Context: Divergence between GH and IGF-I values is regularly observed in treated acromegalic patients, and its significance is unclear.

Objectives: To explore the frequency and identify potential determinants of discordant serum GH and IGF-I concentrations in non-cured acromegalic patients.

Patients: 229 non-cured acromegalic patients of the Belgian acromegaly registry (AcroBel) were grouped according to their mean GH level ( or > 2 µg/L) and IGF-I z-score ( 2 or > 2). Clinical and metabolic parameters were compared between groups with: "active disease" (high GH and IGF-I; n=81), "high GH" (with normal IGF-I; n=25), "high IGF-I" (with normal GH; n=55) and "controlled disease" (GH and IGF-I normal; n=68).

Results: Compared to the "high IGF-I" group, the "high GH" group was characterized by younger age (52 vs 58 yr p<0.05), female predominance (72 vs 36%, p<0.01), and lower BMI (25 vs 31 kg/m²; p<0.001), fasting glucose (91 vs 99 mg/dl; p<0.05) and HbA1c levels (5.7 vs. 6.1%; p<0.01). There was no difference among the groups regarding baseline characteristics of pituitary adenoma, current medical treatment or symptom score.

Conclusions: 35% of non-cured acromegalic patients exhibit a discordant GH and IGF-I pattern. The "high GH" phenotype was found predominantly in younger estrogen-sufficient females, implying a possible role for age, gender and estrogens in this biochemical divergence. The "high IGF-I" phenotype was associated with a worse metabolic profile, suggesting that high IGF-I, rather than high GH, is indicative of persistently active disease.