Editing Hashimoto's thyroiditis (section)

== Pregnancy ==

=== Conception ===
It is recommended that [[hypothyroidism]] be treated with [[Levothyroxine|levothyoxine]] before conception, to prevent adverse effects on the course of the pregnancy and on the development of the child.<ref name="Klubo-Gwiezdzinska-2022" /> In [[IVF]], [[embryo transfer]] is improved when hypothyroidism is treated.<ref name="Gaberšček-2011" />

=== Pregnancy ===
The [[Endocrine Society]] recommends screening in pregnant women who are considered high-risk for thyroid autoimmune disease.<ref>{{Cite web |date=26 March 2015 |title=Endocrine Experts Support Screening for Thyroid Dysfunction in Pregnant Women |url=https://www.endocrine.org/news-room/current-press-releases/endocrine-experts-support-screening-for-thyroid-dysfunction-in-pregnant-women |url-status=dead |archive-url=https://web.archive.org/web/20151008045642/https://www.endocrine.org/news-room/current-press-releases/endocrine-experts-support-screening-for-thyroid-dysfunction-in-pregnant-women |archive-date=8 October 2015 |access-date=4 October 2015 |website=Endocrine Society}}</ref> Universal screening for thyroid diseases during pregnancy is controversial, however, one study "supports the potential benefit of universal screening".<ref name="Lepoutre-2012">{{cite journal | vauthors = Lepoutre T, Debiève F, Gruson D, Daumerie C | title = Reduction of miscarriages through universal screening and treatment of thyroid autoimmune diseases | journal = Gynecologic and Obstetric Investigation | volume = 74 | issue = 4 | pages = 265–273 | date = 2012-01-01 | pmid = 23147711 | doi = 10.1159/000343759 | s2cid = 1646888 | doi-access =  }}</ref> Pregnant women may have [[Antithyroid autoantibodies|antithyroid antibodies]] (5%–14% of pregnancies<ref name="Klubo-Gwiezdzinska-2022" />), poor thyroid function resulting in hypothyroidism, or both. Each is associated with risks:<ref name="Klubo-Gwiezdzinska-2022" />

==== Anti-thyroid antibodies in pregnancy ====
The presence of Thyroid peroxidase antibodies at the outset of pregnancy are associated with a greater risk to the mother of hypothyroidism and thyroid impairment in the first year after [[Childbirth|delivery]].<ref>{{cite journal | vauthors = Caturegli P, De Remigis A, Rose NR | title = Hashimoto thyroiditis: clinical and diagnostic criteria | journal = Autoimmunity Reviews | volume = 13 | issue = 4–5 | pages = 391–397 | date = 2014-04-01 | pmid = 24434360 | doi = 10.1016/j.autrev.2014.01.007 | series = Diagnostic criteria in Autoimmune diseases }}</ref>

The presence of antibodies is also associated with "a 2 to 4-fold increase in the risk of recurrent [[Miscarriage|miscarriages]], and 2 to 3-fold increased risk of [[preterm birth]]", however the reason why is unclear. Thyroid peroxidase antibodies are speculated to indicate other autoimmune processes against the placental-fetal unit.<ref name="Klubo-Gwiezdzinska-2022" />

Levothyroxine treatment in euthyroid women with thyroid autoimmunity does not significantly impact the relative risk of miscarriage and preterm delivery, or outcomes with live birth. "Therefore, no strong recommendations regarding the therapy in such scenarios could be made, but consideration on a case-by-case basis might be implemented."<ref name="Klubo-Gwiezdzinska-2022" />

==== Hypothyroidism in pregnancy. ====
Women who have low thyroid function that has not been stabilized are at greater risk of complications for both parent and child. Risks to the mother include [[Gestational Hypertension|gestational hypertension]] including [[Pre-eclampsia|preeclampsia]] and [[eclampsia]], [[gestational diabetes]], [[placental abruption]], and [[Postpartum bleeding|postpartum hemorrhage]].<ref name="Klubo-Gwiezdzinska-2022" /> Risks to the infant include miscarriage, preterm delivery, [[low birth weight]], [[Infant respiratory distress syndrome|neonatal respiratory distress]], [[hydrocephalus]], [[hypospadias]], fetal death, infant intensive care unit admission, and [[Developmental disability|neurodevelopmental delays]] (lower child IQ, language delay or [[global developmental delay]]).<ref name="Lepoutre-2012" /><ref name="Gaberšček-2011">{{cite journal | vauthors = Gaberšček S, Zaletel K | title = Thyroid physiology and autoimmunity in pregnancy and after delivery | journal = Expert Review of Clinical Immunology | volume = 7 | issue = 5 | pages = 697–706; quiz 707 | date = September 2011 | pmid = 21895480 | doi = 10.1586/eci.11.42 | doi-access = free }}</ref><ref name="Klubo-Gwiezdzinska-2022" />

Successful pregnancy outcomes are improved when hypothyroidism is treated.<ref name="Gaberšček-2011" /> Levothyroxine treatment may be considered at lower TSH levels in pregnancy than in standard treatment.<ref name="Klubo-Gwiezdzinska-2022" /> Liothyronine does not cross the fetal blood-brain barrier, so liothyronine (T<sub>3</sub>) only or liothyronine + levothyroxine (T<sub>3</sub> + T<sub>4</sub>) therapy is not indicated in pregnancy.<ref name="Klubo-Gwiezdzinska-2022" />

