In a 60‑year‑old woman taking levothyroxine 150 µg daily who has markedly elevated thyroid‑stimulating hormone, low triiodothyronine and low thyroxine, what is the appropriate initial management?

Immediate Assessment: Severe Overt Hypothyroidism with Inadequate Treatment

This patient has severe overt hypothyroidism (TSH 94.4, T4 0.61, T3 1.8) despite taking levothyroxine 150 µg daily, indicating either non-adherence, malabsorption, or inadequate dosing—the first priority is to assess medication adherence and rule out malabsorption before increasing the dose. 1

Critical First Steps: Rule Out Non-Adherence and Malabsorption

Assess Medication Adherence

• Non-adherence is the most common cause of persistent hypothyroidism despite apparently adequate levothyroxine dosing 1, 2
• Directly ask about medication-taking behavior, as scheduling a levothyroxine absorption test may induce patients to start adhering to therapy 3
• Consider a 2-hour levothyroxine absorption test (1000 mcg oral dose with FT4 measured at 0,60, and 120 minutes) to distinguish non-adherence from malabsorption 3

Evaluate for Malabsorption

• Review medications that interfere with levothyroxine absorption: iron supplements, calcium supplements, proton pump inhibitors, antacids (must be taken 4 hours apart from levothyroxine) 1, 4
• Confirm the patient takes levothyroxine on an empty stomach, 30-60 minutes before breakfast 1, 5
• Consider malabsorption syndromes (celiac disease, inflammatory bowel disease, atrophic gastritis) if adherence is confirmed 2
• Dietary fiber and soy products decrease T4 bioavailability 4

Immediate Management Strategy

If Non-Adherence is Confirmed

• Restart levothyroxine at the current dose (150 µg) with strict adherence counseling 3
• Recheck TSH and free T4 in 6-8 weeks to assess response 1, 4
• Consider directly observed therapy or pill counts if adherence remains questionable 2

If Adherence is Confirmed (True Treatment Failure)

• Increase levothyroxine by 25-50 µg (to 175-200 µg daily) based on the severity of hypothyroidism 1
• For a 60-year-old without cardiac disease, more aggressive titration using 25-50 µg increments is appropriate 1
• The full replacement dose is approximately 1.6 mcg/kg/day; for a typical 60-year-old woman (assuming 70 kg), this would be approximately 112 mcg/day, suggesting the current 150 µg dose should be adequate if absorbed 1, 2, 5

Critical Safety Considerations Before Dose Adjustment

Rule Out Adrenal Insufficiency

• Before increasing levothyroxine in severe hypothyroidism, rule out concurrent adrenal insufficiency by checking morning cortisol and ACTH, as thyroid hormone replacement can precipitate life-threatening adrenal crisis 1, 6
• This is particularly important in patients with autoimmune hypothyroidism (Hashimoto's thyroiditis), who have increased risk of concurrent autoimmune adrenal insufficiency 1
• If adrenal insufficiency is present, start physiologic dose corticosteroids at least 1 week before increasing thyroid hormone 1, 2

Cardiac Risk Assessment

• At age 60, initiate dose increases cautiously even without known cardiac disease 1, 4
• Obtain baseline ECG to screen for arrhythmias before aggressive dose escalation 1
• Monitor for angina, palpitations, or dyspnea after dose adjustment 1

Monitoring Protocol After Intervention

Short-Term Monitoring

• Recheck TSH and free T4 in 6-8 weeks after any dose adjustment, as this represents the time needed to reach steady state 1, 4, 2, 5
• Target TSH within the reference range (0.5-4.5 mIU/L) with normal free T4 levels 1, 2
• Continue dose adjustments by 12.5-25 µg increments every 6-8 weeks until TSH normalizes 1

Long-Term Monitoring

• Once adequately treated with stable TSH, repeat testing every 6-12 months 1, 4
• Monitor for symptoms of overtreatment (tachycardia, tremor, heat intolerance, weight loss) 1, 7

Common Pitfalls to Avoid

Do Not Assume Malabsorption Without Evidence

• Approximately 25% of patients on levothyroxine are unintentionally non-adherent, making this the most likely explanation 1
• Jumping to higher doses without confirming adherence risks iatrogenic hyperthyroidism once the patient starts taking medication properly 3

Do Not Overlook Drug Interactions

• Iron, calcium, proton pump inhibitors, and antacids must be taken at least 4 hours apart from levothyroxine 1, 4
• Enzyme inducers (phenytoin, carbamazepine, rifampin) reduce levothyroxine efficacy 7

Do Not Start Thyroid Hormone Before Ruling Out Adrenal Insufficiency

• In severe hypothyroidism with very high TSH (>90 mIU/L), the increased metabolic demand from thyroid hormone replacement can unmask or precipitate adrenal crisis if cortisol deficiency exists 1, 6, 2

Do Not Adjust Doses Too Frequently

• Levothyroxine has a long half-life; adjusting doses before 6-8 weeks leads to inappropriate titration before steady state is reached 1, 4

Special Consideration: Dexamethasone as Adjunct

• In cases of levothyroxine-induced iatrogenic thyrotoxicosis during treatment of severe hypothyroidism, dexamethasone can be added as an adjunct to inhibit TSH and reduce T3/T4 release 6
• However, this is rarely needed and should only be considered if overtreatment symptoms develop during dose escalation 6