Adipose Tissue Redistribution and Ectopic Lipid Deposition in Active Acromegaly and Effects of Surgical Treatment

Abstract

Context: GH and IGF-I have important roles in the maintenance of substrate metabolism and body composition. However, when in excess in acromegaly, the lipolytic and insulin antagonistic effects of GH may alter adipose tissue (AT) deposition.

Objectives: The purpose of this study was to examine the effect of surgery for acromegaly on AT distribution and ectopic lipid deposition in liver and muscle.

Design: This was a prospective study before and up to 2 years after pituitary surgery.

Setting: The setting was an academic pituitary center.

Patients: Participants were 23 patients with newly diagnosed, untreated acromegaly.

Main outcome measures: We determined visceral (VAT), subcutaneous (SAT), and intermuscular adipose tissue (IMAT), and skeletal muscle compartments by total-body magnetic resonance imaging, intrahepatic and intramyocellular lipid by proton magnetic resonance spectroscopy, and serum endocrine, metabolic, and cardiovascular risk markers.

Results: VAT and SAT masses were lower than predicted in active acromegaly, but increased after surgery in male and female subjects along with lowering of GH, IGF-I, and insulin resistance. VAT and SAT increased to a greater extent in men than in women. Skeletal muscle mass decreased in men. IMAT was higher in active acromegaly and decreased in women after surgery. Intrahepatic lipid increased, but intramyocellular lipid did not change after surgery.

Conclusions: Acromegaly may present a unique type of lipodystrophy characterized by reduced storage of AT in central depots and a shift of excess lipid to IMAT. After surgery, this pattern partially reverses, but differentially in men and women. 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.

Trial registration: ClinicalTrials.gov NCT01809808.

Figure 1.

A, Mean percent change in VAT mass from preoperative VAT mass at 6 months, 1 year, and 2 years after surgery in men (striped bars) and women (black bars). The preoperative to postoperative percent change represents that for subjects tested only at the respective postoperative time point, and the P value represents significance of this change: change at 6 months is that for the 17 subjects tested at 6 months, change at 1 year is the that for the 17 tested at 1 year, and change at 2 years is that for the 12 tested at 2 years. B, Mean VAT mass in male (left) and female (right) subjects with acromegaly (shaded bars) compared with predicted values (patterned bars) preoperatively and at follow-up after surgery. P values compare acromegaly with predicted values for subjects with acromegaly tested at that time point. C, Mean percent change in SAT mass from preoperative SAT mass at 6 months, 1 year, and 2 years after surgery in men (striped bars) and women (black bars). P values represent significance of change from preoperative to postoperative follow-up. D, Mean SAT mass in male (left) and female (right) subjects with acromegaly (shaded bars) compared with predicted values (patterned bars) preoperatively and at follow-up after surgery. P values compare acromegaly with predicted values.

Figure 2.

A, Mean percent change in TAT mass (TAT = VAT + SAT + IMAT) from preoperative TAT mass at 6 months, 1 year, and 2 years after surgery in men (striped bars) and women (black bars). P values represent significance of changes from preoperative to postoperative follow-up. B, Mean percent change in trunk AT mass (trunk AT = VAT + trunk SAT + trunk IMAT) from preoperative trunk AT mass at 6 months, 1 year, and 2 years after surgery in men (striped bars) and women (solid black bars). P values represent significance of change from preoperative to postoperative follow-up. C, Mean percent change in IMAT mass from preoperative IMAT mass at 6 months, 1 year, and 2 years after surgery in men (striped bars) and women (black bars). P values represent significance of change from preoperative to postoperative follow-up. D, Mean IMAT mass in male (left) and female (right) subjects with acromegaly (shaded bars) compared with predicted values (patterned bars) preoperatively and at follow-up after surgery. P values compare acromegaly with predicted values.

Figure 3.

A, Mean percent change in SM mass from preoperative SM mass at 6 months, 1 year, and 2 years after surgery in men (striped bars) and women (black bars). P values represent significance of change from preoperative to postoperative follow-up. B, Mean SM mass in male (left) and female (right) subjects with acromegaly (shaded bars) compared with predicted values (patterned bars) preoperatively and at follow-up after surgery. P values compare acromegaly with predicted values.

Figure 4.

Mean IHL (A) and IMCL (B) in men, women, and men and women combined before and at 1 year postoperatively. IHL increased significantly from preoperative levels in men and women combined (P = .013).

Figure 5.

Mean IGF-I levels, fasting GH levels, OGTT nadir GH levels, HOMA for insulin resistance (HOMA IR) score, and percent increase in leptin levels from preoperative to 6 months, 1 year, and 2 years postoperatively. P values represent significance compared with preoperative levels.