Сephalgia and hypothyroidism
DOI: 10.32364/2587-6821-2023-7-10-4
E.V. Parkhomenko1, E.V. Ekusheva2,3, S.I. Kulikova 1
1Altai State Medical University, Barnaul, Russian Federation
2Academy of Postgraduate Education of the Federal Scientific and Clinical Center of the Federal Medical Biological Agency of Russian Federation, Moscow, Russian Federation
3Belgorod State University, Belgorod, Russian Federation
Hypothyroidism is usually manifested by a wide range of symptoms from various body systems, including the nervous system. It was found that approximately 30% of patients with decreased thyroid function suffer from cephalgia, which is associated with a thyroid hormone deficiency. Both primary and secondary hypothyroidism can not only lead to secondary cephalgia but also aggravate pre-existing primary cephalgia, most commonly migraine. It is known that cephalgia is more common in women, especially if there is a history of migraine. In everyday clinical practice, cephalgia associated with hypothyroidism is rarely diagnosed as an independent form of secondary cephalgia. More commonly, primary cephalgia, such as migraine and tension headache, are regarded as concomitant diseases in patients with decreased thyroid function. To date, data on the association between hypothyroidism and migraine, as well as hypothyroidism and tension headache are contradictory and it is not always possible to determine which process is primary or secondary. The pathophysiological basis explaining the association between hypothyroidism and cephalgia/migraine has not yet been studied.
Keywords: hypothyroidism, cephalgia, migraine, tension headache, thyroid-stimulating hormone, hypothalamus, levothyroxine, Hashimoto's thyroiditis, Hashimoto's encephalopathy, preventive migraine treatment.
For citation: Parkhomenko E.V., Ekusheva E.V., Kulikova S.I. Сephalgia and hypothyroidism. Russian Medical Inquiry. 2023;7(10):630–634 (in Russ.). DOI: 10.32364/2587-6821-2023-7-10-4.
About the authors:
Ekaterina V. Parkhomenko — C. Sc. (Med.), Associate Professor of the Department of Neurology and Neurosurgery with the course of Continuing Professional Education, Altai State Medical University; 40, Lenin Ave, Moscow, 656038, Russian Federation; ORCID iD 0000-0003-0489-9845.
Evgenia V. Ekusheva — Dr. Sc. (Med.), Professor, Head of the Department of Nervous Diseases and Neurological Rehabilitation, Academy of Postgraduate Education of the Federal Scientific and Clinical Center of the Federal Medical Biological Agency of Russian Federation; 91, Volokolamskoe road, 125371, Moscow, Russian Federation; Senior Researcher of the Laboratory "Problemy Stareniya" (Aging Problems), Belgorod State University; 85, Pobedy Str., Belgorod, 308015, Russian Federation; ORCID iD 0000-0002-3638-6094.
Svetlana I. Kulikova — Assistant Professor of the Department of Propaedeutics of Internal Diseases named after prof. Z.S. Barkagan, Altai State Medical University; 40, Lenin Ave, Moscow, 656038, Russian Federation; ORCID iD 0000-0002-3232-8540.
Contact information: Ekaterina V. Parkhomenko, e-mail: parekva@mail.ru.
Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.
There is no conflict of interest.
Received 12.08.2023.
Revised 05.09.2023.
Accepted 28.08.2023.
2. Jonklaas J., Bianco A.C., Bauer A.J. et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670–1751. DOI: 10.1089/thy.2014.0028.
3. Cooper D.S., Biondi B. Subclinical thyroid disease. Lancet. 2012;379(9821):1142–1154. DOI: 10.1016/S0140-6736(11)60276-6.
4. Jurado-Flores M., Warda F., Mooradian A. Pathophysiology and Clinical Features of Neuropsychiatric Manifestations of Thyroid Disease. J Endocr Soc. 2022;6(2):bvab194. DOI: 10.1210/jendso/bvab194.
5. Вербовой А.Ф., Долгих Ю.А., Вербовая Н.И. Гипотиреоз — междисциплинарная проблема. РМЖ. Медицинское обозрение. 2022;6(9):509–515. DOI: 10.32364/2587-6821-2022-6-9-509-515. [Verbovoy A.F., Dolgikh Yu.A., Verbovaya N.I. Hypothyroidism is an interdisciplinary problem. Russian Medical Inquiry. 2022;6(9):509–515 (in Russ.)]. DOI: 10.32364/2587-6821-2022-6-9-509-515.
6. Carlé A., Pedersen I.B., Knudsen N. et al. Hypothyroid symptoms and the likelihood of overt thyroid failure: a population-based case-control study. Eur J Endocrinol. 2014;171(5):593–602. DOI: 10.1530/EJE-14-0481.
7. Fenichel N.M. Chronic headache due to masked hypothyroidism. Ann Intern Med. 1948;29(3):456–460. DOI: 10.7326/0003-4819-29-3-456.
