Skip to main content

Advertisement

SpringerLink
Log in

Ectopic acromegaly due to growth hormone releasing hormone

  • Review
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Acromegaly secondary to extra-pituitary tumors secreting growth hormone releasing hormone (GHRH) is rarely encountered. We review the literature on ectopic acromegaly and present the index report of ectopic acromegaly secondary to GHRH secretion from a mediastinal paraganglioma. Clinical and pathological manifestations and therapeutic management of 99 patients with ectopic acromegaly are reviewed. Acromegaly secondary to ectopic GHRH secretion is usually caused by a neuroendocrine tumor in the lung and pancreas. We report an additional cause of ectopic acromegaly from a mediastinal paraganglioma. Diagnostic criteria of ectopic GHRH syndrome include biochemical and pathologic tumoral confirmation of GHRH secretion and expression. Management of ectopic acromegaly consists of surgical resection of the primary tumor and biochemical normalization, with possible adjuvant use of somatostatin analogs. The review demonstrates that there are several tumor types, including paragangliomas which may secrete GHRH, leading to acromegaly. Clinical and laboratory manifestations of the syndrome and challenges in diagnosis and management of these rarely encountered patients require early diagnosis and appropriate treatment to prevent long-term morbidity and mortality with ectopic acromegaly.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. M.O. Thorner, L.A. Frohman, D.A. Leong, J. Thominet, T. Downs, P. Hellmann, J. Chitwood, J.M. Vaughan, W. Vale, Extrahypothalamic growth-hormone-releasing factor (GRF) secretion is a rare cause of acromegaly: plasma GRF levels in 177 acromegalic patients. J. Clin. Endocrinol. Metab. 59, 846–849 (1984)

    Article  PubMed  CAS  Google Scholar 

  2. G. Faglia, M. Arosio, N. Bazzoni, Ectopic acromegaly. Endocrinol. Metab. Clin. North Am. 21, 575–595 (1992)

    PubMed  CAS  Google Scholar 

  3. M. Losa, K. von Werder, Pathophysiology and clinical aspects of the ectopic GH-releasing hormone syndrome. Clin. Endocrinol. (Oxf.) 47, 123–135 (1997)

    Article  CAS  Google Scholar 

  4. M. Doga, S. Bonadonna, A. Burattin, A. Giustina, Ectopic secretion of growth hormone-releasing hormone (GHRH) in neuroendocrine tumors: relevant clinical aspects. Ann. Oncol. 12(Suppl 2), S89–S94 (2001)

    Article  PubMed  Google Scholar 

  5. M. Gola, M. Doga, S. Bonadonna, G. Mazziotti, P.P. Vescovi, A. Giustina, Neuroendocrine tumors secreting growth hormone-releasing hormone: pathophysiological and clinical aspects. Pituitary 9, 221–229 (2006)

    Article  PubMed  CAS  Google Scholar 

  6. S. Melmed, Medical progress: acromegaly. N. Engl. J. Med. 355, 2558–2573 (2006)

    Article  PubMed  CAS  Google Scholar 

  7. S. Melmed, C. Ezrin, K. Kovacs, R.S. Goodman, L.A. Frohman, Acromegaly due to secretion of growth hormone by an ectopic pancreatic islet-cell tumor. N. Engl. J. Med. 312, 9–17 (1985)

    Article  PubMed  CAS  Google Scholar 

  8. F. Beuschlein, C.J. Strasburger, V. Siegerstetter, D. Moradpour, P. Lichter, M. Bidlingmaier, H.E. Blum, M. Reincke, Acromegaly caused by secretion of growth hormone by a non-Hodgkin’s lymphoma. N. Engl. J. Med. 342, 1871–1876 (2000)

    Article  PubMed  CAS  Google Scholar 

  9. S. Biswal, B. Srinivasan, P. Dutta, P. Ranjan, K. Vaiphei, R.S. Singh, S.S. Thingnam, Acromegaly caused by ectopic growth hormone: a rare manifestation of a bronchial carcinoid. Ann. Thorac. Surg. 85, 330–332 (2008)

    Article  PubMed  Google Scholar 

  10. J. Rivier, J. Spiess, M. Thorner, W. Vale, Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature 300, 276–278 (1982)

    Article  PubMed  CAS  Google Scholar 

  11. R. Guillemin, P. Brazeau, P. Bohlen, F. Esch, N. Ling, W.B. Wehrenberg, Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science 218, 585–587 (1982)

    Article  PubMed  CAS  Google Scholar 

  12. F.T. Dabek, Bronchial carcinoid tumour with acromegaly in two patients. J. Clin. Endocrinol. Metab. 38, 329–333 (1974)

    Article  PubMed  CAS  Google Scholar 

  13. P.H. Sonksen, A.B. Ayres, M. Braimbridge, B. Corrin, D.R. Davies, G.M. Jeremiah, S.W. Oaten, C. Lowy, T.E. West, Acromegaly caused by pulmonary carcinoid tumours. Clin. Endocrinol. (Oxf.) 5, 503–513 (1976)

