What is the initial treatment for a patient with severe hypothyroidism (elevated Thyroid-Stimulating Hormone (TSH))?

Initial Treatment for Severe Hypothyroidism (TSH ~300)

For a patient with severely elevated TSH around 300 mIU/L, initiate levothyroxine immediately at a dose of 1.6 mcg/kg/day for patients under 70 years without cardiac disease, or start at 25-50 mcg/day for elderly patients or those with known cardiac disease, and monitor TSH every 6-8 weeks during dose titration. 1, 2

Critical Pre-Treatment Assessment

Before starting levothyroxine, you must rule out concurrent adrenal insufficiency, particularly if there are any signs of central hypothyroidism (low TSH with low free T4 in other contexts) or hypophysitis. Always start corticosteroids several days before thyroid hormone if adrenal insufficiency is present or suspected, as initiating levothyroxine first can precipitate adrenal crisis. 3, 1

• Measure morning cortisol and ACTH to exclude adrenal insufficiency 3
• Confirm the diagnosis with both TSH and free T4 levels; a TSH of 300 with low free T4 confirms overt primary hypothyroidism 2, 4
• Check for symptoms of severe hypothyroidism: fatigue (68-83% of patients), weight gain (24-59%), cognitive issues (45-48%), and menstrual irregularities (23%) 4

Initial Dosing Strategy

For Patients Under 70 Years Without Cardiac Disease

Start with full replacement dose of 1.6 mcg/kg/day taken on an empty stomach. 1, 5

• This approach reduces the need for multiple follow-up visits and repeated dose adjustments 6
• Rapid restoration of normal thyroid hormone levels is essential to prevent complications 7
• Most young, otherwise healthy patients tolerate full-dose initiation well 6, 8

For Elderly Patients (>70 Years) or Those With Cardiac Disease

Start with a conservative dose of 25-50 mcg/day and titrate gradually. 1, 7, 5

• Elderly patients have increased prevalence of cardiovascular disease requiring cautious initiation 7
• Atrial fibrillation is the most common arrhythmia with levothyroxine overtreatment in the elderly 7
• Even minor over-replacement during initial titration can trigger cardiac events in patients with coronary artery disease 6
• Increase dose by 12.5-25 mcg every 6-8 weeks based on TSH response 1

Monitoring Protocol

Check TSH and free T4 every 6-8 weeks while titrating the dose until TSH normalizes within the reference range (0.5-4.5 mIU/L). 1, 2, 4

• Free T4 helps interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 1, 2
• Wait the full 6-8 weeks between dose adjustments to allow levothyroxine to reach steady state 1
• For patients with atrial fibrillation or serious cardiac conditions, consider more frequent monitoring within 2 weeks of dose adjustment 1

Long-Term Management

Once TSH is stable within the reference range:

• Monitor TSH every 6-12 months or when symptoms change 1, 2, 4
• Target TSH of 0.5-2.0 mIU/L for optimal replacement 8
• Development of low TSH on therapy suggests overtreatment; reduce dose by 12.5-25 mcg 1, 2

Critical Pitfalls to Avoid

Overtreatment occurs in 14-21% of treated patients and significantly increases morbidity. 1

• TSH suppression (<0.1 mIU/L) increases risk of atrial fibrillation, especially in elderly patients 1, 7
• Chronic over-replacement causes osteoporosis and fractures, particularly in postmenopausal women 6, 9
• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses that fully suppress TSH 1

Never start thyroid hormone before ruling out and treating adrenal insufficiency in patients with suspected central causes. 3, 1

• This can precipitate life-threatening adrenal crisis 3
• If both conditions are present, start hydrocortisone several days before levothyroxine 3

Avoid adjusting doses too frequently before steady state is reached. 1

• Levothyroxine has a long half-life requiring 6-8 weeks to reach equilibrium 9
• Premature dose changes lead to overcorrection and cycling between over- and under-treatment 1

Special Considerations

Pregnancy

If the patient is pregnant or planning pregnancy, treatment is urgent. 1, 7, 5

• Untreated hypothyroidism increases risk of spontaneous abortion, preeclampsia, stillbirth, and adverse fetal neurocognitive development 7
• Pregnant women should increase their weekly levothyroxine dosage by 30% (take one extra dose twice per week) 5
• Monitor TSH monthly during pregnancy and adjust doses promptly 7

Myxedema Coma Risk

With TSH of 300, assess for signs of severe decompensation (myxedema coma): hypothermia, hypotension, altered mental status. 4

• This is a medical emergency requiring ICU treatment with mortality up to 30% 4
• If present, this requires immediate high-dose intravenous levothyroxine and supportive care 4