What is the appropriate treatment for a woman with Hashimoto’s thyroiditis presenting with fatigue, cold intolerance, weight gain, menstrual changes, dry skin, and low free T4?

Treatment of Hashimoto's Thyroiditis with Symptomatic Hypothyroidism

Initiate levothyroxine immediately at 1.6 mcg/kg/day for this woman with overt hypothyroidism (low free T4) due to Hashimoto's thyroiditis, as her symptoms of fatigue, cold intolerance, weight gain, menstrual changes, and dry skin combined with low free T4 indicate thyroid hormone deficiency requiring prompt replacement therapy. 1, 2

Confirming the Diagnosis

Before starting treatment, confirm the diagnosis with:

• Measure TSH and free T4 together to distinguish overt hypothyroidism (elevated TSH with low free T4) from subclinical hypothyroidism (elevated TSH with normal free T4), as both require different management approaches 1
• Check anti-thyroid peroxidase (anti-TPO) antibodies to confirm Hashimoto's thyroiditis as the underlying cause, which predicts higher progression risk (4.3% per year vs 2.6% in antibody-negative patients) 1
• Rule out concurrent adrenal insufficiency by measuring morning cortisol and ACTH before starting levothyroxine, as initiating thyroid hormone before adequate corticosteroid coverage can precipitate life-threatening adrenal crisis 1, 3

Initial Levothyroxine Dosing Strategy

For patients under 70 years without cardiac disease:

• Start levothyroxine at 1.6 mcg/kg/day as a single daily dose on an empty stomach, 30-60 minutes before breakfast 1, 2
• This full replacement dose rapidly normalizes thyroid function and prevents complications including cardiovascular dysfunction and adverse lipid profiles 1

For patients over 70 years or with cardiac disease:

• Start at a lower dose of 25-50 mcg/day and titrate gradually by 12.5-25 mcg every 6-8 weeks to avoid unmasking cardiac ischemia or precipitating arrhythmias 1, 3
• Elderly patients with coronary disease are at increased risk of cardiac decompensation even with therapeutic levothyroxine doses 1

Monitoring and Dose Adjustment

Initial monitoring phase:

• Recheck TSH and free T4 every 6-8 weeks after any dose adjustment, as this represents the time needed to reach steady state 1, 3
• Target TSH within the reference range of 0.5-4.5 mIU/L with normal free T4 levels 1
• Adjust levothyroxine by 12.5-25 mcg increments based on TSH response until target is achieved 1

Long-term maintenance:

• Once stable, repeat TSH testing every 6-12 months or sooner if symptoms change 1, 3
• Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 1

Special Considerations for Women of Reproductive Age

If planning pregnancy:

• Optimize thyroid function before conception, targeting TSH <2.5 mIU/L in the first trimester 1
• Untreated maternal hypothyroidism increases risk of preeclampsia, low birth weight, and permanent neurodevelopmental deficits in the child 1
• Levothyroxine requirements typically increase by 25-50% during pregnancy, requiring immediate dose adjustment upon pregnancy confirmation 1, 3
• Monitor TSH every 4 weeks during pregnancy until stable, then at minimum once per trimester 3

Critical Safety Precautions

Before initiating levothyroxine:

• Never start thyroid hormone before ruling out adrenal insufficiency in patients with suspected central hypothyroidism or hypophysitis, as this can precipitate adrenal crisis 1, 3
• If adrenal insufficiency is present, start hydrocortisone at least one week prior to levothyroxine initiation 1

Avoiding overtreatment:

• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, increasing risks for atrial fibrillation, osteoporosis, fractures, and cardiovascular mortality 1
• If TSH falls below 0.1 mIU/L, reduce levothyroxine dose by 25-50 mcg immediately 1
• For TSH 0.1-0.45 mIU/L, decrease dose by 12.5-25 mcg, particularly in elderly or cardiac patients 1

Expected Symptom Improvement Timeline

Symptomatic relief occurs within:

• 6-8 weeks for fatigue, weight stabilization, and improved energy levels 1
• 3-4 months for extensive hair loss, which is a cardinal symptom of hypothyroidism 1
• Cold intolerance, dry skin, and menstrual irregularities typically improve within the first 2-3 months of adequate replacement 2

Common Pitfalls to Avoid

• Do not treat based on a single elevated TSH value, as 30-60% normalize on repeat testing and may represent transient thyroiditis in recovery phase 1
• Avoid adjusting doses too frequently before reaching steady state—wait 6-8 weeks between adjustments 1
• Do not ignore persistent symptoms despite normalized TSH, as this may indicate inadequate absorption, poor compliance, drug interactions, or need for reassessment of other causes 3
• Never assume hypothyroidism is permanent without reassessment, especially in children and adolescents where Hashimoto's thyroiditis can go into remission 4, 5

Alternative Considerations

Combination T4/T3 therapy:

• Adding liothyronine (T3) to levothyroxine is not routinely recommended, even in patients with persistent symptoms and normal TSH levels 2
• Some patients with persistent symptoms despite adequate levothyroxine dosing may benefit from combination therapy, though robust selection criteria remain undefined 6

Adjunctive therapies:

• Selenium supplementation has shown modest benefit in reducing thyroid autoantibody titers and may improve symptoms in some patients 6, 5
• Vitamin D supplementation may provide additional symptomatic relief, though evidence quality is limited 6