    Article  CAS  Google Scholar 

  14. M. Saeed uz Zafar, R.C. Mellinger, G. Fine, M. Szabo, L.A. Frohman, Acromegaly associated with a bronchial carcinoid tumor: evidence for ectopic production of growth hormone-releasing activity. J. Clin. Endocrinol. Metab. 48, 66–71 (1979)

    Article  PubMed  CAS  Google Scholar 

  15. S.M. Shalet, C.G. Beardwell, I.A. MacFarlane, M.L. Ellison, C.M. Norman, L.H. Rees, M. Hughes, Acromegaly due to production of a growth hormone releasing factor by a bronchial carcinoid tumor. Clin. Endocrinol. (Oxf.) 10, 61–67 (1979)

    Article  CAS  Google Scholar 

  16. B.W. Scheithauer, P.C. Carpenter, B. Bloch, P. Brazeau, Ectopic secretion of a growth hormone-releasing factor. Report of a case of acromegaly with bronchial carcinoid tumor. Am. J. Med. 76, 605–616 (1984)

    Article  PubMed  CAS  Google Scholar 

  17. F. Hawkins, V. Sanchez Moro, M. Aguirre, M. Leon, D. Rigopoulou, J.L. Martin de Nicolas, J. Toledo, Acromegaly and bronchial carcinoid. Effect of removal of the latter. Chest 88, 149–152 (1985)

    Article  PubMed  CAS  Google Scholar 

  18. R. Boizel, S. Halimi, F. Labat, R. Cohen, I. Bachelot, Acromegaly due to a growth hormone-releasing hormone-secreting bronchial carcinoid tumor: further information on the abnormal responsiveness of the somatotroph cells and their recovery after successful treatment. J. Clin. Endocrinol. Metab. 64, 304–308 (1987)

    Article  PubMed  CAS  Google Scholar 

  19. P.P. Garcia-Luna, A. Leal-Cerro, C. Montero, B.W. Scheithauer, A. Campanario, C. Dieguez, R. Astorga, K. Kovacs, A rare cause of acromegaly: ectopic production of growth hormone-releasing factor by a bronchial carcinoid tumor. Surg. Neurol. 27, 563–568 (1987)

    Article  PubMed  CAS  Google Scholar 

  20. D.G. Carroll, J.W. Delahunt, C.A. Teague, R.R. Cooke, E.F. Adams, N.D. Christofides, S.R. Bloom, G. Terenghi, J.M. Polak, Resolution of acromegaly after removal of a bronchial carcinoid shown to secrete growth hormone releasing factor. Aust. N. Z. J. Med. 17, 63–67 (1987)

    Article  PubMed  CAS  Google Scholar 

  21. A.L. Barkan, Y. Shenker, R.J. Grekin, W.W. Vale, R.V. Lloyd, T.F. Beals, Acromegaly due to ectopic growth hormone (GH)-releasing hormone (GHRH) production: dynamic studies of GH and ectopic GHRH secretion. J. Clin. Endocrinol. Metab. 63, 1057–1064 (1986)

    Article  PubMed  CAS  Google Scholar 

  22. S. Melmed, F.H. Ziel, G.D. Braunstein, T. Downs, L.A. Frohman, Medical management of acromegaly due to ectopic production of growth hormone-releasing hormone by a carcinoid tumor. J. Clin. Endocrinol. Metab. 67, 395–399 (1988)

    Article  PubMed  CAS  Google Scholar 

  23. D.E. Moller, A.C. Moses, K. Jones, M.O. Thorner, M.L. Vance, Octreotide suppresses both growth hormone (GH) and GH-releasing hormone (GHRH) in acromegaly due to ectopic GHRH secretion. J. Clin. Endocrinol. Metab. 68, 499–504 (1989)

    Article  PubMed  CAS  Google Scholar 

  24. P.E. Harris, P.M. Bouloux, J.A. Wass, G.M. Besser, Successful treatment by chemotherapy for acromegaly associated with ectopic growth hormone releasing hormone secretion from a carcinoid tumour. Clin. Endocrinol. (Oxf.) 32, 315–321 (1990)

    Article  CAS  Google Scholar 

  25. V. Popovic, D. Micic, S. Damjanovic, M. Petakov, D. Manojlovic, J. Micic, Discordance between growth hormone responses after growth hormone-releasing hormone (GHRH) and insulin hypoglycemia in ectopic GHRH syndrome. Endocrinol. Exp. 24, 167–173 (1990)

    PubMed  CAS  Google Scholar 

  26. R.J. Barth, R.B. Constant, M.W. Parker, G.L. Mueller, K. Kovacs, M.O. Thorner, Preoperative diagnosis of acromegaly by growth hormone-releasing factor radioimmunoassay. Mil. Med. 156, 375–378 (1991)

    PubMed  CAS  Google Scholar 

  27. M. Glikson, I. Gil-Ad, E. Galun, R. Dresner, S. Zilberman, Y. Halperin, E. Okon, Z. Laron, A. Rubinow, Acromegaly due to ectopic growth hormone-releasing hormone secretion by a bronchial carcinoid tumour. Dynamic hormonal responses to various stimuli. Acta Endocrinol. (Copenh) 125, 366–371 (1991)

