There is some variability in the absorption of thyroxine; dosage will also vary depending on age and weight. Infants and children require more T4 per kilogram of body weight than adults. The average dosage for an infant 1–6 months of age is 10–15 mcg/kg per day, whereas the average dosage for an adult is about 1.7 mcg/kg per day (0.8 mcg/lb per day ) or 125 mcg/d. Older adults (>65 years of age) may require less thyroxine (1.6 mcg/kg per day or 0.7 mcg/lb per day ) for replacement as body mass declines. In patients requiring suppression therapy post-thyroidectomy for thyroid cancer, the average daily dosage of T4 is 2.2 mcg/kg or 1 mcg/lb. Higher thyroxine requirements have also been reported in patients with celiac disease and Helicobacter pylori gastritis; thyroxine doses may be lower following treatment.
TABLE 38–5 Etiology and pathogenesis of hypothyroidism.
1Iodides, lithium, fluoride, thioamides, aminosalicylic acid, phenylbutazone, amiodarone, perchlorate, ethionamide, thiocyanate, cytokines (interferons, interleukins), bexarotene, tyrosine kinase inhibitors, etc. See Table 38–3.
2See Table 38–3 for specific pathogenesis.
Since interactions with certain foods (eg, bran, soy, coffee) and drugs (Table 38–3) can impair its absorption, thyroxine should be administered on an empty stomach (eg, 60 minutes before meals, 4 hours after meals, or at bedtime) to maintain TSH within an optimal range of 0.5–2.5 mIU/L. Its long half-life of 7 days permits once-daily dosing. Children should be monitored for normal growth and development. Serum TSH and free thyroxine should always be measured before a change in dosage to avoid transient serum alterations. It takes 6–8 weeks after starting a given dose of thyroxine to reach steady-state levels in the bloodstream. Thus, dosage changes should be made slowly.
In younger patients or those with very mild disease, full replacement therapy may be started immediately. In older patients (>50 years) without cardiac disease, levothyroxine can be started at a dosage of 50 mcg/d. In long-standing hypothyroidism and in older patients with underlying cardiac disease, it is imperative to start with reduced dosages of levothyroxine, 12.5–25 mcg/d for 2 weeks, before increasing by 12.5–25 mcg/d every 2 weeks until euthyroidism or drug toxicity is observed. In cardiac patients, the heart is very sensitive to the level of circulating thyroxine, and if angina pectoris or cardiac arrhythmia develops, it is essential to stop or reduce the thyroxine dosage immediately.
Thyroxine toxicity is directly related to the hormone level. In children, restlessness, insomnia, and accelerated bone maturation and growth may be signs of thyroxine toxicity. In adults, increased nervousness, heat intolerance, episodes of palpitation and tachycardia, or unexplained weight loss may be the presenting symptoms. If these symptoms are present, it is important to monitor serum TSH and FT4 levels (Table 38–2), which will determine whether the symptoms are due to excess thyroxine blood levels. Chronic overtreatment with T4, particularly in elderly patients, can increase the risk of atrial fibrillation and accelerated osteoporosis.
Special Problems in Management of Hypothyroidism
A. Myxedema and Coronary Artery Disease