8. Jones A.C.Jr. Hypothyroidism as a cause of headache. AMA Arch Otola-ryngol. 1955;62(6):583–585. DOI: 10.1001/archotol.1955.03830060015004.
9. Spanou I., Bougea A., Liakakis G. et al. Relationship of Migraine and Tension-Type Headache With Hypothyroidism: A Literature Review. Headache. 2019;59(8):1174–1186. DOI: 10.1111/head.13600.
10. Moreau T., Manceau E., Giroud-Baleydier F. et al. Headache in hypothyroidism. Prevalence and outcome under thyroid hormone therapy. Cephalalgia. 1998;18(10):687–689. DOI: 10.1046/j.1468-2982.1998.1810687.x.
11. Lima M.F., Vilar L., Carvalho A.H.F. et al. Headache attributed to hypothyroidism. Headache Medicine. 2010;1:41–45.
12. Caponnetto V., Deodato M., Robotti M. et al. Comorbidities of primary headache disorders: a literature review with meta-analysis. J Headache Pain. 2021;22(1):71. DOI: 10.1186/s10194-021-01281-z.
13. Spanou I., Christidi F., Liakakis G. et al. Primary headache subtypes and thyroid dysfunction: Is there any association? Arq Neuropsiquiatr. 2020;78(11):695–699. DOI: 10.1590/0004-282X20200070.
14. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211. DOI: 10.1177/0333102417738202.
15. Lima Carvalho M.F., de Medeiros J.S., Valença M.M. Headache in recent onset hypothyroidism: Prevalence, characteristics and outcome after treatment with levothyroxine. Cephalalgia. 2017;37(10):938–946. DOI: 10.1177/0333102416658714.
16. Lisotto C., Mainardi F., Maggioni F. et al. The comorbidity between migraine and hypothyroidism. J Headache Pain. 2013;14:2377. DOI: 10.1186/1129-2377-14-s1-p138.
17. Tietjen G.E., Herial N.A., Hardgrove J. et al. Migraine comorbidity constellations. Headache. 2007;47(6):857–865. DOI: 10.1111/j.1526-4610.2007.00814.x.
18. Martin A.T., Pinney S.M., Xie C. et al. Headache Disorders May Be a Risk Factor for the Development of New Onset Hypothyroidism. Headache. 2017;57(1):21–30. DOI: 10.1111/head.12943.
19. Bigal M.E., Sheftell F.D., Rapoport A.M. et al. Chronic daily headache: identification of factors associated with induction and transformation. Headache. 2002:42(7):575–581. DOI: 10.1046/j.1526-4610.2002.02143.
20. Mirouliaei M., Fallah R., Bashardoost N. et al. Efficacy of levothyroxine in migraine headaches in children with subclinical hypothyroidism. Iran J Child Neurol. 2012;6(4):23–26. PMID: 24665276.
21. Khan H.B., Shah P.A., Bhat M.H. et al. Association of hypothyroidism in patients with migraine and tension-type headache disorders in Kashmir, North India. Neurology Asia. 2015;20(3):257–261.
22. Rubino E., Rainero I., Garino F. et al. Subclinical hypothyroidism is associated with migraine: A case-control study. Cephalalgia. 2019;39(1):15–20. DOI: 10.1177/0333102418769917.
23. Tasnim S., Nyholt D.R. Migraine and thyroid dysfunction: Co-occurrence, shared genes and biological mechanisms. Eur J Neurol. 2023;30(6):1815–1827. DOI: 10.1111/ene.15753.
24. Tasnim S., Wilson S.G., Walsh J.P. et al. Cross-Trait Genetic Analyses Indicate Pleiotropy and Complex Causal Relationships between Headache and Thyroid Function Traits. Genes (Basel). 2022;21;14(1):16. DOI: 10.3390/genes14010016.
25. Balcziak L.K., Russo A.F. Dural immune cells, CGRP, and migraine. Front Neurol. 2022;13:874193. DOI: 10.3389/fneur.2022.874193.
26. Wenzek C., Boelen A., Westendorf A.M. et al. The interplay of thyroid hormones and the immune system — where we stand and why we need to know about it. Eur J Endocrinol. 2022;186(5):R65–R77. DOI: 10.1530/EJE-21-1171.
27. May A., Burstein R. Hypothalamic regulation of headache and migraine. Cephalalgia. 2019;39(13):1710–1719. DOI: 10.1177/0333102419867280.
28. Greer J.M., Broadley S., Pender M.P. Reactivity to novel autoantigens in patients with coexisting central nervous system demyelinating disease and autoimmune thyroid disease. Front Immunol. 2017;8:514. DOI: 10.3389/fimmu.2017.00514.
29. Jacqies-Jean B., Demesster-Mirkine N., Borkowski A. et аl. Calcitonin deficiency in primary hypothyroidism. J Clin Endocrinol Metab. 1986;62(4):700–703. DOI: 10.1210/jcem-62-4-700.
