Impact of strict IGF1 control on quality-of-life scores in patients with acromegaly

Abstract

Objective: Examine, in a real-world setting, whether strict normalization of modestly elevated insulin-like growth factor 1 (IGF1) results in clinical and health-related quality of life benefits in patients with acromegaly using an open-label, non-randomized, 6-month prospective interventional study.

Methods: In patients with acromegaly and modest IGF1 elevation, strict IGF1 control was achieved by addition or dose escalation of pegvisomant. Clinical and biochemical parameters were assessed at baseline, 1 and 3 months for pegvisomant dose titration, and at 6 months. The Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), the Acromegaly Quality of Life questionnaire (AcroQoL) and the Acromegaly Disease Activity Tool (ACRODAT^®) were completed at baseline and at 6 months.

Results: Ten patients (8 males) with mean age of 50.7 years participated in the study. All patients had a macroadenoma and nine had prior transsphenoidal surgeries. At time of screening, six patients were on a somatostatin analog, two on pegvisomant, and two on pegvisomant and a somatostatin analog. After six months of dose escalation or the addition of pegvisomant, IGF1 decreased from 1.22 ± 0.14 to 0.87 ± 0.20 times the upper limit of normal (p=0.001). PASQ score decreased by 3.5 (p=0.02) and the ACRODAT^® overall status decreased by 50.5 (p=0.001); however, there was no difference in the AcroQoL score. Hemoglobin A1c and liver enzymes did not differ and repeat MRI of the sella at 6 months showed no change.

Conclusions: In this pilot study, stricter control of modest IGF1 elevations led to symptomatic improvement as measured by the PASQ score. These findings prompt larger prospective trials.

Keywords: acromegaly; clinical trial; insulin-like growth factor 1; pegvisomant; quality-of-life.

Figure 1

A flow chart illustrating the recruitment process; IGF1, insulin-like growth factor 1; PEGV, pegvisomant.

Figure 2

Effects of addition and/or dose escalation of pegvisomant on IGF1 and PASQ in individual patients. IGF1 at baseline and the lowest IGF1 attained at 3 or 6 months (left panel), and the sum of PASQ1 to PASQ6 at baseline and at 6 months (right panel) after the addition or dose escalation of pegvisomant; IGF1, insulin-like growth factor 1; PASQ, Patient-Assessed Acromegaly Symptom Questionnaire.