How should I manage a patient with a TSH of 395 µIU/mL?

Management of TSH 395 µIU/mL

Initiate levothyroxine immediately at a dose of 1.6 mcg/kg/day for patients under 70 years without cardiac disease, or 25-50 mcg/day for elderly patients or those with cardiac disease, after first ruling out adrenal insufficiency to prevent life-threatening adrenal crisis. 1, 2, 3

Critical Safety Assessment Before Treatment

Before starting levothyroxine, you must exclude adrenal insufficiency by measuring morning cortisol and ACTH. 1, 2 A TSH this profoundly elevated (395 µIU/mL) indicates severe, long-standing hypothyroidism, which raises concern for possible concurrent adrenal insufficiency, especially if autoimmune thyroiditis is the underlying cause. 1, 4 Starting thyroid hormone before adequate corticosteroid coverage can precipitate life-threatening adrenal crisis because levothyroxine accelerates cortisol metabolism. 1, 2, 3

• If morning cortisol is low or adrenal insufficiency is suspected, start hydrocortisone 20 mg in the morning and 10 mg in the afternoon for at least one week before initiating levothyroxine. 1
• If central hypothyroidism is suspected (though unlikely with TSH this high), evaluate for other pituitary hormone deficiencies, as approximately 50% have panhypopituitarism. 2

Confirm the Diagnosis

• Measure free T4 to confirm overt hypothyroidism (which will be profoundly low with TSH 395). 1, 2, 5
• Check anti-TPO antibodies to identify autoimmune thyroiditis as the cause, which predicts ongoing thyroid dysfunction and supports the need for lifelong treatment. 1, 2, 5
• Obtain baseline complete blood count to screen for anemia, which commonly coexists with severe hypothyroidism and contributes to fatigue. 1
• Measure lipid profile, as severe hypothyroidism causes marked elevations in LDL cholesterol and triglycerides. 1, 4

Levothyroxine Dosing Strategy

For Patients Under 70 Years Without Cardiac Disease

Start with full replacement dose of 1.6 mcg/kg/day based on ideal body weight. 1, 2, 3 With TSH this severely elevated, the patient has profound thyroid hormone deficiency requiring prompt normalization. 1, 4

For Patients Over 70 Years OR With Cardiac Disease

Start with 25-50 mcg/day and titrate gradually by 12.5-25 mcg every 6-8 weeks. 1, 2, 3 Rapid normalization of thyroid hormone levels can unmask or worsen cardiac ischemia, precipitate arrhythmias, or trigger heart failure in patients with underlying coronary disease. 1, 6

• Elderly patients with coronary disease are at highest risk of cardiac decompensation even with therapeutic levothyroxine doses. 1
• Obtain baseline ECG to screen for arrhythmias before starting treatment. 1
• Monitor closely for angina, palpitations, dyspnea, or worsening heart failure symptoms during titration. 1

Special Dosing Considerations

• For obese patients, calculate dose using ideal body weight rather than actual body weight. 1
• For patients with long-standing severe hypothyroidism (which TSH 395 certainly represents), start at lower doses even in younger patients to avoid precipitating cardiac complications. 4, 7

Monitoring Protocol

Recheck TSH and free T4 in 6-8 weeks after starting treatment, as this represents the time needed to reach steady state. 1, 2, 3 Free T4 helps interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize. 1

• Continue dose adjustments by 12.5-25 mcg increments every 6-8 weeks until TSH normalizes to 0.5-4.5 mIU/L. 1, 2, 5
• Target TSH in the lower half of the reference range (0.5-2.5 mIU/L) for most adults. 5, 7
• Once adequately treated, repeat testing every 6-12 months or if symptoms change. 1, 2

Expected Clinical Response

With TSH this profoundly elevated, the patient likely has severe hypothyroid symptoms including:

• Profound fatigue and lethargy 1, 4
• Significant weight gain 1, 4
• Severe cold intolerance 1, 4
• Marked cognitive slowing or "brain fog" 1
• Constipation 1, 4
• Extensive hair loss 1
• Possible cardiac dysfunction including delayed myocardial relaxation, reduced cardiac output, and diastolic heart failure 1, 4

Symptoms should begin improving within 2-4 weeks, with substantial improvement by 6-8 weeks of adequate replacement. 1 Hair loss should improve within 3-4 months. 1

Critical Pitfalls to Avoid

• Never start levothyroxine before ruling out adrenal insufficiency in severe hypothyroidism—this can be fatal. 1, 2, 3
• Do not use TSH alone to guide treatment in the first 6-8 weeks—free T4 provides critical additional information during initial titration. 1, 2
• Avoid adjusting doses more frequently than every 6-8 weeks before reaching steady state, as this leads to inappropriate dose adjustments. 1, 2
• Do not overtitrate—approximately 25% of patients on levothyroxine are unintentionally maintained on doses that suppress TSH, increasing risks for atrial fibrillation, osteoporosis, fractures, and cardiovascular mortality. 1, 6
• In elderly patients or those with cardiac disease, never start at full replacement dose—this can precipitate myocardial infarction, heart failure, or fatal arrhythmias. 1, 4

Long-Term Management

• Once TSH normalizes, monitor annually or sooner if clinical status changes. 1, 2
• Educate patient to take levothyroxine on empty stomach, 30-60 minutes before breakfast, at least 4 hours apart from iron, calcium supplements, or antacids. 2
• Recognize that this patient will require lifelong levothyroxine therapy. 1, 4
• If patient becomes pregnant, levothyroxine requirements typically increase by 25-50%—check TSH immediately upon pregnancy confirmation and every 4 weeks during pregnancy. 1, 3