Management of Subclinical Hypothyroidism
For patients with subclinical hypothyroidism, treatment with levothyroxine is definitively recommended when TSH is persistently >10 mIU/L, while those with TSH between 4.5-10 mIU/L should only be treated in specific circumstances such as symptoms, positive TPO antibodies, or pregnancy. 1, 2
Definition and Diagnosis
- Subclinical hypothyroidism is defined as elevated TSH with normal free T4 levels 1
- 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
- Consider treatment in the following situations:
- Symptomatic patients with symptoms compatible with hypothyroidism 2
- Patients with positive TPO antibodies (higher risk of progression to overt hypothyroidism - 4.3% vs 2.6% per year) 2
- Patients with infertility or goiter 3
- All pregnant women (to reduce risks of pregnancy complications and adverse effects on fetal neurocognitive development) 2
- For patients without these factors, monitoring with thyroid function tests at 6-12 month intervals is recommended 2, 4
Levothyroxine Dosing Guidelines
- For patients <70 years without cardiac disease or multiple comorbidities, the full replacement dose of approximately 1.6 mcg/kg/day is recommended 1, 5
- For patients >70 years or with cardiac disease/multiple comorbidities, start with a lower dose of 25-50 mcg/day and titrate gradually 1, 5
- Take levothyroxine on an empty stomach 6
Dose Adjustments and Monitoring
- 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
- Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 1
- Target TSH should be within the reference range (0.5-4.5 mIU/L) with normal free T4 levels 6
Role of Liothyronine (T3) in Treatment
- Levothyroxine (T4) monotherapy remains the current standard for management of hypothyroidism 3
- Liothyronine (T3) may be considered in select patients who remain symptomatic despite adequate levothyroxine therapy and normalized TSH levels, particularly those with a polymorphism in type 2 deiodinase 7
- When using liothyronine, the FDA recommends starting at 25 mcg daily with increases of up to 25 mcg every 1-2 weeks, with usual maintenance doses of 25-75 mcg daily 8
- The wide swings in serum T3 levels that follow liothyronine administration and potential for more pronounced cardiovascular side effects must be considered 8
Special Populations
Elderly Patients
- Treatment should be initiated at a lower dose (25-50 mcg/day) 1, 5
- TSH goals are age-dependent, with higher upper limits considered normal in older patients 7
- Treatment of subclinical hypothyroidism in patients with TSH up to 10 mIU/L should probably be avoided in those aged >85 years 3, 7
Pregnant Women
- All pregnant women with subclinical hypothyroidism should be treated regardless of TSH level 2
- More aggressive normalization of TSH is warranted during pregnancy 1
- Levothyroxine requirements often increase during pregnancy, requiring more frequent monitoring 1
Risks and Pitfalls
- Overtreatment is common in clinical practice and is associated with increased risk of atrial fibrillation, osteoporosis, and fractures 3, 6
- Development of low TSH on therapy suggests overtreatment; dose should be reduced with close follow-up 1
- Undertreatment risks include persistent hypothyroid symptoms, adverse effects on cardiovascular function, lipid metabolism, and quality of life 1
- Certain drugs, such as iron and calcium supplements, reduce the gastrointestinal absorption of levothyroxine 6