A Case of Ectopic Growth Hormone Releasing Hormone (GHRH) from Pancreatic Neuroendocrine Tumor Resistant to Therapy

Abstract

Introduction: Ectopic secretion of GHRH is a rare cause of acromegaly. However, its recognition is clinically important because different therapeutic approaches are required. Case Presentation: We present a challenging case of acromegaly secondary to ectopic GHRH secretion from pancreatic neuroendocrine tumor in a 52-year-old female. The patient is treated with different modalities which include pegvisomant in an attempt to control the stimulated GH-axis considering the limited data about its use in treatment of ectopic acromegaly. Conclusion: GHRH-secreting tumor is a rare cause of acromegaly. Surgical resection of the tumor is the therapy of choice whenever possible. However, further studies are warranted for unresectable tumor or resistant cases.

Share and Cite:

O. Almohareb and J. Rivera, "A Case of Ectopic Growth Hormone Releasing Hormone (GHRH) from Pancreatic Neuroendocrine Tumor Resistant to Therapy," Open Journal of Endocrine and Metabolic Diseases, Vol. 3 No. 7, 2013, pp. 271-275. doi: 10.4236/ojemd.2013.37037.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] E. Verrua, C. L. Ronchi, E. Ferrante, et al., “Acromegaly Secondary to an Incidentally Discovered Growth-Hor- mone-Releasing Hormone Secreting Bronchial Carcinoid Tumour Associated to a Pituitary Incidentaloma,” Pituitary, Vol. 13, No. 3, 2010, pp. 289-292. http://dx.doi.org/10.1007/s11102-008-0146-y
[2] D. C. Metz and R. T. Jensen, “Gastrointestinal Tumors: Pancreatic Endocrine Tumors,” Gastroenterology, Vol. 135, No. 5, 2008, pp. 1469-1492.
http://dx.doi.org/10.1053/j.gastro.2008.05.047
[3] M. H. Kulke, L. B. Anthony, D. L. Bushnell, et al., “WellDifferentiated Neuroendocrine Tumors of the Stomach and Pancreas,” Pancreas, Vol. 39, No. 6, 2010, pp. 735-752. http://dx.doi.org/10.1097/MPA.0b013e3181ebb168
[4] R. T. Jensen, M. J. Berna, D. B. Bingham, et al., “Inherited Pancreatic Endocrine Tumor Syndromes: Advances in Molecular Pathogenesis, Diagnosis, Management and Controversies,” Cancer, Vol. 113, Suppl. 7, 2008, pp. 1807-1843. http://dx.doi.org/10.1002/cncr.23648
[5] F. Ehehalt, H. D. Saeger, C. M. Schmidt, et al., “Neuroendocrine Tumors of the Pancreas,” The Oncologist, Vol. 14, No. 5, 2009, pp. 456-467.
http://dx.doi.org/10.1634/theoncologist.2008-0259
[6] S. Ezziddin, T. Logvinski, C. Yong-Hing, et al., “Factors Predicting Tracer Uptake in Somatostatin Receptor and MIBG Scintigraphy of Metastatic Gastroenteropancreatic Neuroendocrine Tumors,” Journal of Nuclear Medicine, Vol. 47, No. 2, 2006, pp. 223-233.
[7] L. V. Neto, G. F. Taboada, L. L. Corrêa, et al., “Acromegaly Secondary to Growth Hormone-Releasing Hormone Secreted by an Incidentally Discovered Pheochromocytoma,” EndoChoice Pathology, Vol. 18, No. 1, 2007, pp. 46-52. http://dx.doi.org/10.1007/s12022-007-0006-8
[8] Y. Shintani, K. Yoshimoto, H. Horie, et al., “Two Different Pituitary Adenomas in a Patient with Multiple Endocrine Neoplasia Type 1 Associated with Growth Hormone-Releasing Hormone-Producing Pancreatic Tumor: Clinical and Genetic Features,” Endocrine Journal, Vol. 42, No. 3, 1995, pp. 331-340.
http://dx.doi.org/10.1507/endocrj.42.331
[9] D. Zimmerman, W. F. Young Jr., M. J. Ebersold, et al., “Congenital Gigantism Due to Growth Hormone-Releasing Hormone Excess and Pituitary Hyperplasia with Adenomatous Transformation,” JCEM, Vol. 76, No. 1, 1993, pp. 216-222.
[10] S. L. Asa, K. Kovacs, L. Stefaneanu, et al., “Pituitary Adenomas in Mice Transgenic for Growth Hormone-Releasing Hormone,” Endocrinology, Vol. 131, No. 5, 1992, pp. 2083-2089. http://dx.doi.org/10.1210/en.131.5.2083
[11] R. V. Lloyd, L. Jin, A. Chang, et al., “Morphologic Effects of hGRH Gene Expression on the Pituitary, Liver, and Pancreas of MT-hGRH Transgenic Mice. An in Situ Hybridization Analysis,” American Journal of Pathology, Vol. 141, No. 4, 1992, pp. 895-906.
[12] J. Rivier, J. Spiess, M. Thorner, et al., “Characterization of a Growth Hormone-Releasing Factor from a Human Pancreatic Islet Tumor,” Nature, Vol. 300, No. 5889, 1982, pp. 276-278. http://dx.doi.org/10.1038/300276a0
