| Category | Item | Details (include quantitative stats where available) | Ontology/Identifier suggestions | Key supporting sources |
|---|---|---|---|---|
| Disease overview / identifiers / synonyms | Definition | Autoimmune thyroid disease characterized by chronic lymphocytic inflammation of the thyroid, thyroid autoantibodies, progressive follicular damage, and frequent progression to hypothyroidism; standard treatment after hypothyroidism develops is lifelong levothyroxine replacement (pqac-00000000, pqac-00000001, pqac-00000003) | MeSH: **Hashimoto Disease**; ICD-10: **E06.3 Autoimmune thyroiditis**; ICD-11: autoimmune thyroiditis; MONDO: Hashimoto thyroiditis if mapped in KB; UBERON: **thyroid gland** | Huwiler 2024, DOI: 10.1089/thy.2023.0556; Kolanu 2024, DOI: 10.7759/cureus.54393; Huang 2024, DOI: 10.3390/antiox13070868 |
| Disease overview / identifiers / synonyms | Synonyms | Common synonyms: **chronic autoimmune thyroiditis**, **chronic lymphocytic thyroiditis**, **autoimmune thyroiditis**, **Hashimoto disease** (pqac-00000000, pqac-00000004) | MeSH synonym set; SNOMED/ICD cross-map as available | Huwiler 2024, DOI: 10.1089/thy.2023.0556; Kolanu 2024, DOI: 10.7759/cureus.54393 |
| Epidemiology | Prevalence / incidence / sex | Review sources report global prevalence about **7.5%**, rising to **11.4% in LMICs**; incidence about **0.3–1.5 per 1,000 persons**; women affected **4–10×** more often than men (pqac-00000004, pqac-00000006, pqac-00000000) | HPO modifier: female predominance; epidemiology fields in KB | Kolanu 2024, DOI: 10.7759/cureus.54393; Durá-Travé 2024, DOI: 10.3390/ijms25063154; Huwiler 2024, DOI: 10.1089/thy.2023.0556 |
| Epidemiology | Age / natural history | Often insidious, chronic, and progressive; incidence rises after childhood and commonly presents in adolescents/adults, with hypothyroidism emerging over time (pqac-00000004, pqac-00000006) | HPO onset modifiers: adult onset / childhood onset variable | Kolanu 2024, DOI: 10.7759/cureus.54393; Durá-Travé 2024, DOI: 10.3390/ijms25063154 |
| Core diagnostic biomarkers | Thyroid autoantibodies | **Anti-TPO (TPOAb)** and **anti-thyroglobulin (TgAb)** are core serologic markers; seronegative disease occurs in about **5–10%** of cases (pqac-00000001, pqac-00000004) | LOINC/SNOMED for TPOAb and TgAb; HPO: **Positive circulating thyroid autoantibody level** | Kolanu 2024, DOI: 10.7759/cureus.54393 |
| Core diagnostic biomarkers | Thyroid function tests | Typical biochemical pattern: **elevated TSH** with **low FT4/FT3** in overt hypothyroid disease; TSH/FT4 central to diagnosis and follow-up (pqac-00000001, pqac-00000003) | LOINC: TSH, free T4, free T3; HPO: **Hypothyroidism**, **Abnormal thyroid-stimulating hormone level** | Kolanu 2024, DOI: 10.7759/cureus.54393; Huang 2024, DOI: 10.3390/antiox13070868 |
| Core diagnostic biomarkers | Common symptoms / phenotype anchors | Frequent symptoms include fatigue, weight gain, cold intolerance, dry skin, constipation; reflect hypothyroid physiology rather than disease-specific autoimmunity (pqac-00000001) | HPO: **Fatigue**, **Weight gain**, **Cold intolerance**, **Dry skin**, **Constipation**, **Hypothyroidism** | Kolanu 2024, DOI: 10.7759/cureus.54393 |
| Imaging / histopathology | Ultrasound | Typical ultrasonography: **heterogeneous echotexture** and **diffuse hypoechogenicity**; characteristic but not fully specific (pqac-00000001, pqac-00000000) | RadLex/SNOMED thyroid US findings; HPO: **Abnormality of the thyroid gland** | Kolanu 2024, DOI: 10.7759/cureus.54393; Huwiler 2024, DOI: 10.1089/thy.2023.0556 |
| Imaging / histopathology | Histopathology | Fine-needle aspiration / pathology may show **dense lymphocytic infiltrates** and **germinal centers**; thyroid tissue in HT contains T cells, B cells, macrophages around follicles (pqac-00000001, pqac-00000008) | GO: **lymphocyte activation**, **germinal center formation**; CL: **T cell**, **B cell**, **macrophage** | Kolanu 2024, DOI: 10.7759/cureus.54393; Martínez-Hernández 2024, DOI: 10.1038/s41467-024-50192-5 |
| Genetics | GWAS scale / susceptibility architecture | Large AITD GWAS meta-analysis included **110,945 cases** and **1,084,290 controls** and identified **290 variants at 225 loci**, including **115 previously unreported**; highlights T-cell regulatory genes outside MHC (pqac-00000011) | GWAS Catalog entries; genes to prioritize: **LAG3, ZAP70**, HLA-region; disease inheritance: multifactorial/polygenic | Saevarsdottir 2024, DOI: 10.1038/s41467-024-50007-7 |
