What is the primary treatment for hypothyroidism?

Primary Treatment for Hypothyroidism

Levothyroxine monotherapy is the first-line treatment for hypothyroidism and should be initiated immediately upon diagnosis to normalize thyroid-stimulating hormone (TSH) levels and prevent serious complications including heart failure, cardiovascular disease, and myxedema coma. 1, 2, 3, 4

Etiology and Epidemiology

Primary Causes

• Hashimoto's thyroiditis (chronic autoimmune thyroiditis) is the most common cause of primary hypothyroidism in iodine-sufficient areas, accounting for up to 85% of cases 4, 5
• Iodine deficiency remains the most common cause worldwide in areas with inadequate nutritional iodine intake 4, 5
• Other causes include thyroid surgery, radioactive iodine therapy, radiation to the neck, and certain medications (immune checkpoint inhibitors, amiodarone) 4

Prevalence and Risk Factors

• Hypothyroidism affects 0.3% to 12% of the general population worldwide, with an additional estimated 5% remaining undiagnosed 4, 5
• The condition is significantly more common in women and older adults 4, 6
• Risk factors include having a first-degree relative with hypothyroidism, environmental iodine deficiency, pregnancy with underlying autoimmune thyroid disease, and use of specific medications 4

Treatment Algorithm

Immediate Initiation of Levothyroxine

Levothyroxine sodium is the drug of choice and should be started without delay for all patients with overt hypothyroidism (elevated TSH with low free T4) 1, 2, 3, 7, 4

Initial Dosing Strategy

• For patients <70 years without cardiac disease or multiple comorbidities: Start with full replacement dose of approximately 1.6 mcg/kg/day 1, 5
• For patients >70 years or with cardiac disease/multiple comorbidities: Start with lower dose of 25-50 mcg/day and titrate gradually 1, 3, 7
• Elderly patients and those with coronary artery disease require lower starting doses to avoid cardiac decompensation, angina, or arrhythmias 3, 7, 4

Monitoring and Dose Adjustment

• Monitor TSH every 6-8 weeks while titrating hormone replacement until target TSH of 0.5-4.5 mIU/L is achieved 1, 4
• Adjust dose in increments of 12.5-25 mcg based on patient's current dose and clinical characteristics 1
• Once adequately treated, repeat TSH testing every 6-12 months or if symptoms change 1

Special Populations

Pregnancy

• Levothyroxine should not be discontinued during pregnancy, and hypothyroidism diagnosed during pregnancy must be promptly treated 3
• Untreated maternal hypothyroidism is associated with spontaneous abortion, gestational hypertension, pre-eclampsia, stillbirth, premature delivery, and adverse effects on fetal neurocognitive development 3, 4
• TSH levels may increase during pregnancy, requiring dose adjustments; monitor TSH every 6-8 weeks during pregnancy 1, 3
• Postpartum, return to pre-pregnancy dose immediately after delivery 3

Pediatric Patients

• Rapid restoration of normal serum T4 concentrations is essential for preventing adverse effects on cognitive development and physical growth 3
• Initiate levothyroxine therapy immediately upon diagnosis in neonates and children 3
• Monitor infants closely during the first 2 weeks for cardiac overload and arrhythmias 3

Subclinical Hypothyroidism

• Treat all patients with TSH >10 mIU/L regardless of symptoms, as this carries approximately 5% annual risk of progression to overt hypothyroidism 1, 7
• For TSH 4.5-10 mIU/L, consider treatment in symptomatic patients, pregnant women or those planning pregnancy, patients with positive anti-TPO antibodies, or those with infertility or goiter 1, 7
• Patients with positive anti-TPO antibodies have 4.3% annual progression risk versus 2.6% in antibody-negative individuals 1

Critical Pitfalls to Avoid

Overtreatment Risks

• 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
• Overtreatment occurs in 14-21% of treated patients and is particularly dangerous in elderly patients 1
• Atrial fibrillation is the most common arrhythmia observed with levothyroxine overtreatment in the elderly 3

Undertreatment Consequences

• Untreated or undertreated hypothyroidism leads to cardiovascular disease, heart failure, increased mortality, insulin resistance, hyperglycemia in diabetic patients, and reproductive health issues including infertility and miscarriage 4, 5
• In severe cases, untreated hypothyroidism may progress to myxedema coma with hypothermia, hypotension, and altered mental status, carrying a mortality rate up to 30% 4

Adrenal Insufficiency

• In patients with suspected central hypothyroidism or concurrent adrenal insufficiency, always start corticosteroids before initiating levothyroxine to prevent precipitating adrenal crisis 1, 7

Why Levothyroxine Monotherapy Remains Standard

• Levothyroxine monotherapy is the current standard for management of primary and central hypothyroidism based on decades of clinical experience 7, 8
• While combination therapy with levothyroxine plus liothyronine has been evaluated in 15 clinical trials, clear advantages have not been demonstrated, and levothyroxine alone should remain the treatment of choice 8
• The thyroid gland secretes both T4 and T3, but levothyroxine (synthetic T4) is converted to the more active T3 in peripheral tissues, providing adequate hormone replacement 8