocrinology (R.D.M., S.M.S.), Christie Hospital, Manchester M20 4BX, United Kingdom; and Clinical Radiology (J.E.A.), Imaging Science and Biomedical Engineering, the University of Manchester, Manchester M13 9PL, United Kingdom

Address all correspondence and requests for reprints to: Professor S. M. Shalet, Department of Endocrinology, Christie Hospital National Health Service Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom. E-mail: stephen.m.shalet{at}man.ac.uk.

The current biochemical definition of severe GH deficiency (stimulated peak GH < 3 µg/liter) provides good separation of GH-deficient (GHD) adults from normal subjects, although it may not account for all patients with impaired GH secretion. The vast majority of normal subjects display a peak GH level in excess of 7 µg/liter in response to the insulin tolerance test. Using a peak GH response of 7 µg/liter as an arbitrary upper limit, we investigated the effects of partial GH deficiency (GH insufficiency, GHI; peak GH response of 3–7 µg/liter) on the body composition of hypopituitary adults.

GHD adults (n = 30, peak GH < 3 µg/liter) were of shorter stature than the controls. Body mass index was not significantly increased, but waist/hip ratio (0.885 vs. 0.818, P = 0.001) and skinfold thickness (78.2 vs. 59.6 mm, P = 0.003) were greater than control subjects. Bioimpedance analysis revealed these patients to have reduced lean body mass (LBM) (44.4 vs. 51.2 kg, P = 0.023) and increased fat mass (FM) (25.7 vs. 18.4 kg, P = 0.039). Dual-energy x-ray absorptiometry (DXA) analysis of body composition confirmed reduced LBM (43.6 vs. 50.6 kg, P = 0.010) and increased FM (26.0 vs. 19.2 kg, P = 0.015). The excess FM was observed to be primarily truncal in distribution. Similarly, GHI adults were of shorter stature but with increased waist/hip ratio (0.871 vs. 0.818, P = 0.006) and skinfold thickness (80.8 vs. 59.6 mm, P = 0.003), compared with controls. Bioimpedance analysis revealed a reduction in LBM (44.9 vs. 51.2 kg, P = 0.020). DXA studies confirmed the reduced LBM (45.0 vs. 50.6 kg, P = 0.041) and additionally noted an increase in percent FM (32.9 vs. 27.4%, P = 0.019). All measures of body composition in the GHI patients were intermediate between those of the controls and GHD patients. Serum leptin levels were significantly elevated in both the GHD (41.5 vs. 20.7 ng/ml, P = 0.009) and GHI (36.7 vs. 20.7 ng/ml, P = 0.022) adults, compared with healthy controls. The excess FM observed using DXA in the GHD and GHI adults equated to 6.5 kg (8%) and 3.5 kg (5.5%), respectively, relative to healthy controls.

In summary, we have shown that adults with GHI have abnormalities of body composition characteristic of GHD. The degree of abnormality of body composition lies between that of healthy subjects and GHD adults and correlates with the IGF-I level. Any future trials of GH replacement in patients with GHI must await further studies to establish the exact impact of this relative deficiency on the broad spectrum of biological end points influenced by GH status.

This work was supported by Pfizer UK.

Abbreviations: CV, Coefficient of variation; DXA, dual-energy x-ray absorptiometry; FM, fat mass; %FM, percent FM; GHD, GH deficiency; GHI, GH insufficiency; GHR, GH replete; GST, glucagon stimulation test; ITT, insulin tolerance test; LBM, lean body mass; WHR, waist/hip ratio.

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