Etiology of Pituitary Adenomas

  • Seymour Reichlin


Although pituitary adenomas have been found by routine autopsy study to be surprisingly common, their emergence as clinical problems is far less frequent. The factors that determine the incidence of adenoma and their growth are the subject of this chapter.


Pituitary Adenoma Pituitary Tumor Medullary Thyroid Carcinoma Growth Hormone Level Plasma Growth Hormone 
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  1. 1.
    R.T. Costello, Subclinical adenomas of the pituitary gland, Am. J. Pathol 12:205, 1936.PubMedGoogle Scholar
  2. 2.
    W.F. McCormick and N.S. Halmi, Absence of chromophobe adenomas from a large series of pituitary tumors, Arch. Pathol. 92:231, 1971.PubMedGoogle Scholar
  3. 3.
    A.M.T. Sirek, B. Corenblum, E. Horvath, B. Newcastle, C. Ezrin, and K. Kovacs, A new look at pituitary adenomas: Structure elucidating function, Can. Med. Assoc. J. 114:225, 1976.PubMedGoogle Scholar
  4. 4.
    A.M. Landholt and H. Krayenbuhl, Progress in pituitary adenoma biology: Results of research and clinical applications, in: Advances and Technical Standards in Neurosurgery, Vol. 5, pp. 3–49, Springer-Verlag, Vienna and New York, 1971.Google Scholar
  5. 5.
    L.W. Conway, D.S. Schalch, R.D. Utiger, and S. Reichlin, Hormones in human pituitary sinusoid blood: Concentration of LH, GH and TSH, J. Clin. Endocrinol. Metab. 29:446, 1969.PubMedCrossRefGoogle Scholar
  6. 6.
    L.G. Lipson, I.Z. Beitins, P.D. Kornblith, J.W. McArthur, H.G. Friesen, B. Kliman, and R.N. Kjellberg, Tissue culture studies on human pituitary tumors: Radioimmunoassayable anterior pituitary hormones in the culture medium, Acta Endocrinol 88:239, 1978.PubMedGoogle Scholar
  7. 7.
    J.A. del Regato and H.J. Spjut, Cancer, C.V. Mosby, St. Louis, Missouri, 1977.Google Scholar
  8. 8.
    S. Reichlin, The prolactinoma problem (editorial), N. Engl. J. Med. 300:313, 1979.PubMedCrossRefGoogle Scholar
  9. 9.
    B.M. Sherman, J. Schlechte, N.S. Halmi, K.K. Chapler, C.E. Harris, T.M. Duello, J. VanGilder, and D.K. Granner, Pathogenesis of prolactin-secreting pituitary adenomas, Lancet 2:1019–1021, 1978.PubMedCrossRefGoogle Scholar
  10. 10.
    M. Banna, Terminology, embryology and anatomy, in: Pituitary and Parapituitary Tumors (J. Hankinson and M. Banna, eds.), pp. 1–12, W.B. Saunders, London, 1976.Google Scholar
  11. 11.
    T. Takor Takor and A.G.E. Pearse, Cytochemical identification of human and murine pituitary corticotrophs and somatotrophs as APUD cells, Histochemie 37:207, 1973.PubMedCrossRefGoogle Scholar
  12. 12.
    A.G.E. Pearse and T. Takor Takor, Neuroendocrine embryology and the APUD concept, Clin. Endocrinol. 5(Suppl.):229, 1976.CrossRefGoogle Scholar
  13. 13.
    B. Corenblum, A.M.T. Sirek, E. Horvath, K. Kovacs, and C. Ezrin, Human mixed somato-trophic and lactotrophic pituitary adenomas, J. Clin. Endocrinol. Metab. 42(5):857, 1976.PubMedCrossRefGoogle Scholar
  14. 14.
    G. Teitelman, H. Baker, T.H. Joh, and D.J. Reis, Appearance of catecholamine synthesizing enzymes during development of rat sympathetic nervous system: Possible role of tissue environment, Proc. Natl Acad. Sci. U.SA. 76(1):509, 1979.CrossRefGoogle Scholar
  15. 15.
    R.B. Campenot, Local control of neurite development by nerve growth factor, Proc. Natl Acad. Sci. U.S.A. 74:4516, 1977.CrossRefGoogle Scholar
  16. 16.
