Effects of Growth Hormone Receptor Antagonism and Somatostatin Analog Administration on Quality of Life in Acromegaly

Laura E. Dichtel; Allison Kimball; Kevin C. J. Yuen; Whitney Woodmansee; Melanie S. Haines; Qiu Xia Guan; Brooke Swearingen; Lisa B. Nachtigall; Nicholas A. Tritos; Julie L. Sharpless; Ursula B. Kaiser; Anu V. Gerweck; Karen K. Miller

Disclosures

Clin Endocrinol. 2021;94(1):58-65. 

In This Article

Abstract and Introduction

Abstract

Objective: Acromegaly is associated with impaired quality of life (QoL). We investigated the effects of biochemical control of acromegaly by growth hormone receptor antagonism vs somatostatin analog therapy on QoL.

Design: Cross-sectional.

Patients: 116 subjects: n = 55 receiving a somatostatin analog (SSA group); n = 29 receiving pegvisomant (PEG group); n = 32 active acromegaly on no medical therapy (ACTIVE group).

Measurements: Acromegaly QoL Questionnaire (AcroQoL), Rand 36-Item Short Form Survey (SF-36) and Gastrointestinal QoL Index (GIQLI); fasting glucose, insulin and IGF-1 levels (LC/MS, Quest Diagnostics).

Results: There were no group differences in mean age, BMI or sex [(whole cohort mean ± SD) age 52 ± 14 years, BMI 30 ± 6 kg/m2, and male sex 38%]. Mean IGF-1 Z-scores were higher in ACTIVE (3.9 ± 1.0) vs SSA and PEG, which did not differ from one another (0.5 ± 0.7 and 0.5 ± 0.7, P < .0001 vs ACTIVE). Eighty-three per cent of PEG previously received somatostatin analogs, which had been discontinued due to lack of efficacy (52%) or side effects (41%). There were no differences in the four QoL primary end-points (AcroQoL Global Score, SF-36 Physical Component Summary Score, SF-36 Mental Health Summary Score and GIQLI Global Score) between SSA and PEG. Higher HbA1c, BMI and IGF-1 Z-scores were associated with poorer QoL in several domains.

Conclusion: Our data support a comparable QoL in patients receiving pegvisomant vs somatostatin analogs, despite the fact that the vast majority receiving pegvisomant did not respond to or were not able to tolerate somatostatin analogs.

Introduction

Growth hormone (GH) excess in acromegaly is associated with an impaired quality of life (QoL) and increased insulin resistance, both of which improve with biochemical control of the disease.[1–6] When pituitary surgery does not result in remission of acromegaly, pharmacologic approaches, including administration of a GH receptor antagonist and/or somatostatin analogs, are frequently used to achieve biochemical control, which can be achieved in nearly 100% of patients with acromegaly.[7–9] However, little is known about the differential effects of these medications on QoL. Data suggest that somatostatin analogs may be associated with gastrointestinal side effects and inhibit pancreatic insulin secretion.[10] The latter may result in a worsening of glucose homeostasis despite biochemical control of acromegaly. Few deleterious effects of GH receptor blockade have been identified other than skin rash, injection site lipohypertrophy and reversible transaminitis in a minority of patients.[11–13] It is not known whether these side effect profiles or differential effects on glucose homeostasis with pegvisomant vs somatostatin analog treatment affect QoL.

Our study investigated the effects of biochemical control of acromegaly by GH receptor antagonism vs somatostatin analog therapy on QoL from three tertiary care pituitary referral centres. We hypothesized that QoL would be better in patients with acromegaly with biochemical control receiving a GH receptor antagonist than those receiving a somatostatin analog. We also hypothesized that QoL may be related to measures of glucose homeostasis and IGF-1 levels.

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