What is the recommended management for hypothyroidism?

Hypothyroidism Management

Diagnostic Confirmation and Initial Assessment

Start levothyroxine immediately for overt hypothyroidism (elevated TSH with low free T4), and confirm subclinical hypothyroidism (elevated TSH with normal free T4) with repeat testing after 3-6 weeks before initiating treatment, as 30-60% of elevated TSH levels normalize spontaneously. 1, 2

• Measure both TSH and free T4 to distinguish between overt hypothyroidism (low free T4) and subclinical hypothyroidism (normal free T4) 1
• TSH is the most sensitive screening test with sensitivity above 98% and specificity greater than 92% 1
• Consider anti-TPO antibody testing to identify autoimmune etiology and predict progression risk (4.3% vs 2.6% per year in antibody-negative individuals) 1, 2
• Evaluate for precipitating factors: recent iodine exposure from CT contrast, medications (amiodarone, immune checkpoint inhibitors), neck surgery or radiation, pregnancy, and family history 1, 3

Treatment Algorithm Based on TSH Levels

Overt Hypothyroidism (Elevated TSH + Low Free T4)

Initiate levothyroxine immediately at full replacement dose for most patients. 1, 3

• For patients <70 years without cardiac disease: Start levothyroxine 1.6 mcg/kg/day 1, 2, 4
• For patients >70 years OR with cardiac disease/atrial fibrillation: Start at 25-50 mcg/day and titrate gradually to avoid cardiac complications 5, 1, 2, 3
• For patients with long-standing severe hypothyroidism: Use lower starting doses regardless of age 6

Subclinical Hypothyroidism (Elevated TSH + Normal Free T4)

For TSH >10 mIU/L: Initiate levothyroxine therapy regardless of symptoms, as this carries approximately 5% annual risk of progression to overt hypothyroidism. 1, 2, 6

For TSH 4.5-10 mIU/L: Do not routinely treat, but monitor TSH every 6-12 months. 1, 2, 6

• Treat TSH 4.5-10 mIU/L in these specific situations: 1, 2, 6

  • Pregnant women or women planning pregnancy (any TSH elevation warrants treatment due to risk of preeclampsia, low birth weight, and neurodevelopmental effects) 1, 2
  • Symptomatic patients with fatigue, weight gain, cold intolerance, or cognitive complaints—consider 3-4 month trial with clear evaluation of benefit 1, 2
  • Positive anti-TPO antibodies (higher progression risk) 1, 2
  • Presence of goiter 2, 6
  • Infertility 6

• Avoid treatment in patients >85 years with TSH 4.5-10 mIU/L unless symptomatic 6

Critical Pre-Treatment Considerations

In patients with suspected central hypothyroidism or hypophysitis, always initiate corticosteroids BEFORE starting levothyroxine to prevent adrenal crisis. 5, 1

• Evaluate morning cortisol and ACTH if central hypothyroidism suspected 5
• Start hydrocortisone 15 mg AM and 5 mg at 3 PM before thyroid hormone replacement 5

Monitoring and Dose Adjustment

Recheck TSH and free T4 every 6-8 weeks after initiating therapy or changing dose until TSH normalizes to 0.5-4.5 mIU/L. 5, 1, 2, 3

• Dose adjustment increments: Increase or decrease by 12.5-25 mcg based on current dose 5, 1
• Target TSH range: 0.5-2.0 mIU/L for primary hypothyroidism 2, 6
• Once stable: Monitor TSH annually or sooner if symptoms change 5, 1, 3

Managing Persistent Elevation Despite Treatment

If TSH remains elevated on adequate dose, evaluate: 1, 6

• Poor compliance (most common cause)
• Malabsorption (celiac disease, inflammatory bowel disease, gastric bypass)
• Drug interactions (calcium, iron, proton pump inhibitors, bile acid sequestrants taken within 4 hours of levothyroxine)
• Inadequate dose (increase by 12.5-25 mcg) 1

Managing Suppressed TSH on Treatment

If TSH <0.1 mIU/L: Reduce levothyroxine dose by 25-50 mcg immediately to prevent atrial fibrillation, osteoporosis, and cardiovascular complications. 1

• First confirm indication for therapy—thyroid cancer patients may require intentional TSH suppression (consult endocrinology) 1
• For primary hypothyroidism without thyroid cancer, dose reduction is mandatory 1
• Prolonged TSH suppression increases risk of atrial fibrillation (especially elderly), osteoporosis, fractures, and cardiovascular mortality 5, 1

Special Populations

Pregnancy

Increase levothyroxine dose by 25-50% immediately upon pregnancy confirmation in women with pre-existing hypothyroidism. 4

• Monitor TSH every 6-8 weeks during pregnancy and adjust to maintain TSH in lower half of reference range 2, 4
• Untreated hypothyroidism causes spontaneous abortion, preeclampsia, stillbirth, premature delivery, and impaired fetal neurocognitive development 4, 3
• Return to pre-pregnancy dose immediately after delivery 4

Elderly Patients

Start at 25-50 mcg/day in patients >70 years to minimize cardiac risk, even if this delays achieving target TSH. 1, 2, 3

• Atrial fibrillation is the most common arrhythmia with levothyroxine overtreatment in elderly 4
• For elderly with TSH 4.5-10 mIU/L and asymptomatic, consider monitoring without treatment 1

Immune Checkpoint Inhibitor-Induced Hypothyroidism

Continue checkpoint inhibitors while treating hypothyroidism with standard levothyroxine replacement. 5

• Most patients develop permanent hypothyroidism requiring lifelong treatment 5
• Often preceded by transient thyrotoxicosis phase—monitor TSH every 2-3 weeks initially to catch transition 5
• Beta-blockers (atenolol 25-50 mg daily) for symptomatic relief during hyperthyroid phase 5

Critical Pitfalls to Avoid

• Never treat based on single elevated TSH—30-60% normalize on repeat testing 1, 2
• Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism 5, 1
• Avoid overtreatment—occurs in 14-21% of patients and 25% are unintentionally maintained on TSH-suppressive doses 5, 1
• Do not adjust doses more frequently than every 6-8 weeks—levothyroxine requires this time to reach steady state 1
• Do not use combination levothyroxine plus liothyronine as first-line therapy—15 clinical trials show no clear superiority over levothyroxine monotherapy 7, 8, 9

Risks of Inadequate Treatment vs Overtreatment

Undertreatment risks: 1, 3

• Persistent hypothyroid symptoms (fatigue, weight gain, cognitive impairment)
• Cardiovascular dysfunction including heart failure
• Increased cardiovascular mortality
• Adverse pregnancy outcomes

Overtreatment risks: 5, 1, 4

• Atrial fibrillation (1 excess case per 114 patients with suppressed TSH)
• Osteoporosis and fractures (especially postmenopausal women)
• Left ventricular hypertrophy
• Increased cardiovascular mortality