Growth hormone deficiency after treatment of acromegaly: a randomized, placebo-controlled study of growth hormone replacement

Abstract

Context: The effects of GH replacement therapy in patients who develop GH deficiency (GHD) after cure of acromegaly have not been established in a placebo-controlled study.

Objective: The objective of the study was to determine whether GH replacement improves body composition, cardiovascular risk markers and quality of life in patients with GHD and prior acromegaly.

Design: This was a 6-month, randomized, placebo-controlled study.

Setting: The study was conducted at a clinical translational science center.

Study participants: Participants included 30 subjects with prior acromegaly and current GHD.

Intervention: INTERVENTIONs included GH or placebo.

Main outcome measures: Body composition (dual-energy x-ray absorptiometry and cross-sectional computed tomography at L4), cardiovascular risk markers (high-sensitivity C-reactive protein (hsCRP), total, high-density lipoprotein and low-density lipoprotein cholesterol, fibrinogen, and carotid intimal-medial thickness), and quality of life were measured.

Results: The mean GH dose at 6 months was 0.58 +/- 0.26 mg/d. Total fat mass, visceral adipose tissue (-15.3 +/- 18.6 vs. 1.3 +/- 12.5%, P = 0.01), and total abdominal fat decreased, and fat-free mass increased, in the GH vs. placebo group. Mean hsCRP levels decreased, but there was no GH effect on other cardiovascular risk markers. There was no change in glycosylated hemoglobin or homeostasis model assessment insulin resistance index. Quality of life improved with GH. Side effects were minimal.

Conclusions: This is the first randomized, placebo-controlled study of the effects of GH replacement therapy on body composition and cardiovascular end points in patients who have developed GH deficiency after treatment for acromegaly, a disease complicated by metabolic and body composition alterations and increased cardiovascular risk. GH replacement decreased visceral adipose tissue, increased fat-free mass, decreased hsCRP, and improved quality of life in patients with GHD after cure of acromegaly, with minimal side effects and without an increase in insulin resistance.

Figure 1

Mean (±sem) IGF-I (A) and IGF-I SDS (B) in the GH-treated and placebo-treated study participants at baseline and 6 months. *, P < 0.05 vs. placebo-treated subjects.

Figure 2

Mean (±sem) change in total body fat, measured by DXA (A), fat-free mass, measured by DXA (B), total abdominal fat, measured by cross-sectional CT (C), and visceral adipose tissue, measured by cross-sectional CT (D) over 6 months in the GH-treated and placebo-treated study participants. *, P < 0.05 vs. placebo-treated study subjects.

Figure 3

Mean (±sem) change in the GH and placebo groups over 6 months in quality of life, as measured by the QOL-AGHDA (A), Symptom Questionnaire (B), and SF-36 (C). PF, Physical functioning; RLPH, role limitations due to physical health; RLEH, role limitations due to emotional health; MH, mental health; SF, social functioning; BP, bodily pain; Gen Health, general health. Higher scores reflect a poorer quality of life on the QOL-AGHDA and Symptom Questionnaire and a better quality of life on the SF-36. *, P < 0.05 vs. placebo-treated study subjects.