Risks and Potential Applications

 

Lithium, when used as a medication in high doses, has well known side effects. Among them are short and long-term changes in thyroid function. Goitre and hypothyroidism are often reported, although increased levels of hyperthyroidism have also been documented. Due to the unique effects of lithium on the thyroid gland, its use as an adjunctive therapy during radioiodine treatment has also been explored.

The Thyroid Effects of Lithium


Hypothyroidism

The thyroid suppressing effects of lithium have been widely recognized with research from case reviews estimating that 12% of patients prescribed lithium will have an elevated level of thyroid stimulating hormone (TSH) within about one month (Phelps 2020). Results showing suppression of thyroid function are seen even with treatment doses in the lower range of standard recommendations.

Most research appears to indicate that standard lithium treatment for bipolar does not induce autoimmune antibodies in treated patients. Interestingly, there is evidence that bipolar disorder itself may be linked to autoimmune thyroid disease (Barbuti 2017) although the data doesn’t absolve lithium of its effects on thyroid function. Data clearly documents increased TSH and thyroid size with its use (Kuman Tuncel 2017). Estimates suggest that up to 40% of treated patients develop at least a mild goitre and 20% develop hypothyroidism (Lazarus 2009).

Lithium and Hyperthyroidism

While much less common, hyperthyroidism is also becoming a recognized risk with lithium treatment. And while the potential mechanism for how lithium induces increased thyroid hormones is not well understood, hypotheses include direct toxic effects on thyroid cells, increased iodine levels in the thyroid gland inducing hyperthyroidism in susceptible individuals or stimulation of immune system responses against the TSH receptor (Fairbrother 2019).

Mechanism of Action of Lithium on Thyroid Function

It has been known for a while that lithium is concentrated at least three-fold above serum levels in the thyroid gland (Berens 1970). Thus lithium has stronger effects on thyroid tissue due to higher concentrations present throughout the gland. Other consistent findings show that lithium blocks release of iodine from the thyroid, decreasing the release of thyroid hormones (Spaulding 1972). The reduction in thyroid hormones results in higher TSH levels that can contribute to goitre through increased thyroid stimulation. In addition, thyroid cells may increase their growth due to changes in cellular signalling from adenyl cyclase activity and cyclic adenosine monophosphate levels induced by lithium (Urabe 1991). Overall, the effects of lithium on the thyroid gland are complex with research ongoing to understand the underlying biochemistry (Czarnywojtek 2020).

Due to changes induced in the thyroid gland with lithium treatment, some research has suggested ultrasound visualization before initiating lithium therapy (Dar 2020). Patients with preexisting thyroid antibodies or goitre appear to be at higher risks of thyroid problems with lithium (Lazarus 1986). However, it is worth noting that nutritional interventions may help reduce lithium’s problematic effects on the thyroid. A study in rats showed that zinc supplementation almost normalized changes in thyroid function induced by lithium treatment (Pathak 2020).

Lithium and Radioiodine Therapy for Hyperthyroidism

Hyperthyroidism is generally treated with two approaches: radioiodine therapy and anti-thyroid medication. Radioiodine is used to destroy a portion of active thyroid tissue and decrease thyroid hormone levels. Anti-thyroid medications are employed to directly decrease thyroid function. Radioiodine therapy works through the concentrating effects of the thyroid gland on iodine. By administering radioactive iodine, the thyroid gland concentrates the radioactive element leading to destruction of active thyroid tissue.

Due to lithium’s effects on increasing iodine uptake and retention, trials have explored its combination with radioiodine therapy. Of the four trials, the three that administered lithium prior to radioiodine therapy appeared to show increased success. A recent brief review recommends lithium in cases where anti-thyroid medications are not effective or contraindicated and the first round of radioiodine therapy was unsuccessful (Basu 2017). While interesting, it remains to be seen if lithium use during radioiodine therapy becomes a more accepted practice.

Conclusions

Lithium has numerous, complex interactions with the thyroid gland. Through an understanding of these effects, it may be possible to better screen for risks before the initiation of lithium therapy. Checking antibody levels against the thyroid and ultrasound visualization of the gland may be useful to include before initiating treatment. While data is thin and only from a single animal study, the possibility of reducing the negative impact of lithium on the thyroid gland with zinc or other measures may also be feasible through additional research. Finally, lithium may have a place combined with radioiodine therapy for the treatment of thyrotoxicosis patients.

References

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Dar SA, Bhat BA, Khanam A, Wani ZA, Nabi J, Sheikh S. Thyroid hormone levels and Thyroid Hormone Levels and Ultrasonographic Changes in the Thyroid Gland of Patients on Long-Term Lithium Treatment for Affective Disorders: A Controlled Study. J Med Ultrasound. 2020;28(2):104-110. Published 2020 Mar 26. doi:10.4103/JMU.JMU_26_19

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