Review
Thyroid follicular cell carcinogenesis

https://doi.org/10.1016/0272-0590(89)90001-8Get rights and content

Abstract

Ample information in experimental animals indicates a relationship between inhibition of thyroid-pituitary homeostasis and the developmental thyroid follicular cell neoplasms. This is generally the case when there are long-term reductions in circulating thyroid hormones which have triggered increases in circulating thyroid stimulating hormone. Such hormonal derangements leading to neoplasms have been produced by different regimens, including dietary oidide deficiency, subtotal thyroidectomy, and administration of natural and xenobiotic chemical substances. The carcinogenic process proceeds through a number of stages, including follicular cell hypertrophy, hyperplasia, and benign and sometimes malignant neoplasms. Given the interrelationship between the thyroid and pituitary glands, conditions that result in stimulation of the thyroid can also result in stimulation of the pituitary, with the development of hyperplastic and neoplastic changes. The progression of events leading to thyroid (and pituitary) neoplasms can be reversed under certain circumstances be reestablishing thyroid-pituitary homeostasis. Most chemicals that have induced follicular cell tumors seem to operate through inhibition of the synthesis of thyroid hormone or an increase in their degradation and removal. For some of these compounds, it appears that genotoxic reactions may not be playing a dominant role in the carcinogenic process. A seemingly small group of thyroid carcinogens seems to lack influence on thyroid-pituitary status and may in part be operating via their genotoxic potential. In contrast with the well-established relationship between thyroid-pituitary derangement and follicular cell neoplasms in animals, the state of information in humans is much less certain. At this time, ionizing radiation is the only acknowledged human thyroid carcinogen, a finding well established in experimental systems as well. Although humans respond to goitrogenic stimuli as do animals, with the development of cellular hypertrophy, hyperplasia, and under certain circumstances nodular lesions, disagreement exists as to whether malignant transformation occurs in any predictable manner. It would seem that if humans develop thyroid tumors following long-term derangement in thyroid-pituitary status, they may be less sensitive than the commonly used animal models.

References (338)

  • J. Ginsberg et al.

    Protein kinase C activators modulate differentiated thyroid function in vitro

    FEBS Lett.

    (1986)
  • J.M. Adams et al.

    The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice

    Nature (London)

    (1985)
  • C. Agrello et al.

    DNA repair in human fibroblasts. (1981)

  • M.R. Alderson

    Thyroid cancer epidemiology

    Recent Results Cancer Res.

    (1980)
  • C.F. Allen-Rowlands et al.

    Effect of polybrominated biphenyls (PBB) on the pituitary-thyroid axis of the rat

  • A.P. Alvares et al.

    Polychlorinated biphenyls: A new type of inducer of cytochrome P-448 in the liver

  • D. Anderson et al.

    Appendix II. The bacterial mutation test

    Brit. J. Cancer

    (1978)
  • A. ar-Rushdi et al.

    Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma

    Science

    (1983)
  • E.B. Astwood et al.

    Further studies on the chemical nature of compounds which inhibit the function of the thyroid gland

    Endocrinology

    (1945)
  • E.B. Atswood et al.

    Action of certain sulfonamides and of thiourea upon the function of the thyroid gland of the rat

    Endocrinology

    (1943)
  • A.A. Axelrod et al.

    Induction of thyroid tumors in rats by a low iodine diet

    Cancer

    (1955)
  • L.K. Bachrach et al.

    Phorbol esters stimulate growth and inhibit differentiation in cultured thyroid cells

    Endocrinology

    (1985)
  • A.K. Bahn et al.

    Hypothyroidism in workers exposed to polybrominated biphenyls

    N. Engl. J. Med.

    (1980)
  • B.L. Baker et al.

    Hypophyseal changes induced by thyroid deficiency and thyroxine administration as revealed by immunochemical staining

    Endocrinology

    (1971)
  • A. Balsam et al.

    Pituitary tumor with primary hypothyroidism

    N.Y. State J. Med.

