Skip to main content
SpringerLink
Log in

Environmental Endocrinology and the Hypothalamus-Pituitary-Thyroid Axis

  • Living reference work entry
  • First Online:
Environmental Endocrinology and Endocrine Disruptors

Part of the book series: Endocrinology ((ENDOCR))

  • 41 Accesses

Abstract

The hypothalamus represents a potential target for a wide spectrum of endocrine-disrupting chemicals (EDCs). Their effects can be exerted at a lower dose which may not be predicted at higher doses, there being a nonlinear relationship (nonmonotonic dose-response) between dose and effect. Among the various categories of EDCs that may disrupt thyroid function, some are more analytically discussed. Polychlorinated biphenyls (PCBs), which are halogenated organochlorines, show variable biodegradation depending on various congeners which may interfere at the different levels of thyroid hormone (TH) production, transportation, and metabolism; they may also display agonist or antagonist action by binding to TH receptor and affecting TH signaling. Pesticides, which are associated with low T4 and T3 levels, appear to be involved in the development of autoimmune thyroiditis. Plasticizers, like bisphenol A (BPA), widely used in consumer products, may perturb thyroid function altering the hypothalamic-pituitary thyroid axis when the fetus is exposed to these compounds prenatally. Heavy metals, even at low concentrations, can interfere with thyroid function by decreasing iodine uptake and accelerating thyroid parenchymal transformation, and, depending on duration of exposure, they may ultimately induce hypothyroidism. As stated by the WHO in 2010, “Humans are actively squandering and destroying nature’s wealth and abundance” (Gristle: From Factory Farms to Food Safety (Thinking Twice About the Meat We Eat) – Moby & Miyun Park (editors) – March 2010), thus what is needed is an entire reevaluation of our relationship with nature – and this obviously includes drastic reduction of the present-day tsunami of EDCs in our world.

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Abramowicz MJ, Duprez L, Parma J, Vassart G, Heinrichs C. Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. J Clin Invest. 1997;99:3018–24.

    Article  CAS  Google Scholar 

  • Ahlbom BD, Yaqoob M, Larsson A, Ilicki A, Anneren G, Wadelius C. Genetic and linkage analysis of familial congenital hypothyroidism: exclusion of linkage to the TSH receptor gene. Hum Genet. 1997;99:186–90.

    Article  CAS  Google Scholar 

  • Ahmed RG, El-Gareib AW, Shaker HM. Gestational 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) exposure disrupts fetoplacental unit: fetal thyroid-cytokines dysfunction. Life Sci. 2018;192:213–20. https://doi.org/10.1016/j.lfs.2017.11.033.

    Article  CAS  Google Scholar 

  • Andrade MN, Santos-Silva AP, Rodrigues-Pereira P, Paiva-Melo FD, de Lima Junior NC, Teixeira MP, Soares P, Dias GRM, Graceli JB, de Carvalho DP, Ferreira ACF, Miranda-Alves L. The environmental contaminant tributyltin leads to abnormalities in different levels of the hypothalamus-pituitary-thyroid axis in female rats. Environ Pollut. 2018;241:636–45. https://doi.org/10.1016/j.envpol.2018.06.006.

    Article  CAS  Google Scholar 

  • Baba T, Ito S, Yuasa M, Yoshioka E, Miyashita C, Araki A, Sasaki S, Kobayashi S, Kajiwara J, Hori T, Kato S, Kishi R. Association of prenatal exposure to PCDD/Fs and PCBs with maternal and infant thyroid hormones: the Hokkaido Study on Environment and Children’s Health. Sci Total Environ. 2018;615:1239–46. https://doi.org/10.1016/j.scitotenv.2017.09.038.

    Article  CAS  Google Scholar 

  • Bacci V, Schussler GC, Kaplan TB. The relationship between serum triiodothyronine and thyrotropin during systemic illness. J Clin Endocrinol Metab. 1982;54:1229–35.

    Article  CAS  Google Scholar 

  • Benson K, Yang E, Dutton N, Sjodin A, Rosenbaum PF, Pavuk M. Polychlorinated biphenyls, indicators of thyroid function and thyroid autoantibodies in the Anniston Community Health Survey I (ACHS-I). Chemosphere. 2018;195:156–65. https://doi.org/10.1016/j.chemosphere.2017.12.050.

