Thyroxine (Levothyroxine) for Hypothyroidism
Levothyroxine (T4) is the first-line and standard treatment for hypothyroidism, administered as a single daily oral dose to normalize TSH levels and restore thyroid hormone function. 1, 2, 3
Why Levothyroxine is the Treatment of Choice
Levothyroxine monotherapy remains the definitive treatment despite the thyroid gland naturally secreting both T4 and T3, because T4 is converted to the more active T3 at the cellular level, providing stable hormone levels throughout the day. 1, 4
Combined levothyroxine plus liothyronine (T3) therapy has been evaluated in 15 clinical trials, but no clear advantages have been demonstrated to justify routine combination therapy over levothyroxine alone. 4
The synthetic levothyroxine used is chemically identical to the T4 produced by the human thyroid gland, making it a physiologic replacement. 2
Initial Dosing Strategy
Dosing must be tailored based on age and cardiac status to prevent complications:
For patients <70 years without cardiac disease: Start with full replacement dose of approximately 1.6 mcg/kg/day to rapidly normalize thyroid function. 1
For patients >70 years or with cardiac disease/multiple comorbidities: Start with a lower dose of 25-50 mcg/day and titrate gradually to avoid cardiac decompensation, arrhythmias, or unmasking coronary ischemia. 1, 2
For elderly patients specifically: Atrial fibrillation is the most common arrhythmia observed with levothyroxine overtreatment, making cautious dosing critical. 2
When to Initiate Treatment
Treatment indications are based on TSH levels and clinical context:
TSH >10 mIU/L: Initiate levothyroxine therapy regardless of symptoms, as this carries approximately 5% annual risk of progression to overt hypothyroidism. 1, 3
TSH 4.5-10 mIU/L (subclinical hypothyroidism): Routine treatment is not recommended, but consider therapy for symptomatic patients, those with positive anti-TPO antibodies (4.3% vs 2.6% annual progression risk), women planning pregnancy, or patients with goiter. 1
Confirm diagnosis: Repeat TSH testing after 3-6 weeks before initiating treatment, as 30-60% of elevated TSH levels normalize spontaneously. 1
Monitoring and Dose Adjustment
Follow a structured monitoring protocol to avoid under- or overtreatment:
During dose titration: Check TSH every 6-8 weeks after initiating therapy or changing doses. 1, 3
Once stable: Monitor TSH every 6-12 months or sooner if symptoms change. 1
Dose adjustments: Use increments of 12.5-25 mcg based on current dose; larger adjustments risk overtreatment, especially in elderly or cardiac patients. 1
Target TSH range: 0.5-4.5 mIU/L for most patients. 1
Critical Special Populations
Pregnancy requires immediate attention and dose adjustments:
Pregnancy increases levothyroxine requirements by 25-50% above pre-pregnancy doses; TSH should be monitored and dosage adjusted throughout pregnancy. 2
Untreated maternal hypothyroidism is associated with spontaneous abortion, gestational hypertension, pre-eclampsia, stillbirth, premature delivery, and adverse fetal neurocognitive development. 2
Levothyroxine should not be discontinued during pregnancy and hypothyroidism diagnosed during pregnancy must be promptly treated. 2
Postpartum, return to pre-pregnancy dose immediately after delivery. 2
Pediatric patients require rapid normalization:
Initiate levothyroxine immediately upon diagnosis in children to prevent adverse effects on cognitive development and physical growth. 2
Monitor infants closely during the first 2 weeks for cardiac overload and arrhythmias. 2
Administration Guidelines
Optimal absorption requires specific timing:
Standard recommendation: Take levothyroxine on an empty stomach, 30-60 minutes before breakfast, as food significantly decreases absorption and bioavailability of tablet formulations. 5
Novel liquid formulation (Tirosint-SOL): May be taken as early as 15 minutes before a high-fat meal with equivalent bioavailability to 30-minute interval, potentially improving adherence. 5
Levothyroxine is present in breast milk but no adverse effects on breastfed infants have been reported; adequate treatment may normalize milk production in hypothyroid mothers. 2
Risks of Improper Dosing
Both undertreatment and overtreatment carry significant morbidity:
Undertreatment risks: Persistent hypothyroid symptoms, adverse cardiovascular effects, abnormal lipid metabolism, and reduced quality of life. 1
Overtreatment risks (affecting 14-21% of treated patients): Iatrogenic hyperthyroidism increases risk for atrial fibrillation (especially in elderly), osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy. 1
Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, highlighting the critical importance of regular monitoring. 1
Critical Safety Consideration
Never initiate levothyroxine before ruling out adrenal insufficiency in patients with suspected central hypothyroidism or concurrent adrenal disease, as this can precipitate life-threatening adrenal crisis. Start corticosteroids first, then levothyroxine. 1
Alternative Formulations for Refractory Cases
- When patients fail to maintain target TSH levels on standard oral tablets despite optimization of ingestion routines, consider liquid oral, intravenous, intramuscular, or rectal formulations for refractory hypothyroidism. 6
Long-Term Prognosis
Levothyroxine is generally continued for life in patients with primary hypothyroidism. 2
With appropriate treatment and monitoring, symptoms can be effectively managed and most patients lead normal, healthy lives. 7
Untreated hypothyroidism can progress to myxedema coma, a life-threatening condition with hypothermia, hypotension, altered mental status requiring ICU care, and mortality rates up to 30%. 3