Paradoxical GH Increase During OGTT Is Associated With First-Generation Somatostatin Analog Responsiveness in Acromegaly

The oral glucose tolerance test (OGTT) is considered the most useful method for diagnosing active acromegaly and for patient follow-up after neurosurgery. Despite its widespread use, only a few small studies have so far focused on patients' clinical features associated with different GH responsiveness to OGTT. We aimed to investigate the association between glucose-induced GH response and endocrine profiles, clinical manifestations, and response to therapy in a large cohort of patients with acromegaly. According to GH response to OGTT, patients were grouped as paradoxical (GH-Par) or nonparadoxical (GH-NPar), and their clinical and pathological features were compared in terms of pituitary tumor size, invasiveness, biochemical profiles, and response to therapy. The study concerned 496 patients with acromegaly. At diagnosis, those with GH-Par (n = 184) were older than those with GH-NPar (n = 312) (mean ± SD, 44.1 ± 13.7 years vs 40.5 ± 12.7 years; P < 0.01) and had smaller tumors (0.82 vs 1.57 cm3; P < 0.01) that less frequently invaded the cavernous sinus (15% vs 27%; P < 0.01). The GH-Par group also had a higher basal GH per volume ratio (14.3 vs 10.5 μg/L ⋅ cm3; P < 0.05) and a lower incidence of hyperprolactinemia (17% vs 30%; P < 0.01) than the GH-NPar group. Importantly, the GH-Par group had a higher rate of remission in response to somatostatin analogues (52% vs 26%; P < 0.01) and a more marked drop in IGF-1 and GH after 6 months of therapy. Our data strongly suggest that serum GH responsiveness to oral glucose challenge reflects some important biological features of pituitary tumors and that the OGTT may have some prognostic value.