Skip to main content

Advertisement

Log in

Cognitive functioning and quality of life in patients with Hashimoto thyroiditis on long-term levothyroxine replacement

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Objective

Intrinsic imperfections of thyroid hormone replacement therapy may affect long-term general well-being. In patients with Hashimoto thyroiditis (HT), cognitive functioning may be affected via altered thyroid hormones action as well as by the autoimmune process. The aim of this study was to evaluate cognitive function and quality of life (QoL) in patients on long-term levothyroxine replacement for HT in relation to thyroid function tests and TPO (thyroid-peroxidase) antibody (TPOAb) status.

Design

Retrospective cross-sectional study.

Patients and measurements

One-hundred-and thirty patients with HT on long-term levothyroxine replacement and 111 euthyroid control subjects. Both groups were divided into two age subgroups, 20–49 years (N = 59 vs N = 79) and > 50 years (N = 71 vs N = 32). Evaluation included biochemical and neuropsychological tests, evaluating attention, global cognitive status, verbal and working memory, executive function, depression and anxiety, and quality of life. We used ANOVA and partial correlations to test for significant associations.

Results

FT4 (free-thyroxine), FT3 (free-triiodothyronine) levels and FT3/FT4 ratio were not different between patients and controls. Mean TSH (thyroid-stimulating hormone) was normal in all subjects but significantly higher in the patients (20–49 yrs:3.64 ± 2.74 vs 1.93 ± 1.10, >50 yrs:3.93 ± 2.84 vs 1.91 ± 0.90). Antibodies (TgAb,TPOAb) were higher in patients. Global cognitive function (MMSE-Mini mental state examination), conceptual tracking (TMT-Trail Making Test:A/B), verbal divergent thinking (like Phonemic fluency test), and anxiety and depression scores were significantly worse in patients vs controls. QoL was impaired in patients. there was a significant negative correlation between antibodies (TPOAb, TgAb) and quality in life (total SF36 score).

Conclusion

Patients on long-term levothyroxine replacement show persistent impairments in both cognitive functioning and general well-being.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. J.A. Romijn, J.W.A. Smit, S.W.J. Lamberts, Intrinsic imperfections of endocrine replacement therapy. Eur. J. Endocrinol. 149, 91–97 (2003)

    Article  CAS  PubMed  Google Scholar 

  2. M. Ritchie, B.B. Yeap, Thyroid hormone: influences on mood and cognition in adults. Maturitas 81, 266–275 (2015)

    Article  CAS  PubMed  Google Scholar 

  3. T. Leyhe, K. Müssig, Cognitive and affective dysfunctions in autoimmune thyroiditis. Brain Behav. Immun. 41, 261–266 (2014)

    Article  CAS  PubMed  Google Scholar 

  4. J. Parle, L. Roberts, S. Wilson et al. Randomized controlled trial of the effect of thyroxine replacement on cognitive function in community-living elderly subjects with subclinical hypothyroidism: The Birmingham Elderly thyroid study. J. Clin. Endocrinol. Metab. 95, 3623–3632 (2010)

    Article  CAS  PubMed  Google Scholar 

  5. A.E. Budson, B.H. Price, Memory Dysfunction. N. Engl. J. Med. 352, 692–699 (2005)

    Article  CAS  PubMed  Google Scholar 

  6. M. Bauer, T. Goetz, T. Glenn, P.C. Whybrow, The thyroid-brain interaction in thyroid disorders and mood disorders. J. Neuroendocrinol. 20, 1101–1114 (2008)

    Article  CAS  PubMed  Google Scholar 

  7. S. Volpato, J.M. Guralnik, L.P. Fried, A.T. Remaley, A.R. Cappola, L.J. Launer, Serum thyroxine level and cognitive decline in euthyroid older women. Neurology 58, 1055–1061 (2002)

    Article  CAS  PubMed  Google Scholar 

  8. N. Correia, S. Mullally, G. Cooke et al. Evidence for a specific defect in hippocampal memory in overt and subclinical hypothyroidism. J. Clin. Endocrinol. Metab. 94, 3789–3797 (2009)

