Gspmutation in acromegaly and its influence on TRH-induced paradoxical GH response

Abstract

We recently reported that paradoxical GH response to TRH administration reflects biological characteristics in patients with acromegaly. The aim of this study is to elucidate the relationship between gsp mutations and the paradoxical GH response to TRH. Sixty-seven patients with acromegaly were included for analysis. Paradoxical increase in serum GH level to TRH, GH suppression by octreotide and bromocriptine, radiological profiles and histopathological findings were analysed with respect to tumour gsp-mutation status. Twenty-six (38·8%) gsp mutations were detected, and the number of paradoxical GH responders to TRH, defined as an increase of 100% or more in GH after TRH, was 49 (73·1%). Among the paradoxical GH responders to TRH, 21 patients (42·9%) had a gsp mutation and 28 patients (57·1%) did not. The percentage of paradoxical GH responders to TRH in gsp-positive and gsp-negative patients was not significantly different (80·8% and 68·3%, respectively). The gsp-positive group showed a significantly higher paradoxical increase in serum GH level by TRH administration (1830% vs 650% GH increase, P = 0·045) and greater GH suppression by octreotide (88·7% vs 75·4% GH decrease, P = 0·003) than the gsp-negative group. Paradoxical GH response to TRH was observed regardless of gsp mutation, although the rate of increase was significantly higher in gsp-positive patients. These results suggest that gsp mutation is not sufficient to cause the paradoxical GH response to TRH, while other unidentified factors have a strong influence on paradoxical GH response to TRH in patients with acromegaly.