What are the starting doses of levothyroxine (T4 replacement) and prednisone (corticosteroid) for a patient presenting with hypothyroidism, characterized by low Thyroid-Stimulating Hormone (TSH) and T4 levels?

Levothyroxine Dosing for Central Hypothyroidism (Low TSH and Low T4)

For a patient with low TSH and low T4 (central hypothyroidism), start levothyroxine at 1.6 mcg/kg/day in adults under 70 without cardiac disease, or 25-50 mcg/day in elderly or cardiac patients, and titrate based on free T4 levels (not TSH) targeting the upper half of the normal range. 1, 2 Critically, if central hypothyroidism is suspected, always initiate corticosteroid replacement (typically hydrocortisone 15-20 mg/day in divided doses) at least 1 week before starting levothyroxine to prevent life-threatening adrenal crisis. 1

Critical Safety Consideration: Rule Out Adrenal Insufficiency First

• Before initiating any thyroid hormone replacement in central hypothyroidism, you must rule out or empirically treat concurrent adrenal insufficiency, as starting levothyroxine before corticosteroids can precipitate adrenal crisis. 1
• In patients with suspected pituitary or hypothalamic disease causing central hypothyroidism, always start physiologic dose corticosteroids (hydrocortisone 15-20 mg/day in divided doses) at least 1 week prior to thyroid hormone replacement. 1
• This is non-negotiable in central hypothyroidism, as these patients frequently have concurrent ACTH deficiency. 1

Levothyroxine Starting Dose Algorithm

For Adults Under 70 Without Cardiac Disease:

• Start levothyroxine at full replacement dose of 1.6 mcg/kg/day. 1, 2
• This can be initiated immediately after ensuring adrenal sufficiency is addressed. 1

For Adults Over 70 OR With Cardiac Disease:

• Start at a lower dose of 25-50 mcg/day. 1, 2
• Titrate more slowly (every 6-8 weeks) to avoid exacerbating cardiac symptoms or precipitating arrhythmias. 1, 2
• Elderly patients with coronary disease are at increased risk of cardiac decompensation even with therapeutic levothyroxine doses. 1

For Patients at Risk of Atrial Fibrillation:

• Use lower starting doses (less than 1.6 mcg/kg/day) and titrate every 6-8 weeks. 2
• More frequent monitoring may be warranted—consider repeating testing within 2 weeks of dose adjustment rather than waiting 6-8 weeks. 1

Monitoring and Titration in Central Hypothyroidism

TSH is unreliable and should NOT be used to monitor therapy in central hypothyroidism. 1, 2 Instead:

• Use serum free T4 levels to titrate levothyroxine dosing, targeting the upper half of the normal range (typically 16-19 pmol/L or equivalent). 1, 2
• Recheck free T4 (and free T3 if available) every 6-8 weeks after dose adjustments until stable. 1
• Adjust levothyroxine dose by 12.5-25 mcg increments based on free T4 levels and clinical response. 1, 2
• Once adequately treated, repeat testing every 6-12 months or if symptoms change. 1

Why Free T4 Targeting Matters in Central Hypothyroidism

• In central hypothyroidism, TSH levels are inappropriately low or normal despite low thyroid hormone levels, making TSH useless for monitoring. 1, 2
• Studies show that pituitary patients are at significant risk of under-replacement when not guided by free T4 levels—38.9% of pituitary patients on levothyroxine had free T4 ≤13 pmol/L compared to only 9.5-13.4% of primary hypothyroidism controls. 3
• The median free T4 in adequately treated primary hypothyroidism patients is 16 pmol/L with a 20-80th centile range of 14-19 pmol/L, which should guide replacement targets in central hypothyroidism. 3

Additional Monitoring Parameters

• Both free T4 and free T3 levels should be measured to assess adequacy of replacement. 4
• Some biochemical indexes of thyroid hormone action (such as serum-soluble interleukin-2 receptor concentrations) may help identify overtreatment when free T3 is borderline high despite normal free T4. 4
• Clinical parameters alone lack the required specificity for diagnosis or follow-up of central hypothyroidism patients. 4

Prednisone Dosing for Adrenal Insufficiency

If concurrent adrenal insufficiency is confirmed or suspected in the context of central hypothyroidism, initiate hydrocortisone 15-20 mg/day in divided doses (typically 10 mg in morning, 5-10 mg in afternoon) at least 1 week before starting levothyroxine. 1

Note: The question asks about "prednisone," but hydrocortisone is the preferred glucocorticoid for physiologic replacement in adrenal insufficiency. If prednisone must be used, the equivalent dose would be approximately 5 mg/day (as prednisone is roughly 4 times more potent than hydrocortisone), but this is not standard practice for chronic adrenal insufficiency replacement.

Common Pitfalls to Avoid

• Never start thyroid hormone before ruling out adrenal insufficiency in patients with suspected central hypothyroidism—this can precipitate adrenal crisis. 1
• Do not use TSH to monitor therapy in central hypothyroidism—it will remain low regardless of adequate replacement. 1, 2
• Avoid under-replacement by targeting free T4 in the upper half of normal range, not just "within normal limits." 3
• Do not adjust doses more frequently than every 6-8 weeks, as levothyroxine has a long half-life and steady state takes 4-6 weeks to achieve. 1, 2
• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH (though this is less relevant in central hypothyroidism), increasing risks for atrial fibrillation, osteoporosis, and cardiac complications. 1

Administration Instructions

• Levothyroxine should be taken on an empty stomach, 30-60 minutes before breakfast, for optimal absorption. 1, 5
• Take at least 4 hours apart from iron, calcium supplements, or antacids, which reduce gastrointestinal absorption. 1
• Changing administration time from morning to evening reduces therapeutic efficacy (TSH increases by 1.47 µIU/mL on average). 6