What is the treatment for Hashimoto's (Hashimoto's thyroiditis)?

Hashimoto's Thyroiditis: Clinical Overview and Management

Definition and Pathophysiology

Hashimoto's thyroiditis (also called chronic autoimmune thyroiditis) is an autoimmune disorder where the immune system attacks the thyroid gland, leading to lymphocytic infiltration, destruction of thyroid tissue, and progressive hypothyroidism. 1, 2, 3

• The disease results from T and B cell-mediated autoimmunity, with antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG) causing thyroid destruction 2, 3, 4
• Hashimoto's is the most common autoimmune thyroid disease and the most frequent cause of hypothyroidism in industrialized nations 1
• Women are affected 7-10 times more often than men 2
• The disease develops from genetic susceptibility combined with environmental triggers including iodine exposure, selenium deficiency, vitamin D deficiency, stress, and microbiota dysbiosis 5, 2, 4

Clinical Presentation Phases

Hashimoto's thyroiditis progresses through distinct clinical phases 2:

• Hashitoxicosis (early phase): Transient hyperthyroidism occurs when stored thyroid hormones are released from destroyed follicles; patients may experience tremors, nervousness, tachycardia, and heat intolerance 1, 2
• Euthyroid phase: Remaining thyroid tissue compensates for destroyed thyrocytes; TSH may be normal or mildly elevated with normal free T4 2
• Hypothyroid phase: Insufficient thyroid hormone production develops, causing fatigue, weight gain, cold intolerance, constipation, hair loss, and cognitive slowing 1, 2

Diagnostic Approach

Diagnosis is established by elevated TSH with or without low free T4, positive anti-TPO antibodies (present in 80-85% of cases), and characteristic ultrasound findings showing heterogeneous hypoechoic thyroid parenchyma. 1, 2, 3

• Measure TSH as the initial screening test, followed by free T4 to distinguish subclinical from overt hypothyroidism 6
• Anti-TPO antibodies are more sensitive than anti-thyroglobulin antibodies for diagnosis 2, 3
• Thyroid ultrasound reveals diffuse heterogeneous hypoechogenicity with increased vascularity 1
• Fine needle aspiration cytology shows lymphocytic infiltration with Hürthle (oxyphilic) cells when nodules are present 3

Treatment Algorithm

Primary Treatment: Levothyroxine Replacement

Lifelong levothyroxine (LT4) therapy is the cornerstone of treatment for Hashimoto's thyroiditis once hypothyroidism develops. 7, 5, 2

Indications for Starting Levothyroxine:

• Overt hypothyroidism: TSH >10 mIU/L with low free T4 - treat immediately regardless of symptoms 6, 2
• Subclinical hypothyroidism with TSH >10 mIU/L: Initiate treatment even with normal free T4, as progression risk is approximately 5% per year 6
• Subclinical hypothyroidism with TSH 4.5-10 mIU/L: Consider treatment if symptomatic, pregnant, planning pregnancy, or positive TPO antibodies 6
• Pregnancy or planning pregnancy: Treat any TSH elevation due to risks of preeclampsia, low birth weight, and neurodevelopmental effects 1, 6

Levothyroxine Dosing Strategy:

• For patients <70 years without cardiac disease: Start with full replacement dose of 1.6 mcg/kg/day based on lean body mass 6, 2
• For patients >70 years or with cardiac disease: Start with 25-50 mcg/day and titrate gradually to avoid cardiac decompensation 6
• Target TSH: 0.5-4.5 mIU/L for most patients; slightly higher targets (up to 5-6 mIU/L) may be acceptable in very elderly patients 6

Monitoring Protocol:

• Check TSH and free T4 every 6-8 weeks during dose titration 6
• Once stable, monitor TSH every 6-12 months or when symptoms change 6
• Adjust dose by 12.5-25 mcg increments based on TSH response 6

Management of Hashitoxicosis Phase

When transient hyperthyroidism occurs, manage symptoms with beta-blockers rather than antithyroid drugs, as this phase is self-limited. 1, 2

