What is the recommended approach for managing hypothyroidism?

Hypothyroidism Management

Diagnosis and Initial Assessment

For patients with suspected hypothyroidism, measure TSH as the primary screening test, and if elevated, confirm with repeat testing after 3-6 weeks along with free T4 measurement, as 30-60% of elevated TSH levels normalize spontaneously. 1

• TSH >10 mIU/L with low free T4 indicates overt primary hypothyroidism requiring immediate treatment 1, 2
• TSH >10 mIU/L with normal free T4 defines subclinical hypothyroidism that warrants treatment regardless of symptoms 1, 3
• TSH 4.5-10 mIU/L with normal free T4 represents mild subclinical hypothyroidism requiring individualized decision-making 1, 3
• Measure anti-TPO antibodies to identify autoimmune etiology (Hashimoto's thyroiditis), which predicts higher progression risk (4.3% vs 2.6% annually in antibody-negative patients) 1

Treatment Initiation with Levothyroxine

Levothyroxine monotherapy is the first-line treatment for hypothyroidism, with dosing based on patient age, cardiac status, and comorbidities. 1, 4, 2

Dosing Algorithm

• For patients <70 years without cardiac disease: Start with full replacement dose of 1.6 mcg/kg/day 1, 5
• For patients >70 years or with cardiac disease/multiple comorbidities: Start with 25-50 mcg/day and titrate gradually to avoid cardiac complications 6, 1, 4
• For pregnant women: Increase dose by 25-50% above pre-pregnancy requirements immediately upon pregnancy confirmation, as maternal hypothyroidism causes adverse fetal neurodevelopmental outcomes 1, 4

Critical Safety Considerations

• In patients with suspected central hypothyroidism or concurrent adrenal insufficiency, always initiate corticosteroids before starting levothyroxine to prevent adrenal crisis 6, 1
• Elderly patients with coronary disease face increased risk of cardiac decompensation, angina, or arrhythmias even with therapeutic levothyroxine doses 1, 3

Monitoring and Dose Adjustment

Monitor TSH every 6-8 weeks during dose titration, then every 6-12 months once stable, targeting TSH 0.5-4.5 mIU/L. 1, 2

Dose Adjustment Protocol

• If TSH remains >10 mIU/L: Increase levothyroxine by 12.5-25 mcg 6, 1
• If TSH 4.5-10 mIU/L on treatment: Increase by 12.5-25 mcg, using smaller increments (12.5 mcg) for elderly or cardiac patients 6, 1
• If TSH <0.1 mIU/L: Decrease dose by 25-50 mcg to prevent iatrogenic hyperthyroidism complications 1
• If TSH 0.1-0.45 mIU/L: Decrease dose by 12.5-25 mcg, particularly in elderly patients or those with atrial fibrillation 1

Special Monitoring Situations

• For patients with atrial fibrillation, cardiac disease, or serious medical conditions, repeat testing within 2 weeks of dose adjustment rather than waiting 6-8 weeks 1
• Free T4 measurement helps interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 1

Treatment Decisions for Subclinical Hypothyroidism

TSH >10 mIU/L with Normal Free T4

Initiate levothyroxine therapy regardless of symptoms, as this threshold carries approximately 5% annual risk of progression to overt hypothyroidism. 1, 2, 3

• Treatment may improve symptoms and lower LDL cholesterol, though mortality benefit is unproven 1
• Evidence quality is rated as "fair" by expert panels 1

TSH 4.5-10 mIU/L with Normal Free T4

Routine levothyroxine treatment is not recommended; instead, monitor thyroid function tests every 6-12 months. 1, 3

Consider treatment in specific situations:

• Symptomatic patients with fatigue, weight gain, cold intolerance, or constipation may benefit from a 3-4 month trial 1
• Positive anti-TPO antibodies (4.3% annual progression risk vs 2.6% in antibody-negative individuals) 1
• Women planning pregnancy or currently pregnant (subclinical hypothyroidism causes preeclampsia, low birth weight, and adverse neurodevelopmental outcomes) 1, 4
• Patients on immune checkpoint inhibitors with hypothyroid symptoms 1

Risks of Overtreatment

Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, significantly increasing morbidity risks. 1, 2

Major Complications of TSH Suppression (<0.1 mIU/L)

• Atrial fibrillation: 5-fold increased risk in individuals ≥45 years, especially elderly patients 1, 3
• Osteoporosis and fractures: Particularly hip and spine fractures in women >65 years 1
• Cardiovascular mortality: Association with increased cardiovascular death 1
• Cardiac dysfunction: Left ventricular hypertrophy and abnormal cardiac output 1

Common Pitfalls to Avoid

• Never treat based on a single elevated TSH value without confirmation testing, as 30-60% normalize spontaneously 1
• Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism, as this precipitates adrenal crisis 6, 1
• Avoid adjusting doses too frequently before reaching steady state—wait 6-8 weeks between adjustments 1
• Do not overlook non-thyroidal causes of TSH abnormalities, including acute illness, medications, or recent iodine exposure from CT contrast 1
• Failing to distinguish between transient and permanent hypothyroidism leads to unnecessary lifelong treatment 1

Alternative Therapy Considerations

Levothyroxine monotherapy remains the standard treatment; combination therapy with levothyroxine plus liothyronine is not routinely recommended. 7, 8

• Two studies showed potential benefits on mood and quality of life with combination therapy, but clear advantages have not been demonstrated 7
• Liothyronine addition risks postabsorptive elevated T3 levels causing thyrotoxic symptoms 8
• Patients with DIO2 gene polymorphism may benefit from combination therapy, though this requires confirmation 1