Body Composition Changes With Long-Term Pegvisomant Therapy of Acromegaly

Adriana P. Kuker; Wei Shen; Zhezhen Jin; Simran Singh; Jun Chen; Jeffrey N. Bruce; Pamela U. Freda

Disclosures

J Endo Soc. 2021;5(3) 

In This Article

Results

Endocrine and Metabolic Markers, Liver Function, and Pituitary Tumor Monitoring

Pre- and postpegvisomant levels of endocrine and metabolic markers are shown in Table 2. IGF-1 levels were <1.2 times the upper limit of normal in all patients after pegvisomant therapy. None had a rise in liver function tests. Tumor size did not change in 19 (6 with no visible tumor, 7 micro- and 6 macroadenomas) and 2 macroadenomas had nonclinically significant increases in tumor size of 2 mm (at 10 years) and 3 mm (at 2 years) of therapy.

Body Composition Measurements

Anthropometric Testing. Waist circumference increased, but weight, BMI, and waist/hip ratio did not change with pegvisomant therapy (Table 2).

Total Body Magnetic Resonance Imaging. Visceral Adipose Tissue: Prepegvisomant, VAT was 66% (median) (range 19–280%) of predicted (Figure 1A). VAT rose with pegvisomant therapy (Figure 1B). Prepegvisomant, VAT was below predicted in 14/16 patients, and on pegvisomant it was above predicted in all 16 (P < .0001). VAT increase tended to be larger in males, 110% (1.56–228%), than in females, 27% (19.9–92%) (P = .058). Overall, on pegvisomant, VAT mass did not differ significantly from predicted (Figure 1A) or between time points of follow-up.

Figure 1.

Total body MRI measured adipose tissue mass before and during pegvisomant therapy. VAT (A), SAT (C) and IMAT (E) mass in acromegaly patients (solid bar) compared to predicted values (patterned bar) at prepegvisomant baseline and at 1 to 2 years, 3 to 4 years, 5 to 6 years, and ≥ 8 years of pegvisomant. P values compare acromegaly to predicted values. Data are mean ± SE. Changes in VAT (B), SAT (D), and IMAT (F) mass from prepregvisomant baseline to VAT mass at 1 to 2 years, 3 to 4 years, 5 to 6 years, and ≥ 8 years of pegvisomant therapy. P-values represent significance of change from prepegvisomant to on pegvisomant time points. AT changes from baseline did not differ between on pegvisomant time points. For example, for VAT mass, for patients followed >8 years mean % change in VAT mass was 128% at 1 to 2 or 3 to 4 years compared with 138% at >8 years The duration of follow-up testing by MRI was 1 to <3 years in 6 patients, 3 to <5 years in 2, 5 to <7 years in 4, and ≥8 to 13.23 years in 4 patients. Data are mean ± SE.

Subcutaneous Adipose Tissue: Prepegvisomant SAT was 82.5% (median) (range 52–108%) of predicted (Figure 1C). SAT rose significantly after 3 to 4 years of pegvisomant therapy (Figure 1D). The proportion of patients with SAT above predicted did not differ from prepegvisomant, 2/16, to on pegvisomant, 5/16 (all males) (P = .39). Overall, SAT did not differ from predicted or between time points of follow-up on pegvisomant. The percent increase in VAT was greater than that of SAT in all patients combined, VAT 87% (1.56–229%) vs SAT 9% (–17 to 57%) (P < .001), in males VAT 110% (1.56–228)% vs SAT 12%(–17 to 50.3%) (P < .001), but not in females VAT 27% (19.9–92%) vs SAT 5% (–8.9 to 57%) (P = .13).

Intermuscular Adipose Tissue: IMAT was above predicted prepegvisomant (P = .02) (Figure 1E); 198% (median) (range 59–470%) overall, and 200% (59-470%) in males vs 172% (86-227%) in females (P = .44), of predicted. IMAT did not change with pegvisomant therapy (Figure 1F). The proportion of patients with IMAT that was above predicted did not change from prepegvisomant, 8/11 without and 5/5 with diabetes, to on pegvisomant (P = ns). Four of the 5 patients with DM had a fall in IMAT (range 12–30% decrease) by 1 to 2 years of therapy that was sustained in 2 of them. Overall, IMAT remained significantly above predicted and did not differ between time points of follow-up on pegvisomant.

