Context: GH and IGF-I are important regulators of metabolism and body composition. In acromegaly, a state of GH and IGF-I excess, the lipolytic and insulin antagonistic effects of GH may alter adipose tissue (AT) distribution.

Objectives: To test the hypothesis that in acromegaly whole-body AT mass is less and to examine for the first time the relationship between GH/IGF-I excess and inter-muscular AT (IMAT), an AT depot associated with insulin resistance in other populations.

Design, Setting and Patients: A cross-sectional study in 24 adults with active acromegaly compared to predicted models developed in 315 healthy non-acromegaly subjects.

Outcome Measures: Mass of adipose tissue in the visceral (VAT), subcutaneous (SAT) and inter-muscular (IMAT) compartments from whole-body magnetic resonance imaging and serum levels of GH, IGF-I, insulin and glucose were measured.

Results: VAT and SAT were less in active acromegaly (p < 0.0001); these were 68.2 ± 27% and 79.5 ± 15% of predicted values, respectively. By contrast, IMAT was greater (p=0.0052) by 185.6 ± 84% of predicted. VAT/Trunk AT ratios were inversely related to IGF-I levels (r=0.544, p=0.0054). Acromegaly subjects were insulin resistant.

Conclusions: VAT and SAT, most markedly VAT, are less in acromegaly. The proportion of trunk AT that is VAT is less with greater disease activity. IMAT is greater in acromegaly, a novel finding, which suggests that increased AT in muscle could be associated with GH induced insulin resistance. These findings have implications for understanding the role of GH in body composition and metabolic risk in acromegaly and other clinical settings of GH use.