In a 45‑year‑old woman with Hashimoto’s thyroiditis and elevated thyroid‑stimulating hormone, when should levothyroxine be initiated, what initial dose is recommended, and how should therapy be monitored?

Management of Hashimoto's Thyroiditis with Elevated TSH

When to Initiate Levothyroxine

Initiate levothyroxine immediately for any patient with Hashimoto's thyroiditis and TSH >10 mIU/L, regardless of symptoms or age. 1

• For TSH persistently >10 mIU/L with normal free T4 (subclinical hypothyroidism), treatment is mandatory due to approximately 5% annual risk of progression to overt hypothyroidism 1
• Treatment may prevent cardiovascular dysfunction, adverse lipid profiles, and deterioration in quality of life 1
• The presence of positive TPO antibodies (characteristic of Hashimoto's) increases progression risk to 4.3% per year versus 2.6% in antibody-negative individuals 1

For TSH 4.5-10 mIU/L with normal free T4, treatment decisions require more nuance:

• Treat immediately if the patient is symptomatic (fatigue, weight gain, cold intolerance, constipation) 1
• Treat immediately if the patient is pregnant or planning pregnancy, targeting TSH <2.5 mIU/L in first trimester 1
• Consider treatment if positive TPO antibodies are present (which they are in Hashimoto's), given the higher progression risk 1
• For asymptomatic patients without pregnancy plans, monitoring TSH every 6-12 months is acceptable 1

Before initiating treatment, confirm the diagnosis:

• Repeat TSH measurement after 3-6 weeks, as 30-60% of elevated TSH levels normalize spontaneously 1
• Measure both TSH and free T4 to distinguish subclinical from overt hypothyroidism 1
• Never treat based on a single elevated TSH value 1

Critical safety consideration: Before starting levothyroxine, rule out concurrent adrenal insufficiency by checking morning cortisol and ACTH, as thyroid hormone can precipitate life-threatening adrenal crisis 1, 2

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Initial Levothyroxine Dosing

For patients <70 years without cardiac disease or multiple comorbidities:

• Start with full replacement dose of approximately 1.6 mcg/kg/day based on lean body weight 1, 2, 3
• This approach rapidly normalizes thyroid function and prevents prolonged hypothyroid symptoms 1

For patients >70 years OR with cardiac disease/multiple comorbidities:

• Start with a lower dose of 25-50 mcg/day 1, 2
• Titrate gradually by 12.5-25 mcg increments every 6-8 weeks 1, 2
• This conservative approach prevents unmasking cardiac ischemia or precipitating arrhythmias 1
• Elderly patients with coronary disease are at increased risk of cardiac decompensation even with therapeutic levothyroxine doses 1

Dosing considerations specific to Hashimoto's:

• The dose typically ranges from 1.4 to 1.8 mcg/kg/day based on degree of preserved thyroid functionality and lean body mass 3
• Use ideal body weight rather than actual body weight for obese patients 1

Administration instructions:

• Take levothyroxine on an empty stomach, 30-60 minutes before breakfast 1, 2
• Separate from iron, calcium supplements, or antacids by at least 4 hours 1

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Monitoring and Dose Adjustment

Initial monitoring during dose titration:

• Recheck TSH and free T4 every 6-8 weeks after any dose adjustment 1, 2
• This 6-8 week interval is critical because it represents the time needed to reach steady state 1
• The peak therapeutic effect may not be attained for 4-6 weeks 2

Target TSH levels:

• For primary hypothyroidism, target TSH within the reference range of 0.5-4.5 mIU/L with normal free T4 1, 2
• Titrate by 12.5-25 mcg increments based on patient's current dose and clinical characteristics 1
• Use smaller increments (12.5 mcg) for elderly patients or those with cardiac disease 1

Long-term monitoring after stabilization:

• Once TSH is stable in target range, monitor every 6-12 months 1, 2
• Recheck sooner if symptoms change or new medications are started 1

Interpreting results during therapy:

• Free T4 can help interpret ongoing abnormal TSH levels, as TSH may take longer to normalize 1
• Development of low TSH (<0.1-0.45 mIU/L) suggests overtreatment—reduce dose by 12.5-25 mcg 1
• TSH <0.1 mIU/L requires immediate dose reduction by 25-50 mcg to prevent atrial fibrillation, osteoporosis, and cardiovascular complications 1

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Common Pitfalls and How to Avoid Them

Overtreatment is extremely common and dangerous:

• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH 1
• Prolonged TSH suppression increases risk of atrial fibrillation (3-5 fold), osteoporosis, fractures, and cardiovascular mortality 1
• This risk is particularly high in elderly patients and postmenopausal women 1

Adjusting doses too frequently:

• Never adjust levothyroxine before 6-8 weeks have elapsed since the last change 1
• Premature adjustments lead to inappropriate dosing before steady state is reached 1

Missing transient thyroiditis:

• Some patients with Hashimoto's experience an initial thyrotoxic phase (Hashitoxicosis) when stored thyroid hormones are released from destroyed follicles 3
• This may be followed by euthyroidism, then eventual hypothyroidism 3
• Failure to recognize transient hypothyroidism may lead to unnecessary lifelong treatment 1

Inadequate monitoring in special populations:

• Pregnant women with pre-existing hypothyroidism require TSH checks every 4 weeks until stable, then at minimum once per trimester 1, 2
• Levothyroxine requirements typically increase by 25-50% during pregnancy 1, 2
• Untreated or inadequately treated maternal hypothyroidism increases risk of preeclampsia, low birth weight, and neurodevelopmental deficits 1

Missing concurrent adrenal insufficiency:

• Patients with autoimmune hypothyroidism have increased risk of concurrent autoimmune adrenal insufficiency (Addison's disease) 1
• Always start corticosteroids at least 1 week before levothyroxine if adrenal insufficiency is present 1, 2
• Starting thyroid hormone before addressing adrenal insufficiency can precipitate life-threatening adrenal crisis 1, 2