Sex difference in patients with controlled acromegaly-A multicentre survey

Abstract

Objective: Active acromegaly is subject to sex differences in growth hormone (GH) and Insulin like growth factor 1 (IGF-I) patterns as well as clinical features but whether this also pertains to controlled disease is unclear.

Design: In a cross-sectional, multi-centre study, 84 patients with acromegaly (F = 43, M = 41), who were considered controlled after surgery alone (n = 23) or during continued somatostatin receptor ligand (SRL) treatment (n = 61), were examined.

Methods: Serum concentrations of GH, insulin, glucose and free fatty acid (FFA) were measured during an oral glucose tolerance test (OGTT) together with baseline serum IGF-I and completion of two HR-Qol questionnaires (acromegaly quality of life questionnaire [AcroQol] and Patient-assessed Acromegaly Symptom Questionnaire [PASQ]).

Results: The mean age at the time of the study was 57 (±1.1) years and the majority of females (were postmenopausal. Females had significantly higher fasting GH but comparable IGF-I standard deviation scores (SDS). Using fasting GH < 1.0 µg/L as cut off, disease control was less prevalent in females (F: 56% vs. M: 83%, p = .007) whereas a comparable figure was observed using IGF-I SDS < 2 (F:79% vs. M:76%, p = .71). Compared with males, female patients showed impaired AcroQol physical score (p = .05), higher fasting FFA (p = .03) and insulin concentrations during the OGTT (p = .04).

Conclusion: In patients with acromegaly considered controlled, postmenopausal females exhibited higher GH levels than males despite comparable IGF-I levels, which also translated into impaired metabolic health and well-being. Our findings point to the relevance of including GH measurements in the assessment of disease control and suggest that disease-specific sex differences prevail after treatment.

Keywords: FFA; GH; IGF-I; acromegaly; age; insulin; pituitary adenoma; quality of life; sex.

Figure 1

Mean + SE serum levels of GH during an oral glucose tolerance test (OGTT) in females (hollow circle) and males (filled circle) with acromegaly. OGTT, oral glucose tolerance test.

Figure 2

Boxplots showing IGF‐I SDS in females and males with acromegaly. SDS, standard deviation scores.

Figure 3

Correlations between fasting GH and IGF‐I SDS. Females and males are depicted with hollow symbols and dashed regression line or filled symbols and full regression line, respectively. Patients with acromegaly treated with surgery (triangle) or a somatostatin receptor antagonist (circle). References lines for IGF‐I SDS = 2 and fasting GH = 1 µg/L is shown (dashed lines). SDS, standard deviation scores.

Figure 4

Distribution of females and males into one of the four predefined groups: concordantly elevated GH and IGF‐I levels (black, uncontrolled), elevated GH and normalised IGF‐I levels (dark grey, high GH), elevated IGF‐I with normalised GH levels (light grey, high IGF‐I) and concordantly normalised GH and IGF‐I levels (white, controlled). Floating pie represents all cases with elevated GH levels and combines the group of high GH and uncontrolled persons.