What medication should be started for a patient with severe primary hypothyroidism (TSH ~141 mU/L, free T4 <0.1 ng/dL, T3 ~0.11 ng/mL) who presents with xerosis?

Levothyroxine for Severe Primary Hypothyroidism with Xerosis

Start levothyroxine immediately for this patient with severe overt primary hypothyroidism (TSH 141 mU/L, T4 <0.1 ng/dL, T3 0.11 ng/mL), as this represents life-threatening thyroid failure requiring urgent hormone replacement. 1, 2

Critical Safety Assessment Before Starting Treatment

Before initiating levothyroxine, you must rule out concurrent adrenal insufficiency, as starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis. 1

• Measure morning (8 AM) serum cortisol and ACTH immediately 1
• If cortisol is low or if the patient has hypotension, hyponatremia, or unexplained symptoms suggesting adrenal insufficiency, start hydrocortisone 20/10 mg for at least 1 week before initiating levothyroxine 3, 1
• The increased cortisol metabolism from thyroid hormone can trigger adrenal crisis in patients with occult adrenal insufficiency 1

Initial Levothyroxine Dosing Strategy

For this patient with severe hypothyroidism, start with a conservative dose and titrate gradually, as rapid normalization can cause serious complications. 1, 2

If Patient is <70 Years Without Cardiac Disease:

• Start levothyroxine 50-75 mcg daily (NOT full replacement dose of 1.6 mcg/kg/day) 1, 2
• The severity of hypothyroidism (TSH 141) mandates cautious initiation even in younger patients 1

If Patient is >70 Years OR Has Any Cardiac Disease:

• Start levothyroxine 25 mcg daily 1, 2
• Rapid normalization can unmask cardiac ischemia, precipitate arrhythmias, or cause heart failure 1
• Elderly patients with underlying coronary disease are at increased risk of cardiac decompensation even with therapeutic doses 1

Dosing Administration

Administer levothyroxine as a single daily dose on an empty stomach, one-half to one hour before breakfast with a full glass of water. 2

• Take at least 4 hours before or after iron, calcium supplements, or antacids 1, 2
• Avoid administration with soybean-based foods that decrease absorption 2

Monitoring and Titration Protocol

Recheck TSH and free T4 in 6-8 weeks after starting therapy, as this represents the time needed to reach steady state. 1

• Increase dose by 12.5-25 mcg increments every 6-8 weeks based on TSH response 1, 2
• For elderly or cardiac patients, use smaller increments (12.5 mcg) and longer intervals (8 weeks) 1
• Target TSH within reference range (0.5-4.5 mIU/L) with normal free T4 1
• Once stable, monitor TSH every 6-12 months 1

Why Xerosis Will Improve

The patient's xerosis (dry skin) is a cardinal manifestation of severe hypothyroidism and will improve within 3-4 months of adequate levothyroxine replacement. 1

• Hypothyroidism causes decreased sweat and sebaceous gland activity, leading to dry, coarse skin 1
• Skin symptoms typically resolve as thyroid hormone levels normalize 1
• Other symptoms (fatigue, cold intolerance, weight changes) should improve within 6-8 weeks 1

Critical Pitfalls to Avoid

Never start at full replacement dose (1.6 mcg/kg/day) in severe hypothyroidism, as this can precipitate myocardial infarction, heart failure, or fatal arrhythmias. 1

• Approximately 25% of patients are unintentionally overtreated, leading to TSH suppression and increased risk of atrial fibrillation, osteoporosis, and cardiac complications 1
• Do not adjust doses more frequently than every 6-8 weeks, as steady state has not been reached 1
• Never ignore the possibility of central hypothyroidism or hypophysitis—if suspected, always start corticosteroids before levothyroxine 3, 1

Special Monitoring Considerations

Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize than free T4. 1

• T3 measurement adds no value in monitoring levothyroxine replacement therapy 4, 5
• In levothyroxine-treated patients, T3 levels do not correlate with thyroid status and normal T3 can be seen even in over-replaced patients 4
• TSH is the most sensitive test for monitoring with sensitivity >98% and specificity >92% 1, 5

Long-term Management

Once adequately treated with TSH in target range, repeat testing every 6-12 months or if symptoms change. 1

• Development of low TSH (<0.1-0.45 mIU/L) suggests overtreatment requiring dose reduction 1
• Patients should ensure adequate calcium (1200 mg/day) and vitamin D (1000 units/day) intake if TSH becomes chronically suppressed 1
• Monitor for symptoms of overtreatment: tachycardia, tremor, heat intolerance, weight loss 1