Skip to main content
SpringerLink
Log in

Ectopic Hormone Syndromes

  • Chapter
Endocrine Pathology

Abstract

Ectopic or inappropriate hormone production (paraneoplastic endocrine syndrome) is the synthesis of hormones by tumors from tissues that do not normally produce the hormone (3,22). This is in contrast to eutopic or entopic hormone production by tumors whose precursor tissues normally produced the hormone. These definitions of ectopic and eutopic hormone production remain valid. However, recent advances in receptor biology, immunohistochemistry, radioimmunoassay, and cell culture techniques have shown that polypeptide hormones are more widely distributed in normal tissues than was previously recognized. Many nonneuroendocrine tissues and derived tumors can also produce polypeptide hormones with multidirectional differentiation (13).

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Asa SL, Scheitauer BW, Bilbao JM, Horvath E, Ryan N, Kovacs K, Randall RV, Laws ER Jr, Singer W, Linfoot JA, Thorner MO, Vale W (1984) A case for hypothalamic acromegaly: a clinicopathological study of six patients with hypothalamic gangliocytomas producing growth hormone-releasing factor. J Clin Endocrinol Metab 58:796–803.

    Article  PubMed  CAS  Google Scholar 

  2. Asa SL, Singer W, Kovacs K, Horvath E, Murray D, Colapinto N, Thorner MO (1987) Pancreatic endocrine tumour producing growth hormone-releasing hormone associated with multiple endocrine neoplasia type I syndrome. Acta Endocrinol 115: 331–337.

    PubMed  CAS  Google Scholar 

  3. Baylin SB, Mendelsohn G (1980) Ectopic (inappro-priate) hormone production by tumors: Mechanisms involved and the biological and clinical implications. Endocrinol Rev 1:45–77.

    Article  CAS  Google Scholar 

  4. Beck C, Burger HG (1972) Evidence for the presence of immunoreactive growth hormone in cancers of the lung and stomach. Cancer 30:75–79.

    Article  PubMed  CAS  Google Scholar 

  5. Belsky JL, Cuello B, Swanson LW, Simmons DM, Jarrett RM, Braza F (1985) Cushing’s syndrome due to ectopic production of corticotropin-releasing factor. J Clin Endocrinol Metab 60:496–500.

    Article  PubMed  CAS  Google Scholar 

  6. Bondy PK, Gilby ED (1982) Endocrine function in small cell undifferentiated carcinoma of the lung. Cancer 50:2147–2153.

    Article  PubMed  CAS  Google Scholar 

  7. Braunstein GD, Vaitukaitis JL, Barbone PP (1973) Ectopic production of human chorionic gonadotropin by lung neoplasms. Ann Intern Med 88:805.

    Google Scholar 

  8. Broadhus AE, Mangin M, Ikeda K, Insogna KL, Weir EC, Burtis WJ, Stewart AF (1988) Humoral hypercalcemia of cancer. Identification of a novel parathyroid hormone-like peptide. N Engl J Med 319:556–563.

    Google Scholar 

  9. Carey RM, Varma SK, Drake CR, Thorner MO, Kovacs K, Riview J, Vale W (1984) 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.

    Article  PubMed  CAS  Google Scholar 

  10. Cunnah D, Jessop DS, Millar JGB, Neville E, Coates P, Doniach I, Hale AC, Besser GM, Rees LH (1986) An adrenal medullary tumour presenting with Cushing’s syndrome associated with elevated levels of human corticotropin-releasing factor in plasma. J Endocrinol 108:272.

    Google Scholar 

  11. Daughaday WH, Emanuele MA, Brooks MH, Barbato AL, Kapadia M, Rotwein P (1988) Synthesis and secretion of insulin-like growth factor II by a leiomyosarcoma with associated hypoglycemia. N Engl J Med 319:1434–1440.