[13] H. Kiaris, M. Koutsilieris, A. Kalofoutis, et al., “Growth Hormone-Releasing Hormone and Extra-Pituitary Tu- morigenesis: Therapeutic and Diagnostic Applications of Growth Hormone-Releasing Hormone Antagonists,” Ex- pert Opinion on Investigational Drugs, Vol. 12, No. 8, 2003, pp. 1385-1394. http://dx.doi.org/10.1517/13543784.12.8.1385
[14] A. Plonowski, A. V. Schally, M. Letsch, et al., “Inhibition of Proliferation of PC-3 Human Prostate Cancer by Antagonists of Growth Hormone-Releasing Hormone: Lack of Correlation with the Levels of Serum IGF-I and Expression of Tumoral IGF-II and Vascular Endothelial Growth Factor,” Prostate, Vol. 52, No. 3, 2002, pp. 173-182. http://dx.doi.org/10.1002/pros.10105
[15] A. Plonowski, J. L. Vagra, A. V. Schally, et al., “Inhibition of PC-3 Human Prostate Cancers by Analogs of Growth Hormone-Releasing Hormone (GH-RH) Endowed with Vasoactive Intestinal Peptide (VIP) Antagonistic Activity,” International Journal of Cancer, Vol. 98, No. 4, 2002, pp. 624-629. http://dx.doi.org/10.1002/ijc.10221
[16] I. Chatzistamoul, A. V. Schally, J. L. Vagra, et al., “Inhibition of Growth and Metastases of MDA-MB-435 Human Estrogen-Independent Breast Cancers by an Antagonist of Growth Hormone-Releasing Hormone,” Anticancer Drugs, Vol. 12, No. 9, 2001, pp. 761-768.
http://dx.doi.org/10.1097/00001813-200110000-00008
[17] N. Barabutis and A. V. Schally, “Growth Hormone-Releasing Hormone: Extrapituitary Effects in Physiology and Pathology,” Cell Cycle, Vol. 9, No. 20, 2010, pp. 4110-4116. http://dx.doi.org/10.4161/cc.9.20.13787
[18] M. Doga, S. Bonadonna, A. Burattin, et al., “Ectopic Secretion of Growth Hormone-Releasing Hormone (GHRH) in Neuroendocrine Tumors: Relevant Clinical Aspects,” Annals of Oncology, Vol. 12, Suppl. 2, 2001, pp. S89S94. http://dx.doi.org/10.1093/annonc/12.suppl_2.S89
[19] C. Jaffe, R. DeMott-Friberg, L. Frohman, et al., “Suppression of Growth Hormone Hypersecretion Due to Ectopic GHRH by Selective GHRH Antagonist,” JCEM, Vol. 82, No. 2, 1997, pp. 634-637.
[20] M. Gola, M. Doga, S. Bonadonna, et al., “Neuroendocrine Tumors Secreting Growth Hormone-Releasing Hormone,” Pituitary, Vol. 9, No. 3, 2006, pp. 221-229.
http://dx.doi.org/10.1007/s11102-006-0267-0
[21] L. A. Frohman, T. R. Downs, T. C. Williams, et al., “Rapid Enzymatic Degradation of Growth Hormone-Releasing Hormone by Plasma in Vitro and in Vivo to a Biologically Inactive Product Cleaved at the NH2 Terminus,” Journal of Clinical Investigation, Vol. 78, No. 4, 1986, pp. 906-913. http://dx.doi.org/10.1172/JCI112679
[22] N. H. Othman, S. Ezzat, K. Kovacs, et al., “Growth Hormone-Releasing Hormone (GHRH) and GHRH Receptor (GHRH-R) Isoform Expression in Ectopic Acromegaly,” Clinical Endocrinology, Vol. 55, No. 1, 2001, pp. 135-140.
[23] L. Szalontay, R. J. Benveniste, A. V. Schally, et al., “Inhibitory Effects of GHRH Antagonists on Human GHSecreting Adenoma Tissue,” Neuroendocrinology, Vol. 96, No. 1, 2012, pp. 81-88.
http://dx.doi.org/10.1159/000335989
[24] M. C. Zatelli, D. Piccin, F. Tagliati, et al., “Somatostatin Receptor Subtype 1 Selective Activation in Human Growth Hormone (GH) and Prolactin (PRL) Secreting Pituitary Adenomas: Effects on Cell Variability, GH, and PRL Secretion,” JCEM, Vol. 88, No. 6, 2003, pp. 2797-2802.
[25] G. Sassolas and J. A. Chayvialle, “GRFomas, Somatostati- nomas: Clinical Presentation, Diagnosis and Advances in Management,” In: M. Mignon and R. T. Jensen, Eds., Endocrine Tumors of the Pancreas: Recent Advances in Research and Management, Vol. 23, Basel, Karger, 1995, pp. 194-207.
[26] D. E. Weiss, H. Vogel, M. B. S. Lopes, et al., “Ectopic Acromegaly Due to a Pancreatic Neuroendocrine Tumor Producing Growth Hormone Releasing Hormone,” Endocrine Practice, Vol. 17, No. 1, 2011, pp. 79-84.
[27] A. Agha, L. Farrell, P. Downey, et al., “Acromegaly Secondary to Growth Hormone Releasing Hormone Secretion,” Irish Journal of Medical Science, Vol. 173, No. 4, 2004, pp. 215-216.
http://dx.doi.org/10.1007/BF02914554
[28] L. Garby, P. Caron, F. Claustrat, et al., “Clinical Characteristics and Outcome of Acromegaly Induced by Ectopic Secretion of Growth Hormone-Releasing Hormone (GHRH): A French Nationwide Series of 21 Cases,” JCEM, Vol. 97, No. 6, 2012, pp. 2093-2104.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.