Growth hormone isoforms in acromegalic patients before and after treatment with octreotide LAR.

Background: Human growth hormone (hGH) circulates as a mixture of different isoforms. It has been previously reported that the ratio of 20kDa to 20kDa plus 22kDa (%20kDa-hGH) is increased in patients with active acromegaly.

Objectives: To evaluate the GH isoforms (20kDa- and 22kDa-hGH) in acromegalic patients before and after six months of treatment with octreotide LAR, and to compare the results with those in healthy controls. In addition, the relationships between the %20kDa-hGH, tumor size and biochemical measurements were also investigated.

Design: Random serum samples from 23 acromegalic patients evaluated before and after six months of treatment with octreotide LAR and from 23 matched healthy controls were studied. Growth hormone, IGF-I and prolactin (PRL) were measured by chemiluminescence immunometric assay and the 20kDa- and 22kDa-hGH isoforms were measured by specific time-resolved fluorescence immunoassays.

Results: In acromegalic patients before treatment, there was a significantly higher median %20Da-hGH in comparison to healthy controls (14.31% vs. 9.59%, p<0.001). After six months of treatment, the median %20kDa-hGH was similar to the baseline values. Patients with GH<2.5ng/mL after six months of treatment had already lower GH and %20kDa-hGH at baseline (p<0.01). The IGF-I (SD-scores) was positively correlated to total GH levels in acromegalic patients after treatment. There was no correlation between the %20kDa-hGH and PRL levels or tumor size.

Conclusions: Our study confirmed that acromegalic patients have an increased proportion of circulating 20kDa-hGH isoform. Consequently, the use of a 22kDa-hGH specific assay may underestimate the tumor production of total GH. Although octreotide LAR promoted a significant decrease in the GH and IGF-I levels, it did not normalize the GH isoforms composition and suggests that the secretion of GH isoforms is equally inhibited by somatostatin analogues and that it is the disease control that normalizes the GH isoforms composition in acromegaly.