30. Hargreaves R., Olesen J. Calcitonin gene-related peptide modulators — the history and renaissance of a new migraine drug class. Headache. 2019;59(6):951–970. DOI: 10.1111/head.13510.
31. Filipchuk M., Gassmann J., Castro Zamparella T. et al. High rates of (treated) hypothyroidism among chronic migraine patients consulting a specialized headache clinic: are we missing something? Neurol Sci. 2022;43(2):1249–1254. DOI: 10.1007/s10072-021-05424-7.
32. Sharma L.K., Sharma N., Gadpayle A.K. et al. Prevalence and predictors of hyperprolactinemia in subclinical hypothyroidism. Eur J Intern Med. 2016:35:106–110. DOI: 10.1016/j.ejim.2016.07.012.
33. Al-Karagholi M.A., Kalatharan V., Ghanizada H. et al. Prolactin in headache and migraine: A systematic review of clinical studies. Cephalalgia. 2023;43(2):3331024221136286. DOI: 10.1177/03331024221136286.
34. Cavestro C., Rosatello A., Marino M.P. et al. High prolactin levels as a worsening factor for migraine. J Headache Pain. 2006;7:83–89. DOI: 10.1007/s10194-006-0272-8.
35. Szewczyk A.K., Ulutas S., Aktürk T. et al. European Headache Federation School of Advanced Studies (EHF-SAS). Prolactin and oxytocin: potential targets for migraine treatment. J Headache Pain. 2023;27;24(1):31. DOI: 10.1186/s10194-023-01557-6.
36. Avona A., Mason B.N., Burgos-Vega C. et al. Meningeal CGRP-Prolactin Interaction Evokes Female-Specific Migraine Behavior. Ann Neurol. 2021;89:1129–1144. DOI: 10.1002/ana.26070.
37. Diogenes A., Patwardhan A.M., Jeske N.A. et al. Prolactin modulates TRPV1 in female rat trigeminal sensory neurons. J Neurosci. 2006;26(31):8126–8136. DOI: 10.1523/JNEUROSCI.0793-06.2006.
38. Kallestrup M-M., Kasch H., Østerby T. et al. Prolactinoma-associated headache and dopamine agonist treatment. Cephalalgia. 2014;34:493–502. DOI: 10.1177/0333102413515343.
39. Bussone G., Usai S., Moschiano F. How to investigate and treat: headache and hyperprolactinemia. Curr Pain Headache Rep. 2012;16:365–370. DOI: 10.1007/s11916-012-0267-x.
40. Müller E.E., Locatelli V., Cella S. et al. Prolactin-lowering and -releasing drugs mechanisms of action and therapeutic applications. Drugs. 1983;25:399–432. DOI: 10.2165/00003495-198325040-00004.
41. Weetman A.P. An update on the pathogenesis of Hashimoto's thyroiditis. J Endocrinol Invest. 2021;44:883–890. DOI: 10.1007/s40618-020-01477-1.
42. Ragusa F., Fallahi P., Elia G. et al. Hashimotos' thyroiditis: Epidemiology, pathogenesis, clinic and therapy. Best Pract Res Clin Endocrinol Metab. 2019;33:101367. DOI: 10.1016/j.beem.2019.101367.
43. Huete A.J., Sanchez-Del-Rio M., Franch O. Hashimoto's encephalopathy mimicking migraine with aura. Headache. 2007;47(1):130–131. DOI: 10.1111/j.1526-4610.2006.00660.
44. Jacome D. New Daily Persistent Headache As A Presenting Symptom Of Hashimoto's Encephalopathy. WebmedCentral NEUROLOGY. 2010;1(10):WMC00960. DOI: 10.9754/journal.wmc.2010.00960.
45. Chaudhuri A., Behan P.O. The clinical spectrum, diagnosis, pathogenesis and treatment of Hashimoto's encephalopathy (recurrent acute disseminated encephalomyelitis). Curr Med Chem. 2003;10(19):1945–1953. DOI: 10.2174/0929867033456945.
46. Castillo P., Woodruff B., Caselli R. et al. Steroid-responsive encephalopathy associated with autoimmune thyroiditis. Arch Neurol. 2006;63(2):197–202. DOI: 10.1001/archneur.63.2.197.
47. Chaudhuri J., Mukherjee A., Chakravarty A. Hashimoto's Encephalopathy: Case Series and Literature Review. Curr Neurol Neurosci Rep. 2023;23(4):167–175. DOI: 10.1007/s11910-023-01255-5.
48. Mocellin R., Walterfang M., Velakoulis D. Hashimoto's encephalopathy: Epidemiology, pathogenesis and management. CNS Drugs. 2007;21:799–811. DOI: 10.2165/00023210-200721100-00002.

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