Editing Hashimoto's thyroiditis (section)

==Treatment==
There is no cure for Hashimoto's Thyroiditis.<ref name="Ludgate-2024">{{cite journal | vauthors = Ludgate ME, Masetti G, Soares P | title = The relationship between the gut microbiota and thyroid disorders | journal = Nature Reviews. Endocrinology | volume = 20 | issue = 9 | pages = 511–525 | date = September 2024 | pmid = 38906998 | doi = 10.1038/s41574-024-01003-w }}</ref><ref name="Australia-2023">{{Cite web | author = Healthdirect Australia |date=2023-02-03 |title=Hashimoto's disease |url=https://www.healthdirect.gov.au/hashimotos-disease |access-date=2024-12-05 |website=www.healthdirect.gov.au |language=en-AU}}</ref> There is currently no known way to stop auto-immune [[Lymphocyte|lymphocytes]] infiltrating the thyroid or to stimulate [[Regeneration (biology)|regeneration]] of thyroid tissue.<ref name="Ramos-Levi2023" /> However, the condition can be managed.<ref name="Ludgate-2024" /><ref name="Australia-2023" />
[[File:T4 LT4 LT4 Sodium - T3 LT3 LT3 Sodium.png|alt=Molecular structure of Thyroxine, Levothyroxine, Levothyroxine Sodium, Tri-iodothyronine, Liothyronine, and Liothyronine Sodium.|thumb|Molecular structure of Thyroxine, Levothyroxine, Levothyroxine Sodium, Tri-iodothyronine, Liothyronine, and Liothyronine Sodium.]]

===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>

=== Persistent Symptoms ===
Multiple studies have demonstrated persistent symptoms in Hashimoto's patients with normal thyroid hormone levels (euthyroid)<ref name=":6" /><ref name="Taylor-2024">{{cite journal | vauthors = Taylor PN, Medici MM, Hubalewska-Dydejczyk A, Boelaert K | title = Hypothyroidism | journal = Lancet | volume = 404 | issue = 10460 | pages = 1347–1364 | date = October 2024 | pmid = 39368843 | doi = 10.1016/S0140-6736(24)01614-3 }}</ref><ref name="Klubo-Gwiezdzinska-2022" /><ref name="Groenewegen-2021" /> and an estimated 10%-15% of patients treated with levothyroxine monotherapy are dissatisfied due to persistent symptoms of hypothyroidism.<ref name="Jonklaas-2019">{{cite journal | vauthors = Jonklaas J, Razvi S | title = Reference intervals in the diagnosis of thyroid dysfunction: treating patients not numbers | journal = The Lancet. Diabetes & Endocrinology | volume = 7 | issue = 6 | pages = 473–483 | date = June 2019 | pmid = 30797750 | doi = 10.1016/S2213-8587(18)30371-1 }}</ref><ref name="Hegedüs-2022">{{cite journal | vauthors = Hegedüs L, Bianco AC, Jonklaas J, Pearce SH, Weetman AP, Perros P | title = Primary hypothyroidism and quality of life | journal = Nature Reviews. Endocrinology | volume = 18 | issue = 4 | pages = 230–242 | date = April 2022 | pmid = 35042968 | pmc = 8930682 | doi = 10.1038/s41574-021-00625-8 }}</ref> Several different [[Hypothesis|hypothesised]] causes are discussed in the [[medical literature]]:<ref name=":2" /><ref name="Groenewegen-2021" /><ref name="Klubo-Gwiezdzinska-2022" />