    A.S. Tischler, M.A. Dichter, B. Biales, and L. Greene, Neuroendocrine neoplasms and their cells of origin, N. Engl. J. Med. 296:919, 1977.PubMedCrossRefGoogle Scholar
  17. 17.
    S.B. Baylin, The multiple endocrine neoplasia syndromes: Implications for the study of in- herited tumors, Semin. Oncol. 5:35, 1978.PubMedGoogle Scholar
  18. 18.
    R.A. DeLellis and H.J. Wolfe, Multiple endocrine adenomatosis syndromes: Origins and interrelationships, in: Cancer Medicine, 2nd ed. (J. Holland and E. Frei, eds.), Lea and Febiger, Philadelphia, 1979 (in press).Google Scholar
  19. 19.
    M. Vandeweghe, J. Schutyser, K. Braxel, and A. Vermuelen, A case of multiple endocrine adenomatosis with primary amenorrhea, Postgrad. Med. J. 54:618, 1978.PubMedCrossRefGoogle Scholar
  20. 20.
    H.E. Carlson, G.A. Levine, N.J. Goldberg, and J.M. Hershman, Hyperprolactinemia in multiple endocrine adenomatosis, Type I, Arch. Intern. Med. 138:1807, 1978.PubMedCrossRefGoogle Scholar
  21. 21.
    J.D. Veldhuis, J.E. Green III, E. Kovacs, T.J. Worgul, F.T. Murray, and J. M. Hammond, Prolactin-secreting pituitary adenomas. Association with multiple endocrine neoplasia, Type I, Am. J. Med. 67:830–837, 1979.PubMedCrossRefGoogle Scholar
  22. 22.
    H.J. Wolfe, K.E.W. Melvin, S.J. Cervi-Skinner, A.A. AlSaadi, J.F. Juliar, C.E. Jackson, and A.H. Tashjian, C-cell hyperplasia preceding medullary thyroid carcinoma, N. Engl. J. Med. 289:437, 1973.PubMedCrossRefGoogle Scholar
  23. 23.
    R.F. Gagel, K.E.W. Melvin, A.H. Tashjian, H.H. Miller, Z.T. Feldman, H.J. Wolfe, R.A. DeLellis, S. Cervi-Skinner, and S. Reichlin, Natural history of the familial medullary thyroid car-cinoma-pheochromocytoma syndrome and the identification of preneoplastic stages by screening studies: A five year report, Trans. Assoc. Am. Phys. 88:177, 1975.PubMedGoogle Scholar
  24. 24.
    K. Graze, I.J. Spiler, A.H. Tasjian Jr., K.E.W. Melvin, S. Cervi-Skinner, R.F. Gagel, H.H. Miller, H.J. Wolfe, R.A. DeLellis, L. Leape, Z.T. Feldman, and S. Reichlin, Natural history of familial medullary thyroid carcinoma: Effect of a program for early diagnosis, N. Engl. J. Med. 299:980, 1978.PubMedCrossRefGoogle Scholar
  25. 25.
    R.A. DeLellis, H.J. Wolfe, R.F. Gagel, Z.T. Feldman, H.H. Miller, D.L. Gang, and S. Reichlin, Adrenal medullary hyperplasia: A morphometric analysis in patients with familial medullary thyroid carcinoma, Am J. Pathol. 83:177, 1976.PubMedGoogle Scholar
  26. 26.
    A.M. Landolt, Ultrastructure of human sella tumors, Acta Neurochir., Suppl. 22, 1975.Google Scholar
  27. 27.
    J. Furth and K.H. Clifton, Experimental pituitary tumours, in: The Pituitary Gland (G.W. Harris and B.T. Donovan, eds.), pp. 460–497, Butterworths, London, 1966.Google Scholar
  28. 28.
    A.B. Russfield, Tumors of endocrine glands and secondary sex organs, Public Health Service Publ. No. 1332, U.S. Government Printing Office, Washington, D.C., 1966.Google Scholar
  29. 29.
    G. Ueda, S. Takizawa, P. Moy, F. Marolla, and J. Furth, Characterization of four transplantable mammotropic pituitary tumor varients in the rat, Cancer Res. 10 and 28, 1963 and 1968.Google Scholar
  30. 30.
