Endocrine Pathology

, Volume 11, Issue 3, pp 277–285 | Cite as

Corticotropin-releasing hormone-producing medullary thyroid carcinoma causing cushing’s syndrome: Clinical and pathological findings

  • Shannon K. Oates
  • Sanford I. Roth
  • Mark E. Molitch
Case Report


A 62-yr-old woman presented with progressive fatigue and weakness and was found to have hypercalcemia due to a parathyroid adenoma. Following resection of the adenoma, she developed intractable diarrhea with progressive weakness. Further evaluation showed very high serum calcitonin levels and high cortisol and adrenocorticotropic hormone (ACTH) levels along with elevated urinary 5-hydroxindole acetic acid (5-HIAA) levels. Liver biopsy showed metastatic medullary thyroid carcinoma which did not stain positively for ACTH but stained positively for corticotropin-releasing hormone (CRH) and serotonin. Further examination of the parathyroid tissue showed medullary thyroid carcinoma cells invading the adenoma. This is the first report of a patient with hyperparathyroidism and metastatic medullary carcinoma of the thyroid producing serotonin and CRH resulting in Cushing’s syndrome.

Key Words

CRH corticotropin-releasing hormone medullary thyroid carcinoma Cushing’s syndrome Hyperparathyroidism 


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  1. 1.
    Suda T, Tomori N, Tozawa F, Demura H, Shizume K, Mouri T, Miura Y, Sasano N. Immunoreactive corticotropin and corticotropin-releasing factor in human hypothalamus, adrenal, lung cancer, and pheochromocytoma. J Clin Endocrinol Metab 58:919–924, 1984.PubMedCrossRefGoogle Scholar
  2. 2.
    Suda T, Tomori N, Tozawa F, Mouri T, Demura H, Shizume K. Distribution and characterization of immunoreactive corticotropin-releasing factor in human tissues. J Clin Endocrinol Metab 59:861–866, 1984.PubMedGoogle Scholar
  3. 3.
    Wakabayshi J, Ibara T, Hattori M, Tonegawa Y, Shibasaki T, Hashimoto K. Presence of corticotropin-releasing factor-like immunoreactivity in human tumors. Cancer 55:995–1000, 1985.CrossRefGoogle Scholar
  4. 4.
    Asa SL, Kovacs K, Vale W, Petrusz P. Vecsei P: Immunohistologic localization of corticotropin-releasing hormone in human tumors. Am J Clin Path 87:327, 1987.PubMedGoogle Scholar
  5. 5.
    Tsuchihashi T, Yamaguchi K, Abe K, Yanaihara N, Saito S. Production of immunoreactive corticotropin-releasing hormone in various neuroendocrine tumors. Jpn J Clin Oncol 22:232–237, 1992.PubMedGoogle Scholar
  6. 6.
    Carey RM, Varma SK, Drake CR Jr, Thorner MO, Kovacs K, Rivier J, Vale W. Ectopic secretion of corticotropin-releasing factor as a cause of Cushing’s syndrome. A clinical, morphological, and biochemical study. N Engl J Med 311:13–20, 1984.PubMedCrossRefGoogle Scholar
  7. 7.
    Belsky JL, Cuello B, Swanson LW, Simmons DM, Jarrett RM, Braza F. Cushing’s syndrome due to ectopic production of corticotropin-releasing factor. J Clin Endocrinol Metab 60:496–500, 1985.PubMedGoogle Scholar
  8. 8.
    Case Records of the Massachusetts General Hospital. Weekly Clinicopathological Exercises. Case 52-1987. A 20-year-old woman with Cushing’s disease and a pulmonary nodule. N Engl J Med 317:1648–1658, 1987.CrossRefGoogle Scholar
  9. 9.
    Fjellestad-Paulsen A, Abrahamson P-A, Bjartell A, Grino M, Grimelius L, Hedeland H, Falmer S. Carcinoma of the prostate with Cushing’s syndrome. A case report with histochemical and chemical demonstration of immunoreactive corticotropin-releasing hormone in plasma and tumoral tissue. Acta Endocrinol 119:506–516, 1988.PubMedGoogle Scholar
  10. 10.
    Tournaire J, Rebattu B, Conte-Devlox B, Trouillas J, Grino M, Berger-Dutrieux N, Peix J-L, Pugeat M. Syndrome de Cushing secondaire a la production ectopique de CRF par un carcinoma medullaire du corps thyroide. Ann Endocrinol 49:61, 1988.Google Scholar
  11. 11.
    Gerl H, Knappe G, Rohde W, Stahl F, Wolff H, Martin H. Cushing-syndrom bei CRF-produzierendem mediastinalem Karzinoid. Dtsch Med Wschr 115:332–336, 1990.PubMedCrossRefGoogle Scholar
  12. 12.
    De Herder WW, Krenning EP, Malchoff CD, Hofland LJ, Reubi J-C, Kwekkeboom DJ, Oei HY, Pols HAP, Bruining JA, Nobels FRE, Lamberts SWJ. Somatostatin receptor scintigraphy: its value in tumor localization in patients with Cushing’s syndrome caused by ectopic corticotropin or corticotropin-releasing hormone secretion. Am J Med 96:305–312, 1994.PubMedCrossRefGoogle Scholar
  13. 13.
