Editing Hashimoto's thyroiditis (section)

===Managing hormone levels===
{| class="wikitable floatright"
|+Hormone Terminology
!
!Endogenous
!Synthetic
|-
!'''T<sub>3</sub>'''
|Tri-iodothyronine
|Liothyronine
|-
!'''T<sub>4</sub>'''
|Thyroxine
|Levothyroxine
|}
[[Hypothyroidism]] caused by Hashimoto's thyroiditis is treated with thyroid hormone replacement agents such as [[levothyroxine]] (LT<sub>4</sub>),<ref name=":6" /> [[liothyronine]] (LT<sub>3</sub>),<ref name="Ramos-Levi2023" /> or [[desiccated thyroid extract]] (T<sub>4</sub>+T<sub>3</sub>).<ref name=":7" /> In most cases, the treatment needs to be taken for the rest of the person's life.<ref name=":6" />

The standard of care is [[levothyroxine]] (LT<sub>4</sub>) therapy, which is an oral medication identical in molecular structure to [[Endogeny (biology)|endogenous]] thyroxine (T<sub>4</sub>).<ref name=":6" /> Levothyroxine sodium has a [[sodium]] salt added to increase the [[Intestinal epithelium|gastrointestinal]] absorption of levothyroxine.<ref>{{Cite book | vauthors = Wiersinga WM |title=Endocrinology: Adult and Pediatric |year=2016 |edition=7th |volume=2 |pages=1540–1556}}</ref> Levothyroxine has the benefits of a long [[half-life]]<ref name="Groenewegen-2021">{{cite journal |vauthors=Groenewegen KL, Mooij CF, van Trotsenburg AS |date=2021 |title=Persisting symptoms in patients with Hashimoto's disease despite normal thyroid hormone levels: Does thyroid autoimmunity play a role? A systematic review |journal=Journal of Translational Autoimmunity |volume=4 |pages=100101 |doi=10.1016/j.jtauto.2021.100101 |pmc=8122172 |pmid=34027377}}</ref> leading to stable thyroid hormone levels,<ref name="McAninch-2019">{{cite journal | vauthors = McAninch EA, Bianco AC | title = The Swinging Pendulum in Treatment for Hypothyroidism: From (and Toward?) Combination Therapy | language = English | journal = Frontiers in Endocrinology | volume = 10 | pages = 446 | date = 2019-07-09 | pmid = 31354624 | pmc = 6629976 | doi = 10.3389/fendo.2019.00446 | doi-access = free }}</ref> ease of [[Monitoring (medicine)|monitoring]],<ref name="McAninch-2019" /> excellent safety<ref name="McAninch-2019" /><ref>{{cite book | vauthors = Brown DC | chapter = Chapter 37 - Thyroid hormones, antithyroid drugs |date=2012-01-01 | title = Clinical Pharmacology | edition = Eleventh |pages=587–595 | veditors = Bennett PN, Brown MJ, Sharma P |chapter-url=https://www.sciencedirect.com/science/article/abs/pii/B9780702040849000768 |access-date=2024-12-05 |place=Oxford |publisher=Churchill Livingstone | doi = 10.1016/B978-0-7020-4084-9.00076-8 |isbn=978-0-7020-4084-9 }}</ref> and efficacy record,<ref name="Welsh-2016" /> and usefulness in pregnancy as it can cross the fetal [[Blood–brain barrier|blood-brain barrier]].<ref name="Klubo-Gwiezdzinska-2022" /> 

