What is the treatment for hypothyroidism?

Treatment of Hypothyroidism

Levothyroxine monotherapy is the standard treatment for hypothyroidism, with dosing tailored to age, cardiac status, and comorbidities, targeting normalization of TSH levels to 0.5-4.5 mIU/L. 1, 2

Initial Treatment Selection

• Levothyroxine (T4) is the first-line and only recommended treatment for hypothyroidism, as it remains the current standard for management of both primary and central hypothyroidism 1, 3
• Combination therapy with levothyroxine plus liothyronine should not be used routinely, as clear advantages have not been demonstrated and levothyroxine alone should remain the treatment of choice 4
• Synthetic levothyroxine is chemically identical to that produced in the human thyroid gland and is one of the world's most widely prescribed medicines 5, 6

Initial Dosing Strategy

For Younger Patients Without Cardiac Disease

• Start with full replacement dose of approximately 1.6 mcg/kg/day for patients <70 years without cardiac disease or multiple comorbidities 1, 7
• This approach allows for rapid restoration of normal thyroid function and prevents complications of untreated hypothyroidism 1

For Elderly or High-Risk Patients

• For patients >70 years or with cardiac disease/multiple comorbidities, start with a lower dose of 25-50 mcg/day and titrate gradually 1, 7, 5
• This conservative approach is critical because atrial fibrillation is the most common arrhythmia observed with levothyroxine overtreatment in the elderly 5
• Elderly patients have increased prevalence of cardiovascular disease, making lower starting doses essential to avoid cardiac overload and arrhythmias 5, 3

Special Populations Requiring Immediate Treatment

• Pregnant women with hypothyroidism must continue levothyroxine throughout pregnancy, as untreated maternal hypothyroidism is associated with spontaneous abortion, gestational hypertension, pre-eclampsia, stillbirth, premature delivery, and adverse effects on fetal neurocognitive development 5, 2
• Pregnancy increases levothyroxine requirements by 25-50% above pre-pregnancy doses, necessitating TSH monitoring every 6-8 weeks during pregnancy with dose adjustments as needed 1, 7, 5
• Return to pre-pregnancy dose immediately after delivery, as postpartum TSH levels are similar to preconception values 5

Monitoring and Dose Adjustment Protocol

Initial Titration Phase

• Monitor TSH every 6-8 weeks after initiating levothyroxine or changing the dose 1, 2
• Adjust levothyroxine dose in increments of 12.5-25 mcg based on the patient's current dose and clinical status 1
• Larger adjustments may lead to overtreatment and should be avoided, especially in elderly patients or those with cardiac disease 1

Maintenance Monitoring

• Once TSH is at goal, monitor annually or sooner if symptoms change 1, 2
• Target TSH range is 0.5-2.0 mIU/L in primary hypothyroidism, though the broader reference range of 0.4-4.5 mIU/L is acceptable 1, 3, 6
• Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 1

Treatment Based on Severity

Overt Hypothyroidism (High TSH, Low Free T4)

• All patients with overt hypothyroidism require treatment with levothyroxine 3
• Untreated overt hypothyroidism can cause serious complications including heart failure, myxedema coma (with mortality up to 30%), cardiovascular disease, and increased mortality 2, 6

Subclinical Hypothyroidism (High TSH, Normal Free T4)

• For TSH >10 mIU/L: Initiate levothyroxine therapy regardless of symptoms, as this level carries approximately 5% annual risk of progression to overt hypothyroidism 1, 7, 3
• For TSH 4.5-10 mIU/L: Routine treatment is not recommended, but monitor thyroid function tests every 6-12 months 1, 7
• Consider treatment for TSH 4.5-10 mIU/L in specific situations: symptomatic patients, pregnant women or those planning pregnancy, patients with positive anti-TPO antibodies (4.3% vs 2.6% annual progression risk), or patients with goiter 1, 7, 3

Critical Safety Considerations

Before Initiating Treatment

• In patients with suspected central hypothyroidism or concurrent adrenal insufficiency, always start corticosteroids before levothyroxine to avoid precipitating adrenal crisis 8, 1
• Confirm elevated TSH with repeat testing after 3-6 weeks, as 30-60% of high TSH levels normalize on repeat testing 1

Avoiding Overtreatment

• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, increasing risks for atrial fibrillation, osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy 1
• Development of low TSH on therapy suggests overtreatment or recovery of thyroid function; dose should be reduced or discontinued with close follow-up 1, 7
• Overtreatment occurs in 14-21% of treated patients and is associated with increased cardiovascular mortality, particularly in elderly patients 1, 3

Avoiding Undertreatment

• Undertreatment risks include persistent hypothyroid symptoms, adverse effects on cardiovascular function, lipid metabolism, and quality of life 1
• Untreated or under-treated hypothyroidism increases risk for cardiovascular events such as heart failure and negatively affects female reproductive health, causing disrupted ovulation, infertility, and increased risk of miscarriage 2

Common Pitfalls to Avoid

• Do not treat based on a single elevated TSH value, as transient elevations are common and 30-60% normalize spontaneously 1
• Never adjust doses too frequently before reaching steady state—wait 6-8 weeks between adjustments 1
• Do not fail to distinguish between patients requiring TSH suppression (thyroid cancer) versus those who don't (primary hypothyroidism) 1
• Avoid excessive dose increases that could lead to iatrogenic hyperthyroidism, which increases risk for osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy 1
• For patients with persistently elevated TSH despite apparently adequate replacement dose, check for poor compliance, malabsorption, and drug interactions before increasing the dose 3

Lifelong Management

• Levothyroxine is generally continued for life in patients with hypothyroidism 5
• Nearly one-third of patients with treated hypothyroidism still exhibit symptoms, highlighting the importance of appropriate levothyroxine dosing and regular monitoring 6
• Optimal treatment requires partnership between patient and physician, with vigilant appraisal of the patient's status based on thorough clinical and laboratory assessment 9