    Article  PubMed  CAS  Google Scholar 

  12. DeBold CR, Menefee JK, Nicholson WE, Orth DN (1988) Proopiomelanocortin gene is expressed in many normal human tissues and in tumors not associated with ectopic adrenocorticotropin syndrome. Mol Endocrinol 2:862–876.

    Article  PubMed  CAS  Google Scholar 

  13. DeLellis RA, Tischler AS, Wolfe HJ (1984) Multidirectional differentiation in neuroendocrine neoplasms. J Histochem Cytochem 32:899–904.

    Article  PubMed  CAS  Google Scholar 

  14. Drezner MK, Feinglos MN (1977) Osteomalacia due to a 1 a,25-dihydroxycholecalciferol deficiency. J Clin Invest 60:1046–1053.

    Article  PubMed  CAS  Google Scholar 

  15. Faiman C, Col well JA, Ryan RJ, Hershman JM, Shields TW (1967) Gonadotropin secretion from a bronchogenic carcinoma. Demonstration by radio-immunoassay. N Engl J Med 277:1395–1399.

    CAS  Google Scholar 

  16. Falchuk KR (1973) Inappropriate antidiuretic hormone-like syndrome associated with an adrenocortical carcinoma. Am J Med 266:393–395.

    Article  CAS  Google Scholar 

  17. Field JB, Keen H, Johnson P, Herring B (1963) Insulin-like activity of nonpancreatic tumors associated with hypoglycemia. J Clin Endocrinol Metab 23:1229–1236.

    Article  PubMed  CAS  Google Scholar 

  18. Gellhorn A (1969) Ectopic hormone production in cancer and its implications for basic research on abnormal growth. Adv Intern Med 15:299–316.

    PubMed  CAS  Google Scholar 

  19. Gorden P, Hendricks CM, Kahn CR, Megyesi K, Roth J (1981) Hyperglycemia associated with non-islet-cell tumor and insulin-like growth factors. N Engl J Med 305:1452–1455.

    Article  PubMed  CAS  Google Scholar 

  20. Hammond D, Winnick S (1974) Paraneoplastic erythrocytosis and ectopic erythropoietins. Ann NY Acad Sei 230:219–227.

    Article  CAS  Google Scholar 

  21. Heath E, Edis AJ (1979) Pheochromocytoma associated with hypercalcemia and ectopic secretion of calcitonin. Ann Intern Med 91:208–210.

    PubMed  Google Scholar 

  22. Imura H (1980) Ectopic hormone syndromes. Clin Endocrinol Metab 9:235–260.

    Article  PubMed  CAS  Google Scholar 

  23. Johannessen JV, Gould VE (1980) Neuroendocrine skin carcinoma associated with calcitonin production. A Merkel cell carcinoma. Hum Pathol 2:586–589.

    Google Scholar 

  24. Kahn CR, Rosen SW, Weintraub BD, Fajans SS, Gorden P (1977) Ectopic production of chorionic gonadotropin and its subunits by islet cell tumors. A specific marker for malignancy. N Engl J Med 297:565–569.

    CAS  Google Scholar 

  25. Lacaza-Masmonteil T, DeKeyzer Y, Luton J-P, Kahn A, Bertagna X (1987) Characterization of proopiomelanocortin transcripts in human nonpituitary tissues. Proc Natl Acad Sei USA 84:7261–7265.

    Article  Google Scholar 

  26. Lokich JJ (1982) The frequency and clinical biology of the ectopic hormone syndromes of small cell carcinoma. Cancer 50:2111–2114.

    Article  PubMed  CAS  Google Scholar 

  27. Mangin M, Webb AC, Dreyer B, Pbsillico JT, Ikeda K, Weir EC, Stewart AF, Bander NH, Milstone L, Barton DE, Francke U, Broadhus AE (1988) Identification of a cDNA extracting a parathyroid hormone¬like peptide from a human tumor associated with humoral hypercalcemia of malignancy. Proc Natl Acad Sei USA 85:597–601.

