How is Hashimoto's thyroiditis diagnosed and managed in adults, including treatment thresholds for overt hypothyroidism versus subclinical hypothyroidism?

Hashimoto's Thyroiditis: Diagnosis and Management

Diagnosis

Hashimoto's thyroiditis is diagnosed clinically through the combination of elevated anti-thyroid antibodies (particularly anti-TPO), characteristic ultrasound findings, and thyroid function tests showing hypothyroidism or subclinical hypothyroidism. 1, 2

Clinical Presentation

• Most common autoimmune thyroid disease, particularly affecting women, representing the leading cause of primary hypothyroidism in iodine-sufficient regions 3, 1
• Patients may present with systemic manifestations of hypothyroidism: fatigue, weight gain, cold intolerance, constipation, cognitive slowing, or may be completely asymptomatic 2, 4
• Initial thyroid status varies: patients can be euthyroid (36.5%), have subclinical hypothyroidism (39.5%), overt hypothyroidism (18.5%), or rarely present with transient hyperthyroidism (Hashitoxicosis) 1, 5

Diagnostic Criteria

Measure TSH as the primary screening test (sensitivity >98%, specificity >92%), followed by free T4 if TSH is abnormal to distinguish subclinical from overt hypothyroidism 6

Key laboratory findings:

• Anti-thyroid peroxidase (anti-TPO) antibodies: confirms autoimmune etiology and predicts progression risk (4.3% annual progression to overt hypothyroidism vs 2.6% in antibody-negative patients) 6, 7, 2
• Anti-thyroglobulin antibodies: less predictive than anti-TPO but frequently present 2, 8
• TSH elevation with normal or low free T4 defines the degree of thyroid dysfunction 4

Thyroid ultrasound findings:

• Hypoechogenic, inhomogeneous parenchyma is characteristic 8
• However, imaging has no role in the routine workup of hypothyroidism in adults—it does not differentiate among causes and does not change management 3

Confirmation Before Treatment

Repeat TSH and free T4 after 3-6 weeks before initiating therapy, as 30-60% of elevated TSH values normalize spontaneously 3, 6

Exclude transient causes of TSH elevation:

• Recovery from severe illness or nonthyroidal illness 6, 9
• Recovery from destructive thyroiditis 6, 7
• Recent iodine exposure (CT contrast) 6
• Medications (amiodarone, lithium) 9, 7
• Heterophilic antibodies causing assay interference 9

---

Management: Treatment Thresholds

Overt Hypothyroidism (Elevated TSH + Low Free T4)

Initiate levothyroxine immediately for all patients with overt hypothyroidism (elevated TSH with low free T4), regardless of symptoms 6, 10

Dosing:

• Adults <70 years without cardiac disease: start at full replacement dose of 1.6 mcg/kg/day 6, 10
• Adults >70 years OR with cardiac disease/multiple comorbidities: start at 25-50 mcg/day and titrate gradually by 12.5-25 mcg every 6-8 weeks 6, 10
• Pregnant women: increase pre-pregnancy dose by 25-50% immediately upon pregnancy confirmation; target TSH <2.5 mIU/L in first trimester 6, 10

Critical safety consideration: Before initiating levothyroxine, rule out concurrent adrenal insufficiency (check morning cortisol and ACTH), as starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis 6, 10

---

Subclinical Hypothyroidism (Elevated TSH + Normal Free T4)

TSH >10 mIU/L with Normal Free T4

Initiate levothyroxine therapy regardless of symptoms for confirmed TSH >10 mIU/L 3, 6

Rationale:

• ~5% annual risk of progression to overt hypothyroidism 3, 6, 4
• Associated with cardiac dysfunction (delayed relaxation, abnormal cardiac output) 3, 6
• Associated with adverse lipid profile (elevated LDL cholesterol) 3, 6
• Evidence quality rated as "fair" by expert panels 3, 6

Dosing: Same as overt hypothyroidism based on age and comorbidities 6, 10

TSH 4.5-10 mIU/L with Normal Free T4

Routine levothyroxine treatment is NOT recommended for asymptomatic patients with TSH 4.5-10 mIU/L, as randomized trials show no symptomatic benefit 3, 6

Instead, monitor TSH every 6-12 months without treatment 3, 6

Consider treatment in specific situations:

• Symptomatic patients with fatigue, weight gain, cold intolerance, or constipation: offer 3-4 month trial with clear evaluation of benefit 3, 6
• Pregnant women or those planning pregnancy: treat any TSH elevation, targeting TSH <2.5 mIU/L in first trimester 3, 6
• Positive anti-TPO antibodies: higher progression risk (4.3% vs 2.6% annually) supports treatment consideration 3, 6
• Goiter or infertility in the setting of elevated TSH 6

---

Monitoring and Dose Adjustment

Monitor TSH and free T4 every 6-8 weeks after any dose change until TSH reaches target range (0.5-4.5 mIU/L) 6, 10

Once stable, repeat TSH every 6-12 months or sooner if symptoms change 6, 10

Target TSH range:

• Primary hypothyroidism: 0.5-4.5 mIU/L 6
• Pregnant women: <2.5 mIU/L in first trimester, then trimester-specific ranges 6, 10
• Thyroid cancer patients: varies by risk stratification (0.1-2 mIU/L depending on risk) 6

---

Critical Pitfalls to Avoid

Do not treat based on a single elevated TSH value—confirm with repeat testing, as 30-60% normalize spontaneously 3, 6

Approximately 25% of patients on levothyroxine are unintentionally overtreated (TSH suppressed <0.1 mIU/L), increasing risks for atrial fibrillation (3-5 fold), osteoporosis, fractures, and cardiovascular mortality 6

If TSH falls <0.1 mIU/L on therapy, reduce levothyroxine by 25-50 mcg immediately; if TSH 0.1-0.45 mIU/L, reduce by 12.5-25 mcg, especially in elderly or cardiac patients 6

Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism or hypophysitis—this can precipitate adrenal crisis 6, 10

Recognize transient causes of TSH elevation (acute illness, iodine exposure, recovery from thyroiditis) to avoid unnecessary lifelong treatment 6, 9

In elderly patients (>80 years), TSH reference ranges shift upward (upper limit ~7.5 mIU/L), so mild elevations may not represent true pathology 6, 4

---

Special Populations

Pregnancy

Levothyroxine requirements increase by 25-50% during pregnancy in women with pre-existing hypothyroidism 6, 10 Check TSH and free T4 as soon as pregnancy is confirmed, then at minimum once per trimester 10 Reduce to pre-pregnancy dose immediately after delivery and recheck TSH 4-8 weeks postpartum 10

Cardiac Disease

Start at 25-50 mcg/day regardless of age to avoid precipitating myocardial infarction, heart failure, or arrhythmias 6, 10 Titrate slowly by 12.5-25 mcg every 6-8 weeks with close cardiac monitoring 6

Immune Checkpoint Inhibitor Therapy

Thyroid dysfunction occurs in 6-9% with anti-PD-1/PD-L1 therapy and 16-20% with combination immunotherapy 6 Consider treatment even for subclinical hypothyroidism if fatigue or symptoms present 6 Continue immunotherapy in most cases—thyroid dysfunction rarely requires treatment interruption 6