    CAS  Google Scholar 

  28. J. Bertherat, G. Turpin, C. Rauch, J.Y. Li, J. Epelbaum, G. Sassolas, G. Schaison, Presence of somatostatin receptors negatively coupled to adenylate cyclase in ectopic growth hormone-releasing hormone- and alpha-subunit-secreting tumors from acromegalic patients responsive to octreotide. J. Clin. Endocrinol. Metab. 79, 1457–1464 (1994)

    Article  PubMed  CAS  Google Scholar 

  29. S. Ezzat, S.L. Asa, L. Stefaneanu, R. Whittom, H.S. Smyth, E. Horvath, K. Kovacs, L.A. Frohman, Somatotroph hyperplasia without pituitary adenoma associated with a long standing growth hormone-releasing hormone-producing bronchial carcinoid. J. Clin. Endocrinol. Metab. 78, 555–560 (1994)

    Article  PubMed  CAS  Google Scholar 

  30. S. Lefebvre, L. De Paepe, R. Abs, J. Rahier, P. Selvais, D. Maiter, Subcutaneous octreotide treatment of a growth hormone-releasing hormone-secreting bronchial carcinoid: superiority of continuous versus intermittent administration to control hormonal secretion. Eur. J. Endocrinol. 133, 320–324 (1995)

    Article  PubMed  CAS  Google Scholar 

  31. J.K. Platts, D.F. Child, P. Meadows, J.N. Harvey, Ectopic acromegaly. Postgrad. Med. J. 73, 349–351 (1997)

    Article  PubMed  CAS  Google Scholar 

  32. M.R. Drange, S. Melmed, Long-acting lanreotide induces clinical and biochemical remission of acromegaly caused by disseminated growth hormone-releasing hormone-secreting carcinoid. J. Clin. Endocrinol. Metab. 83, 3104–3109 (1998)

    Article  PubMed  CAS  Google Scholar 

  33. J. Krassowski, W. Zgliczynski, W. Jeske, S. Zgliczynski, Comment of long-acting lanreotide inducing clinical and biochemical remission of acromegaly caused by disseminated GHRH secreting carcinoid. J. Clin. Endocrinol. Metab. 84, 1761–1762 (1999)

    Article  PubMed  CAS  Google Scholar 

  34. N.H. Othman, S. Ezzat, K. Kovacs, E. Horvath, E. Poulin, H.S. Smyth, S.L. Asa, Growth hormone-releasing hormone (GHRH) and GHRH receptor (GHRH-R) isoform expression in ectopic acromegaly. Clin. Endocrinol. (Oxf.) 55, 135–140 (2001)

    Article  CAS  Google Scholar 

  35. M. Bolanowski, J. Schopohl, M. Marciniak, M. Rzeszutko, K. Zatonska, J. Daroszewski, A. Milewicz, J. Malczewska, R. Badowski, Acromegaly due to GHRH-secreting large bronchial carcinoid. Complete recovery following tumor surgery. Exp. Clin. Endocrinol. Diabetes 110, 188–192 (2002)

    Article  PubMed  CAS  Google Scholar 

  36. A. Bhansali, S.S. Rana, S. Bhattacharya, R. Muralidharan, R.J. Dash, A.K. Banerjee, Acromegaly: a rare manifestation of bronchial carcinoid. Asian Cardiovasc. Thorac. Ann. 10, 273–274 (2002)

    PubMed  Google Scholar 

  37. G. Osella, F. Orlandi, P. Caraci, M. Ventura, D. Deandreis, M. Papotti, M. Bongiovanni, A. Angeli, M. Terzolo, Acromegaly due to ectopic secretion of GHRH by bronchial carcinoid in a patient with empty sella. J. Endocrinol. Invest. 26, 163–169 (2003)

    PubMed  CAS  Google Scholar 

  38. V. Reuters, E. Dias, M.S.R.S. Pupo, M.R. Gadelha, Ectopic growth hormone-releasing hormone-secreting bronchial carcinoid cured after pneumectomy. Endocrinologist 13, 376–379 (2003)

    Article  Google Scholar 

  39. K. Athanassiadi, D. Exarchos, S. Tsagarakis, I. Bellenis, Acromegaly caused by ectopic growth hormone-releasing hormone secretion by a carcinoid bronchial tumor: a rare entity. J. Thorac. Cardiovasc. Surg. 128, 631–632 (2004)

    Article  PubMed  Google Scholar 

  40. M.B. Fessler, C.D. Cool, Y.E. Miller, M.I. Schwarz, K.K. Brown, Idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells in a patient with acromegaly. Respirology 9, 274–277 (2004)

    Article  PubMed  Google Scholar 

  41. O. Morel, P. Giraud, M.O. Bernier, J.J. Le Jeune, V. Rohmer, P. Jallet, Ectopic acromegaly: localization of the pituitary growth hormone-releasing hormone producing tumor by In-111 pentetreotide scintigraphy and report of two cases. Clin. Nucl. Med. 29, 841–843 (2004)

