Can lithium (lithium carbonate) cause thyroid issues, such as hypothyroidism, in patients, particularly those with pre-existing thyroid conditions or other risk factors like women, older adults, or a family history of thyroid disease?

Lithium and Thyroid Dysfunction

Yes, lithium definitively causes thyroid issues, most commonly hypothyroidism and goiter, with women over 50 years and those with pre-existing thyroid autoimmunity at highest risk. 1, 2

Mechanisms of Lithium-Induced Thyroid Dysfunction

Lithium affects thyroid function through multiple pathways that directly impair hormone production and release 2:

• Inhibits thyroid hormone synthesis and release at the cellular level, which is the critical mechanism underlying most thyroid complications 2, 3
• Decreases peripheral conversion of T4 to T3 by reducing type I 5'-deiodinase enzyme activity 2
• Enhances thyroid autoimmunity by augmenting B lymphocyte activity and reducing the ratio of suppressor to cytotoxic T cells in susceptible individuals 2

Spectrum of Thyroid Abnormalities

Hypothyroidism (Most Common)

Hypothyroidism is the most prevalent thyroid abnormality, developing in approximately 40% of patients on long-term lithium therapy 4, 2:

• Women are affected 3 times more frequently than men (25.8% vs 8.7%) 5
• Risk increases dramatically with age, reaching 50% in women by age 65 5
• Annual incidence is 1.5% in patients on chronic lithium therapy 6
• Onset typically occurs within the first few years of treatment, particularly in middle-aged women 3

The FDA drug label explicitly warns that "euthyroid goiter and/or hypothyroidism (including myxedema) accompanied by lower T3 and T4" are established adverse reactions to lithium 1.

Goiter

• Goiter develops frequently and can be detected both clinically and ultrasonographically 2
• Results from compensatory TSH elevation in response to lithium's inhibition of thyroid hormone release 3
• May occur with or without hypothyroidism 1, 3

Hyperthyroidism (Rare)

• Hyperthyroidism is very infrequent, with the FDA noting "paradoxically, rare cases of hyperthyroidism have been reported" 1
• Annual incidence is extremely low (1 case per 976 patient-years in one study) 6
• Frequency is very low even in long-term follow-up studies 5

Thyroid Autoimmunity

• Annual rate of newly developed thyroid antibodies is 1.7% 6
• Thyroid autoimmunity is found in excess among patients with affective disorders, even before lithium exposure 3
• Presence of thyroid antibodies increases risk of hypothyroidism 8.4-fold (6.4% annual rate vs 0.8% in antibody-negative patients) 6

High-Risk Populations Requiring Intensified Monitoring

Women Over 50 Years

Middle-aged and older women face the highest risk of lithium-induced hypothyroidism 2, 3, 5:

• Women over 60 years develop hypothyroidism more frequently (34.6%) compared to women under 60 (31.9%) 4
• By age 65, risk in women reaches 50% 5
• Hypothyroidism develops particularly during the first years of lithium treatment in middle-aged women 3

Patients with Family History of Thyroid Disease

Family history dramatically accelerates onset of hypothyroidism 4:

• Patients with first-degree relatives affected by thyroid illness develop hypothyroidism at 3.7 years after starting lithium 4
• Patients without family history develop hypothyroidism at 8.6 years after starting lithium 4
• More frequent assessment is recommended among patients with family history of thyroid disease 2

Patients with Thyroid Autoimmunity

Pre-existing thyroid antibodies substantially increase risk 2, 6:

• Subjects with thyroid antibodies have 8.4 times higher risk of requiring levothyroxine compared to antibody-negative subjects 6
• Lithium increases propensity to thyroid autoimmunity in susceptible individuals 2
• More frequent assessment is recommended among those positive for thyroid auto-antibodies 2

Additional Risk Factors

• Environmental factors such as iodine deficiency reduce compensatory potential and increase risk of clinically relevant consequences 3
• Immunogenetic background may predispose to thyroid dysfunction when combined with lithium exposure 3

Monitoring Protocol

Baseline Assessment (Before Starting Lithium)

The American Academy of Child and Adolescent Psychiatry recommends baseline laboratory assessment including thyroid function tests before initiating lithium therapy 7:

• Measure TSH, free T4, free T3, and thyroid antibodies (anti-thyroid peroxidase and TSH receptor antibodies) 2, 3
• Perform clinical assessment of thyroid size and consider thyroid ultrasonography 2, 3

During Lithium Stabilization and Maintenance

Regular monitoring every 3-6 months is required during lithium stabilization and maintenance 7:

• Repeat full thyroid panel at one year (TSH, free thyroid hormones, antibodies, ultrasonic scanning) 3
• Annual TSH measurements are sufficient to prevent overt hypothyroidism in stable patients 3
• In presence of raised TSH or thyroid autoimmunity, assess every 4-6 months 3
• Repeat antibody measurements and ultrasonic scanning every 2-3 years 3

High-Risk Patients Require More Frequent Monitoring

More frequent assessment is recommended among 2:

• Middle-aged females (≥50 years)
• Patients with family history of thyroid disease
• Those positive for thyroid auto-antibodies

Management of Lithium-Induced Thyroid Dysfunction

When Hypothyroidism Develops

The FDA explicitly states that "where hypothyroidism occurs during lithium stabilization and maintenance, supplemental thyroid treatment may be used" 1:

• Continue lithium therapy while initiating levothyroxine 7, 1
• Previously existing thyroid disorders do not contraindicate lithium treatment 1
• Careful monitoring during lithium stabilization allows correction of changing thyroid parameters 1
• Thyroid function abnormalities should not constitute outright contraindication to lithium, and lithium should not be stopped if patient develops thyroid abnormalities 3

Levothyroxine Dosing and Monitoring

• Monitor TSH and free T4 every 6-8 weeks during levothyroxine titration 7
• Target TSH within reference range (0.5-4.5 mIU/L) with normal free T4 8
• Once stabilized, monitor every 6-12 months 8

When to Refer to Endocrinologist

Refer to endocrinologist if 3:

• TSH concentrations are repeatedly abnormal
• Goiter or nodules are detected on examination or ultrasound
• Complex management decisions are required

Critical Clinical Considerations

Compensatory Mechanisms

• Compensatory mechanisms operate and prevent hypothyroidism in the majority of patients 3
• When additional risk factors are present (environmental or intrinsic), compensatory potential may be reduced 3

Long-Term Outcomes

• In patients on lithium for several years, outcomes of hypothyroidism, goiter, and thyroid autoimmunity do not differ much from general population 3
• Hyperthyroidism and thyroid cancer are observed rarely during lithium treatment 3
• Three patients underwent thyroidectomy over 976 patient-years (two for multinodular goiter, one for papillary carcinoma) 6

Calcium and Parathyroid Effects

Lithium also affects calcium metabolism 4:

• After lithium treatment, calcium levels are higher than baseline or control levels 4
• Lithium counteracts the decrease in plasma calcium associated with aging 4
• Familial thyroid illness is a risk factor for hypercalcemia during lithium therapy 4
• Magnesium levels remain unchanged from baseline 4

Common Pitfalls to Avoid

• Never discontinue lithium solely because of thyroid dysfunction—manage with levothyroxine supplementation while continuing lithium 1, 3
• Do not assume thyroid function will remain stable—hypothyroidism may develop particularly during first years of treatment 3
• Avoid inadequate monitoring in high-risk groups—women over 50, those with family history, and antibody-positive patients require more frequent assessment 2, 5
• Do not overlook the importance of baseline testing—identifying pre-existing thyroid abnormalities or antibodies guides monitoring intensity 2, 3
• Remember that lithium is perhaps the only efficient means of reducing excessive mortality associated with affective disorders—thyroid abnormalities should not prevent its use when clinically indicated 3