Lithium-Induced Hypothyroidism in Bipolar Disorder

Patient Background

A 45-year-old female with bipolar I disorder was recently hospitalized for an acute manic episode. Following clinical stabilization, her psychiatrist initiated lithium carbonate 300 mg twice daily for long-term mood stabilization. Baseline laboratory evaluation, including TSH and free T4, demonstrated normal thyroid function prior to lithium initiation.

Clinical Presentation

Over the subsequent months, the patient developed progressive fatigue, weight gain, dry skin, cold intolerance, and subtle depressive symptoms. She attributed these changes to life stressors, delaying further assessment. During a routine outpatient follow-up, repeat thyroid function tests revealed a TSH of 22.15 mIU/L (markedly elevated) and low free T4, confirming the diagnosis of lithium-induced hypothyroidism.

Clinical Issue Identified

Lithium is a well-established mood stabilizer with recognized endocrine adverse effects, most notably its impact on thyroid function. Lithium alters thyroid physiology through several mechanisms:

Impaired thyroid hormone synthesis and release: Inhibition of iodide uptake and reduced secretion of T4/T3 from thyroid follicles.

Decreased peripheral conversion: Reduced transformation of T4 into the active T3 form.

Risk of autoimmune thyroiditis: Increased susceptibility to autoimmune-mediated thyroid dysfunction with chronic therapy.

These mechanisms collectively contribute to clinical hypothyroidism, which can mimic or precipitate depressive phases in bipolar disorder, complicating diagnostic clarity and treatment response.

Pharmacist Intervention and Management Plan

Assessment and Confirmation

• Validate laboratory findings consistent with overt hypothyroidism.

• Rule out other causes such as autoimmune thyroid disease or recent iodine exposure.

Therapeutic Strategy

• Continue lithium therapy, given its demonstrated psychiatric benefit, unless the patient’s clinical response is inadequate or alternative mood stabilizers are being considered.

• Initiate levothyroxine replacement therapy (e.g., 25–50 µg daily), titrating according to TSH and symptom resolution.

• Reassess thyroid function in 6–8 weeks to evaluate response and adjust dosing accordingly.

Ongoing Monitoring

• Monitor TSH and free T4 every 6–12 months, or sooner if symptoms recur.

• Continue routine serum lithium monitoring, renal function testing, and symptom surveillance.

• Educate the patient on recognizing signs of both hypothyroidism and lithium toxicity.

Interdisciplinary Coordination

• Communicate with psychiatry to ensure alignment between mood stabilization goals and endocrine management.

• Consider endocrinology consultation if thyroid dysfunction persists or autoimmune markers are present.

Clinical Rationale and Ramifications

Lithium-induced hypothyroidism is a common and predictable adverse effect, particularly in long-term therapy. If unrecognized, hypothyroidism can lead to significant physical morbidity and may be misinterpreted as bipolar depression, increasing the risk of inappropriate psychiatric medication adjustments or dose escalations.

Timely identification and initiation of thyroid hormone replacement allow patients to continue benefiting from lithium’s unique mood-stabilizing properties while restoring metabolic and neuropsychiatric stability. Failure to detect this condition early may result in worsening mood symptoms, avoidable fatigue and metabolic slowdown, and unnecessary modification of an otherwise effective mood stabilizer.

This case emphasizes the need for routine thyroid monitoring, clinical vigilance for endocrine symptoms, and integrated care in the long-term management of bipolar disorder with lithium therapy.