What to do if someone on lithium (lithium carbonate) has elevated Thyroid-Stimulating Hormone (TSH) levels?

Management of Elevated TSH in Patients on Lithium

For patients on lithium with elevated TSH, initiate levothyroxine therapy, particularly when TSH is >10 mIU/L or when symptoms of hypothyroidism are present, while continuing lithium treatment if clinically indicated. 1

Assessment and Diagnosis

• 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
• Evaluate for symptoms of hypothyroidism such as fatigue, weight gain, cold intolerance, and constipation 1
• Lithium affects thyroid function through multiple mechanisms, including inhibition of thyroid hormone release, which is the critical mechanism in the development of hypothyroidism and goiter 2

Treatment Algorithm Based on TSH Levels

• For TSH >10 mIU/L with normal free T4 (subclinical hypothyroidism):

  • Initiate levothyroxine therapy regardless of symptoms 1
  • This level of elevation carries a higher risk of progression to overt hypothyroidism (approximately 5% per year) 1

• For TSH 4.5-10 mIU/L with normal free T4:

  • Consider treatment if symptoms of hypothyroidism are present 1
  • Consider treatment if positive anti-TPO antibodies are present, as lithium may support the appearance of thyroid autoantibodies 3
  • Treatment decisions should be individualized based on symptom severity and risk factors 1

Levothyroxine Dosing Guidelines

• For patients <70 years without cardiac disease:

  • Start with full replacement dose of approximately 1.6 mcg/kg/day 1

• For patients >70 years or with cardiac disease:

  • Start with a lower dose of 25-50 mcg/day and titrate gradually 1
  • This approach minimizes risk of exacerbating cardiac symptoms 1

Monitoring Protocol

• 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
• Continue lithium treatment as indicated for psychiatric management - thyroid abnormalities should not constitute an outright contraindication to lithium treatment 2

Special Considerations for Lithium Patients

• Lithium concentrates in the thyroid gland at levels 3-4 times higher than in plasma 4
• Lithium inhibits thyroidal iodine uptake, iodotyrosine coupling, alters thyroglobulin structure, and inhibits thyroid hormone secretion 5
• The prevalence of hypothyroidism in lithium-treated patients is higher due to lithium's immunostimulating effects 3
• Women and middle-aged patients are at higher risk for developing lithium-induced hypothyroidism 2
• Patients with pre-existing thyroid autoimmunity are at increased risk for developing hypothyroidism during lithium treatment 2

Ongoing Thyroid Monitoring for Lithium Patients

• Prior to starting lithium, perform baseline thyroid function tests (TSH, free thyroid hormones) and thyroid antibody testing 2
• Repeat comprehensive thyroid assessment at one year after starting lithium 2
• For routine monitoring, annual TSH measurements may be sufficient to prevent overt hypothyroidism 2
• If TSH is elevated or thyroid autoantibodies are present, monitor more frequently (every 4-6 months) 2
• Consider thyroid ultrasound at baseline and every 2-3 years during lithium treatment 2

Common Pitfalls to Avoid

• Do not discontinue lithium solely due to thyroid abnormalities - the FDA label specifically states: "Previously existing underlying thyroid disorders do not necessarily constitute a contraindication to lithium treatment" 6
• Avoid undertreatment of hypothyroidism, which can lead to persistent symptoms, adverse effects on cardiovascular function, lipid metabolism, and quality of life 1
• Be cautious about overtreatment with levothyroxine, which can lead to iatrogenic hyperthyroidism, increasing 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, highlighting the importance of regular monitoring 1

When to Refer to an Endocrinologist

• If TSH concentrations are repeatedly abnormal despite appropriate levothyroxine adjustments 2
• If goiter or nodules are detected on physical examination or ultrasound 2
• For complex cases with multiple endocrine abnormalities 1