Skeletal Muscle: SM mass was below predicted before (median 95% of predicted) and at 1 to 2 years of pegvisomant therapy (93.7%) (Figure 2A) and was similarly below predicted in males and females (not shown). Prepegvisomant, SM was below predicted in 12/16 and at or above predicted in 4/16 (range 100–114% predicted) patients. SM mass did not change with pegvisomant therapy (Figure 2B). At last follow-up, SM change was –1.6% of baseline in males and 0.03% of baseline in females. On pegvisomant, SM was below predicted in 11/16 and at or above predicted in 5/16 (range 100–117%). The proportion of patients above predicted did not change on therapy(P = ns). Overall, SM mass did not differ from predicted or between time points of follow-up on pegvisomant.

Figure 2.

Dual-energy x-ray absorptiometry (DXA) measured fat before and during pegvisomant therapy. Changes in total body (A) and trunk fat (B) mass and percent body fat (C) from prepegvisomant baseline to 1 to 2 years, 3 to 4 years, 5 to 6 years, and ≥8 years of pegvisomant therapy. P-values represent significance of change from prepegvisomant to on pegvisomant time points. The duration of follow-up by DXA was 1 to <3 years in 4 patients, 2 to <5 years in 4, 5 to <7 years in 3, and ≥8 to 13.44 years in 8 patients. Data are mean ± SE.

Intrahepatic and Intramyocellular Lipid: IHL and IMCL were tested in a subset of 8 patients (1 F, 7 M). IHL rose from 1.75% of water signal (median) (range 0.7–5%) to 3.5% (1.55–10.6%) (P = .04). Compared with matched healthy subjects, IHL showed a trend to be lower in acromegaly patients prepegvisomant, 1.75% (0.7–5%), than in controls, 3.04% (1.57–13.2%) (P = .049), but did not differ in the patients on pegvisomant, 3.5%, from controls, 3.04% (P = .85). There was no change in IMCL/water ratio with pegvisomant therapy (P = .29).

Dual-energy X-ray Absorptiometry. Total body, trunk, and percent body fat rose (Figure 3A-3C) and lean tissue fell with pegvisomant therapy (Figure 2C). SMDXA did not change (Figure 3D), but non-SM lean tissue fell with pegvisomant therapy (Figure 3E). Thus, the reduction in lean tissue with pegvisomant therapy was due to that of non-SM lean tissue, which includes soft tissues, organs and other lean tissues and not to a reduction in SM mass.

Figure 3.

MRI measured skeletal muscle mass and DXA measured lean tissue and estimated skeletal muscle mass. (A) MRI measured SM mass in acromegaly patients (solid bar) compared with predicted values (patterned bar) at prepegvisomant baseline and at 1 to 2 years, 3 to 4 years, 5 to 6 years, and ≥8 years of pegvisomant. P values compare acromegaly with predicted values. (B) Changes in SM mass (MRI) from prepregvisomant baseline to 1 to 2 years, 3 to 4 years, 5 to 6 years, and ≥8 years of pegvisomant therapy. P values represent significance of change from prepegvisomant to on pegvisomant time points. DXA measured changes in lean tissue (C), SMDXA (skeletal muscle estimated by DXA) (D) and lean tissue other than SMDXA (E) from prepregvisomant baseline to 1 to 2 years, 3 to 4 years, 5 to 6 years, and ≥8 years of pegvisomant therapy. P values represent significance of change from prepegvisomant to on pegvisomant time point. Data are mean ± SE.

Relationship of Body Composition to Endocrine Changes

Reduction in IGF-1 level correlated with that of lean tissue (DXA) (r = 0.459, P = .048), weight (r = 0.642, P = .002) and BMI (r = 0.63, P = .003). Percent change in leptin level correlated with that of SAT (r = 0.536, P = .03), IMAT (r = 0.601, P = .014), total body fat (DXA) (r = 0.472, P = .048) and % body fat (DXA) (r = 0.525, P = .025). QUICKI change correlated inversely with change in BMI (r = –0.469, P = .049) and showed a trend to correlate inversely with that of weight (r = –0.422, P = .07).

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