Close cooperation between the [[endocrinologist]] and [[obstetrician]] benefits the woman and the infant.<ref name="Lepoutre-2012" /><ref>{{cite journal | vauthors = Budenhofer BK, Ditsch N, Jeschke U, Gärtner R, Toth B | title = Thyroid (dys-)function in normal and disturbed pregnancy | journal = Archives of Gynecology and Obstetrics | volume = 287 | issue = 1 | pages = 1–7 | date = January 2013 | pmid = 23104052 | doi = 10.1007/s00404-012-2592-z | url = https://opus.bibliothek.uni-augsburg.de/opus4/frontdoor/index/index/docId/84394 | url-status = live | access-date = 16 January 2022 | s2cid = 24969196 | archive-url = https://web.archive.org/web/20220123170145/https://opus.bibliothek.uni-augsburg.de/opus4/frontdoor/index/index/docId/84394 | archive-date = 23 January 2022 }}</ref><ref>{{cite journal | vauthors = Balucan FS, Morshed SA, Davies TF | title = Thyroid autoantibodies in pregnancy: their role, regulation and clinical relevance | journal = Journal of Thyroid Research | volume = 2013 | pages = 182472 | date = 2013 | pmid = 23691429 | pmc = 3652173 | doi = 10.1155/2013/182472 | doi-access = free }}</ref>

==== Immune changes during pregnancy ====
Hormonal changes and [[trophoblast]] expression of key [[Immunomodulation|immunomodulatory]] molecules lead to [[immunosuppression]] and fetal tolerance. The main players in regulation of the immune response are [[Tregs]]. Both [[Cell-mediated immunity|cell-mediated]] and [[Humoral immunity|humoral]] immune responses are attenuated, resulting in [[Immune tolerance in pregnancy|immune tolerance]] and suppression of autoimmunity. It has been reported that during pregnancy, levels of thyroid peroxidase and thyroglobulin antibodies decrease.<ref name="Weetman-2010" />

=== Postpartum ===
Thyroid peroxidase antibodies testing is recommended for women who have ever been pregnant regardless of pregnancy outcome. "[P]revious pregnancy plays a major role in development of autoimmune overt hypothyroidism in [[premenopausal]] women, and the number of previous pregnancies should be taken into account when evaluating the risk of hypothyroidism in a young women [''sic'']."<ref name="Carlé-2014" />

[[Postpartum thyroiditis]] can occur in women with Hashimoto's.<ref name="Ramos-Levi2023" /> In healthy women, Postpartum thyroiditis can occur up to 1 year after [[Childbirth|delivery]] and should be differentiated from Hashimoto's thyroiditis as it is treated differently.<ref>{{cite journal | vauthors = Lee SY, Pearce EN | title = Assessment and treatment of thyroid disorders in pregnancy and the postpartum period | journal = Nature Reviews. Endocrinology | volume = 18 | issue = 3 | pages = 158–171 | date = March 2022 | pmid = 34983968 | pmc = 9020832 | doi = 10.1038/s41574-021-00604-z }}</ref>

After giving birth, [[Regulatory T cell|Tregs]] rapidly decrease and immune responses are re-established. It may lead to the occurrence or aggravation of autoimmune thyroid disease.<ref name="Weetman-2010">{{cite journal | vauthors = Weetman AP | title = Immunity, thyroid function and pregnancy: molecular mechanisms | journal = Nature Reviews. Endocrinology | volume = 6 | issue = 6 | pages = 311–318 | date = June 2010 | pmid = 20421883 | doi = 10.1038/nrendo.2010.46 | s2cid = 9900120 }}</ref> In up to 50% of females with thyroid peroxidase antibodies in the early pregnancy, thyroid autoimmunity in the postpartum period exacerbates in the form of postpartum thyroiditis.<ref>{{cite journal | vauthors = Lazarus JH | title = The continuing saga of postpartum thyroiditis | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 96 | issue = 3 | pages = 614–616 | date = March 2011 | pmid = 21378224 | doi = 10.1210/jc.2011-0091 | doi-access = free }}</ref> Higher secretion of [[Interferon gamma|IFN-γ]] and [[Interleukin 4|IL-4]], and lower plasma [[cortisol]] concentration during pregnancy has been reported in females with postpartum thyroiditis than in healthy females. It indicates that weaker immunosuppression during pregnancy could contribute to the postpartum thyroid dysfunction.<ref>{{cite journal | vauthors = Kokandi AA, Parkes AB, Premawardhana LD, John R, Lazarus JH | title = Association of postpartum thyroid dysfunction with antepartum hormonal and immunological changes | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 3 | pages = 1126–1132 | date = March 2003 | pmid = 12629095 | doi = 10.1210/jc.2002-021219 | doi-access = free }}</ref>

=== Fetal microchimerism ===

Several years after the delivery, the [[Chimera (genetics)|chimeric]] male cells can be detected in the maternal peripheral blood, thyroid, lung, skin, or lymph nodes. The fetal immune cells in the maternal thyroid gland may become activated and act as a trigger that may initiate or exaggerate the autoimmune thyroid disease. In Hashimoto's disease patients, fetal [[Microchimerism|microchimeric]] cells were detected in thyroid in significantly higher numbers than in healthy females.<ref>{{cite journal | vauthors = Koopmans M, Kremer Hovinga IC, Baelde HJ, Harvey MS, de Heer E, Bruijn JA, Bajema IM | title = Chimerism occurs in thyroid, lung, skin and lymph nodes of women with sons | journal = Journal of Reproductive Immunology | volume = 78 | issue = 1 | pages = 68–75 | date = June 2008 | pmid = 18329105 | doi = 10.1016/j.jri.2008.01.002 }}</ref>