(PSYCHIATRIC TIMES) - The exact therapeutic mechanism of lithium in bipolar disorder (BD) remains unclear, due in part to its many actions on the cells of the central nervous system. The same complexity applies to the interactions between lithium and the thyroid. Lithium is widely known to impair the function of the thyroid through a variety of mechanisms.
In 1998, Lazarus listed impaired thyroidal uptake of iodine, impaired iodination of tyrosine, altered thyroglobulin structure and impaired release of thyroxine from the thyroid gland as the mechanisms by which lithium induces hypothyroidism. Impaired release of thyroxine is considered the most clinically significant, and this phenomenon has been used to enhance the effectiveness of radioactive iodine when treating thyrotoxicosis (Bogazzi et al., 1999). Lithium has also been used, with reported success, to treat refractory hyperthyroidism (Dickstein et al., 1997).
Elevation of thyrotropin in response to lowered circulating thyroxine is probably the main stimulant for goiter formation, which has been reported with incidences of 3% to 60% in lithium-treated patients; much of this variation is related to varying definitions of goiter and differences in the methods used to measure thyroid size (Lazarus, 1998).
Thyroxine is secreted as T4 and then metabolized to its active form, T3, by the enzyme 5'deiodinase. Lithium appears to impair the process of deiodination of T4 peripherally (deiodinase I) and within some cells (deiodinase III) (Terao et al., 1995). Eravci et al. (2000) found varying effects of lithium on different isoenzymes of deiodinase and noted that it appeared to enhance the activity of deiodinase II present in rat frontal lobes. This effect may contribute to alterations in cellular responsiveness to thyroxine.
It is widely known that patients receiving lithium therapy commonly develop hypothyroidism. Johnston and Eagles (1999) found hypothyroidism in 10.4% of 718 patients treated with lithium. Women suffered a higher risk of developing hypothyroidism within two years of therapy, compared to the general population of the geographical area studied. Hypothyroidism occurred in 14% of women, significantly more frequently than in men (4.5%), however, both sexes had a significantly increased risk. Women who were 40 to 59 years of age had the highest risk, with an incidence of 20%.
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