    Article  CAS  Google Scholar 

  • Bigos ST, Ridgway EC, Kourides IA, Maloof F. Spectrum of pituitary alterations with mild and severe thyroid impairment. J Clin Endocrinol Metab. 1978;46:317–25.

    Article  CAS  Google Scholar 

  • Boelen A, Platvoet-Ter Schiphorst MC, Wiersinga WM. Association between serum interleukin-6 and serum 3,5,3′-triiodothyronine in nonthyroidal illness. J Clin Endocrinol Metab. 1993;77:1695–9.

    CAS  Google Scholar 

  • Brent GA, Hershman JM, Braunstein GD. Patients with severe nonthyroidalillness and serum thyrotropin concentrations in the hypothyroid range. Am J Med. 1986;81:463–6.

    Article  CAS  Google Scholar 

  • Brucker-Davis F, Hiéronimus S, Fénichel P. Thyroid and the environment. Presse Med. 2016;45:78–87. https://doi.org/10.1016/j.lpm.2015.06.015.

    Article  Google Scholar 

  • Curtis SW, Terrell ML, Jacobson MH, Cobb DO, Jiang VS, Neblett MF, Gerkowicz SA, Spencer JB, Marder EM, Barr DB, Conneely KN, Alicia K, Smith AK, Marcus M. Thyroid hormone levels associate with exposure to polychlorinated biphenyls and polybrominated biphenyls in adults exposed as children. Environ Health. 2019;18:75. https://doi.org/10.1186/s12940-019-0509-z.

    Article  CAS  Google Scholar 

  • de Oliveira M, Rodrigues BM, Olimpio RMC, Graceli JB, Gonçalves BM, Costa SMB, da Silva TM, De Sibio MT, Moretto FCF, Mathias LS, Cardoso DBM, Tilli HP, Freitas-Lima LC, Nogueira CR. Disruptive effect of organotin on thyroid gland function might contribute to hypothyroidism. Int J Endocrinol. 2019;2019:7396716. https://doi.org/10.1155/2019/7396716.eCollection.

    Article  Google Scholar 

  • Decherf S, Seugnet I, Fini JB, Clerget-Froidevaux MS, Demeneix BA. Disruption of thyroid hormone-dependent hypothalamic set-points by environmental contaminants. Mol Cell Endocrinol. 2010;323:172–82.

    Article  CAS  Google Scholar 

  • Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC. Endocrine-disrupting chemicals: an Endocrine Society Scientific Statement. Endocr Rev. 2009;30:293–342.

    Article  CAS  Google Scholar 

  • Duntas LH. Environmental factors and autoimmune thyroiditis. Nat Clin Pract Endocrinol Metab. 2008;4:454–60. https://doi.org/10.1038/ncpendmet0896.

    Article  CAS  Google Scholar 

  • Duntas LH. Chemical contamination and the thyroid. Endocrine. 2015;48:53–64. https://doi.org/10.1007/s12020-014-0442-4.

    Article  CAS  Google Scholar 

  • Duntas LH, Stathatos N. Toxic chemicals and thyroid function: hard facts and lateral thinking. Endocrine Rev Endocr Metab Disord. 2016;16:311–8. https://doi.org/10.1007/s11154-016-9331-x.

    Article  CAS  Google Scholar 

  • El Majidi N, Bouchard M, Carrier G. Systematic analysis of the relationship between standardized biological levels of polychlorinated biphenyls and thyroid function in pregnant women and newborns. Chemosphere. 2014;98:1–17. https://doi.org/10.1016/j.chemosphere.2013.10.006.

    Article  CAS  Google Scholar 

  • Emerson CH, Dysno WL, Utiger RD. Serum thyrotropin and thyroxine concentrations in patients receiving lithium carbonate. J Clin Endocrinol Metab. 1973;36:338–46.

    Article  CAS  Google Scholar 

  • EU green deal promises new chemicals strategy for toxic-free environment. NGOs hail stronger commitment to non-toxic environment 12 December 2019. Alternatives assessment & substitution, Europe, REACH, Substances of concern.