    Article  CAS  PubMed  Google Scholar 

  9. E.M. Wekking, B.C. Appelhof, E. Fliers et al. Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism. Eur. J. Endocrinol. 153, 747–753 (2005)

    Article  CAS  PubMed  Google Scholar 

  10. M.H. Samuels, K.G. Schuff, N.E. Carlson, P. Carello, J.S. Janowsky, Health status, psychological symptoms, mood, and cognition in L-thyroxine-treated hypothyroid subjects. Thyroid 17, 249–258 (2007)

    Article  CAS  PubMed  Google Scholar 

  11. V. Giannouli, K. Toulis, N. Syrmos, Cognitive function in Hashimoto’s thyroiditis under levothyroxine treatment. Hormones 13(3), 430–433 (2014)

    Article  PubMed  Google Scholar 

  12. V. Giannouli, N. Syrmos, A 2-year preliminary longitudinal study of neuropsychological functioning in Hashimoto’s thyroiditis under levothyroxine treatment: only Trail Making Test is making a difference. Probl. Psychol. 21st Century 11(1), 15–21 (2017)

    Google Scholar 

  13. K. Müssig, A. Künle, A.L. Säuberlich et al. Thyroid peroxidase antibody positivity is associated with symptomatic distress in patients with Hashimoto’s thyroiditis. Brain Behav. Immun. 26, 559–563 (2012)

    Article  CAS  PubMed  Google Scholar 

  14. G.P. Bianchi, V. Zaccheroni, E. Solaroli et al. Health-related quality of life in patients with thyroid disorders. Qual. Life Res. 13, 45–54 (2004)

    Article  CAS  PubMed  Google Scholar 

  15. J. Ott, R. Promberger, F. Kober et al. Hashimoto’s thyroiditis affects symptom load and quality of life unrelated to hypothyroidism: a prospective case-control study in women undergoing thyroidectomy for benign goiter. Thyroid 21, 161–167 (2011)

    Article  PubMed  Google Scholar 

  16. A. Engum, T. Bjoro, A. Mykletun, A.A. Dahl, Thyroid autoimmunity, depression and anxiety; are there any connections? An epidemiological study of a large population. J. Psychosom. Res. 59, 263–268 (2005)

    Article  PubMed  Google Scholar 

  17. M. Kaya, T.F. Cermik, D. Bedel, Y. Kutucu, C. Tuglu, O.N. Yigitbasi, Assessment of alterations in regional cerebral blood flow in patients with hypothyroidism due to Hashimoto’s thyroiditis. J. Endocrinol. Invest. 30, 491–496 (2007)

    Article  CAS  PubMed  Google Scholar 

  18. M. Piga, A. Serra, L. Deiana et al. Brain perfusion abnormalities in patients with euthyroid autoimmune thyroiditis. Eur. J. Nucl. Med. Mol. Imaging 31, 1639–1644 (2004)

    Article  CAS  PubMed  Google Scholar 

  19. P. Forti, V. Olivelli, E. Rietti et al. Serum thyroid-stimulating hormone as a predictor of cognitive impairment in an elderly cohort. Gerontology 58, 41–49 (2012)

    Article  CAS  PubMed  Google Scholar 

  20. S. Pearce, G. Brabant, L. Duntas et al. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur. Thyroid J. 2, 215–228 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. M.D. Pavlovic. Diagnostic tests in Neuropsychology. (Kaligraf, Belgrade, 2003). in Serbian

    Google Scholar 

  22. D. Wechsler. WAIS-R. Wechsler Adult Intelligence Scale-Revised. Manual. (Psychological Corporation, San Antonio, 1981)

    Google Scholar 

  23. I. Bjelland, A.A. Dahl, T.T. Haug, D. Neckelmann, The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J. Psychosom. Res. 52, 69–77 (2002)

