Lithium and the thyroid
- Martin I Surks, MD
Martin I Surks, MD
- Professor of Medicine and Pathology
- Albert Einstein College of Medicine
The antithyroid actions of lithium were first investigated in detail when it was noted that patients with psychiatric disease treated with lithium carbonate developed hypothyroidism and goiter. Animal and human studies subsequently revealed that lithium increases intrathyroidal iodine content, inhibits the coupling of iodotyrosine residues to form iodothyronines (thyroxine [T4] and triiodothyronine [T3]) [1-3], and inhibits release of T4 and T3 [2-4].
The mechanism by which lithium inhibits thyroid hormone release is not well understood. In vitro, lithium decreases colloid droplet formation within thyroid follicular cells, a reflection of decreased pinocytosis of colloid from the follicular lumen . The efficiency of proteolytic digestion of thyroglobulin within phagolysosomes also may be impaired.
This topic will review the clinical effects of lithium on thyroid function. In addition to inducing hypothyroidism, the magnitude of the lithium-induced inhibition of thyroid hormone secretion is sufficient to make lithium useful in the treatment of some patients with hyperthyroidism or thyroid cancer.
THYROID DISEASE IN LITHIUM-TREATED PATIENTS
Lithium can cause goiter and hypothyroidism, and its use has been associated with both thyroid autoimmunity and hyperthyroidism . Because of the high incidence of thyroid dysfunction that occurs during lithium treatment, patients should have a careful thyroid physical examination and determination of serum thyroid-stimulating hormone (TSH) and antithyroid peroxidase antibody titers before lithium treatment is begun. Patients with normal thyroid function initially should be reevaluated every 6 to 12 months for several years, and thyroid dysfunction should be treated if diagnosed. The development of thyroid dysfunction does not typically require discontinuation of lithium. If thyroid function is abnormal at the initial evaluation, lithium can still be given, if necessary, but the thyroid dysfunction should be treated.
Goiter — Goiter is the most common thyroid abnormality in lithium treated patients, occurring in approximately 40 to 50 percent [7-10]. The inhibition of thyroid hormone secretion that occurs during lithium treatment results in decreased serum thyroxine (T4) and triiodothyronine (T3) concentrations, a compensatory increase in pituitary secretion of TSH and, in a new steady state, secretion of a normal amount of thyroid hormone by an enlarged thyroid gland . Thyroid enlargement may also occur as a result of lithium induced alterations in the function of insulin-like growth factor, tyrosine kinase, and/or Wnt/beta-catenin signalling [10,11]. In affected patients, the thyroid is enlarged to about twice the normal size, and the goiter is usually diffuse, although nodular goiter has also been reported . The goiters usually occur within the first two years of treatment.
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