    Article  PubMed  Google Scholar 

  42. M.C. Zatelli, P. Maffei, D. Piccin, C. Martini, F. Rea, D. Rubello, A. Margutti, M.D. Culler, N. Sicolo, E.C. degli Uberti, Somatostatin analogs in vitro effects in a growth hormone-releasing hormone-secreting bronchial carcinoid. J. Clin. Endocrinol. Metab. 90, 2104–2109 (2005)

    Article  PubMed  CAS  Google Scholar 

  43. C. Nasr, A. Mason, M. Mayberg, S.M. Staugaitis, S.L. Asa, Acromegaly and somatotroph hyperplasia with adenomatous transformation due to pituitary metastasis of a growth hormone-releasing hormone-secreting pulmonary endocrine carcinoma. J. Clin. Endocrinol. Metab. 91, 4776–4780 (2006)

    Article  PubMed  CAS  Google Scholar 

  44. N.R. Biermasz, J.W. Smit, A.M. Pereira, M. Frolich, J.A. Romijn, F. Roelfsema, Acromegaly caused by growth hormone-releasing hormone-producing tumors: long-term observational studies in three patients. Pituitary 10, 237–249 (2007)

    Article  PubMed  Google Scholar 

  45. P. Fainstein Day, L. Frohman, H. Garcia Rivello, J.C. Reubi, G. Sevlever, M. Glerean, T. Fernandez Gianotti, M. Pietrani, A. Rabadan, S. Racioppi, M. Bidlingmaier, Ectopic growth hormone-releasing hormone secretion by a metastatic bronchial carcinoid tumor: a case with a non hypophysial intracranial tumor that shrank during long acting octreotide treatment. Pituitary 10, 311–319 (2007)

    Article  PubMed  Google Scholar 

  46. C.M. de Jager, L.J. de Heide, G. van den Berg, A. Wolthuis, W.D. van Schelven, Acromegaly caused by a growth hormone-releasing hormone secreting carcinoid tumour of the lung: the effect of octreotide treatment. Neth. J. Med. 65, 263–266 (2007)

    PubMed  Google Scholar 

  47. M. van Hoek, L.J. Hofland, Y.B. de Rijke, F.H. van Nederveen, R.R. de Krijger, P.M. van Koetsveld, S.W. Lamberts, A.J. van der Lely, W.W. de Herder, R.A. Feelders, Effects of somatostatin analogs on a growth hormone-releasing hormone secreting bronchial carcinoid, in vivo and in vitro studies. J. Clin. Endocrinol. Metab. 94, 428–433 (2009)

    Article  PubMed  CAS  Google Scholar 

  48. P.W. Butler, C.S. Cochran, M.J. Merino, D.M. Nguyen, D.S. Schrump, P. Gorden, Ectopic growth hormone-releasing hormone secretion by a bronchial carcinoid tumor: clinical experience following tumor resection and long-acting octreotide therapy. Pituitary 15, 260–265 (2012)

    Article  PubMed  Google Scholar 

  49. E. Verrua, C.L. Ronchi, E. Ferrante, D.I. Ferrari, S. Bergamaschi, S. Ferrero, M.C. Zatelli, V. Branca, A. Spada, P. Beck-Peccoz, A.G. Lania, Acromegaly secondary to an incidentally discovered growth-hormone-releasing hormone secreting bronchial carcinoid tumour associated to a pituitary incidentaloma. Pituitary 13, 289–292 (2010)

    Article  PubMed  CAS  Google Scholar 

  50. T. Gudbjartsson, B.A. Agnarsson, P.S. Palsson, A. Johannesson, Acromegaly caused by ectopic growth hormone-releasing hormone production from a bronchial carcinoid tumor. Thorac. Cardiovasc. Surg. 59, 184–185 (2011)

    Article  PubMed  CAS  Google Scholar 

  51. L. Garby, P. Caron, F. Claustrat, P. Chanson, A. Tabarin, V. Rohmer, G. Arnault, F. Bonnet, O. Chabre, S. Christin-Maitre, H. du-Boullay, A. Murat, I. Nakib, J.L. Sadoul, G. Sassolas, B. Claustrat, G. Raverot, F. Borson-Chazot, Clinical Characteristics and Outcome of Acromegaly Induced by Ectopic Secretion of Growth Hormone-Releasing Hormone (GHRH): a French Nationwide Series of 21 Cases. J. Clin. Endocrinol. Metab. 97, 2093–2104 (2012)

    Article  PubMed  CAS  Google Scholar 

  52. R.H. Caplan, L. Koob, R.M. Abellera, A.S. Pagliara, K. Kovacs, R.V. Randall, Cure of acromegaly by operative removal of an islet cell tumor of the pancreas. Am. J. Med. 64, 874–882 (1978)

