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Calculate appropriate levothyroxine starting doses based on patient characteristics and indication
Levothyroxine (L-thyroxine, T4) is synthetic thyroid hormone used to treat hypothyroidism. It's converted to the active form triiodothyronine (T3) in peripheral tissues. The goal of treatment is to restore normal thyroid function by replacing deficient hormone, guided by TSH normalization and symptom resolution.
Levothyroxine has a long half-life (7 days), so steady-state levels aren't reached for 6-8 weeks after starting or changing doses. This is why TSH should be rechecked 6-8 weeks after any dose adjustment. Daily dosing at the same time each day (typically morning, 30-60 minutes before breakfast) ensures stable levels.
Dosing strategies vary based on patient age, cardiovascular status, and indication. Young healthy adults can often start at full replacement doses (1.6 mcg/kg/day), achieving target TSH more quickly. Elderly patients and those with cardiac disease require conservative "start low, go slow" approaches to avoid precipitating cardiac complications from rapid metabolic increases.
Thyroid hormone increases cardiac output, heart rate, and myocardial oxygen demand. Rapid replacement in patients with coronary artery disease can precipitate angina or myocardial infarction. In patients with atrial fibrillation risk, overreplacement can trigger arrhythmias. Start with 12.5-25 mcg daily and increase by 12.5-25 mcg every 4-8 weeks, monitoring cardiac symptoms closely.
Older adults have higher prevalence of subclinical cardiac disease and increased sensitivity to thyroid hormone. Starting doses should be 25-50 mcg daily with slow titration. Target TSH may be higher (upper half of normal range) to avoid risks of overtreatment including atrial fibrillation and bone loss. Some very elderly patients may not require treatment for mild TSH elevations.
Thyroid hormone requirements increase 25-50% during pregnancy due to increased TBG (thyroid binding globulin), increased renal clearance, and placental transfer. Women with known hypothyroidism should increase their dose by 25-30% immediately upon pregnancy confirmation. TSH should be checked every 4 weeks with tight control (T1: <2.5, T2/T3: <3.0 mIU/L) as maternal hypothyroidism impairs fetal neurological development.
Patients after total thyroidectomy produce no endogenous thyroid hormone, requiring full replacement (typically 1.6 mcg/kg/day). For differentiated thyroid cancer, TSH targets vary by risk stratification: high-risk may require TSH suppression (<0.1 mIU/L), intermediate-risk 0.1-0.5 mIU/L, and low-risk 0.5-2.0 mIU/L. Discuss with endocrinology and oncology.
Levothyroxine absorption occurs primarily in the small intestine and is affected by food, medications, and gastrointestinal disorders. Take on empty stomach 30-60 minutes before breakfast for optimal absorption. Separate from calcium supplements, iron, PPIs, antacids, and soy by at least 4 hours. Malabsorption disorders (celiac disease, IBD, atrophic gastritis) may increase requirements.
Many medications affect levothyroxine absorption, metabolism, or protein binding. Estrogen (including oral contraceptives and HRT) increases TBG, raising total T4 and potentially requiring dose increases. Antiepileptics (phenytoin, carbamazepine) and rifampin increase hepatic metabolism. Amiodarone and lithium can cause hypothyroidism or interfere with conversion.
Significant weight changes alter levothyroxine requirements. Weight gain may require dose increases, while weight loss may necessitate decreases. Obesity doesn't necessarily require higher doses - base calculations on ideal body weight rather than actual weight in significantly obese patients to avoid overtreatment.
TSH is the primary monitoring parameter for levothyroxine therapy in primary hypothyroidism. Free T4 provides additional information, particularly in central hypothyroidism, pregnancy, or when assessing compliance. Total T3 is not routinely measured but may help assess peripheral conversion in specific cases.
After initiating therapy or changing doses, recheck TSH in 6-8 weeks (4 weeks in pregnancy). Once target TSH is achieved and stable on a consistent dose, monitoring frequency can decrease to every 6-12 months. More frequent monitoring is needed during pregnancy, significant weight changes, after starting interacting medications, or if symptoms develop.
Adjust doses in 12.5-25 mcg increments (smaller increments in elderly or cardiac patients). Each 12.5-25 mcg change typically alters TSH by approximately 1.5 mIU/L, though individual responses vary. If TSH remains abnormal despite apparent adequate dosing and compliance, investigate absorption issues, drug interactions, or laboratory accuracy.
Food, particularly fiber, calcium, and iron-rich foods, can interfere with levothyroxine absorption. Taking it 30-60 minutes before breakfast (or at bedtime, 4 hours after eating) ensures consistent absorption. Coffee even without additives may reduce absorption, so wait 30-60 minutes after medication before drinking coffee. Consistent timing and conditions are crucial for stable levels.
Levothyroxine products have narrow therapeutic indices, and bioavailability differences between formulations can affect TSH control. While FDA considers approved products interchangeable, subtle differences may impact some patients. Ideally, maintain the same brand/formulation. If switching, recheck TSH in 6-8 weeks. Many providers prefer brand-name products (Synthroid, Levoxyl) for consistency, especially in pregnancy or tight TSH targets.
Due to levothyroxine's long half-life (7 days), missing one dose has minimal impact. Take the missed dose as soon as you remember the same day, or skip it and resume normal dosing the next day. Don't double up doses. Missing occasional doses won't significantly affect TSH, but frequent missed doses will lead to symptom recurrence and TSH elevation. Set reminders to improve adherence.
Common causes include: non-compliance (most frequent), taking with food or medications that interfere with absorption, dose too low/high for current needs, malabsorption disorders, drug interactions, pregnancy, significant weight change, or lab error. Assess adherence first, review medications/supplements, ensure proper administration, and recheck TSH with free T4. Consider checking TSH 2-4 hours after observed dose to verify absorption.
Treatment of subclinical hypothyroidism (elevated TSH with normal free T4) is individualized. Generally treat if: TSH persistently >10 mIU/L, symptoms present, TPO antibodies positive (high progression risk), planning pregnancy, age <65-70, or other factors favoring treatment. For TSH 4.5-10 in asymptomatic older adults, observation may be reasonable. Treatment benefits are most established for TSH >10 and symptomatic patients.
Most patients do well on levothyroxine (T4) alone, as it converts to T3 peripherally. Combination T4/T3 therapy remains controversial. Some patients report persistent symptoms despite normal TSH on T4 monotherapy and may benefit from T3 trial, though clinical trials show inconsistent results. T3 has short half-life requiring multiple daily doses and can cause palpitations. Reserve for selected patients under endocrinology guidance.
Overtreatment (iatrogenic hyperthyroidism) causes: palpitations, tremor, anxiety, insomnia, heat intolerance, weight loss despite increased appetite, diarrhea, and muscle weakness. Long-term overtreatment increases risks of atrial fibrillation (especially in elderly) and accelerated bone loss. If TSH is suppressed (<0.4 mIU/L) or symptoms suggest overtreatment, reduce dose by 12.5-25 mcg and recheck in 6-8 weeks.
It depends on the cause. Permanent hypothyroidism (Hashimoto's thyroiditis, post-thyroidectomy, radioiodine therapy) requires lifelong treatment. Transient hypothyroidism (postpartum thyroiditis, subacute thyroiditis, medication-induced) may resolve, allowing discontinuation after 6-12 months. Subclinical hypothyroidism may improve with weight loss or iodine supplementation in deficiency. Discuss with your provider whether a trial off medication is appropriate after addressing reversible factors.