Management of Thyroid Disease: Hypothyroidism and Hyperthyroidism
Evaluation of Hypothyroidism
Initial Laboratory Assessment
Measure TSH first, followed by free T4 to distinguish subclinical from overt hypothyroidism. 1
- TSH has >98% sensitivity and >92% specificity for detecting thyroid dysfunction, making it the optimal screening test 1
- If TSH is elevated, measure free T4 to classify the disorder:
- Confirm elevated TSH with repeat testing after 3–6 weeks, as 30–60% of elevated values normalize spontaneously 1
- Measure anti-TPO antibodies to identify autoimmune etiology (Hashimoto's thyroiditis), which predicts higher progression risk: 4.3% per year versus 2.6% in antibody-negative patients 1
Special Diagnostic Considerations
- Low TSH with low free T4 suggests central (secondary/tertiary) hypothyroidism—requires evaluation for pituitary or hypothalamic disease 2
- In pregnant women, measure both TSH and free T4 as soon as pregnancy is confirmed 2
- Free T3 measurement is generally not needed for hypothyroidism diagnosis, as it may remain normal even in overt disease 1
Treatment of Hypothyroidism
Treatment Thresholds Based on TSH Level
Initiate levothyroxine immediately for TSH >10 mIU/L regardless of symptoms, as this carries ~5% annual risk of progression to overt hypothyroidism and is associated with cardiac dysfunction and adverse lipid profiles 1
- TSH >10 mIU/L with normal free T4: Start levothyroxine 1
- TSH 4.5–10 mIU/L with normal free T4: Do NOT routinely treat asymptomatic patients, as randomized trials show no symptomatic benefit 1
- Any TSH elevation with low free T4 (overt hypothyroidism): Start levothyroxine immediately 1, 2
Levothyroxine Dosing
For adults <70 years without cardiac disease: Start with full replacement dose of 1.6 mcg/kg/day 1, 3
For adults >70 years OR with cardiac disease/multiple comorbidities: Start with 25–50 mcg/day and titrate slowly 1, 2, 3
- Increase by 12.5–25 mcg increments every 6–8 weeks based on TSH response 1, 3
- Smaller increments (12.5 mcg) are preferred for elderly or cardiac patients to avoid precipitating angina, arrhythmias, or heart failure 1
For pregnant women with pre-existing hypothyroidism: Increase levothyroxine dose by 25–50% immediately upon pregnancy confirmation 1, 3
- Target TSH <2.5 mIU/L in first trimester 1
- Monitor TSH and free T4 every 4 weeks until stable, then at minimum once per trimester 1
Critical Safety Precaution
Before starting levothyroxine, ALWAYS rule out adrenal insufficiency, especially in suspected central hypothyroidism or patients with autoimmune disease 1, 2
- Measure morning cortisol and ACTH 1
- If adrenal insufficiency is present, start hydrocortisone 20 mg AM + 10 mg afternoon for at least 1 week BEFORE initiating levothyroxine to prevent adrenal crisis 1
Monitoring and Dose Adjustment
Recheck TSH and free T4 every 6–8 weeks after any dose change until target TSH is achieved 1, 2
- Target TSH: 0.5–4.5 mIU/L for primary hypothyroidism 1
- For central hypothyroidism, do NOT use TSH to guide therapy—instead, target free T4 in the upper half of normal range 2, 3
- Once stable, monitor TSH every 6–12 months or sooner if symptoms change 1
Common Pitfalls to Avoid
- Never treat based on a single elevated TSH—confirm with repeat testing 1
- Approximately 25% of patients on levothyroxine are unintentionally overtreated (TSH <0.1 mIU/L), increasing risk for atrial fibrillation (3–5 fold), osteoporosis, fractures, and cardiovascular mortality 1
- If TSH becomes suppressed (<0.1 mIU/L), reduce levothyroxine by 25–50 mcg immediately 1
- If TSH 0.1–0.45 mIU/L, reduce by 12.5–25 mcg, especially in elderly or cardiac patients 1
Evaluation of Hyperthyroidism
Initial Laboratory Assessment
Measure TSH first; if suppressed, measure free T4 and free T3 to distinguish subclinical from overt hyperthyroidism 4, 5
- Overt hyperthyroidism: Suppressed TSH + elevated free T4 and/or free T3 4, 5
- Subclinical hyperthyroidism: Suppressed TSH + normal free T4 and free T3 1