    Article  CAS  Google Scholar 

  28. McFadzean AJS, Yeung RTT (1969) Further observations on hypoglycemia in hepatocellular carcinoma. Am J Med 47:220–235.

    Article  PubMed  CAS  Google Scholar 

  29. Morley JE, Jacobson RJ, Melamed J, Hershman JM (1976) Choriocarcinoma as a cause of thyrotoxicosis. Am J Med 60:1036–1040.

    Article  PubMed  CAS  Google Scholar 

  30. Mundy GR, Ibbotson KJ, D’Souza SM, Simpson EL, Jacobs JW, Martin TJ (1984) The hypercalcemia of cancer: clinical implications and pathogenic mechanisms. N Engl J Med 310:1718–1727.

    Article  PubMed  CAS  Google Scholar 

  31. Odell WD (1985) Hormonal manifestation of cancer. In: Wilson JD, Foster DW (eds) Williams Textbook of Endocrinology, 7th ed. Philadelphia, Saunders, pp 1327–1344.

    Google Scholar 

  32. Odell WD, Wolfsen A, Yoshimoto Y (1977) Ectopic peptide synthesis: A universal concomitant of neo-plasia. Trans Assoc Am Phys 90:204.

    PubMed  CAS  Google Scholar 

  33. Pearse AGE (1968) Common cytochemical and ultra-structural characteristics of cells producing polypeptide hormones (the APUD series) and their relevance to thyroid and ultimobranchial C cells and calcitonin. Proc Soc London Ser B 170:71–80.

    Article  CAS  Google Scholar 

  34. Pearse AGE (1986) The diffuse neuroendocrine system: Peptides, amines, placodes and the APUD theory. Prog Brain Res 68:25–31.

    Article  PubMed  CAS  Google Scholar 

  35. Plimpton CH, Gellhorn A (1956) Hypercalcemia in malignant disease without evidence of bone destruction. Am J Med 21:750–759.

    Article  PubMed  Google Scholar 

  36. Rees LH, Ratcliffe JG (1974) Ectopic hormone production by nonendocrine tumours. Clin Endocrinol 3:263–299.

    Article  CAS  Google Scholar 

  37. Rosen SW, Weintraub BD (1974) Ectopic production of the isolated alpha subunit of the glycoprotein hormones. A quantitative marker in certain cases of cancer. N Engl J Med 290:1441–1447.

    CAS  Google Scholar 

  38. Rosen SW, Weintraub BD, Vaitukaitis JL, Sussman HH, Hershman JM, Muggia FM (1975) Placental proteins and their subunits as tumor markers. Ann Intern Med 82:71–83.

    Google Scholar 

  39. Said SI, Faloona GR (1975) Elevated plasma and tis-sue levels of vasoactive intestinal polypeptide in the watery diarrhea syndrome due to pancreatic, bronchogenic and other tumors. N Engl J Med 293: 155–160.

    Article  PubMed  CAS  Google Scholar 

  40. Sano T, Asa SL, Kovacs K (1988) Growth hormone-releasing hormone-producing tumors: clinical, biochemical and morphological manifestations. Endocrinol Rev 9:357–373.

    Article  CAS  Google Scholar 

  41. Schalet SM, Beardwell CG, MacFarlane IA, Ellison ML, Norman CM, Rees LH, Hughes M (1979) Acromegaly due to production of a growth hormone releasing factor by a bronchial carcinoid tumour. Clin Endocrinol 10:61–67.

    Article  Google Scholar 

  42. Schwartz KE, Wolfsen AR, Forster B (1979) Cal-citonin in nonthyroidal cancer. J Clin Endocrinol Metab 49:438–444.

    Article  PubMed  CAS  Google Scholar 

  43. Sell wood RA, Spencer J, Azzopardi JG, Wapnick S, Welbourn RB, Kulatilake AE (1969) Inappropriate secretion of antidiurectic hormone by carcinoma of the prostate. Br J Surg 56:933–935.