    Google Scholar 

  • Gaum PM, Gube M, Esser A, Schettgen T, Quinete N, Jens B, Putschögl FM, Kraus T, Lang J. Depressive symptoms after PCB exposure: hypotheses for underlying pathomechanisms via the thyroid and dopamine system. Int J Environ Res Public Health. 2019;16:950. https://doi.org/10.3390/ijerph16060950.

    Article  CAS  Google Scholar 

  • Ghassabian A, Trasande L. Disruption in thyroid signalling pathway: a mechanism for the effect of endocrine-disrupting chemicals on child neurodevelopment. Front Endocrinol Lausanne. 2018;9:204.

    Article  Google Scholar 

  • Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, Toppari J, Zoeller RT. Executive summary to EDC-2: the Endocrine Society’s Second Scientific Statement on endocrine-disrupting chemicals. Endocr Rev. 2015;36:593–602.

    Article  CAS  Google Scholar 

  • Gow SM, Kellett HA, Seth J, Sweeting VM, Toft AD, Beckett GJ. Limitations of new thyroid function tests in pregnancy. Clin Chim Acta. 1985;152:325–33.

    Article  CAS  Google Scholar 

  • Grimm FA, Lehmler HJ, Duffel MW. Sulfated metabolites of polychlorinated biphenyls are high-affinity ligands for the thyroid hormone transport protein transthyretin. Environ Health Perspect. 2013;121:657–62. https://doi.org/10.1289/ehp.1206198.

    Article  Google Scholar 

  • Joseph-Bravo P, Jaimes-Hoy L, Uribe RM, Charli JL. 60 years of neuroendocrinology: TRH, the first hypophysiotropic releasing hormone isolated: control of the pituitary-thyroid axis. J Endocrinol. 2015;227(3):X3.

    Article  CAS  Google Scholar 

  • Joseph-Bravo P, Jaimes-Hoy L, Charli JL. Advances in TRH signaling. Rev Endocr Metab Disord. 2016;17:545–58.

    Article  CAS  Google Scholar 

  • Kaplan MM, Larsen PR, Crantz FR, Dzau VJ, Rossing TH, Haddow JE. Prevalence of abnormal thyroid function test results in patients with acute medical illnesses. Am J Med. 1982;72:9–16.

    Article  CAS  Google Scholar 

  • Kaptein EM, Spencer CA, Kamiel MB, Nicoloff JT. Prolonged dopamine administration and thyroid hormone economy in normal and critically ill subjects. J Clin Endocrinol Metab. 1980;51:387–93.

    Article  CAS  Google Scholar 

  • Kim G, Nandi-Munshi D, Diblasi CC. Disorders of the thyroid gland. In: Avery’s diseases of the newborn. Amsterdam: Elsevier; . 2017. p. 1388–402.e2. https://doi.org/10.1016/b978-0-323-40139-5.00098-x.

  • Lechan RM, Toni R. Functional anatomy of the hypothalamus and pituitary. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K, Grossman A, Hershman JM, Hofland HJ, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Purnell J, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth: MDText.com, Inc; 2016 Nov 28. p. 2000.

    Google Scholar 

  • Li ZM, Hernandez-Moreno D, Main KM, Skakkebæk NE, Kiviranta H, Toppari J, Feldt-Rasmussen U, Shen H, Schramm KW, De Angelis M. Association of in utero persistent organic pollutant exposure with placental thyroid hormones. Endocrinology. 2018;159:3473–81. https://doi.org/10.1210/en.2018-00542.

    Article  CAS  Google Scholar 

  • Mariotti S, Beck-Peccoz P. Physiology of the hypothalamic-pituitary-thyroid Axis. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K, Grossman A, Hershman JM, Hofland HJ, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Purnell J, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth: MDText.com, Inc; 2016. p. 2000. PMID: 25905193.

    Google Scholar 

  • Mariotti S, et al. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, EA MG, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Physiology of the hypothalamic-pituitary-thyroid axis. Endotext [Internet]. South Dartmouth: MDText.com, Inc; 2021. p. 2000.