- T3 toxicosis: Suppressed TSH + normal free T4 + elevated free T3 4, 5
Diagnostic Strategy
- Free T3 measurement is essential when hyperthyroidism is suspected, as T3 may be elevated even when free T4 is normal 4, 5
- Free hormone measurements are superior to total hormone levels, as they are unaffected by binding protein abnormalities 5
- Consider TRH stimulation test in equivocal cases, though newer sensitive TSH assays often obviate this need 4
Treatment of Hyperthyroidism
Antithyroid Drug Selection
Methimazole is the preferred first-line antithyroid drug for most patients, including children, due to once-daily dosing and lower risk of severe side effects 6
Propylthiouracil (PTU) is reserved for specific situations:
- First trimester of pregnancy (methimazole is teratogenic) 6
- Thyroid storm 6
- Patients intolerant to methimazole 6
- PTU has additional benefit of blocking peripheral T4-to-T3 conversion, which methimazole does not 7
Dosing
Propylthiouracil (PTU) 8:
- Initial dose: 300 mg daily in 3 divided doses (every 8 hours) 8
- Severe hyperthyroidism or large goiter: May increase to 400 mg daily; occasionally 600–900 mg daily initially 8
- Maintenance dose: 100–150 mg daily 8
- Pediatric dosing (≥6 years): Start with 50 mg daily and titrate carefully based on TSH and free T4 8
- PTU is generally NOT recommended in children except when alternatives are inappropriate 8
Methimazole 6:
- Preferred over PTU due to longer half-life allowing once-daily dosing and fewer side effects at low doses 6
- Drug-related hepatitis and vasculitis are almost exclusively seen with PTU, not methimazole 6
Adjunctive Therapy
Beta-adrenergic antagonists (e.g., propranolol, atenolol) are safe adjunctive therapy to control symptoms (tachycardia, tremor, anxiety) while awaiting antithyroid drug effect 6
Iodine (e.g., Lugol's solution, potassium iodide) may be used for limited periods:
Monitoring
- Recheck TSH, free T4, and free T3 every 4–6 weeks during initial treatment 1
- Once euthyroid, monitor every 3–6 months 1
- Watch for signs of overtreatment (iatrogenic hypothyroidism): rising TSH, falling free T4 1
Special Populations
Elderly Patients
- Start levothyroxine at 25–50 mcg/day regardless of TSH level if cardiac disease or multiple comorbidities present 1, 2
- Titrate slowly by 12.5 mcg increments every 6–8 weeks 1
- TSH reference range shifts upward with age: ~12% of patients >80 years have TSH >4.5 mIU/L without thyroid disease 1
- Avoid TSH suppression (<0.45 mIU/L) due to dramatically increased risk of atrial fibrillation and fractures 1
Cardiac Disease
- Start levothyroxine at 25–50 mcg/day to avoid unmasking ischemia or precipitating arrhythmias 1, 2, 3
- Titrate every 6–8 weeks (slower than non-cardiac patients) 1
- Monitor closely for angina, palpitations, dyspnea, or worsening heart failure 1
Pregnancy
- Treat ANY TSH elevation immediately in pregnant women or those planning pregnancy 1
- Target TSH <2.5 mIU/L in first trimester 1
- Increase pre-pregnancy levothyroxine dose by 25–50% immediately upon pregnancy confirmation 1, 3
- Monitor TSH and free T4 every 4 weeks until stable, then at minimum once per trimester 1
- Use PTU (not methimazole) in first trimester if antithyroid drug needed for hyperthyroidism 6
Large Goiter
- For hyperthyroidism with large goiter, may require higher initial PTU doses (400–900 mg daily) 8
- Consider surgical or radioactive iodine therapy if medical management fails 6
Key Monitoring Intervals Summary
| Clinical Scenario | Monitoring Interval | Target |
|---|---|---|
| Dose titration (hypothyroidism) | Every 6–8 weeks [1] | TSH 0.5–4.5 mIU/L [1] |
| Stable levothyroxine dose | Every 6–12 months [1] | TSH 0.5–4.5 mIU/L [1] |
| Pregnancy (hypothyroidism) | Every 4 weeks until stable, then each trimester [1] | TSH <2.5 mIU/L (1st trimester) [1] |
| Hyperthyroidism treatment | Every 4–6 weeks initially [1] | Normalize TSH, free T4, free T3 [1] |
| Cardiac disease or elderly | Every 6–8 weeks during titration [1] | TSH 0.5–4.5 mIU/L (avoid suppression) [1] |