How Is Thyroid Dysfunction Associated With Bipolar Disorder?

Sarah T. Melton, PharmD


November 30, 2010


What significance does thyroid dysfunction have in patients with bipolar disorder? Does this condition contribute to the morbidity of the disease?

Response from Sarah T. Melton, PharmD
Director of Addiction Outreach, Associate Professor, Appalachian College of Pharmacy, Oakwood, Virginia; Clinical Pharmacist, C-Health, PC, Lebanon, Virginia

Bipolar disorder is a chronic, relapsing brain disorder that causes exaggerated shifts in mood, sleep, energy, concentration, and activity levels, and it impairs function in daily life. Bipolar disorder often develops in the late teens or early adult years, with half of all cases starting before age 25.[1]

Patients with bipolar disorder often have extremes of mania and depression alternating with normal mood. During manic episodes, behavioral changes such as restlessness, insomnia, irritability, risk-taking, or thoughtless behavior will occur. During the depressive phase, patients often become lethargic, lose interest in activities they previously enjoyed, and are at risk for suicidal behavior.[1]

Thyroid disorders also are associated with alterations in mood. Patients with hypothyroidism may present with depressive symptoms while patients with hyperthyroidism may present with symptoms consistent with mania. Therefore, thyroid function should be evaluated before a diagnosis of depression or bipolar disorder is made.

Review of Literature

In a study of twins, autoimmune thyroiditis was related to bipolar disorder and the genetic tendency to develop bipolar disorder. The authors suggest that autoimmune thyroiditis, using the marker of thyroperoxidase antibodies, is a possible endophenotype for bipolar disorder.[2] Another study evaluating outpatients with bipolar disorder found thyroid autoimmunity to be highly prevalent. The presence of thyroperoxidase antibodies appeared to be an independent risk factor for the development of hypothyroidism, particularly in women with bipolar disorder.[3]

Thyroid dysfunction is more common in patients with rapid cycling bipolar disorder (ie, having 4 or more mood swings or episodes in a 12-month period) or mixed states (ie, an episode that simultaneously presents symptoms of both depression and mania) than in patients with classic mania.[4] Levothyroxine may decrease the severity and frequency of manic and depressive episodes.[5]In addition, triiodothyronine has been effectively used as an augmentation agent in treatment-resistant bipolar depression.[6]

In a Danish registry study,[7] patients hospitalized with bipolar disorder were at greater risk for readmission with hyperthyroidism compared with control patients. The authors suggest that hyperthyroidism may be associated with long-term mood disturbances.

While hyperthyroidism is typically associated with mania, there are case reports of mania or hypomania associated with hypothyroidism. These reports typically occurred in young women of reproductive age; however, late-onset mania associated with hypothyroidism in an elderly woman has been reported.[8]

Patients with bipolar depression are sensitive to variations in thyroid function within the normal range of laboratory values. Cole and colleagues[9] evaluated free thyroxine index and thyroid-stimulating hormone (TSH) levels in 65 patients with bipolar depression. A longer time to remission was significantly associated with both lower values of free thyroxine index and higher values of TSH. Patients with free thyroxine index values greater than the median and TSH values below the median had better outcomes. The authors suggest that nearly 75% of patients with bipolar disorder have a thyroid profile that may be suboptimal for antidepressant response.

Treatment Effects on the Thyroid

Associations between lithium, the gold-standard for treatment of bipolar disorder, and thyroid function have been recognized for some time. A review of the literature[10] found that:

  • Inhibition of thyroid hormone release is critical for the development of hypothyroidism and goiter;

  • Hypothyroidism may occur in the early years of lithium use, in middle-aged women, and when thyroid autoimmunity is present;

  • The outcome of thyroid dysfunction in patients who have been on lithium for many years is not greatly different from that observed in the general population; and

  • Hyperthyroidism and thyroid cancer are uncommon during treatment with lithium.

The authors recommend that thyroid function tests be performed at baseline prior to lithium initiation and repeated after 1 year. An annual TSH may then be sufficient to detect hypothyroidism. Thyroid function abnormalities are not a contraindication to lithium treatment and lithium should not be discontinued if thyroid abnormalities occur.[10]

A recent nested, matched, case-control study of patients with bipolar disorder and incident hypothyroidism found that lithium, carbamazepine and valproate increased the risk for hypothyroidism. Combination of agents (especially lithium and valproate) further heightened risk for hypothyroidism. Based on these results, the authors recommend regular monitoring of thyroid function and monotherapy of mood stabilizers for treatment of bipolar disorders.[11]


Function of the thyroid has a complex relationship with bipolar disorder. Any patient presenting with a mood disorder should have thyroid function evaluated before diagnosis and a patient with bipolar disorder should have thyroid function evaluated consistently during treatment. Research continues regarding the association between bipolar disorder and thyroid function, the association between thyroid function and bipolar treatment, and use of thyroid hormone as a potential treatment in bipolar disorder.

Dr. Melton acknowledges the research assistance of Courtney Cole, Heather Fields, and Laurie Peery, Doctor of Pharmacy Candidates at the Appalachian College of Pharmacy.


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