| Genetics | High-impact variant | Rare **LAG3 5′UTR/start-codon variant rs781745126-T** had the largest reported effect, **OR 3.42**, **P = 2.2×10⁻¹⁶**; carrier effect linked to reduced LAG-3 mRNA/surface expression and ~**half** plasma LAG-3 in heterozygotes; all **3 homozygotes** had AITD (pqac-00000011) | HGNC: **LAG3**; variant: **rs781745126-T**; GO: **negative regulation of T cell activation** | Saevarsdottir 2024, DOI: 10.1038/s41467-024-50007-7 |
| Genetics | Classic susceptibility genes | Reviews also cite **HLA-DR** and **CTLA4** among established susceptibility factors in HT/AITD (pqac-00000001) | HGNC: **HLA-DR**, **CTLA4** | Kolanu 2024, DOI: 10.7759/cureus.54393 |
| Mechanisms / cell types | Core immune mechanism | HT is a **T-cell-mediated** autoimmune process with B-cell autoantibody production, thyroid lymphocytic infiltration, and progressive follicular injury leading to hypothyroidism (pqac-00000001, pqac-00000006) | GO: **immune response**, **antigen processing and presentation**, **T cell activation**; CL: **CD4-positive T cell**, **B cell** | Kolanu 2024, DOI: 10.7759/cureus.54393; Durá-Travé 2024, DOI: 10.3390/ijms25063154 |
| Mechanisms / cell types | Thyroid follicular cells / antigen presentation | Spatial transcriptomics identified damaged, de-differentiated **thyroid follicular cells (TFCs)** with increased **CD74** and **MIF** expression, consistent with aberrant MHC-II antigen presentation and a **CD74/MIF autocrine loop** promoting immune recruitment/repair signaling (pqac-00000007, pqac-00000008, pqac-00000010) | CL: **thyroid follicular cell**; GO: **antigen processing and presentation of peptide antigen via MHC class II**, **response to interferon-gamma** | Martínez-Hernández 2024, DOI: 10.1038/s41467-024-50192-5 |
| Mechanisms / cell types | Immune infiltrates | HT tissue showed rich infiltrates with **T cells, B lymphocytes, inflammatory macrophages**, and myeloid cells; T-cell genes (**TRAC, TRBC1, CD3D**) and B-cell markers (**MS4A1, CR2**) were enriched in infiltrated zones (pqac-00000008, pqac-00000009) | CL: **T cell**, **B cell**, **macrophage**, **dendritic cell**; GO: **lymphocyte chemotaxis** | Martínez-Hernández 2024, DOI: 10.1038/s41467-024-50192-5 |
| Mechanisms / cell types | Fibroblast subtypes | Two fibroblast programs were emphasized: inflammatory-associated fibroblasts, including **CXCL12+** and **IGFBP6+** populations linked to immune chemotaxis/ECM remodeling, and myofibroblast-like populations in interfollicular areas (pqac-00000007, pqac-00000010) | CL: **fibroblast**, **myofibroblast**; GO: **extracellular matrix organization**, **chemokine-mediated signaling pathway** | Martínez-Hernández 2024, DOI: 10.1038/s41467-024-50192-5 |
| Mechanisms / cell types | Endothelial / vascular changes | Spatial data showed increased vascular permeability and specialized endothelial structures, including **ACKR1+ high endothelial venules** in HT infiltrates; broader AITD work also noted **PLVAP+ fenestrated vessels** (pqac-00000009, pqac-00000010) | CL: **endothelial cell**; GO: **angiogenesis**, **regulation of vascular permeability**; UBERON: **thyroid vasculature** | Martínez-Hernández 2024, DOI: 10.1038/s41467-024-50192-5 |
| Mechanisms / cell types | Cytokine context | **IFN-γ** and **TNF-α** upregulate CD74 in TFCs and infiltrating immune cells, amplifying receptor-ligand interactions and antigen-presentation signaling (pqac-00000007, pqac-00000009) | CHEBI: interferon gamma, tumor necrosis factor alpha; GO: **cellular response to interferon-gamma**, **inflammatory response** | Martínez-Hernández 2024, DOI: 10.1038/s41467-024-50192-5 |
| Environmental / risk factors | Environment and micronutrients | Reviews cite environmental triggers including **excess dietary iodine** and possible toxicant exposures; vitamin D deficiency is repeatedly associated with HT, though causality/intervention evidence remains incomplete (pqac-00000001, pqac-00000006) | CHEBI: iodine, cholecalciferol; exposure ontology terms as available | Kolanu 2024, DOI: 10.7759/cureus.54393; Durá-Travé 2024, DOI: 10.3390/ijms25063154 |
| Standard treatment | Levothyroxine replacement | Standard of care for overt hypothyroidism due to HT is **lifelong oral levothyroxine (LT4)** to normalize TSH; therapy addresses hormone deficiency but not the upstream autoimmune process, inflammation, or oxidative stress (pqac-00000000, pqac-00000003) | MAXO: **thyroid hormone replacement therapy**, **administration of levothyroxine**; CHEBI: **levothyroxine** | Huwiler 2024, DOI: 10.1089/thy.2023.0556; Huang 2024, DOI: 10.3390/antiox13070868 |
