Treatment refractory hypothyroidism

Versions

PDF (Español (España))
Texto (Español (España))

Keywords

Hipotiroidismo
levotiroxina
malabsorción
hipotiroidismo refractario
refractario
LT4
hormona tiroidea Hypothiroidism
levothyroxine
refractory
malabsorption
LT4

How to Cite

Pantoja-Rosero, M. E., Lara-Viáfara, M. F., & Builes-Barrera, C. A. (2023). Treatment refractory hypothyroidism. Interdisciplinary Journal of Epidemiology and Public Health, 5(2), e–9905. https://doi.org/10.18041/2665-427X/ijeph.2.9905 (Original work published December 30, 2022)

Abstract

Introduction: Refractory hypothyroidism is an entity in which patients require high doses of thyroid hormone, persisting with symptoms of hypothyroidism and high thyroid stimulating hormone (TSH) levels, representing a challenge for the clinician. Understanding its causes allows a better diagnostic approach and avoids overdosage and adverse effects. 

Objective: To present key concepts to help identify the causes of refractoriness to treatment, including adherence, malabsorption, or increased thyroid hormone demand. 

Methods: A search of the main concepts about the causes, diagnosis and treatment of refractory hypothyroidism was performed, according to the review presented at the congress of the Colombian Association of Internal Medicine (ACMI) on May 13 and 14, 2022.

Results: Persistent TSH elevation in patients receiving thyroid hormone supplementation may be present in up to 30% of patients with hypothyroidism. The most frequent cause is poor adherence to treatment, followed by malabsorption and increased demand for the drug. The diagnostic approach should be sequential to find the cause, in some performing specialized studies to rule out malabsorption.

Conclusions: Identifying the causes of refractory hypothyroidism to treatment are key to have an adequate symptomatic and clinical control of the pathology, and likewise avoid the use of supratherapeutic doses of levothyroxine, since it is related to major adverse effects at cardiovascular and bone level.

https://doi.org/10.18041/2665-427X/ijeph.2.9905
PDF (Español (España))
Texto (Español (España))

References

Bekkering GE, Agoritsas T, Lytvyn L, Heen AF, Feller M, Moutzouri E,et al. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019; 365: l2006. Doi: 10.1136/bmj.l2006.

Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Internal Med. 2000; 160(4): 526-534. Doi: 10.1001/archinte.160.4.526.

Surks MI, Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metabolism. 2007; 92(12): 4575-4582. Doi: 10.1210/jc.2007-1499.

Centanni M, Benvenga S, Sachmechi I. Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report. J Endocrinol Invest. 2017; 40(12): 1289-301. Doi: 10.1007/s40618-017-0706-y

Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016; 26(1): 1-133. Doi: 10.1089/thy.2015.0020

Vaisman F, Coeli CM, Ward LS, Graf H, Carvalho G, Montenegro R, et al. How good is the levothyroxine replacement in primary hypothyroidism patients in Brazil? Data of a multicentre study. J Endocrinol Investigat. 2013; 36(7): 485-488. Doi: 10.3275/8810

Eligar V, Taylor P, Okosieme O, Leese G, Dayan C. Thyroxine replacement: a clinical endocrinologist’s viewpoint. Ann Clin Biochem Int J Lab Med. 2016; 53(4): 421-33. Doi: 10.1177/0004563216642255

Virili C, Antonelli A, Santaguida MG, Benvenga S, Centanni M. Gastrointestinal malabsorption of thyroxine. Endocr Rev. 2019; 40(1): 118-36. Doi: 10.1210/er.2018-00168

Robertson HMA, Narayanaswamy AKP, Pereira O, Copland SA, Herriot R, Mckinlay AW, et al. Factors contributing to high levothyroxine doses in primary hypothyroidism: An interventional audit of a large community database. Thyroid. 2014; 24(12): 1765-71. Doi: 10.1089/thy.2013.0661

Wenzel KW, Kirschsieper HE. Aspects of the absorption of oral L-thyroxine in normal man. Metabolism. 1977; 26(1): 1-8.