==== Low tissue tri-iodothyronine (T<sub>3</sub>) hypothesis ====
Peripheral tissue T<sub>4</sub> to T<sub>3</sub> conversion may be inadequate: Some patients on LT<sub>4</sub> monotherapy may have blood T<sub>3</sub> levels low or below the normal range,<ref name=":6" /><ref name="Taylor-2024" /> and/or may have local T<sub>3</sub> deficiency in some tissues.<ref name="Wiersinga-2014">{{cite journal |vauthors=Wiersinga WM |date=March 2014 |title=Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism |journal=Nature Reviews. Endocrinology |volume=10 |issue=3 |pages=164–174 |doi=10.1038/nrendo.2013.258 |pmid=24419358}}</ref> Although both [[Molecule|molecules]] can have biological effects, thyroxine (T<sub>4</sub>) is considered the "storage form" of thyroid hormone with much less effect, while tri-iodothyronine (T<sub>3</sub>) is considered the active form used by [[Tissue (biology)|body tissues]].<ref>{{cite journal | vauthors = Morris JC, Galton VA | title = The isolation of thyroxine (T4), the discovery of 3,5,3'-triiodothyronine (T3), and the identification of the deiodinases that generate T3 from T4: An historical review | journal = Endocrine | volume = 66 | issue = 1 | pages = 3–9 | date = October 2019 | pmid = 31256344 | doi = 10.1007/s12020-019-01990-1 }}</ref><ref name="Abdalla-2014">{{cite journal | vauthors = Abdalla SM, Bianco AC | title = Defending plasma T3 is a biological priority | journal = Clinical Endocrinology | volume = 81 | issue = 5 | pages = 633–641 | date = November 2014 | pmid = 25040645 | pmc = 4699302 | doi = 10.1111/cen.12538 }}</ref> Thus the body must convert thyroxine into tri-iodothyronine.<ref name="Abdalla-2014" /> Tri-iodothyronine is produced primarily by conversion in the [[liver]], [[kidney]], [[skeletal muscle]] and [[pituitary gland]].<ref>{{cite journal | vauthors = Danzi S, Klein I | title = Thyroid hormone and the cardiovascular system | journal = The Medical Clinics of North America | volume = 96 | issue = 2 | pages = 257–268 | date = March 2012 | pmid = 22443974 | doi = 10.1016/j.mcna.2012.01.006 | series = Thyroid Disorders and Diseases }}</ref> 

Adequate conversion requires sufficient levels of the micronutrients [[zinc]],<ref>{{cite journal | vauthors = Knezevic J, Starchl C, Tmava Berisha A, Amrein K | title = Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function? | journal = Nutrients | volume = 12 | issue = 6 | pages = 1769 | date = June 2020 | pmid = 32545596 | pmc = 7353203 | doi = 10.3390/nu12061769 | doi-access = free }}</ref> [[selenium]],<ref name="Winther-2020" /> [[iron]],<ref>{{Cite journal | vauthors = Ghiya R, Ahmad S |date=2019-04-30 |title=SUN-591 Severe Iron-Deficiency Anemia Leading to Hypothyroidism |journal=Journal of the Endocrine Society|volume=3 |issue=Suppl 1 |pages=SUN-591 |doi=10.1210/js.2019-SUN-591 |doi-access=free |pmc=6552785 }}</ref> and possibly [[vitamin A]].<ref>{{cite journal |vauthors=Capriello S, Stramazzo I, Bagaglini MF, Brusca N, Virili C, Centanni M |title=The relationship between thyroid disorders and vitamin A.: A narrative minireview |journal=Frontiers in Endocrinology |volume=13 |pages=968215 |date=2022-10-11 |pmid=36303869 |pmc=9592814 |doi=10.3389/fendo.2022.968215 |doi-access=free}}</ref> Conversion rates may decline with age.<ref>{{cite journal | vauthors = Strich D, Karavani G, Edri S, Gillis D | title = TSH enhancement of FT4 to FT3 conversion is age dependent | journal = European Journal of Endocrinology | volume = 175 | issue = 1 | pages = 49–54 | date = July 2016 | pmid = 27150496 | doi = 10.1530/EJE-16-0007 }}</ref> Since [[DIO2|deiodinase type 2]] is necessary for T<sub>4</sub> to T<sub>3</sub> conversion in some peripheral tissues, "patients with ''DIO2'' gene polymorphisms may have variable peripheral T<sub>3</sub> availability", leading to localised [[hypothyroidism]] in some tissues.<ref name="Groenewegen-2021" /><ref name="Klubo-Gwiezdzinska-2022" /><ref name="Winther-2020" /> The Thr92Ala ''DIO2'' polymorphism is present in 12–36% of the population.<ref name="Groenewegen-2021" />

For the latter patients, levothyroxine monotherapy may not be sufficient<ref name="Groenewegen-2021" /> and patients may have improvement on combination therapy of T<sub>4</sub> and T<sub>3</sub>.<ref name=":6" /><ref name="Winther-2020" /><ref>{{Cite journal | vauthors = Veríssimo D, Reis A, Monteiro M, Dias L |date=2020-08-21 |title=When levothyroxine is not enough- combination therapy with liothyronine |url=https://www.endocrine-abstracts.org/ea/0070/ea0070ep451 |journal=Endocrine Abstracts |language=en |publisher=Bioscientifica |volume=70 |doi=10.1530/endoabs.70.EP451|url-access=subscription }}</ref> As standard immunoassay tests can overestimate blood T<sub>4</sub> and T<sub>3</sub> levels, Ultrafiltration LC-MSMS T<sub>4</sub> and T<sub>3</sub> tests may help to identify patients who would benefit from additional T<sub>3</sub>.<ref name="Welsh-2016" /> 