    C. Sonneschein, U.I. Richardson, and A.H. Tashjian Jr., Chromosomal analysis, organ-specific function and appearance of six clonal strains of rat pituitary tumor cells, Exp. Cell Res. 61:121, 1970.CrossRefGoogle Scholar
  31. 31.
    L. Cacicedo, S.L. Pohl, and S. Reichlin, Biosynthesis of thyrotropin (TSH) by mouse thyrotropic tumor cells in primary culture: Inhibitory effect of triiodothyronine (T3) and thyroxine (T4), Program of the 58th Annual Meeting of the Endocrine Society, San Francisco, 1976 (abstract 259).Google Scholar
  32. 32.
    M.R. Blackman, M.C. Gershengorn, and B.D. Weintraub, Excess production of free alpha subunits by mouse pituitary thyrotropic tumor cells in vitro, Endocrinology 102:499–508, 1978.PubMedCrossRefGoogle Scholar
  33. 33.
    N.A. Samaan, B.M. Osborne, B. MacKay, M.E. Leavens, T.M. Duello, and N.S. Halmi, J. Clin. Endocrinol. Metab. 45:903–911, 1977.PubMedCrossRefGoogle Scholar
  34. 34.
    A.B. Russfield, Pituitary tumors, in: Endocrine Pathology Decennial (S.C. Sommers, ed.), pp. 41–79, Appleton-Century-Crofts, New York, 1975.Google Scholar
  35. 35.
    J.N. Friend, D.M. Judge, B.M. Sherman, and R.J. Santen, FSH secreting pituitary adenomas: Stimulation and suppression studies in two patients, J. Clin. Endocrinol. Metab. 43:650–657, 1976.PubMedCrossRefGoogle Scholar
  36. 36.
    W.H. Daughaday, P.E. Cryer, and L.S. Jacobs, The role of the hypothalamus in the pathogenesis of pituitary tumors, in: Diagnosis and Treatment of Pituitary Tumors (P.O. Kohler and G.T. Ross, eds.), pp. 26–34, Excerpta Medica, Amsterdam and New York, 1973.Google Scholar
  37. 37.
    W. Daughaday and P. Cryer, Growth hormone hypersecretion and acromegaly, Hosp. Pract. pp. 75–80, Aug. 1978.Google Scholar
  38. 38.
    P. Oyer and W. Daughaday, Regulation of growth hormone secretion in acromegaly, J. Clin. Endocrinol. Metab. 29:386, 1969.CrossRefGoogle Scholar
  39. 39.
    A.M. Lawrence, I.D. Goldfine, and L. Kirsteins, Growth hormone dynamics in acromegaly, J. Clin Endocrinol. Metab. 31:239, 1970.PubMedCrossRefGoogle Scholar
  40. 40.
    K. Janew, M. Aida, T. Tano, and K. Yoshinaga, Abnormal growth hormone responses to l-dopa and thyrotropin releasing hormone in patients with acromegaly, Tohoku J. Exp. Med. 121:197, 1977.CrossRefGoogle Scholar
  41. 41.
    G.M. Besser, J.A.H. Wass, and M.O. Thomer, Acromegaly—Results of long term treatment with bromocriptine, Acta Endocrinol. [SuppJ.) (Copenhagen) 88(216):187, 1978.Google Scholar
  42. 42.
    F. Camanni, G.B. Piccotti, F. Massara, G.M. Molinatti, P. Mantegazza, and E.E. Muller, Car-bidopa inhibits the growth hormone and prolactin suppressive effect of L-dopa in acromegalic patients, J. Clin. Endocrinol. Metab. 47:647, 1978.PubMedCrossRefGoogle Scholar
  43. 43.
    K. Maeda, Critical review: Effects of thyrotropin releasing hormone on growth hormone release in normal subjects and in patients with depression, anorexia nervosa and acromegaly, Kobe J. Med. Sci. 22:263, 1976.PubMedGoogle Scholar
  44. 44.
    E.A. Zimmerman, R. Defendini, and A.G. Frantz, Prolactin and growth hormone in patients with pituitary adenomas: A correlative study of hormone in tumor and plasma by im-munoperoxidase technique and radioimmunoassay, J. Clin. Endocrinol. Metab. 38:577, 1974.PubMedCrossRefGoogle Scholar
  45. 45.
