Contradictory clinical implications between paradoxical growth hormone responses to thyrotropin-releasing hormone and those to vasoactive intestinal peptide and luteinizing hormone-releasing hormone in acromegaly

Abstract

There is an almost general agreement on the clinical significance of TRH and bromocriptine (Br) tests in acromegaly. That is that positive GH responses to these tests (with an increase or a decrease, respectively) are known to be very frequently associated with the presence of PRL-containing somatotroph adenomas of the pituitary. In this context, however, very little is known about the clinical significance of paradoxical GH responses to vasoactive intestinal peptide (VIP) and LHRH in acromegaly. We therefore examined, as the principal objective of this study, whether a relationship exists among the GH (in some cases also PRL) responses to TRH, VIP, LHRH and Br in acromegaly. Another aim of this study was to examine whether a sexual difference exists in GH and PRL secretion in acromegaly. We examined a total of 24 patients comprising 8 men and 16 women. In agreement with previous reports, TRH-responders tended to have a higher level of basal PRL than TRH-nonresponders. In contrast, VIP-responders and LHRH-responders tended to have a lower PRL level than their respective counterparts. Although Br responsiveness was unexpectedly similar between TRH-responders and nonresponders, it was revealed that pure TRH-responders who were not responsive to VIP or LHRH were more sensitive to Br and more hyperprolactinemic than the remaining TRH-responders. This suggests that the simultaneous GH responsivity to VIP and/or LHRH in TRH-responders may be a factor which lowers their Br responsiveness and basal PRL levels. With respect to a sexual difference in GH and PRL secretion, it was revealed that female acromegalics had higher levels of basal GH and PRL than male patients. In addition, it was found that female acromegalics had supernormal levels of basal PRL, but a subnormal PRL responsiveness to TRH. As the major implication of this study, we hypothesize that the positive GH response to TRH associated with a high sensitivity to Br may, as already suggested, be characteristic of PRL-containing somatotroph adenomas, whereas the GH responsivity to VIP, and possibly also to LHRH, co-existing with no or low sensitivity to Br may be a feature of pure somatotroph adenomas. Although this study is devoid of immunohistochemical evidence to support this hypothesis, we suggest that the present in vivo data may be of some help in understanding the basis of the great variabilities in the GH responses to various dynamic testing in acromegaly.