==== Inadequate markers hypothesis ====
There is ongoing debate about how to define euthyroidism and whether TSH is its best indicator.<ref name="Jonklaas-2019" /> TSH may be useful to detect poor thyroid output and may reflect the state of thyroid hormones in the [[Hypothalamic–pituitary–thyroid axis|hypothalamic-pituitary-thyroid axis]], but not the presence of hormones in other body tissues.<ref name="Hegedüs-2022" /><ref name="Taylor-2024" /><ref name="Wiersinga-2014" /> As a result, LT<sub>4</sub> monotherapy may not result in a "truly biochemically euthyroid state."<ref name="Groenewegen-2021" /> Patients may express a preference for "low normal or below normal TSH values"<ref name="Wiersinga-2014" /> and/or T<sub>4</sub> and T<sub>3</sub> monitoring. The monitoring of other [[Biomarker (medicine)|biomarkers]] that reflect the action of thyroid hormone on tissues has also been proposed.<ref name="Klubo-Gwiezdzinska-2022" /><ref>{{cite journal | vauthors = McAninch EA, Rajan KB, Miller CH, Bianco AC | title = Systemic Thyroid Hormone Status During Levothyroxine Therapy In Hypothyroidism: A Systematic Review and Meta-Analysis | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 103 | issue = 12 | pages = 4533–4542 | date = August 2018 | pmid = 30124904 | pmc = 6226605 | doi = 10.1210/jc.2018-01361 }}</ref><ref name="Hegedüs-2022" />

As [[immunoassay]] Free T<sub>3</sub> and Free T4 tests can overestimate levels, particularly at low thyroid hormone levels, hypothyroidism may be undertreated.<ref name="Welsh-2016" /> [[Liquid chromatography–mass spectrometry|LC-MSMS]] tests may provide more reliable measures.<ref name="Welsh-2016" />

==== Extra-thyroidal effects of autoimmunity hypothesis ====
It is hypothesised that autoimmunity may play some role in euthyroid symptoms.<ref name="Taylor-2024" /><ref name="Chaker-2022" /><ref name="Groenewegen-2021" /> Hypothesised mechanisms include the proposal that TPO-antibody-producing [[Lymphocyte|lymphocytes]] may travel out of the thyroid to other tissue, creating symptoms and inflammation due to [[Cross-reactivity|cross-reaction]],<ref name="Groenewegen-2021" /><ref name="Guldvog I et al">{{cite journal | vauthors = Guldvog I, Reitsma LC, Johnsen L, Lauzike A, Gibbs C, Carlsen E, Lende TH, Narvestad JK, Omdal R, Kvaløy JT, Hoff G, Bernklev T, Søiland H | title = Thyroidectomy Versus Medical Management for Euthyroid Patients With Hashimoto Disease and Persisting Symptoms: A Randomized Trial | journal = Annals of Internal Medicine | volume = 170 | issue = 7 | pages = 453–464 | date = April 2019 | pmid = 30856652 | doi = 10.7326/M18-0284 }}</ref> or "the inflammatory nature of [...] persistently increased circulating cytokine levels."<ref name="Taylor-2024" /> Multiple studies find that antibodies coincide with symptoms even in euthyroid patients,<ref name="Ramos-Levi2023" /><ref name="Groenewegen-2021" /> and higher levels are associated with increased symptoms,<ref name=":6" /> however "the found [[Association (statistics)|association]] does not prove a [[causality]]".<ref name="Groenewegen-2021" /> No treatment currently exists for Hashimoto's autoimmunity, although observed wellbeing improvements after surgical thyroid removal are hypothesised to be due to removing the autoimmune stimulus.<ref name="Klubo-Gwiezdzinska-2022" /><ref name="Guldvog I et al" />

==== Physical and psychosocial co-morbidities hypothesis ====
It is hypothesised that euthyroid symptoms may not be due to Hashimoto's or hypothyroidism, but some other "physical and psychosocial [[Comorbidity|co-morbidities]]".<ref name=":2" /><ref name="Hegedüs-2022" />

=== Improving wellbeing ===
Some patients may perceive improved wellbeing while in [[thyrotoxicosis]], however overtreatment has risks (known risks for [[levothyroxine]] and unknown risks for [[liothyronine]]).<ref name="Hegedüs-2022" /> One study demonstrated [[Thyroidectomy|surgical thyroid removal]] may substantially improve fatigue and wellbeing,<ref name="Taylor-2024" /><ref name="Ramos-Levi2023" /> see Surgery considerations, below.