    Article  PubMed  Google Scholar 

  24. J. Ware, K. Snow, M. Kosinski, B. Gandek. SF-36 Health Survey: Manual and Interpretation Guide. (The Health Institute, Boston), 1993)

    Google Scholar 

  25. H.J. Wouters, H.C. van Loon, M.M. van der Klauw et al. No effect of the Thr92Ala polymorphism of deiodinase-2 on thyroid hormone parameters, health-related quality of life, and cognitive functioning in a large population-based cohort study. Thyroid 27(2), 147–155 (2017)

    Article  CAS  PubMed  Google Scholar 

  26. A.K. Parsaik, B. Singh, R. Roberts et al. Hypothyroidism and risk of mild cognitive impairment in elderly persons – a population based study. JAMA Neurol. 71(2), 201–207 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  27. H.F. Escobar-Morreale, J.I. Botella-Carretero, F. Escobar del Rey, Morreale de Escobar, G. Review: treatment of hypothyroidism with combinations of levothyroxine plus liothyronine. J. Clin. Endocrinol. Metab. 90, 4946–4954 (2005)

    Article  CAS  PubMed  Google Scholar 

  28. J. Jonklaas, B. Davidson, S. Bhagat, S. Soldin, Triiodothyronine levels in athyreotic individuals during levothyroxine therapy. JAMA 299(7), 769–777 (2008)

    Article  CAS  PubMed  Google Scholar 

  29. M. Zarković, J. Cirić, B. Beleslin et al. Further studies on delineating thyroid-stimulating hormone (TSH) reference range. Horm. Metab. Res. 43, 970–976 (2011). Serbian Thyroid Study Group

    Article  CAS  PubMed  Google Scholar 

  30. E.L. Constant, S. Adam, X. Seron, R. Bruyer, A. Seghers, C. Daumerie, Anxiety and depression, attention and executive functions in hypothyroidism. J. Int. Neuropsychol. Soc. 11, 535–544 (2005)

    Article  CAS  PubMed  Google Scholar 

  31. J.D. Davis, G. Tremont, Neuropsychiatric aspects of hypothyroidism and treatment reversibility. Minerva Endocrinol. 32, 49–65 (2007)

    CAS  PubMed  Google Scholar 

  32. F.V. Schraml, P.W. Goslar, L. Baxter, L.L. Beason-Held, Thyroid stimulating hormone and cognition during severe, transient hypothyroidism. Neuro. Endocrinol. Lett. 32, 279–285 (2011)

    CAS  PubMed  PubMed Central  Google Scholar 

  33. F.V. Schraml, L.L. Beason-Held, Technetium-99m Ethyl Cysteinate Dimer (ECD) cerebral accumulation and symptom and sign severity during hypothyroidism. Neuro. Endocrinol. Lett. 31, 161–167 (2010)

    CAS  PubMed  PubMed Central  Google Scholar 

  34. J.W. Smith, A.T. Evans, B. Costall, J.W. Smythe, Thyroid hormones, brain function and cognition: a brief review. Neurosci. Biobehav. Rev. 26, 45–60 (2002)

    Article  CAS  PubMed  Google Scholar 

  35. K.J. Miller, T.D. Parsons, P.C. Whybrow et al. Memory improvement with treatment of hypothyroidism. Int. J. Neurosci. 116, 895–906 (2006)

    Article  CAS  PubMed  Google Scholar 

  36. V. Panicker, P. Saravanan, B. Vaidya et al. Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. J. Clin. Endocrinol. Metab. 94, 1623–1629 (2009)

    Article  CAS  PubMed  Google Scholar 

  37. W.M. van der Deure, B.C. Appelhof, R.P. Peeters et al. Polymorphisms in the brain-specific thyroid hormone transporter OATP1C1 are associated with fatigue and depression in hypothyroid patients. Clin. Endocrinol. 69, 804–811 (2008)