    K.M. Hoyte and J.B. Martin, Recovery from paradoxical growth hormone responses in acromegaly after transsphenoidal selective adenomectomy, J. Clin. Endocrinol. Metab. 41:656, 1975.PubMedCrossRefGoogle Scholar
  46. 46.
    M. Saeed uz Zafar. R.C. Mellinger, G. Fine, M. Szabo, and 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, 1979.CrossRefGoogle Scholar
  47. 47.
    P.O. Sonkson, A.B. Ayres, M. Braimbridge, B. Corrin, D.R. Davies, G.M. Jeremiah, S.W. Oaten, C. Lowy, and T.E.T. West, Acromegaly caused by pulmonary carcinoid tumors, Clin. Endocrinol (Oxford), 5:503, 1976.CrossRefGoogle Scholar
  48. 48.
    T.C. Hagen, A.M. Lawrence, and L. Kirsteins, In vitro release of monkey pituitary growth hormone by acromegalic plasma, J. Clin. Endocrinol. 33:448, 1978.CrossRefGoogle Scholar
  49. 49.
    Y. Patel, K. Rao, and S. Reichlin, Somatostatin in human cerebrospinal fluid, N. EngJ. J. Med. 296:529, 1977.CrossRefGoogle Scholar
  50. 50.
    C.M. Plotz, A.I. Knowlton, and C. Ragan, The natural history of Cushing’s syndrome, Am. J. Med. 13:597, 1952.PubMedCrossRefGoogle Scholar
  51. 51.
    C.W. Burke and C.G. Beardwell, Cushing’s syndrome, Q. J. Med. N. Ser. 42:175, 1973.Google Scholar
  52. 52.
    R.M. Salassa, E.R. Laws Jr., P.C. Carpenter, and R.C. Northcutt, Transsphenoidal removal of pituitary microadenoma in Cushing’s disease, Mayo Clin. Proc. 53:24, 1978.PubMedGoogle Scholar
  53. 53.
    J.B. Tyrell, R.M. Brooks, PA. Fitzgerald, P. Coifaid, P.H. Forsham, and C. Wilson, Cushings disease: Selective transsphenoidal resection of pituitary mircoadenomas, N. Engl. J. Med. 298:73, 1978.CrossRefGoogle Scholar
  54. 54.
    J. Hardy, Transsphenoidal surgery for hypersecreting adenomas, in: Diagnosis and Treatment of Pituitary Tumors (P.O. Kohler and G.T. Ross, eds.), pp. 179–198, American Elsevier, New York, 1973.Google Scholar
  55. 55.
    R. Clayton, V. Schriever, A.C. Burden, and R.D. Rosenthal, Secondary pituitary hyperplasia in Addison’s disease, Lancet, Nov. 5, p. 954, 1977.Google Scholar
  56. 56.
    M.T. Jones, Control of corticotrophin (ACTH) secretion, in: The Endocrine Hypothalamus (S.L. Jeffcoate and J.S.M. Hutchinson, eds.), pp. 386–419, Academic Press, London, 1978.Google Scholar
  57. 57.
    D.T. Krieger and E.M. Condon, Cyproheptadine treatment of Nelson’s syndrome: Restoration of plasma ACTH circadian periodicity and reversal of response to TRF, J. Clin. Endocrinol. Metab. 46:349, 1978.PubMedCrossRefGoogle Scholar
  58. 58.
    S.W.J. Lamberts and J.C Birkenhagen, Bromocryptine in Cushing’s disease, J. Endocrinol. 70:315, 1976.PubMedCrossRefGoogle Scholar
  59. 59.
    R.M. MacLeod and D.T. Krieger, Differential effect of ergotamine on ACTH and prolactin secretion, Program of the 58th Annual Meeting of the Endocrine Society, San Francisco, 1976 (abstract 317).Google Scholar
  60. 60.
    D.T. Krieger, The central nervous system and Cushing’s disease, Med. Clin. North Am. 62:261, 1978.PubMedGoogle Scholar
  61. 61.
    L.G. Lagerquist, A.W. Meikle, C.D. West, and F.H. Tyler, Cushing’s disease with cure by resection of a pituitary adenoma: Evidence against a primary hypothalamic defect, Am. J. Med. 57:826, 1974.PubMedCrossRefGoogle Scholar
  62. 62.