Levothyroxine dosing to normalise TSH is based on the amount of residual [[Endogeny (biology)|endogenous]] thyroid function and the patient’s weight, particularly [[lean body mass]].<ref name="Klubo-Gwiezdzinska-2022" /> The dose can be adjusted based upon each patient, for example, the dose may be lowered for elderly patients or patients with certain [[Heart|cardiac]] conditions, but is increased in pregnant patients.<ref name="Mincer2022" /> It is administered on a consistent schedule.<ref name=":6" /> Levothyroxine may be dosed daily or weekly, however weekly dosing may be associated with higher [[Thyroid-stimulating hormone|TSH]] levels, elevated thyroid hormone levels, and transient "[[Echocardiography|echocardiographic]] changes in some patients following 2-4 h of thyroxine intake".<ref>{{cite journal | vauthors = Chiu HH, Larrazabal R, Uy AB, Jimeno C | title = Weekly Versus Daily Levothyroxine Tablet Replacement in Adults with Hypothyroidism: A Meta-Analysis | journal = Journal of the ASEAN Federation of Endocrine Societies | volume = 36 | issue = 2 | pages = 156–160 | date = 2021 | pmid = 34966199 | pmc = 8666497 | doi = 10.15605/jafes.036.02.07 }}</ref><ref>{{cite journal | vauthors = Dutta D, Jindal R, Kumar M, Mehta D, Dhall A, Sharma M | title = Efficacy and Safety of Once Weekly Thyroxine as Compared to Daily Thyroxine in Managing Primary Hypothyroidism: A Systematic Review and Meta-Analysis | language = en-US | journal = Indian Journal of Endocrinology and Metabolism | volume = 25 | issue = 2 | pages = 76–85 | date = March–April 2021 | pmid = 34660234 | pmc = 8477739 | doi = 10.4103/ijem.IJEM_789_20 | doi-access = free }}</ref>

Some patients elect combination therapy with both levothyroxine and [[liothyronine]] (which is identical in molecular structure to [[Triiodothyronine|tri-iodothyronine]]) however studies of combination therapy are limited,<ref name="Ramos-Levi2023" /> and five [[Meta-analysis|meta-analyses]]/reviews "suggested no clear advantage of the combination therapy."<ref name="Klubo-Gwiezdzinska-2022" /> However, [[subgroup analysis]] found that patients who remain the most symptomatic while taking levothyroxine may benefit from therapy containing liothyronine.<ref name="Klubo-Gwiezdzinska-2022" />

There is a lack of evidence around the benefits, long-term effects and side effects of desiccated thyroid extract. It is no longer recommended for the treatment of hypothyroidism.<ref name=":7">{{cite journal | vauthors = Riis KR, Larsen CB, Bonnema SJ | title = Potential Risks and Benefits of Desiccated Thyroid Extract for the Treatment of Hypothyroidism: A Systematic Review | journal = Thyroid | volume = 34 | issue = 6 | pages = 687–701 | date = June 2024 | pmid = 38526391 | doi = 10.1089/thy.2023.0649 | url = https://findresearcher.sdu.dk/ws/files/265931781/RiisManuscript_clean.pdf }}</ref>

==== Side Effects ====
Side effects of thyroid replacement therapy are associated with "inadequate or excessive doses."<ref name=":6" /> Symptoms to watch for include, but are not limited to, [[anxiety]], [[tremor]], weight loss, [[Heat intolerance|heat sensitivity]], diarrhea, and shortness of breath. More worrisome symptoms include [[atrial fibrillation]] and [[bone density]] loss.<ref name=":6" /> Long term over-treatment is associated with increased mortality and [[dementia]].<ref name="Hegedüs-2022" />

==== Monitoring ====
Thyroid Stimulating Hormone (TSH) is the laboratory value of choice for monitoring response to treatment with levothyroxine.<ref name=":4a">{{Cite web |title=Hashimoto's Thyroiditis |url=https://www.thyroid.org/hashimotos-thyroiditis/ |url-status=live |archive-url=https://web.archive.org/web/20230923182829/http://www.thyroid.org/hashimotos-thyroiditis/ |archive-date=23 September 2023 |access-date=2023-01-23 |website=American Thyroid Association |language=en-US}}</ref> When treatment is first initiated, TSH levels may be monitored as often as a frequency of every 6–8 weeks.<ref name=":4a" /> Each time the dose is adjusted, TSH levels may be measured at that frequency until the correct dose is determined.<ref name=":4a" /> Once [[Drug titration|titrated]] to a proper dose, TSH levels will be monitored yearly.<ref name=":4a" /> The target level for TSH is the subject of debate, with factors like age, sex, individual needs and special circumstances such as pregnancy being considered.<ref name="Taylor-2024" /> Recent studies suggest that adjusting therapy based on thyroid hormone levels (T<sub>4</sub> and/or T<sub>3</sub>) may be important.<ref name=":6" />

