Objective: Paradoxical growth hormone (GH) response to oral glucose tolerance tests (OGTTs) has been reported in 10-37% of patients with acromegaly, although the consequences remain unclear. The aim of this study was to identify different types of GH responses in pre-treatment OGTTs in patients suspected of acromegaly, and correlate these to clinical parameters.

Methods: Patients who underwent an OGTT between 2007 and 2019 on suspicion of acromegaly were identified, and pre-treatment OGTTs were collected. Patients were divided into a novel classification system, based on GH response during OGTT: paradoxical rise (Par), unsuppressed (Unsup), paradoxical rise with suppression (ParSup), and adequately suppressed (Sup). GH courses were compared between these groups, and correlated to diagnostic parameters and treatment outcomes.

Results: 162 participants were included, of which 74 with acromegaly (51.4% female, 46.2±13.3 years), and 88 without acromegaly (60.2% female, 46.6±15.4 years). The Par (n=28), Unsup (n=44), ParSup (n=17) and Sup (n=73) groups had significantly different GH courses (P=0.016). Acromegaly was diagnosed in 96.4% of patients with Par, 97.7% with Unsup, 11.8% with ParSup, and 2.7% with Sup course. Acromegaly patients with Par course exhibited less cavernous sinus invasion (P=0.002), and a greater remission rate (89% vs 67% for Unsup, P=0.042). Patients with ParSup course had higher fasting insulin than Sup (17.0 (7.3-22.5) mU/L vs 7.0 (4.0-11.0) mU/L, P=0.030) and were more insulin resistant (HOMA-IR 4.3 (1.5-6.4) vs 1.6 (0.7-2.4), P=0.027).

Conclusion: Four distinctive GH courses can occur during OGTT. Acromegaly was predominant in Par (96.4%) and Unsup (97.7%) courses. Acromegaly patients with Par course were less likely to have cavernous sinus invasion, and had greater remission rate after surgery, than with Unsup course. ParSup course was not associated with acromegaly, but these patients were more insulin resistant than patients with Sup course.