Ectopic GHRH production: revisiting a rare cause of acromegaly.

in Reviews in endocrine & metabolic disorders by Matheo A M Stumpf, Nathalie Oliveira Santana, Marcio Carlos Machado, Felipe H Duarte, Andrea Glezer, Gérald Raverot, Véronique Raverot, Raquel S Jallad

TLDR

  • Ectopic GHRH production by neuroendocrine tumors can cause acromegaly with clinical and biochemical features similar to pituitary adenoma origin.
  • Surgical resection of the NET is the preferred treatment option, with somatostatin analogs as an alternative for adjuvant therapy.
  • Life-long follow-up is necessary to detect persistent pituitary hyperplasia or GH-adenomas, and genetic tests for MEN1 mutations may be useful for diagnosis.

Abstract

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.

Overview

  • The study focuses on ectopic production of Growth Hormone-Releasing Hormone (GHRH) by neuroendocrine tumors (NETs), a rare cause of acromegaly.
  • The study aims to identify clinical and biochemical features that distinguish NET-originating acromegaly from pituitary adenoma origin, and explore effective treatment options.
  • The study highlights the importance of detecting pituitary MRI hyperplasia, increased serum GHRH, and extra-pituitary tumor in whole body scans to diagnose NET-originating acromegaly.

Comparative Analysis & Findings

  • The study compares the clinical and biochemical features of NET-originating acromegaly with those of pituitary adenoma origin.
  • The study finds that pituitary MRI harboring hyperplasia, increased serum GHRH, and extra-pituitary tumor in whole body scans are characteristic features of NET-originating acromegaly.
  • The study concludes that surgical resection of the NET is the preferred treatment option, followed by somatostatin analogs for adjuvant therapy in cases with residual tumor.

Implications and Future Directions

  • The study emphasizes the importance of life-long follow-up for patients with NET-originating acromegaly, as some may develop persistent pituitary hyperplasia or GH-adenomas due to prolonged GHRH exposure.
  • The study suggests that medical therapy may be necessary for hyperplasia cases, and transsphenoidal surgery for pituitary adenomas.
  • The study recommends performing genetic tests for MEN1 mutations when available to identify potential cases of multiple endocrine neoplasia type 1.
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