Can lithium cause thyroid dysfunction, particularly in patients with a history of psychiatric disorders, such as bipolar disorder, and are certain demographics like women and older adults more susceptible?

Can Lithium Cause Thyroid Dysfunction?

Yes, lithium definitively causes thyroid dysfunction, with hypothyroidism being the most common manifestation, occurring in approximately 19-22% of patients on chronic lithium therapy. 1, 2, 3

Mechanism and Clinical Significance

Lithium directly interferes with thyroid hormone synthesis and release, leading to compensatory TSH elevation and potential goiter formation. 1 The FDA drug label explicitly states that "previously existing underlying thyroid disorders do not necessarily constitute a contraindication to lithium treatment; where hypothyroidism exists, careful monitoring of thyroid function during lithium stabilization and maintenance allows for correction of changing thyroid parameters." 1

The risk is dose-dependent: patients with low lithium levels (<0.5 mEq/L) experience mean TSH increases of 0.52 mIU/L, while those with antimanic levels (>0.8 mEq/L) show mean TSH increases of 2.16 mIU/L. 4

Specific Thyroid Abnormalities Caused by Lithium

Hypothyroidism (Most Common)

• Subclinical hypothyroidism occurs in 7.1% of lithium-treated patients 5
• Clinical hypothyroidism requiring levothyroxine develops in approximately 19-22% of patients, particularly females 2, 3
• Goiter is detected in 38.1% of lithium-treated patients 5

Less Common Thyroid Effects

• Subclinical hyperthyroidism occurs in 7.1% of patients 5
• Overt hyperthyroidism occurs in 2.4% of patients 5
• Increased conversion of free T4 to free T3 (indicating mild thyroid dysfunction) occurs in 47.6% of patients 5

Autoimmune Thyroid Disease

• A significant percentage of lithium-treated patients develop abnormally high levels of anti-TPO and anti-TG antibodies, which correlate with TSH and fT3 concentrations 2

Demographics at Higher Risk

Women Are Significantly More Susceptible

Female patients are at substantially higher risk for lithium-induced thyroid dysfunction. 2, 3 In one study, 22% of female patients showed features of hypothyroidism (seven requiring levothyroxine, three with elevated TSH), while no male patients showed thyroid hormone abnormalities. 2

The association with female sex is independent of lithium duration, making gender the most important demographic risk factor. 3

Age Considerations

• Younger patients (<40 years) show increased conversion of free T4 to free T3, particularly males with weight gain 5
• Older adults are not specifically identified as higher risk in the available evidence, though general thyroid dysfunction increases with age in the population 6

Duration of Lithium Treatment

• Thyroid abnormalities are related to duration of lithium treatment 3
• However, there is no significant difference in thyroid function between patients receiving lithium for 10-20 years versus those taking it for more than 20 years 2
• Lithium-induced hypothyroidism is likely related to the length of treatment, with exaggerated TSH response to TRH found in patients receiving lithium for more than one year 7

Monitoring Requirements

Baseline Assessment

Before initiating lithium therapy, the FDA label mandates baseline laboratory assessment including thyroid function tests 6

Ongoing Monitoring

• Regular monitoring of thyroid function (TSH, free T4) is required every 3-6 months during lithium stabilization and maintenance 6, 1
• The FDA label states: "Where hypothyroidism occurs during lithium stabilization and maintenance, supplemental thyroid treatment may be used" 1
• Even with very low lithium doses, thyroid monitoring including a pre-lithium TSH is warranted, as the risk is dose-related but still present at low levels 4

Clinical Management Algorithm

For Patients Starting Lithium

1. Obtain baseline TSH and free T4 before initiating therapy 6
2. Check for pre-existing thyroid disease or autoimmune conditions 1
3. Monitor TSH every 3-6 months during stabilization 6

For Patients Developing Hypothyroidism on Lithium

1. Continue lithium therapy while initiating levothyroxine treatment 1
2. The FDA label explicitly states that hypothyroidism during lithium treatment can be managed with supplemental thyroid hormone without discontinuing lithium 1
3. Monitor thyroid function more frequently (every 6-8 weeks) during levothyroxine titration 8

For Patients with Pre-existing Thyroid Disease

• Pre-existing thyroid disorders do not contraindicate lithium treatment 1
• Careful monitoring during stabilization allows for correction of changing thyroid parameters 1

Critical Pitfalls to Avoid

• Do not assume thyroid function remains stable on chronic lithium therapy—regular monitoring every 3-6 months is mandatory 6, 1
• Do not discontinue lithium when hypothyroidism develops—add levothyroxine instead 1
• Do not overlook female patients, who have substantially higher risk of thyroid dysfunction 2, 3
• Do not skip baseline thyroid testing before initiating lithium, as pre-lithium TSH predicts risk of exceeding normal limits 4
• Do not assume low-dose lithium is safe from thyroid effects—even very low levels (<0.5 mEq/L) cause measurable TSH increases requiring monitoring 4