=== Reducing antibodies ===
It is not established that reducing [[Antithyroid autoantibodies|antithyroid antibodies]] in Hashimoto's has benefits.<ref name="Chaker-2022">{{cite journal | vauthors = Chaker L, Razvi S, Bensenor IM, Azizi F, Pearce EN, Peeters RP | title = Hypothyroidism | journal = Nature Reviews. Disease Primers | volume = 8 | issue = 1 | pages = 30 | date = May 2022 | pmid = 35589725 | pmc = 6619426 | doi = 10.1038/s41572-022-00357-7 }}</ref><ref name="Klubo-Gwiezdzinska-2022" /><ref name=":0">{{cite journal | vauthors = Wichman J, Winther KH, Bonnema SJ, Hegedüs L | title = Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis | journal = Thyroid | volume = 26 | issue = 12 | pages = 1681–1692 | date = December 2016 | pmid = 27702392 | doi = 10.1089/thy.2016.0256 }}</ref> A systematic review and meta-analysis of selenium trials found that while selenium reduces TPO antibodies, there was a lack of evidence of effects on "disease [[Remission (medicine)|remission]], progression, lowered levothyroxine dose or improved [[quality of life]]".<ref name="Winther-2020" />

Selenium,<ref>{{cite journal | vauthors = Huwiler VV, Maissen-Abgottspon S, Stanga Z, Mühlebach S, Trepp R, Bally L, Bano A | title = Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials | journal = Thyroid | volume = 34 | issue = 3 | pages = 295–313 | date = March 2024 | pmid = 38243784 | pmc = 10951571 | doi = 10.1089/thy.2023.0556 }}</ref><ref name="Winther-2020" /> [[vitamin D]],<ref>{{cite journal | vauthors = Jiang H, Chen X, Qian X, Shao S | title = Effects of vitamin D treatment on thyroid function and autoimmunity markers in patients with Hashimoto's thyroiditis-A meta-analysis of randomized controlled trials | journal = Journal of Clinical Pharmacy and Therapeutics | volume = 47 | issue = 6 | pages = 767–775 | date = June 2022 | pmid = 34981556 | pmc = 9302126 | doi = 10.1111/jcpt.13605 }}</ref> and [[metformin]]<ref name="Jia-2020">{{cite journal | vauthors = Jia X, Zhai T, Zhang JA | title = Metformin reduces autoimmune antibody levels in patients with Hashimoto's thyroiditis: A systematic review and meta-analysis | journal = Autoimmunity | volume = 53 | issue = 6 | pages = 353–361 | date = September 2020 | pmid = 32741222 | doi = 10.1080/08916934.2020.1789969 }}</ref> can reduce thyroid peroxidase antibodies. There is preliminary evidence that levothyroxine,<ref>{{cite journal | vauthors = Aksoy DY, Kerimoglu U, Okur H, Canpinar H, Karaağaoğlu E, Yetgin S, Kansu E, Gedik O | title = Effects of prophylactic thyroid hormone replacement in euthyroid Hashimoto's thyroiditis | journal = Endocrine Journal | volume = 52 | issue = 3 | pages = 337–343 | date = June 2005 | pmid = 16006728 | doi = 10.1507/endocrj.52.337 }}</ref><ref>{{cite journal | vauthors = Padberg S, Heller K, Usadel KH, Schumm-Draeger PM | title = One-year prophylactic treatment of euthyroid Hashimoto's thyroiditis patients with levothyroxine: is there a benefit? | journal = Thyroid | volume = 11 | issue = 3 | pages = 249–255 | date = March 2001 | pmid = 11327616 | doi = 10.1089/105072501750159651 }}</ref> {{Needs update|date=February 2025|reason=Articles are from the very early 2000s.}}[[aloe vera]] juice<ref>{{cite journal | vauthors = Metro D, Cernaro V, Papa M, Benvenga S | title = Marked improvement of thyroid function and autoimmunity by <i>Aloe barbadensis</i> miller juice in patients with subclinical hypothyroidism | journal = Journal of Clinical & Translational Endocrinology | volume = 11 | pages = 18–25 | date = March 2018 | pmid = 29527506 | pmc = 5842288 | doi = 10.1016/j.jcte.2018.01.003 }}</ref> and [[Black cumin|black cumin seed]]<ref>{{cite journal | vauthors = Osowiecka K, Myszkowska-Ryciak J | title = The Influence of Nutritional Intervention in the Treatment of Hashimoto's Thyroiditis-A Systematic Review | journal = Nutrients | volume = 15 | issue = 4 | pages = 1041 | date = February 2023 | pmid = 36839399 | pmc = 9962371 | doi = 10.3390/nu15041041 | doi-access = free }}</ref> may reduce thyroid peroxidase antibodies. Metformin can reduce thyroglobulin antibodies.<ref name="Jia-2020" /> It is not established that a [[gluten-free diet]] can reduce antibodies when there is no comorbid [[coeliac disease]].<ref name="Szczuko-2022">{{cite journal | vauthors = Szczuko M, Syrenicz A, Szymkowiak K, Przybylska A, Szczuko U, Pobłocki J, Kulpa D | title = Doubtful Justification of the Gluten-Free Diet in the Course of Hashimoto's Disease | journal = Nutrients | volume = 14 | issue = 9 | pages = 1727 | date = April 2022 | pmid = 35565695 | pmc = 9101474 | doi = 10.3390/nu14091727 | doi-access = free }}</ref><ref name="Larsen-2022" /> Gluten-free diets have been shown in several studies to reduce antibodies, and in other studies to have no effect, however there were significant confounding issues in these studies, including not ruling out [[Comorbidity|comorbid]] coeliac disease.<ref name="Szczuko-2022" />

