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.
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.
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
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
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.
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
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
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.
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
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.
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
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.
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
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
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
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
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
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
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.
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
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.
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.
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.
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
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.