When should we treat subclinical hypothyroidism?

Treatment of Subclinical Hypothyroidism

Levothyroxine therapy should be initiated for patients with TSH persistently >10 mIU/L regardless of symptoms, while patients with TSH between 4.5-10 mIU/L generally do not require treatment unless specific risk factors or symptoms are present. 1, 2

Definition and Diagnosis

• Subclinical hypothyroidism is defined as elevated TSH with normal free T4 levels 1, 2
• Before initiating treatment, confirm elevated TSH with repeat testing after 3-6 weeks, as 30-60% of high TSH levels normalize on repeat testing 1
• Measure both TSH and free T4 to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4) 1

Treatment Algorithm Based on TSH Levels

TSH >10 mIU/L

• Initiate levothyroxine therapy regardless of symptoms 1, 2
• This level of elevation carries a higher risk of progression to overt hypothyroidism (approximately 5% per year) 1, 3
• Treatment prevents complications of hypothyroidism in patients who progress 1

TSH 4.5-10 mIU/L

• Routine levothyroxine treatment is generally NOT recommended 2, 4
• Monitor thyroid function tests at 6-12 month intervals 2
• Consider treatment in specific situations:
  • Symptomatic patients (fatigue, weight gain, cold intolerance) 1, 5
  • Patients with positive anti-TPO antibodies (higher risk of progression to overt hypothyroidism) 1, 5
  • Patients with infertility or goiter 5
  • Pregnant women or women planning pregnancy 1, 6
  • Patients <65 years with cardiovascular risk factors 7, 3

Special Populations

Pregnant Women or Women Planning Pregnancy

• Treat subclinical hypothyroidism regardless of TSH level 1, 2
• Subclinical hypothyroidism during pregnancy is associated with adverse outcomes including preeclampsia and low birth weight 1
• More frequent monitoring is required as levothyroxine requirements often increase during pregnancy 1

Elderly Patients (>70 years)

• Treatment should be avoided in those aged >85 years with TSH up to 10 mIU/L 6
• For patients >70 years with cardiac disease or multiple comorbidities, use a lower starting dose (25-50 mcg/day) if treatment is necessary 1
• TSH goals are age-dependent, with upper limits of normal increasing with age (up to 7.5 mIU/L for patients over age 80) 4

Levothyroxine Dosing Guidelines

• For patients <70 years without cardiac disease or multiple comorbidities: full replacement dose of approximately 1.6 mcg/kg/day 1
• For patients >70 years or with cardiac disease/multiple comorbidities: start with 25-50 mcg/day and titrate gradually 1
• Monitor TSH every 6-8 weeks while titrating hormone replacement 1
• Once adequately treated, repeat testing every 6-12 months or if symptoms change 1

Common Pitfalls and Considerations

• Undertreatment risks include persistent hypothyroid symptoms, adverse effects on cardiovascular function, lipid metabolism, and quality of life 1
• Overtreatment risks include development of subclinical hyperthyroidism in 14-21% of treated patients 2
• Iatrogenic hyperthyroidism increases risk for osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy 1
• About 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH 1
• Failure to recognize transient hypothyroidism may lead to unnecessary lifelong treatment 1
• In patients with both adrenal insufficiency and hypothyroidism, steroids should always be started prior to thyroid hormone to avoid an adrenal crisis 1