One study found [[Thyroidectomy|surgical thyroid removal]] can substantially reduce anti-thyroid antibody levels,<ref name="Taylor-2024" /><ref name="Ramos-Levi2023" /> see Surgery considerations, below.

=== Surgery considerations ===
Surgery is not the initial treatment of choice for autoimmune disease, and uncomplicated Hashimoto's thyroiditis is not an [[Indication (medicine)|indication]] for [[thyroidectomy]].<ref name="Ramos-Levi2023" /> Patients generally may discuss surgery with their doctor if they are experiencing significant pressure symptoms, or cosmetic concerns, or have [[Thyroid nodule|nodules]] present on ultrasound.<ref name="Ramos-Levi2023" /> One well-conducted study of patients with troublesome general symptoms and with anti-thyroperoxidase (anti-TPO) levels greater than 1000 IU/ml (normal <100 IU/ml) showed that total thyroidectomy caused the symptoms to resolve and median anti-thyroid peroxidase levels to reduce from 2232 to 152 IU/mL,<ref name="Ramos-Levi2023" /><ref name="Garber-2019">{{Cite web | vauthors = Garber M |date=2019-08-12 |title=Is there a role for surgery in treating Hashimoto's thyroiditis? |url=https://www.health.harvard.edu/blog/is-there-a-role-for-surgery-in-treating-hashimotos-thyroiditis-2019081217443 |access-date=2024-12-05 |website=Harvard Health |language=en}}</ref> but post-operative complications were higher than expected:<ref name="Taylor-2024" /> [[infection]] (4.1%), permanent [[hypoparathyroidism]] (4.1%) and [[recurrent laryngeal nerve]] injury (5.5%).<ref name=":2">{{cite journal | vauthors = Perros P, Van Der Feltz-Cornelis C, Papini E, Nagy EV, Weetman AP, Hegedüs L | title = The enigma of persistent symptoms in hypothyroid patients treated with levothyroxine: A narrative review | journal = Clinical Endocrinology | volume = 98 | issue = 4 | pages = 461–468 | date = April 2023 | pmid = 33783849 | doi = 10.1111/cen.14473 }}</ref>

=== Other ===
[[Zinc]] may increase free T<sub>3</sub> levels.<ref name="Larsen-2022" /> A small pilot study found [[Ashwagandha|Ashwagandha Root]] may increase T<sub>3</sub> and T4 levels, however, there's a lack of strong evidence of this benefit and Ashwagandha has a potential to cause [[adrenal insufficiency]].<ref name="Larsen-2022" />

As of 2022, there has been only one study of low-dose [[naltrexone]] in Hashimoto's, which did not demonstrate efficacy, therefore nothing supports its use; Removing dairy products in those without [[lactose intolerance]] has not been found to be supported.<ref name="Larsen-2022">{{cite journal | vauthors = Larsen D, Singh S, Brito M | title = Thyroid, Diet, and Alternative Approaches | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 107 | issue = 11 | pages = 2973–2981 | date = November 2022 | pmid = 35952387 | doi = 10.1210/clinem/dgac473 }}</ref> While soy [[Isoflavone|isoflavones]] have the potential to theoretically affect T<sub>3</sub> and T<sub>4</sub> production, studies in those with sufficient [[iodine]] find no effect.<ref name="Larsen-2022" />