How should I initiate thyroid hormone replacement in a 67‑year‑old woman with severe primary hypothyroidism (TSH ≈80 mIU/L, low free triiodothyronine and free thyroxine)?

Immediate Levothyroxine Initiation for Severe Overt Hypothyroidism

Start levothyroxine 25–50 mcg daily immediately in this 67‑year‑old woman with severe primary hypothyroidism (TSH ≈80 mIU/L, low free T3 and T4), using a conservative dose due to her age and potential undiagnosed cardiac disease. 1

Critical Pre‑Treatment Safety Assessment

Before initiating or increasing levothyroxine, rule out concurrent adrenal insufficiency by obtaining morning (≈8 AM) serum cortisol and ACTH, as starting thyroid hormone before corticosteroids can precipitate life‑threatening adrenal crisis. 1 If morning cortisol is low or clinical features such as hypotension, hyponatremia, or unexplained symptoms suggest adrenal insufficiency, initiate hydrocortisone 20 mg in the morning and 10 mg in the afternoon for at least one week before starting levothyroxine. 1

Age‑Appropriate Initial Dosing Strategy

• For patients >65–70 years, start with 25–50 mcg daily rather than full replacement dose (1.6 mcg/kg/day), as elderly patients with underlying coronary disease are at increased risk of cardiac decompensation, angina, or arrhythmias even with therapeutic levothyroxine doses. 1, 2

• The full replacement dose of approximately 1.6 mcg/kg/day is reserved for patients <70 years without cardiac disease or multiple comorbidities. 1

• Rapid normalization of thyroid hormone levels can unmask or worsen cardiac ischemia in patients with undiagnosed coronary artery disease, making conservative initiation mandatory in this age group. 1

Proper Administration Protocol

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

• Administer at least 4 hours before or after drugs known to interfere with levothyroxine absorption (iron, calcium supplements, antacids, proton pump inhibitors). 2

• Avoid administration with foods that decrease absorption, such as soybean products, coffee, or high‑fiber meals. 2

Titration and Monitoring Schedule

• Recheck TSH and free T4 every 6–8 weeks after each dose adjustment, as this represents the time needed to reach steady state. 1, 2

• Increase levothyroxine by 12.5–25 mcg increments every 6–8 weeks based on TSH response, using smaller increments (12.5 mcg) for elderly patients to avoid cardiac complications. 1

• Target TSH within the reference range (0.5–4.5 mIU/L) with normal free T4 levels. 1, 3

• Once adequately treated, repeat testing every 6–12 months or if symptoms change. 1

Clinical Rationale for Immediate Treatment

• TSH >10 mIU/L with low free T4 defines overt hypothyroidism requiring immediate treatment regardless of symptoms, as this carries approximately 5% annual risk of progression and is associated with cardiovascular dysfunction, adverse lipid profiles, and quality of life deterioration. 1

• Untreated overt hypothyroidism causes cardiac dysfunction including delayed relaxation, abnormal cardiac output, increased systemic vascular resistance, and diastolic heart failure. 1

• Treatment prevents progression of cardiac dysfunction, reduces LDL cholesterol, and decreases cardiovascular event risk. 1

Common Pitfalls to Avoid

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

• Do not delay treatment to obtain additional testing beyond ruling out adrenal insufficiency—severe hypothyroidism requires prompt intervention. 1

• Avoid adjusting doses too frequently before reaching steady state—wait the full 6–8 weeks between adjustments. 1

• Approximately 25% of patients are unintentionally overtreated with TSH fully suppressed, increasing risks for atrial fibrillation, osteoporosis, fractures, and cardiac complications—careful monitoring prevents this. 1

Expected Clinical Outcomes

• Levothyroxine should stabilize weight and improve energy within 6–8 weeks of adequate replacement. 1

• Symptoms such as fatigue, cold intolerance, and cognitive slowing should progressively improve as TSH normalizes. 1

• The peak therapeutic effect of a given dose may not be attained for 4–6 weeks. 2

Special Monitoring Considerations for This Patient

• Assess for new or worsening angina, palpitations, dyspnea, or arrhythmias at each follow‑up, as elderly patients are at higher risk for cardiac complications during titration. 1

• Consider obtaining an ECG to screen for baseline arrhythmias before initiating therapy. 1

• Monitor blood pressure, as hypothyroidism can cause hypertension that may improve with treatment. 1