    Google Scholar 

  • Müller-Fielitz H, Stahr M, Bernau M, Richter M, Abele S, Krajka V, Benzin A, Wenzel J, Kalies K, Mittag J, Heuer H, Offermanns S, Schwaninger M. Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis. Nat Commun. 2017;8:484.

    Article  Google Scholar 

  • Persani L, Beck-Peccoz P. Central hypothyroidism. In: Braverman L, Cooper D, Kopp P, editors. Werners & Ingbar’s the thyroid. A fundamental and clinical text. 11th ed. Philadelphia: Wolters Kluwer, Lippincott Williams & Wilkins; 2021. p. 566–74.

    Google Scholar 

  • Prummel MF, Brokken LJ, Wiersinga WM. Ultra short-loop feedback control of thyrotropin secretion. Thyroid. 2004;14:825–9.

    Article  CAS  Google Scholar 

  • Refetoff S, Dumitrescu AM. Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination. Best Pract Res Clin Endocrinol Metab. 2007;21:277–305.

    Article  CAS  Google Scholar 

  • Refetoff S, Sunthornthepvarakul T, Gottschalk ME, Hayashi Y. Resistance to thyrotropin and other abnormalities of the thyrotropin receptor. Recent Prog Horm Res. 1996;51:97–120.

    CAS  Google Scholar 

  • Requena M, López-Villén A, Hernández AF, Parrón T, Navarro A, Alarcon R. Environmental exposure to pesticides and risk of thyroid diseases. Toxicol Lett. 2019;15:55–63. https://doi.org/10.1016/j.toxlet.2019.08.017.

    Article  CAS  Google Scholar 

  • Rodrigues-Pereira P, Palmero C, de Mattos RM, da Silva DLSG, Santos-Silva AP, Graceli JB, Soares P, Nasciutti LE, de Carvalho DP, Ferreira ACF, Miranda-Alves L. Influence of organotin on thyroid morphophysiological status. J Environ Health Sci. 2015;1:1–7. https://doi.org/10.15436/2378-6841.15.018.

    Article  Google Scholar 

  • Santisteban P, Costagliola S. Development and anatomy of the hypothalamic-pituitary-thyroid axis. In: Braverman L, Cooper D, Kopp P, editors. Werners & Ingbar’s the thyroid. A fundamental and clinical text. 11th ed. Philadelphia: Wolters Kluwer, Lippincott Williams & Wilkins; 2021. p. 9–38.

    Google Scholar 

  • Santos RA, Piccoli C, Cremonese C, Freire C. Thyroid and reproductive hormones in relation to pesticide use in an agricultural population in Southern Brazil. Environ Res. 2019;173:221–31.

    Article  CAS  Google Scholar 

  • Santos-Silva AP, Andrade MN, Pereira-Rodrigues P, Paiva-Melo FD, Soares P, Graceli JB, Dias GRM, Ferreira ACF, de Carvalho DP, Miranda-Alves L. Frontiers in endocrine disruption: impacts of organotin on the hypothalamus-pituitary-thyroid axis. Mol Cell Endocrinol. 2018;460:246–57. https://doi.org/10.1016/j.mce.2017.07.038.

    Article  CAS  Google Scholar 

  • Sherman SI, Gopal J, Haugen BR, Chiu AC, Whaley K, Nowlakha P, Duvic M. Central hypothyroidism associated with retinoid X receptor-selective ligands. N Engl J Med. 1999;340:1075–9.

    Article  CAS  Google Scholar 

  • Su PH, Chen HY, Chen SJ, Chen JY, Liou SH, Wang SL. Thyroid and growth hormone concentrations in 8-year-old children exposed in utero to dioxins and polychlorinated biphenyls. J Toxicol Sci. 2015;40:309–19. https://doi.org/10.2131/jts.40.30.

    Article  CAS  Google Scholar 

  • Surks MI, Sievert R. Drugs and thyroid function. N Engl J Med. 1995;333:1688–94.