    Article  CAS  Google Scholar 

  38. M.G. Castagna, M. Dentice, S. Cantara et al. DIO2 Thr92Ala reduces deiodinase-2 activity and serum-T3 levels in thyroid-deficient patients. J. Clin. Endocrinol. Metab. 102(5), 1623–1630 (2017)

    Article  PubMed  Google Scholar 

  39. M.H. Samuels, Cognitive Function in Subclinical Hypothyroidism. J. Clin. Endocrinol. Metab. 95, 3611–3613 (2010)

    Article  CAS  PubMed  Google Scholar 

  40. R.T. De Jongh, P. Lips, N.M. van Schoor et al. Endogenous subclinical thyroid disorders, physical and cognitive function, depression, and mortality in older individuals. Eur. J. Endocrinol. 165, 545–554 (2011)

    Article  CAS  PubMed  Google Scholar 

  41. M.H. Samuels, K.G. Schuff, N.E. Carlson, P. Carello, J.S. Janowsky, Health status, mood, and cognition in experimentally induced subclinical hypothyroidism. J. Clin. Endocrinol. Metab. 92, 2545–2551 (2007)

    Article  CAS  PubMed  Google Scholar 

  42. D.J. Stott, N. Rodondi, P.M. Kearney et al. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N. Engl. J. Med. 376(26), 2534–2544 (2017)

    Article  CAS  PubMed  Google Scholar 

  43. R. Peeters, Subclinical hypothyroidism. N. Engl. J. Med. 376, 2556–2565 (2017)

    Article  PubMed  Google Scholar 

  44. M. Pandrc, A. Ristic, V. Kostovski et al. The effect of early substitution on subclinical hypothyroidism on biochemical blood parameters and the quality of life. J. Med. Biochem. 36, 127–136 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  45. K.H. Winther, P. Cramon, T. Watt et al. Disease-specific as well as generic quality of life is widely impacted in autoimmune hypothyroidism and improves during the first six months of levothyroxine therapy. PLoS ONE 11(6), 1–12 (2016)

    Article  CAS  Google Scholar 

  46. J. Jonklaas, Persistent hypothyroid symptoms in a patient with a normal thyroid stimulating hormone level. Curr. Opin. Endocrinol. Diabetes Obes. 24, 356–363 (2017)

    Article  CAS  Google Scholar 

  47. N. Kelderman-Bolk, T.J. Visser, J.P. Tijssen, A. Berghout, Quality of life in patients with primary hypothyroidism related to BMI. Eur. J. Endocrinol. 173, 507–515 (2015)

    Article  CAS  PubMed  Google Scholar 

  48. P.R. Deshpande, S. Rajan, B.L. Sudeepthi, C.P. Abdul Nazir, Patient-reported outcomes: a new era in clinical research. Perspect. Clin. Res. 2, 137–144 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  49. L.A. Burmeister, M. Ganguli, H.H. Dodge, T. Toczek, S.T. DeKosty, R.D. Nebes, Hypothyroidism and cognition: preliminary evidence for specific defect in memory. Thyroid 11, 1177–1185 (2001)

    Article  CAS  PubMed  Google Scholar 

  50. P. Saravanan, W.F. Chau, N. Roberts, K. Vedhara, R. Greenwood, C.M. Dayan, Psychological well-being in patients on ‘adequate’ doses of L-thyroxine: results of a large, controlled community-based questionnaire study. Clin. Endocrinol. 57, 577–585 (2002)

    Article  CAS  Google Scholar 

  51. H.A. Uysal, M. Ayhan, Autoimmunity affects health-related quality of life in patients with Hashimoto’s thyroiditis. Kaohsiung J. Med. Sci. 32, 427–433 (2016)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marina Djurovic.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Djurovic, M., Pereira, A.M., Smit, J.W.A. et al. Cognitive functioning and quality of life in patients with Hashimoto thyroiditis on long-term levothyroxine replacement. Endocrine 62, 136–143 (2018). https://doi.org/10.1007/s12020-018-1649-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-018-1649-6

Keywords

Navigation