    Article  PubMed  CAS  Google Scholar 

  53. M.O. Thorner, R.L. Perryman, M.J. Cronin, A.D. Rogol, M. Draznin, A. Johanson, W. Vale, E. Horvath, K. Kovacs, Somatotroph hyperplasia. Successful treatment of acromegaly by removal of a pancreatic islet tumor secreting a growth hormone-releasing factor. J. Clin. Invest. 70, 965–977 (1982)

    Article  PubMed  CAS  Google Scholar 

  54. G. Berger, J. Trouillas, B. Bloch, G. Sassolas, F. Berger, C. Partensky, J.A. Chayvialle, P. Brazeau, B. Claustrat, F. Lesbros et al., Multihormonal carcinoid tumor of the pancreas. Secreting growth hormone-releasing factor as a cause of acromegaly. Cancer 54, 2097–2108 (1984)

    Article  PubMed  CAS  Google Scholar 

  55. J.L. Ch’ng, N.D. Christofides, M.E. Kraenzlin, A. Keshavarzian, J.M. Burrin, I.L. Woolf, H.J. Hodgson, S.R. Bloom, Growth hormone secretion dynamics in a patient with ectopic growth hormone-releasing factor production. Am. J. Med. 79, 135–138 (1985)

    Article  PubMed  Google Scholar 

  56. H.M. Schulte, G. Benker, R. Windeck, T. Olbricht, D. Reinwein, Failure to respond to growth hormone releasing hormone (GHRH) in acromegaly due to a GHRH secreting pancreatic tumor: dynamics of multiple endocrine testing. J. Clin. Endocrinol. Metab. 61, 585–587 (1985)

    Article  PubMed  CAS  Google Scholar 

  57. D.M. Wilson, G.P. Ceda, D.G. Bostwick, R.J. Webber, J.R. Minkoff, A. Pont, R.L. Hintz, K.G. Bensch, F.B. Kraemer, R.G. Rosenfeld et al., Acromegaly and Zollinger–Ellison syndrome secondary to an islet cell tumor: characterization and quantification of plasma and tumor human growth hormone-releasing factor. J. Clin. Endocrinol. Metab. 59, 1002–1005 (1984)

    Article  PubMed  CAS  Google Scholar 

  58. J.A. Ramsay, K. Kovacs, S.L. Asa, M.J. Pike, M.O. Thorner, Reversible sellar enlargement due to growth hormone-releasing hormone production by pancreatic endocrine tumors in a acromegalic patient with multiple endocrine neoplasia type I syndrome. Cancer 62, 445–450 (1988)

    Article  PubMed  CAS  Google Scholar 

  59. R. Yamasaki, H. Saito, T. Sano, K. Kameyama, K. Yoshimoto, E. Hosoi, M. Matsumura, K. Harada, S. Saito, Ectopic growth hormone-releasing hormone (GHRH) syndrome in a case with multiple endocrine neoplasia type I. Endocrinol. Jpn. 35, 97–109 (1988)

    Article  PubMed  CAS  Google Scholar 

  60. A. Sasaki, S. Yumita, S. Kimura, Y. Miura, K. Yoshinaga, Immunoreactive corticotropin-releasing hormone, growth hormone-releasing hormone, somatostatin, and peptide histidine methionine are present in adrenal pheochromocytomas, but not in extra-adrenal pheochromocytoma. J. Clin. Endocrinol. Metab. 70, 996–999 (1990)

    Article  PubMed  CAS  Google Scholar 

  61. D.E. Price, S.R. Absalom, K. Davidson, A. Bolia, P.R. Bell, T.A. Howlett, A case of multiple endocrine neoplasia: hyperparathyroidism, insulinoma, GRF-oma, hypercalcitoninaemia and intractable peptic ulceration. Clin. Endocrinol. (Oxf.) 37, 187–188 (1992)

    Article  CAS  Google Scholar 

  62. Y. Shintani, K. Yoshimoto, H. Horie, T. Sano, Y. Kanesaki, E. Hosoi, Y. Yokogoshi, H. Bando, H. Iwahana, S. Kannuki 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. Endocr. J. 42, 331–340 (1995)

    Article  PubMed  CAS  Google Scholar 

  63. S.W. Liu, C.J. van de Velde, J.M. Heslinga, J. Kievit, F. Roelfsema, Acromegaly caused by growth hormone-relating hormone in a patient with multiple endocrine neoplasia type I. Jpn. J. Clin. Oncol. 26, 49–52 (1996)

    Article  PubMed  CAS  Google Scholar 

  64. S. Kawa, T. Ueno, A. Iijima, T. Midorikawa, Y. Fujimori, M. Tokoo, H. Oguchi, K. Kiyosawa, Y. Imai, G. Kaneko, T. Kuroda, K. Hashizume, R.Y. Osamura, H. Katakami, Growth hormone-releasing hormone (GRH)-producing pancreatic tumor with no evidence of multiple endocrine neoplasia type 1. Dig. Dis. Sci. 42, 1480–1485 (1997)