    (1975)
  • M. Barbacid

    Oncogenes and human cancer: Cause or consequence

    Carcinogenesis

    (1986)
  • C.H. Bastomsky

    The biliary excretion of thyroxine and its glucuronic acid conjugate in normal and Gunn rats

    Endocrinology

    (1973)
  • C.H. Bastomsky

    Effects of polychlorinated biphenyl mixture (Arochlor 1254) and DDT on biliary thyroxine excretion in rats

    Endocrinology

    (1974)
  • C.H. Bastomsky

    Enhanced thyroxine metabolism and high uptake goiters in rats after a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin

    Endocrinology

    (1977)
  • C.H. Bastomsky

    Goitres in rats fed polychlorinated biphenyls

    Canad. J. Physiol. Pharmacol.

    (1977)
  • C.H. Bastomsky et al.

    Enhanced in vitro hepatic glucuronidation of thyroxine in rats following cutaneous application or ingestion of polychlorinated biphenyls

    Canad. J. Physiol. Pharmacol.

    (1976)
  • C.H. Bastomsky et al.

    Alterations of thyroxine metabolism produced by cutaneous application of microscope immersion oil: Effects due to polychlorinated biphenyls

    Endocrinology

    (1976)
  • C.H. Bastomsky et al.

    Effect of methylcholanthrene on biliary thyroxine excretion in normal and Gunn rats

    J. Endocrinol.

    (1973)
  • D.V. Becker

    Choice of therapy for Graves' hyperthyroidism

    N. Engl. J. Med.

    (1984)
  • F. Bielschowsky

    Chronic iodine deficiency as a cause of neoplasia in thyroid and pituitary of aged rats

    Brit. J. Cancer

    (1953)
  • F. Bielschowsky

    Neoplasia and internal environment

    Brit. J. Cancer

    (1955)
  • F. Bielschowsky et al.

    A reassessment of the thyroid tumors induced by goitrogens in mice

  • S.T. Bigos et al.

    Spectrum of pituitary alterations with mild and severe thyroid impairment

    J. Clin. Endocrinol. Metab.

    (1978)
  • E.A. Bone et al.

    Norepinephrine and thyroid-stimulating hormone induce inositol phosphate accumulation in FRTL-5 cells

    Endocrinology

    (1986)
  • G.A. Boorman

    Follicular cell hyperplasia, thyroid, rat

  • R. Braun et al.

    In vivo formation of N-nitroso compounds and detection of their mutagenic activity in the host-mediated assay

    Cancer Res.

    (1977)
  • B.A. Bridges et al.

    Summary report on the performance of bacterial mutation assays

  • J.J. Byrne et al.

    Hypothyroidism and abnormalities in the kinetics of thyroid hormone metabolism in rats treated chronically with polychlorinated biphenyl and polybrominated biphenyl

    Endocrinology

    (1987)
  • W.W. Carlton et al.

    Adenoma and carcinoma, pars distalis rat

  • J.H. Carver et al.

    Mutation induction and multiple gene loci in Chinese hamster ovary cells: The genetic activity of 15 coded carcinogens and noncarcinogens

  • A.M. Chesney et al.

    Endemic goitre in rabbits: Incidence and characteristics

    Bull. Johns Hopkins Hosp.

    (1928)
  • W.W. Chin et al.

    Regulation of the α- and thyrotropin β-subunit messenger ribonucleic acids by thyroid hormones

    Endocrinology

    (1985)
  • K. Christov

    Thyroid cell proliferation in rats and induction of tumors by X-rays

    Cancer Res.

    (1975)
  • D.B. Clayson et al.

    Carcinogenic aromatic amines and related compounds

  • G. Colletta et al.

    Induction of the c-fos oncogene by thyrotropic hormone in rat thyroid cells in culture

    Science

    (1986)
  • Cited by (0)

    This document has been reviewed in accordance with the U.S. Environmental Protection Agency procedures and has been approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does the mention of trade names or commercial products constitute endorsement or recommendation for use.

    2

    Present address: Clement Associates, Inc., Edison, NJ.

    3

    Present address: U.S. Environmental Protection Agency, Region IX, San Francisco, CA.

    4

    Present address: Versar, Inc., Springfield, VA.

    View full text