Improvement in Symptoms and Health-Related Quality of Life in Acromegaly Patients

A Systematic Review and Meta-Analysis

Leonie H. A. Broersen; Amir H. Zamanipoor Najafabadi; Alberto M. Pereira; Olaf M. Dekkers; Wouter R. van Furth; Nienke R. Biermasz


J Clin Endocrinol Metab. 2021;106(2):577-587. 

In This Article

Abstract and Introduction


Background: Whereas biochemical response is often used as a primary study outcome, improvement in symptoms and health-related quality of life (HRQoL) is the relevant goal for patients to consider treatment successful. We performed a systematic review and meta-analysis to assess the effect of treatment on symptoms and HRQoL in acromegaly.

Methods: Seven electronic databases were searched for longitudinal studies assessing patient-reported symptoms or HRQoL in acromegaly. Meta-analyses were performed to assess differences during treatment for the Acromegaly Quality of Life Questionnaire (AcroQoL) and Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), and standardized mean difference (SMD) for individual symptoms (interpretation: 0.2 small, 0.5 moderate, and 0.8 large effect). Treatment-naive and previously treated patients were assessed separately.

Results: Forty-six studies with 3301 patients were included; 24 contributed to quantitative analyses. Thirty-six studies used medication as main treatment, 1 transsphenoidal adenomectomy, and 9 various treatments. Symptoms and HRQoL both improved: AcroQoL increased 2.9 points (95% CI, 0.5 to 5.3 points), PASQ decreased −2.3 points (95% CI, −1.3 to −3.3 points), and individual symptom scores decreased for paresthesia −0.9 (95% CI, −0.6 to −1.2), hyperhidrosis −0.4 (95% CI, −0.1 to −0.6), fatigue −0.3 (95% CI, −0.1 to −0.6), arthralgia −0.3 (95% CI, −0.1 to −0.5), headache −0.3 (95% CI, 0.0 to −0.6), and soft-tissue swelling −0.2 (95% CI, 0.0 to −0.4).

Conclusion: Symptoms and HRQoL improved during acromegaly treatment. Consensus is needed on which symptoms should be included in a potential core outcome set, taking into account symptom frequency, severity, and sensitivity to change, which can be used in clinical practice and as outcome in trials.


Acromegaly results from an excess secretion of growth hormone (GH), which is usually produced by somatotroph cells in a GH-secreting pituitary adenoma.[1] Hypersecretion of GH, and the resulting excess of insulin-like growth factor 1 (IGF-1), leads to multisystem morbidity, including diabetes mellitus,[2] increased risk of cardiovascular diseases,[3] and increased mortality risk.[4]

Clinical symptoms of acromegaly include among others acral overgrowth, soft-tissue swelling, arthralgia, headache, fatigue, and symptoms due to local tumor effects.[5] Patients with acromegaly report impaired health-related quality of life (HRQoL), which improves in a subset of patients when biochemical remission is achieved, although complete recovery is often not reached.[6] To evaluate disease status during treatment, traditionally only biochemical parameters are evaluated,[1] whereas improvement in symptoms and HRQoL is eventually the ultimate goal for all patients, and thus essential to consider a treatment as successful.[7] Symptom status or HRQoL may respond congruently to biochemical status, but also incongruently.[8] The necessity of using patient-reported outcomes is further accentuated by evidence that patients' perception of their HRQoL might differ substantially from the perception of their physicians.[9]

HRQoL can be described as a comprehensive outcome model, assessing outcomes at different levels from symptoms and bodily limitations to participation restrictions.[10] The measurement of symptoms might be of extra interest, as they may be more directly responsive to acromegaly treatment, and often targetable treatment exists to relieve patients' symptoms. To monitor symptom severity, the Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) has been developed.[11] The PASQ and variations of symptom lists based on the PASQ are frequently used in research, although these instruments have not been validated.[12,13] The PASQ consists of 5 acromegaly-related symptoms (soft-tissue swelling, arthralgia, headache, excessive perspiration, and fatigue), which are measured on a scale of 0 to 8 points (a higher score indicating more severe symptoms), and a cumulative score (scale 0 to 40 points) can be calculated by adding the individual components.[11] To evaluate HRQoL, the disease-specific Acromegaly Quality of Life Questionnaire (AcroQoL) has been developed.[14] The AcroQoL assesses physical and psychological aspects of quality of life in 22 questions, with a score ranging from 22 (worst) to 110 (best).

Study Aim

The aim of the present study was to evaluate the impact of treatment for acromegaly on symptoms and HRQoL in longitudinal clinical studies in a systematic review and meta-analysis.