Relationship between growth hormone and Somatomedin‐C levels in untreated acromegaly, after surgery and radiotherapy and during medical therapy with Sandostatin (SMS 201–995)

Abstract

Several conflicting reports have been published with regard to the relationships between circulating growth hormone (GH), Somatomedin-C (SM-C) levels and clinical activity during different stages of therapy of acromegaly. We did not find a significant correlation between (fasting, post-prandial and mean 24-h) plasma GH and SM-C concentrations in twenty-two untreated acromegalic patients. There was a statistical significant correlation, however, if only the GH levels below 100 .mu.g l-1 were considered (n=8 patients, P < 0.01). The distribution of molecular forms of GH (''little'', ''big'' and ''big-big'') did not differ between the four patients with GH levels above 100 .mu.g l-1 and in four patients with levels between 40 .mu.g l-1 and 80 .mu.g l-1. Therefore, it is suggested that GH levels of 80-100 .mu.g l-1 maximally activate Somatomedin-C production in man and that further increases in GH in general will not result in a further increase in SM-C generation. There was a significant correlation between GH and SM-C levels in forty-nine acromegalic patients after surgery and/or radiotherapy (P < 0.001). In twenty-three of thirty-one patients with elevated SM-C levels the disease was subjectively still active, while this was the case in none of the patients with normal SM-C levels. In eight patients the disease was considered not to be clinically active any more, despite slightly increased SM-C levels. During long-term therapy of ten acromegalic patients for 16-108 weeks (mean 66 .+-. 10) with 200-300 .mu.g Sandostatin subcutaneously, clinical activity of the disease disappeared well before mean 24-h GH and SM-C levels reached the normal levels. There was a close correlation between mean 24-h GH and SM-C levels during Sandostatin therapy (P < 0.001). ''Clinical cure'' during this medical treatment was reached in five patients, as reflected by disappearance of subjective complaints, normalization of SM-C levels and 24-h mean GH levels of 2.8 .+-. 0.2 .mu.g l-1. Conclusions: (i) in untreated acromegaly, circulating GH and SM-C levels correlate well up to GH concentrations of 100 .mu.g l-1. A further increase in GH does not result in a corresponding further increase in SM-C levels, suggesting a maximally activated production, without further GH-dependent capacity. (ii) Clinical ''cure'' of acromegaly often occurs before normalization of the circulating SM-C levels. (iii) The measurement of plasma SM-C concentrations can be used well to adjust the dose and frequency of Sandostatin administration in acromegaly. This avoids the need of measuring extensive 24-h GH profiles.