Ectopic Growth Hormone-Releasing Factor Syndromes

Abstract

The association of carcinoid tumors of the bronchial tree and the intestine with acromegaly was first reported in 1960,⁽¹⁾ and selective case reports appeared throughout the next two decades.^(2–5) The rationale for proposing that growth hormone-releasing factor (GRF) might be produced by tissues other than the hypothalamus was based on these observations which suggested that the association was more than fortuitous. The possibility that the extrapituitary tumors secreted growth hormone (GH) was suggested by the report of Beck et al. ⁽⁶⁾ in which extracts of human lung tumors stimulated GH release from superfused rat pituitaries. The patients from whom the tumors were removed, however, did not exhibit clinical evidence of GH hypersecretion. In the mid 1970s, two reports^(4,5) appeared describing four patients with acromegaly associated with bronchial carcinoid tumors who had remission of the clinical features of their disorders and/or a return of GH levels to normal after removal of the bronchial tumor and without therapy directed to the hypothalamic— pituitary region. Immunoreactive GH was demonstrated in one of these tumors but not in the others. The possibility that GH hypersecretion and pituitary tumor formation could occur on the basis of excessive stimulation of somatotrophs by GRF was further supported by preliminary reports demonstrating the presence of GH-releasing activity in plasma of acromegalic subjects unassociated with carcinoid tumors.⁽⁷⁸⁾