Lithium Associated Hypothyroidism May Be Reversible

Peter Forster Bipolar Treatment, Physical Conditions and Health Leave a Comment

People who develop hypothyroidism while using the mood stabilizer lithium may return to normal thyroid function after the drug is discontinued, according to a study in the Journal of Psychopharmacology.

Hypothyroidism—a condition in which the thyroid gland does not produce enough thyroid hormone—has long been known to be associated with the use of lithium.

Recent studies have clarified the nature of this association. It is not just that lithium causes hypothyroidism, there is strong evidence that there is an association between having bipolar and the risk of developing hypothyroidism. In other words, people with bipolar who are never treated with lithium have about double the risk of developing hypothyroidism as the general population. For more on the relationship see this blog post…

Prevalence estimates of lithium-associated thyroid dysfunction range from 14–17% for overt and from 19–35% for subclinical hypothyroidism (Aliasgharpour et al., 2005; Fagiolini et al., 2006; Kupka et al., 2002).

Before this study there was extremely limited information about outcomes of hypothyroidism after lithium was stopped.

A randomized cross-over study investigated the impact of lithium discontinuation in 14 euthyroid patients with TSH and fT4 in the reference interval. The patients with BPAD had been on lithium for an average of 9.8 years. After stopping lithium, TSH decreased and fT4 increased significantly during the 4-week study period (Souza et al., 1991). However, this study only followed people for 4 weeks, which is obviously too short to evaluate outcomes.

So this study is important because it is the only long term data we have about the risk that lithium associated hypothyroidism will persist after stopping lithium, and the news appears to be good…

“In most patients lithium-associated hypothyroidism seems reversible once lithium has been discontinued,” wrote Ingrid Lieber, M.D., of Umea University in Sweden and colleagues. “Therefore, in such cases, TRT [thyroid replacement therapy] discontinuation could be attempted much more often than is currently done.”

Lieber and colleagues analyzed follow-up data on 85 patients who discontinued lithium because of hypothyroidism and were being treated with thyroid replacement therapy. They were enrolled in the Lithium–Study Into Effects and Side Effects, a large Swedish study of patients using lithium.

On average, thyroid replacement therapy was started 2.3 years after starting lithium. This is longer than what we find in our clinic (where most cases begin in the first year), and the difference may relate to the criteria used for treating hypothyroidism.

The mean TSH at TRT start was 11.1 IU/mL (SD 15.0) with a median of 6.9 IU/mL and a range of 1.6–100 IU/mL. In our clinic we would usually initiate thyroid replacement therapy when TSH is above 3.5 if there are significant symptoms or above 5 without symptoms.

Of the 85 patients, 35 stopped thyroid replacement therapy at some point after discontinuation of lithium. Only six patients had to be placed back on thyroid replacement therapy.

Lieber and colleagues said that it is prudent to allow some weeks for the thyroid gland to recover before stopping thyroid replacement therapy.

Also, people should be closely monitored for thyroid hormone levels for the first six months after stopping thyroid medication.

“Based on the limited evidence of our study, we can expect hypothyroidism to recur early after TRT discontinuation, if at all,” they wrote. “Thus, it is advisable to monitor thyroid function for three to six months. TRT reinsertion should then only be reconsidered if there are unambiguous signs of hypothyroidism … .”

Another way of predicting the risk of low thyroid, involves testing for antibodies to the thyroid gland before starting lithium. This identifies patients this identifies people who may develop low thyroid due to a pre-existing condition (Hashimoto’s thyroiditis) after they start lithium treatment.

Hashimoto’s thyroiditis is a gradually developing low thyroid caused by antibodies to a person’s thyroid gland. It develops over years, but the course may be speeded up when a person gets treated with lithium.

People with anti-thyroid antibodies would have developed low thyroid anyway, and if they stop lithium because of a low thyroid , they are less likely to have their thyroid gland resume normal production of thyroid.

For more information…

Lieber I, Ott M, Öhlund L, Lundqvist R, Eliasson M, Sandlund M, Werneke U. Lithium-associated hypothyroidism and potential for reversibility after lithium discontinuation: Findings from the LiSIE retrospective cohort study. J Psychopharmacol. 2019 Oct 31:269881119882858. doi: 10.1177/0269881119882858. [Epub ahead of print] PubMed PMID: 31670617.

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