GH consists of various molecular isoforms. Most abundant is 22 kDa-GH (8090% of total GH), followed by 20 kDa-GH (515% of total GH). The biological significance of 20 kDa-GH remains unclear, but its effects appear comparable to those of 22 kDa-GH. Acromegaly is characterized by chronic GH excess. Data on GH isoforms in acromegaly are scarce, but an increased 20 kDa-/22 kDa-GH-ratio (20k-ratio) has been described. Our aims were to compare the 20k-ratio in a larger cohort of treatment-naïve patients with acromegaly and healthy controls, to investigate the potential impact of BMI on the 20k-ratio and to compare the dynamics of the 20k-ratio during oral glucose tolerance test in the groups. Forty-one treatment-naïve patients with acromegaly (ACR, 13 microadenomas, 28 macroadenomas) and 137 controls (CON) were included in this study. Serum samples were collected at baseline and 30, 60, 120 and 180 min after oral glucose load (75 g). 22 kDa-GH was measured in all samples using the 22 kDa-GH-specific CLIA-IDS-iSYS (limit of quantification (LoQ) 0.05 ng/ml). In samples with 22 kDa-GH>0.4 ng/ml 20 kDa-GH was measured using an in-house IFMA (LoQ 0.025 ng/ml). Subjects were assigned to BMI-groups A, B, C with BMI<25 kg/m2, 2530 kg/m2 and >30 kg/m2, respectively. At baseline, 20kDa-GH was measurable in 100% (n=41) and 53% (n=73) of ACR and CON, respectively. 60 min following glucose load, 20 kDa-GH was detectable in 100% (n=41) and 31% (n=43) of ACR and CON, respectively. The baseline 20k-ratio was significantly higher in ACR (mean 20k-ratio 13.8% (range 726%); CON: 10.1% (range 218%); P<0.0001). There was no difference between macro- and microdenomas. In CON the 20k-ratio was lower with higher BMI (A (n=43): 11.3%; B (n=19): 8.9% and C (n=11) 7.8%; A vs B and A vs C: P<0.05). In ACR we could not detect a significant impact of BMI on the 20k-ratio (P>0.05 between all BMI-groups). Following glucose load, the mean 20k-ratio significantly increased in CON, starting at 10.1%, increasing to 12.7% and 15.5% after 30 and 60 min respectively, before returning to baseline at 180 min (10.5%). In contrast, the 20k-ratio remained unchanged in ACR. In CON the 20k-ratio was lower with higher BMI and furthermore increased temporarily after glucose load. Our data confirm that the 20k-ratio is higher in ACR, but is, unlike to CON, not regulated by BMI or acute glucose load. Thus, increased GH secretion from somatotrope adenomas seems to be associated with alterations in the regulation of isoform composition.
19 May 2018 - 22 May 2018