Ala S, Akha O, Kashi Z, Bahar A, Askari Rad H, Sasanpour N, et al. Changes in serum TSH and T4 levels after switching the levothyroxine administration time from before breakfast to before dinner. Int J Endocrinol. 2015; 2015: 1-5. doi: 10.1155/2015/156375

Jabbar A, Yawar A, Waseem S, Wasim S, Islam N, Haque NUl, et al. Vitamin B12 deficiency common in primary hypothyroidism. J Pak Med Assoc. 2008; 58(5): 258-61.

Benvenga S, Di Bari F, Vita R. Undertreated hypothyroidism due to calcium or iron supplementation corrected by oral liquid levothyroxine. Endocrin. 2017; 56(1): 138-45. doi: 10.1007/s12020-017-1244-2

Hennessey J V, Malabanan AO, Haugen BR, Levy EG. Adverse event reporting in patients treated with levothyroxine: Results of the Pharmacovigilance Task Force Survey of the American Thyroid Association, American Association of Clinical Endocrinologists, and The Endocrine Society. Endocr Pract. 2010; 16(3): 357-70. doi: 10.4158/EP0362.OR

Zubarik R, Ganguly E, Nathan M, Vecchio J. Celiac disease detection in hypothyroid patients requiring elevated thyroid supplementation: A prospective cohort study. Eur J Intern Med. 2015; 26(10): 825-9. Doi: 10.1016/j.ejim.2015.09.011

Kadiyala R, Peter R, Okosieme OE. Thyroid dysfunction in patients with diabetes: clinical implications and screening strategies. Int J Clin Pract. 2010; 64(8): 1130-9. doi: 10.1111/j.1742-1241.2010.02376.x.

Benvenga S, Vita R, Di Bari F, Fallahi P, Antonelli A. Do not forget nephrotic syndrome as a cause of increased requirement of Levothyroxine replacement therapy. Eur Thyroid J. 2015; 4(2): 138-42. Doi: 10.1159/000381310

Jubiz W, Ramirez M. Effect of vitamin C on the absorption of levothyroxine in patients with hypothyroidism and gastritis. J Clin Endocrinol Metab. 2014; 99(6): E1031-4. doi: 10.1210/jc.2013-4360.

Gonzales KM, Stan MN, Morris JC, Bernet V, Castro MR. The Levothyroxine absorption test: a four-year experience (2015-2018) at the Mayo Clinic. Thyroid. 2019; 29(12): 1734-42. doi: 10.1089/thy.2019.0256.

Yildirim SI, Soyaltin UE, Ozgen AG. Levothyroxine absorption test results in patients with TSH elevation resistant to treatment. Endocrine. 2019; 64(1): 118-21.

Bornschein A, Paz-Filho G, Graf H, de Carvalho GA. Treating primary hypothyroidism with weekly doses of levothyroxine: a randomized, single-blind, crossover study. Arq Bras Endocrinol Metabol. 2012; 56(4): 250-8. Doi: 10.1590/S0004-27302012000400006

Jauk B, Mikosch P, Gallowitsch HJ, Kresnik E, Molnar M, Gomez I, et al. Unusual Malabsorption of Levothyroxine. Thyroid. 2000; 10(1): 93-5. Doi: 10.1089/thy.2000.10.93

Flynn RW, Bonellie SR, Jung RT, MacDonald TM, Morris AD, Leese GP. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab. 2010; 95(1): 186-93. doi: 10.1210/jc.2009-1625.

Turner MR, Camacho X, Fischer HD, Austin PC, Anderson GM, Rochon PA, et al. Levothyroxine dose and risk of fractures in older adults: nested case-control study. BMJ. 2011; 342(7805): d2238. doi: 10.1136/bmj.d2238.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Copyright (c) 2022 Interdisciplinary Journal of Epidemiology and Public Health

Downloads

Download data is not yet available.