Somatostatin Sensitivity and Growth Hormone Responses to Releasing Hormones and Bromocryptine in Acromegaly

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Abstract
Infusion of increasing doses of somatostatin (SRIF) (respectively 60, 120, and 300 μg/hour for 1 h) disclosed the presence of two groups of acromegalics. In group I (n = 8 patients), the elevated serum hGH levels [mean basal value 25 ± 4 ng/ml (±SEM)] decreased to normal values (hGH < 7.5 ng/ ml), whereas in group II (n = 12) serum hGH levels (mean basal value 55 ± 13 ng/ml; P < 0.01 vs. group I) remained elevated (36 ± 18 ng/ml during infusion of 300 μg SRIF). At each dose level of SRIF, the mean percentage decrease in group I was significantly greater than in group II (61 ± 9% vs. 19 ± 4% at 60 /μg/h, 64 ± 7 vs. 25 ± 7% at 120 μg/h, and 83 ± 3 vs. 35 ± 7% at 300 μg/ h; P < 0.01 at each dose level). Serum hGH levels showed a significant rebound above basal values after stopping SRIF infusion only in group I. The difference in SRIF sensitivity between the 2 groups was further substantiated by the much higher rate of decline of hGH in group I [t½ 56 ± 13 min in group I vs. 260 ± 75 min in group II (P < 0.01)]. LHRH (100 μg) elicited a distinct hGH increase only in the group of acromegalics with the higher SRIF sensitivity (5 out of 8 patients in group I against 0 out of 12 patients in group II; P < 0.01). In contrast, the responsiveness to TRH was similar in both groups (6 out of 8 in group I against 9 out of 12 in group II), and acute bromo-cryptine administration (5 mg orally) proved equally potent in lowering hGH levels in both groups (percentage decrease 66 ± 13% in group I vs. 67 ± 8% in group II; P > 0.10). We conclude the following: 1) The present data confirm the existence of two distinct subgroups of acromegalics characterized by differing sensitivities to SRIF. Endogenous SRIF deficiency i n the more sensitive subgroup might account for this difference. 2) LHRH induced a marked hGH increase only in the SRIF normalizers, suggesting a tight connection between the action of these hypothalamic factors. The absence ofsuch linkage between TRH and SRIF responses points to different modes of action of TRH and LRH at the somatotroph; 3) SRIF responsiveness does not parallel the bromocryptine response in acromegaly. Therefore, long-acting hGH-specific SRIF analogs may play a pivotal role in future medical treatment of acromegaly unresponsive to bromocryptine. (J Clin Endocrinol Metab54: 942, 1982)