How should levothyroxine be restarted and what initial dose should be used in an adult who stopped taking 137 µg daily for several months and now has severe untreated hypothyroidism?

Restarting Levothyroxine in Severe Hypothyroidism After Prolonged Discontinuation

Immediate Restart Strategy

Restart levothyroxine immediately at 100–112 mcg daily (approximately 75% of the previous 137 mcg dose) if the patient is under 70 years old without cardiac disease, then titrate upward by 12.5–25 mcg every 6–8 weeks based on TSH response. 1

For a TSH of 211.999 mIU/L, this represents severe overt hypothyroidism requiring prompt treatment to prevent cardiovascular complications, metabolic derangements, and potential progression to myxedema coma. 2

Critical Pre-Treatment Safety Assessment

Before administering the first levothyroxine dose, you must exclude concurrent adrenal insufficiency by obtaining morning (8 AM) serum cortisol and ACTH levels. 1 Starting thyroid hormone before adequate glucocorticoid coverage can precipitate life-threatening adrenal crisis, particularly in patients with autoimmune hypothyroidism who may have concurrent autoimmune adrenal insufficiency. 1

• If morning cortisol is low or clinical features suggest adrenal insufficiency (hypotension, hyponatremia, unexplained symptoms), initiate hydrocortisone 20 mg in the morning and 10 mg in the afternoon for at least one week before starting levothyroxine. 1

Age and Cardiac Risk-Stratified Dosing

For Patients Under 70 Without Cardiac Disease

• Start with 100–112 mcg daily (approximately 75% of the previous 137 mcg dose, rather than the full replacement dose of 1.6 mcg/kg/day). 1, 3
• This approach balances the need for rapid normalization against the risk of unmasking subclinical cardiac disease after months of severe hypothyroidism. 1
• The full replacement dose of 1.6 mcg/kg/day can be considered, but starting slightly lower provides a safety margin given the prolonged period of severe hypothyroidism. 1, 3

For Patients Over 70 or With Cardiac Disease

• Start with 25–50 mcg daily to avoid precipitating myocardial infarction, heart failure, or arrhythmias. 1, 3, 4
• Elderly patients with underlying coronary disease are at increased risk of cardiac decompensation even with therapeutic levothyroxine doses. 1
• Rapid normalization can unmask or worsen cardiac ischemia in patients with coronary artery disease. 1

Titration Protocol

• Recheck TSH and free T4 every 6–8 weeks after each dose adjustment, as levothyroxine requires this interval to reach steady state. 1, 3
• Increase the dose by 12.5–25 mcg increments based on TSH response until the target TSH of 0.5–4.5 mIU/L is achieved. 1
• For elderly patients or those with cardiac disease, use smaller increments (12.5 mcg) to minimize cardiac risk. 1
• Target TSH: 0.5–4.5 mIU/L with normal free T4 levels. 1

Administration Instructions

• Administer as a single daily dose on an empty stomach, 30–60 minutes before breakfast with a full glass of water to optimize absorption and avoid choking. 1, 3
• Wait at least 4 hours before or after taking iron, calcium supplements, or antacids, as these interfere with levothyroxine absorption. 1, 3

Monitoring for Cardiovascular Complications

Given the severity of hypothyroidism (TSH >200 mIU/L), this patient has likely developed cardiac dysfunction including:

• Delayed myocardial relaxation and abnormal cardiac output 1
• Increased systemic vascular resistance 1
• Potential diastolic heart failure 1

Obtain a baseline ECG to screen for bradycardia or conduction abnormalities, and monitor closely for:

• New or worsening angina, palpitations, or dyspnea 1
• Signs of heart failure decompensation 1
• Atrial fibrillation or other arrhythmias 1

Long-Term Monitoring After Stabilization

• Once the target TSH is achieved and the patient is on a stable dose, repeat TSH every 6–12 months or sooner if symptoms change. 1
• Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize. 1

Common Pitfalls to Avoid

Never start at the full previous dose of 137 mcg after months of severe hypothyroidism, as the cardiovascular system has adapted to the hypothyroid state and rapid normalization carries significant cardiac risk. 1

Do not adjust doses more frequently than every 6–8 weeks, as levothyroxine requires this time to reach steady state; premature adjustments risk overcorrection and iatrogenic hyperthyroidism. 1

Approximately 25% of patients on levothyroxine are unintentionally overtreated with suppressed TSH, which increases the risk of atrial fibrillation (3–5 fold), osteoporosis, fractures, and cardiovascular mortality. 1 Regular monitoring is essential to avoid this.

Why the Patient Stopped Taking Levothyroxine

While not directly affecting the restart strategy, explore reasons for non-adherence to prevent future discontinuation:

• Cost or access barriers 5
• Side effects or concerns about medication 5
• Lack of understanding about the need for lifelong therapy 5
• Psychiatric factors (pseudomalabsorption) 5

If non-compliance is suspected to be ongoing, consider supervised weekly dosing of 1,000 mcg levothyroxine as an alternative strategy, though this is controversial and should only be used after psychiatric evaluation. 5