    Article  PubMed  CAS  Google Scholar 

  44. Shields R (1977) Gene derepression in tumours. Nature 269:752–753.

    Article  Google Scholar 

  45. Silva OL, Becker KL, Primack A, Doppman JL, Snider RH (1976) Increased serum calcitonin levels in bronchogenic carcinoma. Chest 69:495–499.

    Article  PubMed  CAS  Google Scholar 

  46. Suva LJ, Winslow GA, Wettenhall REH, Hammonds RG, Moseley JM, Diefenbach-Jagger H, Rodda CP, Kemp BE, Rodriguez H, Chen EY, Hudson PJ, Martin TJ, Wood WI (1987) A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression. Science 237:893–896.

    Article  PubMed  CAS  Google Scholar 

  47. Szabo M, Berelowitz M, Pettengill OS, Sorenson GD, Frohman LA (1980) Ectopic production of somatostatin-like immuno- and bioactivity by cultured human pulmonary small cell carcinoma. J Clin Endocrinol Metab 51:978–987.

    Article  PubMed  CAS  Google Scholar 

  48. Talstad I, Foiling I, Boye NP (1974) Hypoglycemia caused by an intrathoracic tumour. Acta Med Scand 196:347–351.

    Article  PubMed  CAS  Google Scholar 

  49. Tashjian AH Jr, Weintraub BD, Barousky NJ (1973) Subunits of human chorionic gonadotropin: Unbalanced synthesis and secretion by clonal cell strains derived from a bronchogenic carcinoma. Proc Natl Acad Sei USA 70:1419.

    Article  CAS  Google Scholar 

  50. Trump DL, Livingston JN, Baylin SB (1977) Watery diarrhea syndrome in an adult with ganglioneuroma-pheochromocytoma: Identification of vasoactive intestinal peptide, calcitonin, and catecholamines and assessment of their biologic activity. Cancer 40:1526–1532.

    Article  PubMed  CAS  Google Scholar 

  51. Unger RH, Lockner JV, Eisentraut AM (1964) Identification of insulin and glucagon in a bronchogenic metastasis. J Clin Endocrinol Metab 24:823–831.

    Article  PubMed  CAS  Google Scholar 

  52. Upton GV, Amatruda TT (1971) 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.

    Article  PubMed  CAS  Google Scholar 

  53. Weintraub BD, Rosen SW (1973) Ectopic production of the isolated beta subunit of human chorionic gonadotropin. J Clin Invest 52:3135–3142.

    Article  PubMed  CAS  Google Scholar 

  54. Wilber JF, Spihella P (1984) Identification of immunoreactive thyrotropin-releasing hormone in human neoplasia. J Clin Endocrinol Metab 59: 432–435.

    Article  PubMed  CAS  Google Scholar 

  55. Yesner R (1978) Spectrum of lung cancer and ectopic hormones. Pathol Annu 13(Part l):217–240.

    Google Scholar 

  56. Zafar MS, Meilinger RC, Fine G, Szabo M, Frohman LA (1975) Acromegaly associated with a bronchial carcinoid tumor: Evidence for ectopic production of growth hormone-releasing activity. J Clin Endocrinol Metab 48:66–71.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Warthin-Weller Professor of Pathology, University of Michigan Medical Center, Ann Arbor, 48109, Michigan, USA

    Professor Ricardo V. Lloyd MD, PhD (Associate Professor of Pathology)

Authors
  1. Professor Ricardo V. Lloyd MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1990 Springer-Verlag New York Inc.

About this chapter

Cite this chapter

Lloyd, R.V. (1990). Ectopic Hormone Syndromes. In: Endocrine Pathology. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-3346-6_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-3346-6_11

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-7975-4

  • Online ISBN: 978-1-4612-3346-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation