Hormone Production by Bronchial Tumours

  • Sally J. Ratter
  • Lesley H. Rees


The production of polypeptide hormones and various ‘tumour-associated’ proteins by neoplasia occurring in non-endocrine tissues such as the lung is classically referred to as ‘inappropriate’ or ‘ectopic’ hormone production. The detection of ectopic hormone synthesis and release and the appreciation of the role this may play in associated endocrine syndromes has led to their extensive study, which has had particular relevance for clinical diagnosis, treatment of the endocrine syndromes, monitoring tumour therapy and the search for tumour markers. More recently they have been used as an important aid to the understanding of the biosynthetic pathways of peptide hormones and their precursors.


Primary Hyperparathyroidism Bronchial Carcinoma Bronchial Carcinoid Ectopic ACTH Syndrome Humoral Hypercalcaemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aldujaili EAS, Hope J, Estivariz FE, Lowry PJ, Edwards CRW (1981) Circulating human pituitary pro-y-melanotropin enhances the adrenal response to ACTH. Nature 291: 156–159CrossRefGoogle Scholar
  2. Amatruda TT, Upton GV (1974) Hyperadrenocorticism and ACTH-releasing factor. Ann NY Acad Sci 230: 168–180PubMedCrossRefGoogle Scholar
  3. Azzopardi JG, Williams ED (1968) Pathology of `non-endocrine’ tumours associated with Cushing’s syndrome. Cancer 22: 274–286PubMedCrossRefGoogle Scholar
  4. Azzopardi JG, Freeman D, Poole G (1970) Endocrine and metabolic disorders in bronchial carcinoma. Br Med J 4: 528–530PubMedCrossRefGoogle Scholar
  5. Bailey RE (1971) Periodic hormogenesis. A new phenomenon. J Clin Endocrinol Metab 32: 317–327PubMedCrossRefGoogle Scholar
  6. Baylin SB, Mendelsohn G (1980) Ectopic (inappropriate) hormone production by tumours: Mechanisms involved and the biological and clinical implications. Endocr Rev 1: 45–77Google Scholar
  7. Beck C, Burger HG (1972) Evidence for the presence of immunoreactive growth hormone in cancers of the lung and stomach. Cancer 30: 75–79PubMedCrossRefGoogle Scholar
  8. Beck C, Larkins RG, Martin TJ (1973) Stimulation of growth hormone release from superfused rat pituitary by extracts of hypothalamus and of human lung tumours. J Endocrinol 59: 325–333PubMedCrossRefGoogle Scholar
  9. Becker KL, Snider RH, Silver OL (1978) Calcitonin heterogeneity in lung cancer and medullary thyroid cancer. Acta Endocrinol 89: 89–99PubMedGoogle Scholar
  10. Benson RC, Riggs RL, Richard BM, Arnaud CD (1974) Immunoreactive forms of circulating PTH in primary and ectopic hyperparathyroidism. J Clin Invest 54: 175–181PubMedCrossRefGoogle Scholar
  11. Berson SA, Yalow RS (1964) Immunoassay of protein hormones. In: Pincus G, Thompson KV, Astwood EB (eds). The hormones, vol iv. Academic Press, New York, London, pp 557–630Google Scholar
  12. Bertagna XY, Nicholson WE, Pettengill OS (1978) Ectopic production of high molecular weight calcitonin and corticotropin by human small cell carcinoma cells in tissue culture. Evidence for separate precursors. J Clin Endocrinol Metab 47: 1390–1393Google Scholar
  13. Bondy PK (1981) The pattern of ectopic hormone production in lung cancer. Yale J Biol Med 54: 181–185PubMedGoogle Scholar
  14. Bondy PK, Gilby ED (1982) Endocrine function in small cell undifferentiated carcinoma of the lung. Cancer 50: 2147–2153PubMedCrossRefGoogle Scholar
  15. Brown WH (1928) A case of pluriglandular syndrome, ‘diabetes of bearded women’. Lancet 11: 1022CrossRefGoogle Scholar
  16. Connor TB, Thomas WC Jr, Howards JE (1956) Etiology of hypercalcaemia associated with lung carcinoma. J Clin Invest 35: 697 (Abstr)Google Scholar
  17. Coombes RCC, Hillyard C, Greenberg PB, Maclntyre I (1974) Plasmaimmunoreactive calcitonin in patients with non-thyroid tumours. Lancet I: 1080Google Scholar
  18. Dabek JT (1974) Bronchial carcinoid tumour with acromegaly in two patients. J Clin Endocrinol Metab 38: 329–333PubMedCrossRefGoogle Scholar
  19. Dresner MK, Lebovitz HE (1978) Primary hyperparathyroidism in paraneoplastic hypercalcaemia. Lancet 1: 1004–1006CrossRefGoogle Scholar
  20. Drury PL, Ratter SJ, Tomlin S, Williams J, Dacie JE, Rees LH, Besser GM (1982) Experience with selective venous sampling in diagnosis of ACTH-dependent Cushing’s syndrome. Br Med J (Clin Res) 284: 9–12CrossRefGoogle Scholar
  21. Ennis GC, Cameron DP, Burger HG (1973) On the aetiology of hypertrophic pulmonary osteoarthropathy in bronchogenic carcinoma: Lack of relationship to elevated growth hormone levels. Aust NZ J Med 3: 157–161Google Scholar
  22. Frohman LA, Szabo M, Stachura ME, Berelowitz M (1980) Growth hormone-releasing activity from extrapituitary tumours in patients with acromegaly. J Clin Invest 65: 43–54PubMedCrossRefGoogle Scholar
  23. George JM, Capen CC, Phillips AS (1972) Biosynthesis of vasopressin in vitro and ultrastructure of a bronchogenic carcinoma. J Clin Invest 51: 151–158CrossRefGoogle Scholar
  24. Gewirtz G, Schneider B, Krieger DT, Yalow RS (1974) `Big ACTH’ conversion to biologically active ACTH by trypsin. J Clin Endocrinol Metab 38:227–230Google Scholar
  25. Greenberg PB, Beck C, Martin TJ (1972) Synthesis and release of human growth hormone from lung carcinoma in cell culture. Lancet 1: 350–352PubMedCrossRefGoogle Scholar
  26. Gropp C, Haverman K, Scheuer A (1980) Ectopic hormones in lung cancer patients at diagnosis and during therapy. Cancer 46: 347–354PubMedCrossRefGoogle Scholar
  27. Guillemin R, Brazeau P, Bohlen P, Esch F, Ling N, Wehrenberg WB (1982) Growth hormone-releasing factor from a human pancreatic tumour that caused acromegaly. Science 218: 585–587PubMedCrossRefGoogle Scholar
  28. Haefliger JM, Dubied MC, Vallotton MB (1977) Excretion journaliere de l’hormone antidiuretiques lors de carcinome bronchique. Schweiz Med Wochensch 107: 728–732Google Scholar
  29. Hale AC, Lytras N, Ratter SJ, Tomlin S, Besser GM, Rees LH (1984) Immunoreactive -y-MSH in human plasma. Cl in EndocrinolGoogle Scholar
  30. Hamilton BPM, Upton GV Amatruda TT (1972) Evidence for the presence of neurophysin in tumours producing the syndrome of inappropriate antidiuresis. J Clin Endocrinol Metab 35: 764–767PubMedCrossRefGoogle Scholar
  31. Hansen M, Hansen HH, Hirsch FR (1980) Hormonal polypeptides and amine metabolites in small cell carcinoma of the lung, with special reference to stage and subtypes. Cancer 45: 1432–1437PubMedCrossRefGoogle Scholar
  32. Heath DA (1976) Hypercalcaemia and malignancy. Ann Clin Biochem 13: 555–560PubMedGoogle Scholar
  33. Holdaway 1M, Bloomfield GA, Ratcliffe JG, Hinson KWF, Rees GM, Rees LH (1974) Adrenocorticotrophin levels in normal and neoplastic lung tissue. Taylor S (ed) Endocrinology 1973. Heinemann, LondonGoogle Scholar
  34. Hope J, Ratter SJ, Estivariz FE, McLoughlin L, Lowry PJ (1981) Development of a radioimmunoassay for an amino-terminal peptide of pro-opiocortin containing the -y-MSH region. Measurement and characterisation in human plasma. Clin Endocrinol 15: 221–227Google Scholar
  35. Jeffcoate WJ, Rees LH, Tomlin S, Jones AE, Edwards CRW, Besser GM (1977) Metyrapone in the long-term management of Cushing’s disease. Br Med J 2: 215–217PubMedCrossRefGoogle Scholar
  36. Jeffcoate WJ, Tomlin S, McLoughlin L, Rees LH, Besser GM (1978) Plasma i3-endorphin and adrenocorticotrophin in disease of the pituitary adrenal axis. J Enocrinol 80: 6Google Scholar
  37. Krauss S, Macy S, Ichiki AT (1981) A study of immunoreactive calcitonin (CT). Adrenocorticotrophic hormone (ACTH) and carcinoembryonic antigen ( CEA) in lung cancer and other malignancies. Cancer 47: 2485–2492Google Scholar
  38. Liddle GW, Nicholson WE, Island DP, Orth DN, Abe K, Lowder SC (1969) Clinical and laboratory studies of ectopic humoral syndromes. Recent Prog Horm Res 25: 283–314PubMedGoogle Scholar
  39. Mains RW, Eipper B (1976) Biosynthesis of adrenocorticotropic hormone in mouse pituitary tumour cells. J Biol Chem 251: 4115–4120PubMedGoogle Scholar
  40. Mason AMS, Ratcliffe JG, Buckle RM, Stuart Mason A (1972) ACTH secretion by bronchial carcinoid tumours. Clin Endocrinal 1: 3–25CrossRefGoogle Scholar
  41. Merrill WW, Bondy PK (1982) Production of biochemical marker substances by bronchogenic carcinomas. Clin Chest Med 3: 307–320PubMedGoogle Scholar
  42. Moody TW, Russell EK, O’Donohue TL, Lindon CD, Gazdar AF (1983) Bombesin-like peptides in small cell lung cancer: biochemical characterisation and secretion from a cell line. Life Sci 32: 487–493PubMedCrossRefGoogle Scholar
  43. Morton JJ, Kelly P, Padfield PL (1978) Antidiuretic hormone in bronchogenic carcinoma. Clin Endocrinol 9: 357–370CrossRefGoogle Scholar
  44. Nakanishi S, Akira A, Kita T, Nakamura M, Chang ACY, Cohen SN, Noma S (1979) Nucleotide sequence of a cloned cDNA for bovine corticotrophin-13-lipotropin precursor. Nature 278: 423–427PubMedCrossRefGoogle Scholar
  45. North WG, Maurer LH, Valhn H, O’Donnell JF (1980) Human neurophysin as potential tumour markers for small cell carcinoma of the lung. Application of specific radioimmunoassays. J Clin Endocrinol Metab 51: 892–896Google Scholar
  46. Odell WD, Wolfsen A, Yoshimoto Y, Weitzman R, Fisher D, Hirose F (1977) Ectopic peptide synthesis: A universal concomitant of neoplasia. Trans Assoc Am Physicians 90: 204Google Scholar
  47. Pedersen RC, Brownie AC (1980) Adrenocortical response to corticotrophin is potentiated by part of the amino-terminal region of pro-corticotrophin/endorphin. Proc Natl Acad Sci USA 77: 2239–2243PubMedCrossRefGoogle Scholar
  48. Penman E, Wass JAH, Besser GM, Rees LH (1980) Somatostatin secretion by lung and thymic tumours. Clin Endocrinol 13: 613–620CrossRefGoogle Scholar
  49. Pert CB, Schumacher UK (1982) Plasma bombesin concentrations in patients with extensive small cell carcinoma of the lung. Lancet 1: 509PubMedCrossRefGoogle Scholar
  50. Pettengill OS, Faulkner CS, Wurster-Hill DH (1977) Isolation and characterisation of a hormone producing cell line from human small cell anaplastic carcinoma of the lung. J Natl Cancer Inst 58: 511–518PubMedGoogle Scholar
  51. Powell D, Singer FR, Murray TM, Mirkin C, Potts JT Jr (1973) Non-parathyroid humoral hypercalcaemia in patients with neoplastic disease. N Engl J Med 289: 176–181PubMedCrossRefGoogle Scholar
  52. Rabson AS, Rosen SW, Tasjran AH (1973) Production of human chorionic gonadotrophin in vitro by a cell line derived from a carcinoma of the lung. J Natl Cancer Inst 50: 669–674PubMedGoogle Scholar
  53. Ratcliffe JG, Knight RA, Besser GM, Landon J, Stansfield AG (1972) Tumour and plasma ACTH concentrations in patients with and without the ectopic ACTH syndrome. Clin Endocrinal 1: 27–44CrossRefGoogle Scholar
  54. Ratter SJ, Lowry PJ, Besser GM, Rees LH (1980) Chromatographic characterisation of adrenocorticotrophin in human plasma. J Endocrinol 85: 359–369PubMedCrossRefGoogle Scholar
  55. Ratter SJ, Gillies G, hope J, Hale AC, Grossman A, Gaillard R, Cook D, Edwards CRW, Rees LH (1983) Pro-opiocortin related peptides in human pituitary and ectopic ACTH secreting tumours. Clin Endocrinol 18: 211–218CrossRefGoogle Scholar
  56. Rees LH, Bloomfield GA, Rees GM (1974) Multiple hormones in a bronchial tumour. J Clin Endocrinol Metab 38: 1090–1097PubMedCrossRefGoogle Scholar
  57. Rees LH, Bloomfield GA, Gilkes JJH, Besser GM (1977) ACTH as a tumour marker. Ann NY Acad Sci 297: 603–620PubMedCrossRefGoogle Scholar
  58. Rivier J. Spiess J, Thorner MO, Vale W (1982) Characterisation of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature 300: 276–278Google Scholar
  59. Robertson GL (1978) Cancer and inappropriate antidiuresis. In: Ruddon RW (ed) Biological markers of neoplasia: basic and applied aspects. Elsevier, New YorkGoogle Scholar
  60. Roos BA, Lindall AW, Baylin SB, O’Neil JA, Frelinger JI, Birnbaum RS, Lambert PW (1980) Plasma immunoreactive calcitonin in lung cancer. J Clin Endocrinol Metab 50: 659–666PubMedCrossRefGoogle Scholar
  61. Schorr I, Hinshaw HT, Cooper MA, Mahafee D, Ney RL (1972) Adenyl cyclase hormone responses of certain human endocrine tumour. J Clin Endocrinol Metab 34: 447–451PubMedCrossRefGoogle Scholar
  62. Schwartz WB, Bennett W, Curelop S, Bartter FC (1957) A syndrome of renal sodium loss and hyponatraemia probably resulting from inappropriate secretion of antiduretic hormone. Am J Med 23: 529–542PubMedCrossRefGoogle Scholar
  63. Seidah NG, Benjannet S, Routhier R, DeSerres G, Rochemont J, Lis M, Chretien M (1980) Purification and characterisation of the N-terminal fragment of pro-opiocomelanocortin from human pituitaries: homology to the bovine sequence. Biochem Biophys Res Commun 95: 1417–1424PubMedCrossRefGoogle Scholar
  64. Silva OL, Broder LE, Doppman JL, Snider RH, Moore CF, Cohen MH, Becker KL (1979) Calcitonin as a marker for bronchogenic cancer. Cancer 44: 680–684PubMedCrossRefGoogle Scholar
  65. Skrabaneck P, McPartlin J, Powell D (1980) Tumour associated hypercalcaemia and `ectopic hyperparathyroidism’. Medicine 59: 262–282Google Scholar
  66. Sonksen PH, Ayres AB, Braimbridge M, Corrin DR, Davies GM, Jeremiah SW, Oaten C, Lowy TET, West T (1976) Acromegaly caused by pulmonary carcinoid tumours. Clin Endocrinol 5: 503–513CrossRefGoogle Scholar
  67. Sorensen GD, Bloom SR, Ghatei MA, Del Prete SA, Cate CC, Pettengill OS (1982) Bombesin production by human small cell carcinoma of the lung. Regul Pept 4: 59–66CrossRefGoogle Scholar
  68. Sparagna M, Philips G, Hoffman C, Kucera L (1971) Ectopic growth hormone syndrome with lung cancer. Metabolism 20: 730–736CrossRefGoogle Scholar
  69. Stewart AF, Horst R, Deftos LJ (1980) Biochemical evaluation of patients with cancer associated hypercalcaemia. Evidence for humoral and non-humoral groups. N Engl J Med 303: 1377–1383Google Scholar
  70. Suda T, Demura H, Demura R (1977) Corticotrophin-releasing factor-like activity in ACTH producing tumour. J Clin Endocrinol Metab 44: 440–446PubMedCrossRefGoogle Scholar
  71. Thorner MO, Perryman RL, Cronin MJ, Rogol AD, Draynin M, Johanson A, Vale W, Horvath E, Kovacs K (1982) Somatotroph hyperplasia. Successful treatment of acromegaly by removal of a pancreatic islet tumour secreting a growth hormone-releasing factor. J Clin Invest 70: 965–977Google Scholar
  72. Track NS, Cutz E (1982) Bombesin-like immunoreactivity in developing human lung. Life Sci 30: 1553–1556PubMedCrossRefGoogle Scholar
  73. Unger RH, Lochner JD, Eisentraut AM (1964) Identification of insulin and glucagon in a bronchogenic metastasis. J Clin Endocrinol Metab 34: 823–831CrossRefGoogle Scholar
  74. Vale W, Spiess J, Rivier C, Rivier J (1981) Characterisation of.a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotrophin and beta-endorphin. Science 213: 1394–1397PubMedCrossRefGoogle Scholar
  75. Vorherr H (1974) Para-endocrine tumour activity with emphasis on ectopic ADH secretion: Genetic, diagnostic, prognostic and therapeutic aspects. Oncology 29: 382–416PubMedCrossRefGoogle Scholar
  76. Weintraub BD, Rosen SW (1971) Ectopic production of chorionic somatomammotrophin by nontrophoblastic cancers. J Clin Endocrinol Metab 32: 94–101PubMedCrossRefGoogle Scholar
  77. Wharton J, Polak JM, Bloom SR, Ghatei MA, Solcia E, Brown M, Pearse AGE (1978) Bombesin-like immunoreactivity in the lung. Nature 273: 769–770PubMedCrossRefGoogle Scholar
  78. Wood SM, Wood JR, Ghatei MA, Lee YC, O’Shaughnessy D, Bloom SR (1981) Bombesin, somatostatin and neurotensin-like immunoreactivity in bronchial carcinoma. J Clin Endocrinol Metab 53: 1310–1312PubMedCrossRefGoogle Scholar
  79. Yesner R (1978) Spectrum of lung cancer and ectopic hormones. In: Sommers S, Rosen PP (eds) Pathology annual part I. Appleton-Century-Crofts, New York, pp 217–240Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1984

Authors and Affiliations

  • Sally J. Ratter
  • Lesley H. Rees

There are no affiliations available

Personalised recommendations