What is the primary treatment for Myxedema (hypothyroidism)?

Treatment of Myxedema (Hypothyroidism)

The primary treatment for myxedema (hypothyroidism) is levothyroxine (T4) therapy, which is the preferred agent due to its consistent potency, restoration of normal serum levels of both T4 and T3, and ease of monitoring. 1, 2

Initial Treatment Selection

• Levothyroxine sodium is the treatment of choice for myxedema because it provides consistent potency, restores normal constant serum levels of both thyroxine (T4) and triiodothyronine (T3), and allows for easier interpretation of thyroid hormone levels compared to other thyroid preparations 2

• Other thyroid agents (containing T3) result in postabsorptive elevated T3 serum concentrations that may cause thyrotoxic symptoms and reduction of T4 levels, leading to misleading estimates of thyroid dosage 2

Dosing Strategy Based on Patient Characteristics

For Younger Patients Without Cardiac Disease

• For patients <70 years without cardiovascular disease, start levothyroxine at approximately 1.6 mcg/kg/day based on ideal body weight to rapidly normalize thyroid function 1, 3

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

For Elderly or Cardiac Patients

• For patients >70 years OR with cardiovascular disease OR multiple comorbidities, start with a lower dose of 25-50 mcg/day and gradually titrate upward to avoid exacerbating cardiac conditions 1, 3, 4

• Overtreatment with levothyroxine may cause an increase in heart rate, cardiac wall thickness, and cardiac contractility and may precipitate angina or arrhythmias, particularly in elderly patients with cardiovascular disease 4

• The transition from the hypothyroid to the euthyroid state brings about changes that put an added burden on the heart, requiring extreme caution in elderly patients 5

Critical Safety Consideration: Adrenal Insufficiency

• ALWAYS start corticosteroid replacement BEFORE thyroid hormone in patients with suspected adrenal insufficiency or central hypothyroidism to prevent precipitating a life-threatening adrenal crisis 1, 3, 4

• Thyroid hormone increases metabolic clearance of glucocorticoids, and initiation of thyroid hormone therapy prior to glucocorticoid therapy may precipitate acute adrenal crisis 4

• Hydrocortisone should be administered until coexisting adrenal insufficiency is ruled out 6

Monitoring and Dose Adjustment

• Check TSH and free T4 levels 6-8 weeks after starting treatment or changing dose, as this represents the time needed to reach a new steady state 1, 3

• Increase levothyroxine by 12.5-25 mcg increments based on the patient's current dose and clinical characteristics when TSH remains elevated 1

• Use smaller increments (12.5 mcg) for elderly patients (>70 years) or those with cardiac disease to avoid cardiac complications 1

• Once adequately treated with a stable dose, repeat TSH testing every 6-12 months or sooner if symptoms change 1

Special Situation: Myxedema Coma

• Myxedema coma is a life-threatening emergency that should NOT be treated with oral levothyroxine due to unpredictable absorption from the gastrointestinal tract 4

• Administer thyroid hormone products formulated for intravenous administration to treat myxedema coma 4

• Most authorities recommend treatment with intravenous levothyroxine (T4) as opposed to intravenous liothyronine (T3) 6

• However, studies have shown that replacement of thyroid hormone through nasogastric tube with a loading dose and maintenance therapy can be as efficacious as intravenous therapy 7

• High-dose thyroid hormone replacement (LT4 ≥500 mcg/day or LT3 ≥75 mcg/day) is significantly associated with fatal outcome, particularly in elderly patients with cardiac complications 8

• Patients with myxedema coma should be admitted to an intensive care unit for vigorous pulmonary and cardiovascular support 6

Common Pitfalls to Avoid

• Starting thyroid replacement before corticosteroids in patients with adrenal insufficiency can precipitate adrenal crisis—always start corticosteroid replacement first 1, 3, 4

• Inadequate dose adjustment in elderly or cardiac patients can lead to adverse cardiac outcomes—start with lower doses (25-50 mcg) in these populations 1, 3, 4

• Overtreatment occurs in 14-21% of treated patients and increases risk for atrial fibrillation, osteoporosis, fractures, and cardiac complications, especially in elderly patients 1

• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, increasing risks for osteoporosis, fractures, and cardiac complications 1

• Using high-dose thyroid hormone replacement in myxedema coma, particularly in elderly patients with cardiac complications, significantly increases mortality risk 8