• Use propranolol or other beta-blockers for symptom control (tremor, tachycardia, anxiety) 1
• Monitor TSH and free T4 every 2-4 months during this phase 1
• Discontinue treatment if severe hyperthyroidism develops, though this is rare 1
• Most patients progress to hypothyroidism within months; thyroid function may not recover after this phase 1

Role of Triiodothyronine (T3)

There is insufficient evidence to recommend combination T4/T3 therapy over levothyroxine monotherapy for most Hashimoto's patients. 7, 2

• Liothyronine (T3) is FDA-approved for hypothyroidism treatment and can be used in patients allergic to desiccated thyroid products 7
• T3 should not be used during pregnancy as it does not adequately cross the fetal blood-brain barrier 2
• Consider T3 supplementation only in patients with persistent symptoms despite normalized TSH on adequate LT4 doses, though evidence is limited 2

Nutritional and Dietary Management

Address nutritional deficiencies commonly found in Hashimoto's patients, as these may impact thyroid function and autoimmunity. 5, 4

Key Nutritional Considerations:

• Selenium: Supplementation may reduce anti-TPO antibody levels and improve thyroid function; deficiency is common in HT patients 5, 4
• Vitamin D: Deficiency is linked to higher thyroid autoimmunity; supplementation may reduce antibody titers and improve immune regulation 5, 8, 4
• Iodine: Careful supplementation only if deficient; excess iodine can exacerbate autoimmunity 5, 4
• Other micronutrients: Ensure adequate zinc, selenium, iron, magnesium, and B vitamins 4

Dietary Modifications:

• Gluten elimination: Consider gluten-free diet, especially if celiac disease is present or suspected, as gliadin may cross-react with thyroid antigens 5, 4
• Lactose restriction: Eliminate if intolerant, as lactose can interfere with levothyroxine absorption 4
• Anti-inflammatory diet: Emphasize omega-3 fatty acids, adequate protein, dietary fiber, and antioxidant-rich foods 4

Associated Conditions and Complications

Concurrent Autoimmune Diseases

Hashimoto's thyroiditis frequently coexists with other autoimmune conditions, requiring screening and coordinated management. 1

• Autoimmune thyroid disease (AITD): Most common concurrent condition in autoimmune hepatitis patients (10-23% prevalence) 1
• Systemic lupus erythematosus: Occurs in 2.8-3% of HT patients; associated with higher IgG levels and potentially worse prognosis 1
• Sjögren syndrome: Present in 2.8-7% of HT patients 1
• Rheumatoid arthritis: Develops in 2-4% of HT patients, more common in older individuals 1

Malignancy Risk

Hashimoto's thyroiditis is associated with increased risk of thyroid malignancies, requiring vigilant surveillance. 1, 2, 3

• Papillary thyroid cancer: 1.6-fold increased risk compared to general population 1, 2
• Thyroid lymphoma: 60-fold increased risk, particularly primary thyroid lymphoma 2
• Higher cancer risk in HT patients with autoimmune thyroid disease and nodular changes 1
• Perform ultrasound surveillance and fine needle aspiration for suspicious nodules 3

Critical Pitfalls to Avoid

• Never start levothyroxine before ruling out adrenal insufficiency in patients with suspected central hypothyroidism or hypopituitarism, as this can precipitate adrenal crisis 6
• Do not treat based on single elevated TSH value: 30-60% of elevated TSH levels normalize on repeat testing after 3-6 weeks 6
• Avoid overtreatment: Approximately 25% of patients on levothyroxine are maintained on excessive doses causing TSH suppression, increasing risks for atrial fibrillation, osteoporosis, and cardiac complications 6
• Monitor for progression during interferon therapy: If HT develops during hepatitis C treatment with peginterferon-alpha, thyroid function may not recover after cessation and requires ongoing monitoring 1
• Recognize pregnancy-related needs: Levothyroxine requirements increase 25-50% during pregnancy; proactively increase dose when pregnancy is confirmed 6