Hypothyroidism (Hashimoto Thyroiditis)

Risk factors

• Female sex, increasing age, personal/family history of autoimmune disease
• Postpartum state, prior head/neck radiation, prior I-131 therapy or thyroid surgery
• Iodine excess (paradoxically; amiodarone, kelp, contrast)
• Lithium, interferon-alpha, tyrosine kinase inhibitors, immune-checkpoint inhibitors
• Smoking is associated with a LOWER risk of Hashimoto/anti-TPO positivity (but a higher risk of Graves disease and orbitopathy)

Pathophysiology

Lymphocytic infiltration with germinal-center formation and Hürthle cell metaplasia leads to progressive follicular destruction and fibrosis. As thyroid output falls, the pituitary increases TSH. Initially this maintains euthyroidism (subclinical hypothyroidism). Eventually compensation fails and overt hypothyroidism develops. Anti-TPO antibodies are markers but also participate in cytotoxicity.

Clinical presentation

Differential diagnosis

• Subclinical hypothyroidism — Elevated TSH with normal free T4 and minimal/no symptoms; treat if TSH >10; consider if symptomatic or planning pregnancy (in pregnancy, mild elevations are treated only selectively per ATA 2026)
• Central (secondary/tertiary) hypothyroidism — Low or inappropriately normal TSH with low free T4; pituitary or hypothalamic disease; pituitary MRI
• Sick euthyroid (non-thyroidal illness) — Hospitalized/critically ill patients; low T3 with variable TSH; resolves with recovery; do not start levothyroxine unless persistent
• Drug-induced hypothyroidism — Amiodarone, lithium, interferon, checkpoint inhibitors, tyrosine kinase inhibitors
• Iodine deficiency — Endemic regions; goiter; rare in US since salt iodination
• Riedel thyroiditis — Stony-hard fibrotic gland; IgG4-related disease; mimics malignancy
• Congenital hypothyroidism — Detected on newborn screen; thyroid dysgenesis or dyshormonogenesis; treat immediately to prevent cretinism

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Symptoms suggest hypothyroidism] --> B[Check TSH]
  B --> C{TSH elevated?}
  C -->|No| D{TSH normal/low<br/>but symptomatic?}
  D -->|Yes| E[Check free T4<br/>consider central hypothyroidism]
  D -->|No| F[Not thyroid disease]
  C -->|Yes| G[Free T4]
  G --> H{Free T4 low?}
  H -->|Yes| I[Overt hypothyroidism<br/>Start levothyroxine 1.6 mcg/kg]
  H -->|No| J[Subclinical hypothyroidism]
  J --> K{"TSH >10 OR symptomatic<br/>OR trying to conceive<br/>OR goiter?"}
  J -.-> P["Pregnant (ATA 2026): TSH >10 treat<br/>milder: consider levothyroxine only<br/>if found in 1st trimester,<br/>else recheck TSH q4-6 wk"]
  K -->|Yes| I
  K -->|No| L[Monitor q6-12 months]
  I --> M[Anti-TPO confirms<br/>Hashimoto etiology]
  I --> N[Recheck TSH<br/>at 6-8 weeks]

Treatment

Complications

• Myxedema coma (severe decompensation; mortality 30-50%)
• Pericardial effusion, cardiomyopathy, atherogenic dyslipidemia, accelerated CAD
• Infertility, miscarriage, fetal cognitive impairment if untreated in pregnancy
• Primary thyroid lymphoma (rare; rapidly enlarging gland in known Hashimoto)
• Encephalopathy associated with autoimmune thyroiditis (Hashimoto encephalopathy)
• Iatrogenic subclinical hyperthyroidism from levothyroxine over-replacement (suppressed TSH): atrial fibrillation (about 3-fold risk in older adults) and bone loss/fracture, especially in postmenopausal women; lower the dose to bring TSH back into the reference range (intentional TSH suppression only for selected thyroid cancer)

PANCE pearls

• Anti-TPO antibody is the single most sensitive marker for Hashimoto; positive in 90-95%.
• Subclinical hypothyroidism with TSH 4.5-10 and no symptoms does not always require treatment, but DO treat if TSH >10 or clearly symptomatic, and consider it when planning pregnancy. In pregnancy (ATA 2026), mild subclinical hypothyroidism is treated only selectively: confirm on repeat testing, consider levothyroxine if found in the first trimester, and if found later recheck TSH every 4-6 weeks instead of treating.
• If a Hashimoto patient develops rapid goiter growth, suspect primary thyroid lymphoma — biopsy promptly.
• Always rule out and treat adrenal insufficiency BEFORE starting levothyroxine in polyglandular autoimmune syndrome.
• Levothyroxine half-life is 7 days; missed doses can be made up by doubling the next day's dose.

References

• ATA 2014 — Guidelines for the Treatment of Hypothyroidism (Jonklaas et al., Thyroid 2014)
• ATA Pregnancy 2026 — American Thyroid Association 2026 Guidelines for Thyroid Disease in Preconception, Pregnancy, and Postpartum (Korevaar et al., Thyroid 2026;36(5):481-544)
• AACE/ATA 2012 — Clinical Practice Guidelines for Hypothyroidism in Adults (Garber et al., Endocr Pract 2012)