    Article  PubMed  CAS  Google Scholar 

  65. T. Sano, R. Yamasaki, H. Saito, T. Hirose, E. Kudo, K. Kameyama, K. Hiraishi, S. Saito, K. Hizawa, Growth hormone-releasing hormone (GHRH)-secreting pancreatic tumor in a patient with multiple endocrine neoplasia type I. Am. J. Surg. Pathol. 11, 810–819 (1987)

    Article  PubMed  CAS  Google Scholar 

  66. K. Suga, N. Yamashita, K. Chiba, T. Ito, Y. Kaziwara, N. Yokoyama, Multiple endocrine neoplasia type 1 producing growth hormone-releasing factor in an endocrine pancreatic tumor. Acta. Med. Nagasaki. 47, 55–61 (2002)

    Google Scholar 

  67. L. Agha, P. Farrell, P. Downey, P. Keeling, E. Leen, S. Sreenan, Acromegaly secondary to growth hormone releasing hormone secretion. Ir. J. Med. Sci. 173, 215–216 (2004)

    Article  PubMed  CAS  Google Scholar 

  68. H. Sugihara, T. Shibasaki, A. Tatsuguchi, F. Okajima, S. Wakita, Y. Nakajima, K. Tanimura, H. Tamura, S. Ishii, J. Kamegai, H. Akasu, W. Kitagawa, K. Shimizu, Y. Nakamura, E. Uchida, T. Tajiri, Z. Naito, H. Katakami, S. Oikawa, A non-acromegalic case of multiple endocrine neoplasia type 1 accompanied by a growth hormone-releasing hormone-producing pancreatic tumor. J. Endocrinol. Invest. 30, 421–427 (2007)

    PubMed  CAS  Google Scholar 

  69. D.E. Weiss, H. Vogel, M.B. Lopes, S.D. Chang, L. Katznelson, Ectopic acromegaly due to a pancreatic neuroendocrine tumor producing growth hormone-releasing hormone. Endocr. Pract. 17, 79–84 (2011)

    Article  PubMed  Google Scholar 

  70. S.A. Leveston, D.W. McKeel Jr, P.J. Buckley, K. Deschryver, M.H. Greider, B.M. Jaffe, W.H. Daughaday, Acromegaly and Cushing’s syndrome associated with a foregut carcinoid tumor. J. Clin. Endocrinol. Metab. 53, 682–689 (1981)

    Article  PubMed  CAS  Google Scholar 

  71. K. von Werder, O.A. Muller, R. Hartl, M. Losa, G.K. Stalla, Growth hormone releasing factor (hpGRF)-stimulation test in normal controls and acromegalic patients. J. Endocrinol. Invest. 7, 185–191 (1984)

    Google Scholar 

  72. A. Van den Bruel, J. Fevery, J. Van Dorpe, L. Hofland, R. Bouillon, Hormonal and volumetric long term control of a growth hormone-releasing hormone-producing carcinoid tumor. J. Clin. Endocrinol. Metab. 84, 3162–3169 (1999)

    Article  PubMed  Google Scholar 

  73. J. Furrer, A. Hattenschwiler, P. Komminoth, T. Pfammatter, P. Wiesli, Carcinoid syndrome, acromegaly, and hypoglycemia due to an insulin-secreting neuroendocrine tumor of the liver. J. Clin. Endocrinol. Metab. 86, 2227–2230 (2001)

    Article  PubMed  CAS  Google Scholar 

  74. T.J. Altstadt, B. Azzarelli, C. Bevering, J. Edmondson, P.B. Nelson, Acromegaly caused by a growth hormone-releasing hormone-secreting carcinoid tumor: case report. Neurosurgery 50, 1356–1359 (2002). discussion 1360

    PubMed  Google Scholar 

  75. N. Colak Ozbey, Y. Kapran, A. Bozbora, Y. Erbil, C. Tascioglu, S.L. Asa, Ectopic growth hormone-releasing hormone secretion by a neuroendocrine tumor causing acromegaly: long-term follow-up results. Endocr. Pathol. 20, 127–132 (2009)

    Article  PubMed  Google Scholar 

  76. J.O. Jansson, J. Svensson, B.A. Bengtsson, L.A. Frohman, H. Ahlman, B. Wangberg, O. Nilsson, M. Nilsson, Acromegaly and Cushing’s syndrome due to ectopic production of GHRH and ACTH by a thymic carcinoid tumour: in vitro responses to GHRH and GHRP-6. Clin. Endocrinol. (Oxf.) 48, 243–250 (1998)

    Article  CAS  Google Scholar 

  77. E. Boix, A. Pico, R. Pinedo, I. Aranda, K. Kovacs, Ectopic growth hormone-releasing hormone secretion by thymic carcinoid tumour. Clin. Endocrinol. (Oxf.) 57, 131–134 (2002)

    Article  CAS  Google Scholar 

  78. K.A. Roth, D.M. Wilson, J. Eberwine, R.I. Dorin, K. Kovacs, K.G. Bensch, A.R. Hoffman, Acromegaly and pheochromocytoma: a multiple endocrine syndrome caused by a plurihormonal adrenal medullary tumor. J. Clin. Endocrinol. Metab. 63, 1421–1426 (1986)