Monitoring liothyronine treatment or combination treatment can be challenging.<ref name="Taylor-2024" /><ref name="McAninch-2019" /><ref name="Elsevier-2006">{{Citation |title=Thyroid hormones |date=2006-01-01 |pages=3409–3416 | veditors = Aronson JK |url=https://www.sciencedirect.com/science/article/abs/pii/B0444510052009773 |access-date=2024-12-05 |place=Amsterdam |publisher=Elsevier |doi=10.1016/B0-44-451005-2/00977-3 |isbn=978-0-444-51005-1 |encyclopedia=Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions (Fifteenth Edition)|url-access=subscription }}</ref> Liothyronine can suppress TSH to a greater extent than levothyroxine.<ref>{{Cite journal | vauthors = Taylor P, Arooj A, Hanna S, Eligar V, Muhammad Z, Stedman M, Premawardhana L, Okosieme O, Heald A, Dayan C |date=2023-10-31 |title=Thyroid hormone profiles on non-standard thyroid hormone replacement |url=https://www.endocrine-abstracts.org/ea/0094/ea0094p128 |journal=Endocrine Abstracts |language=en |publisher=Bioscientifica |volume=94 |doi=10.1530/endoabs.94.P128|url-access=subscription }}</ref> Short-acting Liothyronine's short half-life can result in large fluctuations of free T<sub>3</sub><ref name="Elsevier-2006" /> over the course of 24 hours.<ref>{{cite journal | vauthors = Saravanan P, Siddique H, Simmons DJ, Greenwood R, Dayan CM | title = Twenty-four hour hormone profiles of TSH, Free T3 and free T4 in hypothyroid patients on combined T3/T4 therapy | journal = Experimental and Clinical Endocrinology & Diabetes | volume = 115 | issue = 4 | pages = 261–267 | date = April 2007 | pmid = 17479444 | doi = 10.1055/s-2007-973071 }}</ref>

Patients may have to adjust their dosage several times over the course of the disease. Endogenous thyroid hormone levels may fluctuate, particularly early in the disease.<ref>{{cite journal | vauthors = Dunne C, De Luca F | title = Long-Term Follow-Up of a Child with Autoimmune Thyroiditis and Recurrent Hyperthyroidism in the Absence of TSH Receptor Antibodies | journal = Case Reports in Endocrinology | volume = 2014 | issue = 1 | pages = 749576 | date = 2014 | pmid = 25114812 | pmc = 4119923 | doi = 10.1155/2014/749576 | doi-access = free }}</ref> Patients may sometimes develop hyperthyroidism, even after long-term treatment.<ref name="Ramos-Levi2023" /> This can be due to a number of factors including acute attacks of destructive [[thyrotoxicosis]] (autoimmune attacks on the thyroid resulting in rises in thyroid hormone levels as thyroid hormones leak out of the damaged tissues).<ref name="Dyrka-2024" /><ref name="Ramos-Levi2023" /> This is usually followed by hypothyroidism.<ref name="Ramos-Levi2023" />  
==== Reverse T<sub>3</sub> ====
Measuring [[Reverse triiodothyronine|reverse tri-iodothyronine]] (rT<sub>3</sub>) is often mentioned in the lay (non-medical) press as a possible marker to inform T<sub>4</sub> or T<sub>3</sub> therapy, "however, there is currently no evidence to support this application" as of 2023.<ref name="Van Uytfanghe-2023" /> Although cited in the lay press as a possible competitor to T<sub>3</sub>, it is unlikely that rT<sub>3</sub> causes hypothyroid symptoms by out-competing T<sub>3</sub> for [[Thyroid hormone receptor|thyroid hormone receptors]], as it has a binding affinity 200 times weaker.<ref name="Halsall-2021" /> It is also unlikely that rT<sub>3</sub> causes poor T<sub>4</sub> to T<sub>3</sub> conversion; despite being demonstrated ''[[in vivo]]'' to have the potential to inhibit [[Iodothyronine deiodinase|DIO]]-mediated T<sub>4</sub> to T<sub>3</sub> conversion, this is considered improbable at normal body hormone concentrations.<ref name="Halsall-2021">{{cite journal | vauthors = Halsall DJ, Oddy S | title = Clinical and laboratory aspects of 3,3',5'-triiodothyronine (reverse T3) | journal = Annals of Clinical Biochemistry | volume = 58 | issue = 1 | pages = 29–37 | date = January 2021 | pmid = 33040575 | doi = 10.1177/0004563220969150 }}</ref>