Ectopic GHRH production: revisiting a rare cause of acromegaly

Growth Hormone-Releasing Hormone (GHRH) is a hypothalamic hormone that stimulates GH secretion by the anterior pituitary gland. Ectopic production of GHRH by neuroendocrine tumors (NETs) is a rare cause of acromegaly, with some clinical and biochemical features indistinguishable from pituitary adenoma origin. Some clues for this diagnosis include pituitary MRI harboring hyperplasia, increased serum GHRH and extra-pituitary tumor detected in whole body scans. The preferable treatment, when possible, should be surgical resection of the NET. In cases with residual tumor, somatostatin analogs could be used as an alternative for adjuvant therapy for both tumoral and biochemical control of IGF-1. Life-long follow-up is needed as some patients may develop persistent pituitary hyperplasia or GH-adenomas due to prolonged GHRH exposure, with elevated IGF-1 levels even without NET recurrence. In such scenarios, medical therapy should be provided for hyperplasia cases and transsphenoidal surgery to patients with pituitary adenoma. If available, genetic test for MEN1 mutations should always be performed.