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

Abstract

Context 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. Objective 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. Patients 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. Results 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. Conclusions 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.

Clinical and Radiological Predictors of Biochemical Response to First-Line Treatment With Somatostatin Receptor Ligands in Acromegaly: A Real-Life Perspective

“…Besides clinical, biochemical, and radiological characteristics, we have investigated the potential role of dynamic tests (OGTT at diagnosis and acute octreotide test) as predictors to first-line SRL treatment. In line with recent data from other authors, we observed that a lower % of GH suppression after OGTT or the presence of a paradoxical GH increase (≥20% vs. baseline) are associated (with a trend towards statistical significance) with a better response to fg-SRL therapy (45). Of note, Scaroni and colleagues observed that patients showing a paradox response to OGTT also had higher baseline IGF-1 xULN values and were older compared to those subjects with a non-paradoxical response (45).…”

“…Considering the results of OGTT (n=32), the median GH nadir was 4.8 µg/L (IQR 2.5-13.6), with a median reduction of 19% (IQR 37.4 and -0.9), while a paradoxical rise in GH levels, defined according to the criteria proposed by Scaroni and colleagues (45), was observed in 4/32 patients (12.5%).…”

Acromegaly Cases Exhibiting Increased Growth Hormone Levels during Oral Glucose Loading with Preadministration of Dipeptidyl Peptidase-4 Inhibitor

“…Patients showing PI-GH were reportedly more likely to have the densely granulated type ( 19 , 20 ), and the two cases in this study were similar to those previously reported. It has also been reported that patients who present with PI-GH have a better response to somatostatin analogues than others ( 9 , 10 ). The two cases in this study also responded well to octreotide, and the staining of SSTR2 was consistent with this.…”

“…The two cases in this study also responded well to octreotide, and the staining of SSTR2 was consistent with this. However, although patients with PI-GH are reported to be older and have smaller tumors than those without it ( 10 ), case 2 was relatively young and had a larger tumor size, which differed from the general characteristics of PI-GH patients.…”

“…However, previous studies have shown that the GH concentration is >1 μg/L during 75-g OGTT (3) in patients with acromegaly, and 10-30% of acromegalic patients show a paradoxical increase in GH (PI-GH) (4)(5)(6)(7)(8). Other studies have shown that GH concentrations are more substantially reduced in individuals with PI-GH than in those without it during octreotide or bromocriptine testing (9), and PI-GH is associated with an increased incidence of remission in response to somatostatin analogues (10). Umahara et al (5) reported that postprandial GH secretion is higher and that continuous intravenous administration of glucose-dependent insulinotropic polypeptide (GIP), a gastrointestinal hormone, causes an increase in the secretion of GH in acromegalic patients with PI-GH.…”