    Tagliabue M, Pagani A, Palestini N, Manieri C, Martina V. Multiple endocrine neoplasia (MEN IIB) with Cushing’s syndrome due to medullary thyroid carcinoma producing corticotropin-releasing hormone. Panminerva Med 38:41–44, 1996.PubMedGoogle Scholar
  14. 14.
    Sawchenko PE, Swanson LW, Vale WW: Coexpression of corticotropin-releasing factor and vasopressin immunoreactivity in parvocellular neurosecretory neurons of the adrenalectomized rat. Proc Natl Acad Sci USA 81:1883–1887, 1984.PubMedCrossRefGoogle Scholar
  15. 15.
    Roth SI. Principles and Practice of Surgical, Pathology and Cytopathology. 3rd ed., The Parathyroid Gland. In: Silverberg SG, DeLellis RA, Frable WJ, eds. New York: Churchill LIvingstone 1997; 2709–2750.Google Scholar
  16. 16.
    Orth DN. Cushing’s syndrome. N Engl J Med 332:791–795, 1995.PubMedCrossRefGoogle Scholar
  17. 17.
    Upton GV, Amatruda TT. Evidence for the presence of tumor peptides with corticotropin-releasing-factor-like activity in the ectopic ACTH syndrome. N Engl J Med 285:419–424, 1971.PubMedCrossRefGoogle Scholar
  18. 18.
    Birkenhager JC, Upton GV, Seldenrath HJ, Krieger DT, Tashjian AH Jr: Medullary thyroid carcinoma: ectopic production of peptides with ACTH-like, corticotropin releasing factor-like and prolactin production-stimulating activities. Acta Endocrinol 83:280–292, 1976.PubMedGoogle Scholar
  19. 19.
    Yamamoto H, Hirota Y, Matsukura S, Imura M, Nakamura M, Tanaka A. Studies on ectopic ACTH-producing tumors IV. CRF-like activity in tumor tissue. Acta Endocrinol 82:183–192, 1976.PubMedGoogle Scholar
  20. 20.
    Suda T, Demura H, Demura R, et al: Corticotropin-releasing factor-like activity in ACTH producing tumor. J Clin Endocrinol Metab 44440–446, 1977.Google Scholar
  21. 21.
    Hashimoto K, Takahara J, Ogawa N, et al. Adrenocorticotropin, beta-lipotropin, beta-endorphin, and corticotropin-releasing factor-like activity in an adrenocorticotropin-producing nephroblastoma. J Clin Endocrinol Metab 50:461–465, 1980.PubMedGoogle Scholar
  22. 22.
    Schteingart ED, Lloyd RV, Akil H, et al. Cushing’s syndrome secondary to ectopic corticotropin-releasing hormone-adrenocorticotropin secretion. J Clin Endocrinol Metab 63:770–775, 1986.PubMedCrossRefGoogle Scholar
  23. 23.
    Zarate A, Kovacs K, Flores M, Moran C, Felix I: ACTH and CRF-producing bronchial carcinoid associated with Cushing’s syndrome. Clin Endocrinol 24:523–529, 1986.Google Scholar
  24. 24.
    Jessob DS, Cunnah D, Millar JGB, et al. A pheochromocytoma presenting with Cushing’s syndrome associated with increased concentrations of circulating corticotrophin-releasing factor. J Endocr 113:133–138, 1987.Google Scholar
  25. 25.
    O’Brien T, Young WF Jr, Davila DG, et al. Cushing’s syndrome associated with ectopic production of corticotrophin-releasing hormone, corticotrophin and vasopressin by a pheochromocytoma. Clin Endocrinol 37:460–467, 1992.Google Scholar
  26. 26.
    Murakami O, Takahashi K, Sone M, Totsune K, Ohneda M, Itoi K, Yoshinaga K, Mouri T. An ACTH-secreting bronchial carcinoid: presence of corticotropin-releasing hormone, neuropeptide Y, and endothelin-1 in the tumor tissue. Acta Endocrinol 128:192–196, 1993.PubMedGoogle Scholar
  27. 27.
    Ozawa Y, Tomoyasu H, Takeshita A, et al. Shift from CRH to ACTH production in a thymic carcinoid with Cushing’s syndrome. Horm Res 45:264–268, 1996.PubMedCrossRefGoogle Scholar
  28. 28.
    Young J, Deneux C, Grino M, Oliver C, Chanson P, Schaison G. Pitfall of petrosal sinus sampling in a Cushing’s syndrome secondary to ectopic adrenocorticotropin-corticotropin releasing hormone (ACTH-CRH) secretion. J Clin Endocrinol Metab 83:305–308, 1998.PubMedCrossRefGoogle Scholar
  29. 29.
    Abe T, Matsumoto K, Iida M, Hayashi M, Sanno N, Osamura Y. Malignant carcinoid tumor of the anterior mediastinum metastasis to a prolactin-secreting pituitary adenoma: a case report. Surg Neurol 48:389–394, 1997.PubMedCrossRefGoogle Scholar
  30. 30.
    Kelley SR, Roth SI, Molitch ME: Corticotropin-releasing hormone (CRH) producing medullary Ca of thyroid (MCT) causing Cushing’s syndrome—confusion with crossed MEN syndromes. Presented at the 75th Annual Meeting of the Endocrine Society, Las Vegas, 1993 (Abstract #1362).Google Scholar

Copyright information

© Humana Press Inc 2000

Authors and Affiliations

  • Shannon K. Oates
    • 2
  • Sanford I. Roth
    • 1
  • Mark E. Molitch
    • 2
  1. 1.Department of PathologyNorthwestern University Medical SchoolChicago
  2. 2.Center for Endocrinology, Metabolism and Molecular Medicine NorthwesternUniversity Medical SchoolChicago

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