    D.T. Krieger, L. Amorosa, and F. Linick, Cyproheptadine-induced remission of Cushing’s disease, N. Engl. J. Med. 293:893, 1975.PubMedCrossRefGoogle Scholar
  63. 63.
    D.T. Krieger and M. Luria, Effectiveness of cyproheptadine in decreasing plasma ACTH concentration in Nelson’s syndrome, J. Clin. Endocrinol. Metab. 43:1179, 1976.PubMedCrossRefGoogle Scholar
  64. 64.
    F.G. Berlinger, H.J. Ruder, and J.F. Wilber, Cushing’s syndrome associated with galactorrhea, amenorrhea, and hypothyroidism: A primary hypothalamic disorder, J. Clin. Endocrinol. Metab. 45:1205, 1977.PubMedCrossRefGoogle Scholar
  65. 65.
    A.M. Schnall, J.S. Brodkey, B. Kaufman, and O.H. Pearson, Pituitary function after removal of pituitary microadenomas in Cushing’s disease, J. Clin. Endocrinol. Metab. 47:410, 1978.PubMedCrossRefGoogle Scholar
  66. 66.
    S.T. Bigos, F. Robert, G. Pelletier, and J. Hardy, Cure of Cushing’s disease by transsphenoidal removal of a microadenoma from a pituitary gland despite a radiographically normal sella turcica, J. Clin. Endocrinol. Metab. 45:1251, 1977.PubMedCrossRefGoogle Scholar
  67. 67.
    R.J. Witorsch and A. Brodish, Conditions for the reliable use of lesioned rats for the assay of CRF in tissue extracts, Endocrinology 90:552, 1972.PubMedCrossRefGoogle Scholar
  68. 68.
    N. Yasuda and M.A. Greer, Distribution of corticotropin releasing factor(s) activity in neural and extraneural tissues of the rat, Endocrinology 99:944, 1976.PubMedCrossRefGoogle Scholar
  69. 69.
    A. Barbarino, L. DeMarinis, G. Maira, E. Menini, and C. Anile, Serum prolactin response to thyrotropin-releasing hormone and metoclopramide in patients with prolactin-secreting tumors before and after transsphenoidal surgery, J. Clin. Endocrinol. Metab. 47:1148, 1978.PubMedCrossRefGoogle Scholar
  70. 70.
    R. Goodman, B. Biller, A.C. Mosses, M. Molitch, S. Feldman, and K. Post, Restoration of normal prolactin secretory dynamics after surgical cure of prolactinoma is evidence against underlying hypothalamic dysregulation, Program of the 61st Annual Meeting of the Endocrine Society, Anaheim, California, June 1979.Google Scholar
  71. 71.
    S.A. Fine and L.A. Frohman, Loss of central nervous system component of dopaminergic inhibition of prolactin secretion in patients with prolactin secreting pituitary tumors, J. Clin. Invest. 61:973, 1978.PubMedCrossRefGoogle Scholar
  72. 72.
    G.R. Van Loon, A defect in catecholamine neurons in patients with prolactin secreting pituitary adenoma, Lancet 2(8095):868, 1978.PubMedGoogle Scholar
  73. 73.
    K. Fuxe, T. Hökfelt, A. Löfström, O. Johansson, L. Agnati, B. Everitt, M. Goldstein, S. Jeffcoate, N. White, P. Eneroth, J.A. Gustafsson, and P. Skett, On the role of neurotransmitters and hypothalamic hormones and their interactions in hypothalamic and extrahypothalamic control of pituitary function and sexual behaviour, in: Subcellular Mechanisms in Reproductive Neuroendocrinology (F. Naftolin, K.J. Ryan, and I.J. Davies, eds.), pp. 193–246, Elsevier, Amsterdam, 1976.Google Scholar
  74. 74.
    T.L. Garthwaite and T.C. Hagen, Plasma prolactin-releasing factor-like activity in the amenorrhea-galactorrhea syndrome, J. Clin. Endocrinol. Metab. 47:885, 1978.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1980

Authors and Affiliations

  • Seymour Reichlin
    • 1
    • 2
  1. 1.Tufts University School of MedicineBostonUSA
  2. 2.Division of Endocrinology, Department of MedicineTufts-New England Medical Center HospitalBostonUSA

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