Growth hormone-releasing hormone-producing tumors: clinical, biochemical, and morphological manifestations.

This paper has reviewed current knowledge of clinical, biochemical, and morphological manifestations of extracranial GRH-producing tumors. Excessive GRH release stimulates pituitary somatotrophs causing elevation of blood GH levels and acromegaly. In some patients with GRH-containing tumor, blood GH concentrations are normal and no acromegaly develops. GRH-producing tumors associated with acromegaly are rare. Based on a critical analysis of the literature, 30 tumors are accepted as definitive. They possess unique features: occurrence in young age, female preponderance, foregut derivation, benign biological behavior, small secretory granules, and frequent association with MEN type I syndrome. The pancreas and lung are common primary sites. GRH-containing tumors unassociated with acromegaly include those of gut and thymus, small cell carcinoma of lung, and medullary carcinoma of thyroid. Several tumors are plurihormonal. In contrast to somatotroph adenoma seen in patients with classical acromegaly, the hypophysial lesion represents somatotroph hyperplasia in acromegalic patients with GRH-producing tumor. This finding indicates that GRH not only increases somatotroph secretory activity but causes somatotroph proliferation. Studies of GRH-producing tumors are of fundamental importance in obtaining a deeper insight into endocrine activity of pituitary somatotrophs and the pathogenesis of GH-secreting pituitary adenomas associated with acromegaly; the importance of GRH in the etiology of acromegaly is still unresolved. The relationship between GRH-secreting tumors and MEN type I syndrome is controversial; further studies are required to elucidate whether they represent two distinct entities or whether GRH-producing tumors accompanied by acromegaly are only forme fruste manifestations of MEN type I syndrome.