| Adjunct / disease-modifying | Selenium meta-analysis | 2024 systematic review/meta-analysis of **35 studies** found selenium lowered **TSH** in patients **without** thyroid hormone replacement (**SMD −0.21, 95% CI −0.43 to −0.02; 7 cohorts, n=869**), lowered **TPOAb** (**SMD −0.96, 95% CI −1.36 to −0.56; 29 cohorts, n=2,358**), lowered **MDA** (**SMD −1.16; 3 cohorts, n=248**), with adverse events similar to control (**OR 0.89, 95% CI 0.46–1.75; 16 cohorts, n=1,339**) (pqac-00000017, pqac-00000016, pqac-00000015) | MAXO: **selenium supplementation**; CHEBI: **selenium**, **selenium-enriched yeast** | Huwiler 2024, DOI: 10.1089/thy.2023.0556 |
| Adjunct / disease-modifying | Selenium QoL RCT | CATALYST RCT: **412** patients with autoimmune thyroiditis on LT4, **332 (81%)** completed 12 months; **200 μg/day selenium** vs placebo improved QoL similarly in both groups with **no between-group difference** in ThyPRO-39 composite score (**28.8 vs 28.0, P=0.602**). TPOAb was lower with selenium after 12 months (**1995 vs 2344 kIU/L, P=0.016**); no meaningful TSH difference (**P=0.688**) and no serious safety signal (pqac-00000012, pqac-00000013, pqac-00000014) | MAXO: **selenium supplementation**, **patient-reported outcome assessment** | Larsen 2024, DOI: 10.1530/etj-23-0175 |
| Adjunct / disease-modifying | Vitamin D | Review-level evidence: HT patients often have lower vitamin D levels; some studies show reduced thyroid autoantibody titers after cholecalciferol in vitamin D-deficient HT, but authors stress need for more randomized double-blind placebo-controlled trials (pqac-00000006) | MAXO: **vitamin D supplementation**; CHEBI: **cholecalciferol** | Durá-Travé 2024, DOI: 10.3390/ijms25063154 |
| Experimental / ongoing trials | Vitamin D adjuvant trial | **NCT05871957**: prospective observational cohort; **30** female participants (18–60 years) with HT and hypothyroidism; **vitamin D drops 2000 IU/day for 1 month**; primary outcome **TPOAb**, secondary **TgAb, FT3, FT4, TSH**; status in registry chunk: **not yet recruiting** (pqac-00000020, pqac-00000024) | NCT: **NCT05871957**; MAXO: **vitamin D supplementation** | ClinicalTrials.gov, NCT05871957 |
| Experimental / ongoing trials | Hydroxychloroquine trial | **NCT01760421**: completed single-group interventional study; **40** euthyroid adults; **hydroxychloroquine 200 mg twice daily for 6 months**; primary outcomes **anti-TPO** and **anti-thyroglobulin**; secondary outcomes included **elastography**, **FT4/TSH**, and inflammatory cytokines (**IL-1, IL-6, TNF-α**) (pqac-00000021) | NCT: **NCT01760421**; MAXO: **hydroxychloroquine therapy** | ClinicalTrials.gov, NCT01760421 |
| Experimental / ongoing trials | Dietary intervention trial | **NCT05949671**: interventional diet study in women with confirmed HT; total registry search reported **40 participants**; compares **gluten-free** and **Mediterranean diet** approaches over **12 weeks** with personalized dietitian support; primary focus is effect on the autoimmune system (pqac-00000022) | NCT: **NCT05949671**; MAXO: **dietary modification**, **gluten-free diet**, **Mediterranean diet** | ClinicalTrials.gov, NCT05949671 |
| Experimental / ongoing trials | Photobiomodulation trial | **NCT06735040**: interventional study in HT patients on LT4; registry search reported **60 participants**; outcomes over about **3 months** included **depression, anxiety, and fatigue** measures, reflecting symptom-focused adjunctive management (pqac-00000023) | NCT: **NCT06735040**; MAXO: **photobiomodulation therapy** | ClinicalTrials.gov, NCT06735040 |
| Visual / reference resource | Mechanistic figure | Figure 8 from the 2024 spatial transcriptomics study provides a concise mechanistic map of HT: damaged CD74-high TFCs, CD74/MIF loop, inflammatory fibroblasts, endothelial remodeling, and immune infiltration (pqac-00000025, pqac-00000026) | Evidence figure linkable in KB; GO/CL mapping support | Martínez-Hernández 2024, DOI: 10.1038/s41467-024-50192-5 |


*Table: This table summarizes high-yield disease-characteristic facts for a Hashimoto’s thyroiditis knowledge-base entry, emphasizing 2023–2024 evidence, ontology suggestions, quantitative findings, and trial identifiers.*