    Article  PubMed  CAS  Google Scholar 

  79. L. Vieira Neto, G.F. Taboada, L.L. Correa, J. Polo, A.F. Nascimento, L. Chimelli, K. Rumilla, M.R. Gadelha, Acromegaly secondary to growth hormone-releasing hormone secreted by an incidentally discovered pheochromocytoma. Endocr. Pathol. 18, 46–52 (2007)

    Article  PubMed  CAS  Google Scholar 

  80. H.J. Southgate, G.P. Archbold, M.E. el-Sayed, J. Wright, V. Marks, Ectopic release of GHRH and ACTH from an adenoid cystic carcinoma resulting in acromegaly and complicated by pituitary infarction. Postgrad. Med. J. 64, 145–148 (1988)

    Article  PubMed  CAS  Google Scholar 

  81. A. Matsuno, H. Katakami, N. Sanno, Y. Ogino, R.Y. Osamura, S. Matsukura, N. Shimizu, T. Nagashima, Pituitary somatotroph adenoma producing growth hormone (GH)-releasing hormone (GHRH) with an elevated plasma GHRH concentration: a model case for autocrine and paracrine regulation of GH secretion by GHRH. J. Clin. Endocrinol. Metab. 84, 3241–3247 (1999)

    Article  PubMed  CAS  Google Scholar 

  82. Pacak, K., Timmers, H.J.L.M., Eisenhofer, G.: Pheochromocytoma. In: Jameson, J.L., DeGroot, L.J., Series (Eds) Pheochromocytoma, 1990-2018. 2010

  83. H. Saito, T. Sano, R. Yamasaki, S. Mitsuhashi, E. Hosoi, S. Saito, Demonstration of biological activity of a growth hormone-releasing hormone-like substance produced by a pheochromocytoma. Acta Endocrinol (Copenh) 129, 246–250 (1993)

    CAS  Google Scholar 

  84. H.P. Neumann, C. Eng, The approach to the patient with paraganglioma. J. Clin. Endocrinol. Metab. 94, 2677–2683 (2009)

    Article  PubMed  CAS  Google Scholar 

  85. W.F. Young Jr, Paragangliomas: clinical overview. Ann. N. Y. Acad. Sci. 1073, 21–29 (2006)

    Article  PubMed  CAS  Google Scholar 

  86. M.L. Brown, G.E. Zayas, M.D. Abel, W.F. Young Jr, H.V. Schaff, Mediastinal paragangliomas: the mayo clinic experience. Ann. Thorac. Surg. 86, 946–951 (2008)

    Article  PubMed  Google Scholar 

  87. D. Erickson, Y.C. Kudva, M.J. Ebersold, G.B. Thompson, C.S. Grant, J.A. van Heerden, W.F. Young Jr, Benign paragangliomas: clinical presentation and treatment outcomes in 236 patients. J. Clin. Endocrinol. Metab. 86, 5210–5216 (2001)

    Article  PubMed  CAS  Google Scholar 

  88. K.P. Koopmans, P.L. Jager, I.P. Kema, M.N. Kerstens, F. Albers, R.P. Dullaart, 111In-octreotide is superior to 123I-metaiodobenzylguanidine for scintigraphic detection of head and neck paragangliomas. J. Nucl. Med. 49, 1232–1237 (2008)

    Article  PubMed  Google Scholar 

  89. A.N. Van Der Horst-Schrivers, P.L. Jager, H.M. Boezen, J.P. Schouten, I.P. Kema, T.P. Links, Iodine-123 metaiodobenzylguanidine scintigraphy in localising phaeochromocytomas–experience and meta-analysis. Anticancer Res. 26, 1599–1604 (2006)

    Google Scholar 

  90. H.J. Timmers, A. Kozupa, C.C. Chen, J.A. Carrasquillo, A. Ling, G. Eisenhofer, K.T. Adams, D. Solis, J.W. Lenders, K. Pacak, Superiority of fluorodeoxyglucose positron emission tomography to other functional imaging techniques in the evaluation of metastatic SDHB-associated pheochromocytoma and paraganglioma. J. Clin. Oncol. 25, 2262–2269 (2007)

    Article  PubMed  Google Scholar 

  91. K.S. King, C.C. Chen, D.K. Alexopoulos, M.A. Whatley, J.C. Reynolds, N. Patronas, A. Ling, K.T. Adams, P. Xekouki, H. Lando, C.A. Stratakis, K. Pacak, Functional imaging of SDHx-related head and neck paragangliomas: comparison of 18F-fluorodihydroxyphenylalanine, 18F-fluorodopamine, 18F-fluoro-2-deoxy-d-glucose PET, 123I-metaiodobenzylguanidine scintigraphy, and 111In-pentetreotide scintigraphy. J. Clin. Endocrinol. Metab. 96, 2779–2785 (2011)

    Article  PubMed  CAS  Google Scholar 

  92. G. Treglia, P. Castaldi, G. Rindi, A. Giordano, V. Rufini, Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis. Endocrine 42, 80–87 (2012)

