Endocrine Abstracts

Background: Growth Hormone (GH) and insulin-like growth factor 1 (IGF-1) are the biomarkers used to assess disease activity in acromegaly. Consensus guidelines from the Endocrine Society (2014) recommend a normal (age/sex-adjusted) IGF-1 in combination with a suppressed random GH<1 μg/l for biochemical remission. However, these results are discordant in some patients. The clinical significance of the IGF-1/GH dichotomy in the follow-up of these patients is unclear and makes treatment decisions challenging.

Methods: We conducted a cross-sectional study to assess the frequency of IGF-1/GH discordance and to identify putative risk factors for its occurrence. Consecutive patients who attended our pituitary service over past 15 years were identified from the local Acromegaly Registry and medical records analysed.

Results: 109 patients with acromegaly were identified (56% male, age 57.4±13.6 years). Ninety-six patients (88%) underwent surgery. Fifty-six patients (51%) received radiotherapy. Fifty-six patients (51%) were on medical therapy at the time of their most recent biochemical assessment of disease status, with the majority (48 patients, 94%) receiving somatostatin analogue (SSA) therapy. Fifty-four patients (50%) had achieved biochemical remission, of whom 29 patients (54%) were not receiving long-term medical therapy. Twenty patients (18%) had both raised IGF-1 and GH>1 μg/l. Thirty-five patients (32%) had discordant IGF-1/GH results (63% (n=22) had high IGF-1 and normal GH (high IGF-1 discordance) and the remaining 13 patients the reverse (high GH discordance)). Age, gender, renal and liver function did not predict IGF-1/GH discordance. Higher BMI (coeff=−2.72, P=0.03) and higher GH level at diagnosis (coeff=−2.31, P=0.01) were significant negative predictors of discordance. Neither surgery nor radiotherapy were associated with an increased risk of IGF-1/GH discordance, although a high IGF-1 discordance was more prevalent post-radiotherapy (coeff=0.43, P=0.02) within the discordant group of patients. One-third (n=16) of patients on SSA therapy had discordant results. Being on SSA at the time of analysis was not associated with discrepant results. However, previous/current exposure to SSA was a positive predictive factor of IGF-1/GH dichotomy (coeff=0.44, P=0.03), although there was no association with treatment duration.

Conclusion: Despite the move to more robust criteria for biochemical remission of acromegaly, IGF-1/GH dichotomy remains present in around one-third of patients. In our cohort, exposure to SSA therapy, a lower BMI and lower GH level at diagnosis were significant determinants of IGF-1/GH discordance.