Changes in Quality of Life After Long-Term Biochemical Control of Acromegaly

Abstract

Acromegaly results in impaired quality of life (QoL), which improves but does not normalize after biochemical control of growth hormone (GH) excess. There are few data regarding long-term QoL in patients with sustained biochemical control of acromegaly. We hypothesized that QoL would continue to improve over time but remain poor. We studied 2 cohorts with biochemically controlled (normal IGF-1 level) acromegaly. MED (n=42) underwent surgery but required somatostatin analog (n=30) or GH receptor antagonist monotherapy (n=12); n=16 had undergone radiation. SURG (n=24) were in remission after surgery ± radiation (n=10). GH stimulation testing was performed in all SURG; n=11 had GH deficiency (GHD). QoL was assessed at 2 timepoints by the 36-Item-Short-Form Health Survey (SF-36) (MED, SURG), Acromegaly Quality of Life Questionnaire (AcroQoL) (MED), Gastrointestinal Quality of Life Index (GIQLI) (MED), Symptom Questionnaire (SQ) (SURG), and QoL-Assessment of GHD in Adults (AGHDA) (SURG). Time between timepoints 1 and 2 was 5.4 ± 1.0 vs 13.6 ± 1.2 years (MED vs SURG, p<0.001), and mean duration of biochemical control for MED vs SURG at timepoint 2 was 14.8 ± 6.6 vs 20.8 ± 8.2 years (p<0.001). At timepoint 2, mean (± SD) age (61 ± 12 years), mean BMI (30 ± 7 kg/m2), sex (68% female), and hypopituitarism (64% with ≥1 pituitary hormone deficiency) were similar between MED and SURG; mean IGF-1 index (IGF-1 level/mean normal range) was 1.00 ± 0.37 for MED vs 0.78 ± 0.40 for SURG (p=0.08); 79% of MED remained on medication. In MED, there was no change in SF-36 scores between timepoints, but all AcroQoL subscales and 2 GIQLI domains (Physical State, Emotions) improved, even after controlling for age, BMI, radiation treatment, and hypopituitarism. Results were similar in the 79% who remained on medication at timepoint 2. In SURG, QoL scores worsened on the SF-36 Pain domain and Physical Health Summary Score and SQ Depression and Somatic subscales (p≤0.01) but did not remain significant after controlling for age, BMI, radiation treatment, GHD, and adrenal insufficiency. After controlling for those variables, QoL by AGHDA worsened (p=0.02). At timepoint 2, % scoring in the lowest quartile (<25%) of normal for age on the SF-36 was similar between MED and SURG: 57% scored <25% of normal on ≥1 SF-36 domain and 29% scored <25% of normal on ≥4 of 8 domains. GHD in SURG was associated with poorer SF-36 scores at timepoint 2 (6 domains and Mental Health Summary Score; p<0.05). Radiation treatment did not predict poorer SF-36 scores. In conclusion, an average of 15 to 20 years after biochemical control of acromegaly by surgery ± radiation ± pharmacologic treatment, QoL remained low in many patients. QoL was poorer in patients with GHD than without but overall did not differ between those on and off pharmacologic therapy. Our data suggest that a history of acromegaly and development of GHD, but not medical treatment, are detrimental to QoL.