    Article  PubMed  CAS  Google Scholar 

  93. K. Oberg, Gallium-68 somatostatin receptor PET/CT: is it time to replace (111)Indium DTPA octreotide for patients with neuroendocrine tumors? Endocrine 42, 3–4 (2012)

    Article  PubMed  CAS  Google Scholar 

  94. K. von Werder, M. Losa, O.A. Muller, L. Schweiberer, R. Fahlbusch, E. Del Pozo, Treatment of metastasising GRF-producing tumour with a long-acting somatostatin analogue. Lancet 2, 282–283 (1984)

    Article  Google Scholar 

  95. S. Genka, H. Soeda, M. Takahashi, H. Katakami, N. Sanno, Y. Osamura, T. Fuchinoue, A. Teramoto, Acromegaly, diabetes insipidus, and visual loss caused by metastatic growth hormone-releasing hormone-producing malignant pancreatic endocrine tumor in the pituitary gland. Case report. J. Neurosurg. 83, 719–723 (1995)

    Article  PubMed  CAS  Google Scholar 

  96. I. Shimon, M. Hadani, D. Nass, S.T. Zwas, Malignant bronchial carcinoid tumor metastatic to the pituitary in a thyroid carcinoma patient: successful treatment with surgery, radiotherapy and somatostatin analog. Pituitary 7, 51–57 (2004)

    Article  PubMed  Google Scholar 

  97. A. Giustina, A. Barkan, F.F. Casanueva, F. Cavagnini, L. Frohman, K. Ho, J. Veldhuis, J. Wass, K. Von Werder, S. Melmed, Criteria for cure of acromegaly: a consensus statement. J. Clin. Endocrinol. Metab. 85, 526–529 (2000)

    Article  PubMed  CAS  Google Scholar 

  98. A. Giustina, P. Chanson, M.D. Bronstein, A. Klibanski, S. Lamberts, F.F. Casanueva, P. Trainer, E. Ghigo, K. Ho, S. Melmed, A consensus on criteria for cure of acromegaly. J. Clin. Endocrinol. Metab. 95, 3141–3148 (2010)

    Article  PubMed  CAS  Google Scholar 

  99. R.M. Huber, J. Schopohl, M. Losa, G. Wolfram, O. Thetter, W. Permanetter, K. v Werder, Growth-hormone releasing hormone in a bronchial carcinoid. Cancer 67, 2538–2542 (1991)

    Article  PubMed  CAS  Google Scholar 

  100. J. Rothenstein, S.P. Cleary, G.R. Pond, D. Dale, S. Gallinger, M.J. Moore, J. Brierley, L.L. Siu, Neuroendocrine tumors of the gastrointestinal tract: a decade of experience at the Princess Margaret Hospital. Am. J. Clin. Oncol. 31, 64–70 (2008)

    Article  PubMed  Google Scholar 

  101. C. Mao, P. Carter, P. Schaefer, L. Zhu, J.M. Dominguez, D.J. Hanson, H.E. Appert, K. Kim, J.M. Howard, Malignant islet cell tumor associated with hypercalcemia. Surgery 117, 37–40 (1995)

    Article  PubMed  CAS  Google Scholar 

  102. K.K. Kazanjian, H.A. Reber, O.J. Hines, Resection of pancreatic neuroendocrine tumors: results of 70 cases. Arch. Surg. 141, 765–769 (2006). discussion 769–70

    Article  PubMed  Google Scholar 

  103. K.L. Yim, Role of biological targeted therapies in gastroenteropancreatic neuroendocrine tumours. Endocrine 40, 181–186 (2011)

    Article  PubMed  CAS  Google Scholar 

  104. K.I. Alexandraki, G. Kaltsas, Gastroenteropancreatic neuroendocrine tumors: new insights in the diagnosis and therapy. Endocrine 41, 40–52 (2012)

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by National Institutes of Health Grant K23DK085148 (O.C.) and Grant CA75979 (S.M.).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Ali A. Ghazi, Alireza Amirbaigloo, Navid Saadat & Siavash Ghazi

  2. Department of Thoracic Surgery, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Azizollah Abbasi Dezfooli

  3. Department of Radiology, Taleghani General Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Marina Pourafkari

  4. Department of Pathology, Imam Khomeini General Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Farrokh Tirgari

  5. Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Dheepti Dhall & Serguei Bannykh

  6. Pituitary Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Becker 131, Los Angeles, CA, 90048, USA

    Shlomo Melmed & Odelia Cooper

Authors
  1. Ali A. Ghazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alireza Amirbaigloo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Azizollah Abbasi Dezfooli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Navid Saadat
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Siavash Ghazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marina Pourafkari
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Farrokh Tirgari
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dheepti Dhall
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Serguei Bannykh
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shlomo Melmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Odelia Cooper
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Odelia Cooper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ghazi, A.A., Amirbaigloo, A., Dezfooli, A.A. et al. Ectopic acromegaly due to growth hormone releasing hormone. Endocrine 43, 293–302 (2013). https://doi.org/10.1007/s12020-012-9790-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-012-9790-0

Keywords

Search

Navigation