    Article  CAS  Google Scholar 

  • Toft AD, Irvine WJ, Hunter WM, Ratcliffe JG, Seth J. Anomalous plasma TSH levels in patients developing hypothyroidism in the early months after 131I therapy for thyrotoxicosis. J Clin Endocrinol Metab. 1974;39:607–9.

    Article  CAS  Google Scholar 

  • Toft AD, Irvine WJ, McIntosh D, Seth J, Cameron EH, Lidgard GP. Temporary hypothyroidism after surgical treatment of thyrotoxicosis. Lancet. 1976;2:817–8.

    Article  CAS  Google Scholar 

  • Vagenakis AG, Braverman LE, Azizi F, Portinay GI, Ingbar SH. Recovery of pituitary thyrotropic function after withdrawal of prolonged thyroid-suppression therapy. N Engl J Med. 1975;293:681–4.

    Article  CAS  Google Scholar 

  • Vandenberg LN, Colborn T, Hayes TB, , Heindel JJ, Jacobs DR, Lee DH Jr, Shioda T, Soto AM, vom Saal FS, Welshons WV, Zoeller RT, Myers JT. 2012 Hormones and endocrine disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev 33, 378–455.

    Article  CAS  Google Scholar 

  • Wuttke W, Jarry H, Seidlova-Wuttke D. Definition, classification and mechanism of action of endocrine disrupting chemicals. Hormones. 2010;9:9–15.

    Article  Google Scholar 

  • Xiang Y, Xing Z, Liu J, Qin W, Huang X. Recent advances in the biodegradation of polychlorinated biphenyls. World J Microbiol Biotechnol. 2020;36:145. https://doi.org/10.1007/s11274-020-02922-2.

    Article  CAS  Google Scholar 

  • Xie J, Pannain S, Pohlenz J, Weiss RE, Moltz K, Morlot M, Asteria C, Persani L, Beck-Peccoz P, Parma J, Vassart G, Refetoff S. Resistance to thyrotropin (TSH) in three families is not associated with mutations in the TSH receptor or TSH. J Clin Endocrinol Metab. 1997;82:3933–40.

    CAS  Google Scholar 

  • Yang H, Chen H, Guo H, Li W, Tang J, Xu B, et al. Molecular mechanisms of 2, 3′, 4, 4′, 5-pentachlorobiphenyl-induced thyroid dysfunction in FRTL-5 cells. PLoS One. 2015;10:e0120133. https://doi.org/10.1371/journal.pone.0120133.eCollection2015.

  • Zani C, Magoni M, Speziani F, Leonardi L, Orizio G, Scarcella C, Gaia A, Donato F. Polychlorinated biphenyl serum levels, thyroid hormones and endocrine and metabolic diseases in people living in a highly polluted area in north Italy: a population-based study. Heliyon. 2019;5:e01870. https://doi.org/10.1016/j.heliyon.2019.e01870. eCollection 2019.

    Article  Google Scholar 

  • Zhang S, Guo X, Lu S, Sang N, Li G, Xie P, Liu C, Zhang L, Xing Y. Exposure to PFDoA causes disruption of the hypothalamus-pituitary-thyroid axis in zebrafish larvae. Environ Pollut. 2018;235:974–82.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Evgenideion Hospital, Unit of Endocrinology, Diabetes and Metabolism, University of Athens, Athens, Greece

    Leonidas H. Duntas

Authors
  1. Leonidas H. Duntas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leonidas H. Duntas .

Editor information

Editors and Affiliations

  1. Endocrinology and Metabolism Dept., University of Naples Federico II, NAPOLI, Napoli, Italy

    Rosario Pivonello

  2. Endocrinology and Diabetes Department, National and Kapodistrian University of, Athens, Greece

    Evanthia Diamanti-Kandarakis

Rights and permissions

Reprints and permissions

Copyright information

© 2023 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Duntas, L.H. (2023). Environmental Endocrinology and the Hypothalamus-Pituitary-Thyroid Axis. In: Pivonello, R., Diamanti-Kandarakis, E. (eds) Environmental Endocrinology and Endocrine Disruptors. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-030-38366-4_3-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-38366-4_3-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-38366-4

  • Online ISBN: 978-3-030-38366-4

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation