Management of Hypothyroidism in Patients on Lithium Prophylaxis for Bipolar Disorder

Joseph F. Goldberg, MD

Disclosures

October 31, 2008

Question

What are the latest guidelines regarding the management of hypothyroidism in patients with bipolar disorder on lithium prophylaxis? Should lithium be withdrawn in such patients?

Response From the Expert

 

Joseph F. Goldberg, MD
Associate Clinical Professor, Department of Psychiatry, Mount Sinai School of Medicine, New York, NY; Director, Affective Disorders Research Program, Sliver Hill Hospital, New Canaan, Connecticut

 

According to the American Psychiatric Association (APA) Practice Guidelines for the Treatment of Patients with Bipolar Disorder,[1] biochemical hypothyroidism develops in 5% to 35% of patients with bipolar disorder, usually within 6 to 18 months of lithium treatment initiation. The wide range of reported prevalence rates has been attributed to methodological differences across studies, such as variable sample sizes, durations of lithium exposure, and assays of varying sensitivity. Risk is somewhat higher in women, in those who have a preexisting vulnerability to autoimmune thyroiditis, and possibly in those with a rapid cycling course.[2]

The mechanism by which lithium can cause hypothyroidism is complex. Lithium induces a decrease in production of thyroxine (T4) from the thyroid gland, as well as interference with the de-iodination of T4 to T3 (tri-iodothyronine, the metabolically active form of thyroid hormone). It may also evoke an exaggerated thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone.[3] . If a patient has thyroid antibodies, it is conceivable that lithium exposure may serve to reveal an underlying diathesis for autoimmune-mediated thyroid disease, necessitating thyroid hormone replacement independent of lithium.

Baseline thyroid function tests should be measured prior to starting lithium therapy to ensure that undetected hypothyroidism is not contributing to mood symptoms. Pertinent thyroid function tests include TSH and free T4 levels, as well as antiperoxidase and antithyroglobulin in the presence of an elevated TSH. Subsequent monitoring of thyroid function tests is usually conducted 3 months after starting lithium and every 6-12 months thereafter.[4,5]

Although lithium-induced hypothyroidism is usually reversible upon cessation of lithium, the development of hypothyroidism is not a contraindication to continuing lithium, and most experts advocate thyroid augmentation therapy. Current practice guidelines do not specify criteria for managing thyroid replacement therapy in patients with lithium-induced hypothyroidism. In the presence of elevated TSH levels without clinical signs of hypothyroidism, some authorities advise monitoring serum TSH levels every 3 months without intervening with adjunctive thyroxine, unless TSH levels rise above 10 mU/L.[4] Others advocate thyroid supplementation whenever TSH levels rise above normal, particularly in the presence of affective symptoms. T4 is generally preferred to T3 because the former tends to produce steadier hormone levels.[4] Typically, thyroxine (T4) is begun at .025 mg, and increased by .025 mg every 3 to 6 weeks until TSH levels have normalized.[4]In the presence of rapid cycling or persistent affective symptoms, thyroxine is increased until the serum T4 level is in the upper quartile of the normal reference range.[6]

Lithium-induced thyroid dysfunction has occasionally been shown to remain normalized after stopping T4 following 1-2 years of thyroid supplementation.[7] Long-term or indefinite adjunctive treatment with thyroxine carries arrhythmogenic potential, as well as an increased risk for bone demineralization , requiring medical monitoring of patients at risk.

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