Diagnosis of Growth Hormone Excess and Hyperprolactinemia

Abstract

Acromegaly is a relatively rare disease that is caused by long- standing growth hormone (GH) hypersecretion. The estimated prevalence of the disease is 60 cases per million with 3– 4 new cases per million per year [1]. In exceptional cases, the disease is diagnosed prior to epiphyseal fusion, leading to pituitary gigantism. After completion of growth, the clinical symptoms become more similar to those in acromegalic adults like coarse facial features, acral changes, hyperhydrosis, headaches and visceromegaly. In most cases, acromegaly is caused by pituitary adenomas, but it has become evident that lesions of hypothalamic, pituitary, or extracranial origin may be responsible for GH excess. Hypersecretion of GH- releasing hormone (GHRH) may be the result of a hypothalamic tumor, for example, hamartoma or ganglioneuroma, which either directly secretes GHRH or, alternatively, may stimulate hypothalamic GHRH production or impair the secretion of somatostatin. More frequently, GHRH secretion occurs from an ectopic GHRH- producing tumor like carcinoid tumors, pancreatic cell tumors, small cell lung cancer, and adrenal tumors [2]. GHRH may lead to GH hypersecretion and eventually pituitary acromegaly. GHRH is a potent mitogenic factor, and transgenic mice expressing the GHRH gene may develop somatotropic adenomas, which shows that GHRH is a direct tropic stimulus for the somatotropic cell [3]. Similarly, in McCune- Albright syndrome, constitutive activation of the GHRH- cAMP signaling pathway caused by an activating GNAS mutation leads to GH hypersecretion and pituitary adenoma formation in up to one third of patients [4, 5]. GHRH may also stimulate prolactin (PRL) secretion in acromegalic subjects, and about one third of such patients have hyperprolactinemia [1]. Several aspects favor the ‘pituitary’ hypothesis underlying acromegaly. In 90% of acromegalics, a pituitary tumor can be found, and these tumors can be plurihormonal,