Elevated Thyroxine Concentration and Lithium Intoxication-An Analysis Based on the LiSIE Retrospective Cohort Study

(1) Background: It has been suggested that hyperthyroxinaemia is a risk factor for lithium intoxication by altering tubular renal function. (2) Methods: We determined the relevance of hyperthyroxinaemia as a risk factor for lithium intoxication in patients with bipolar or schizoaffective disorder in the framework of the LiSIE (Lithium-Study into Effects and Side Effects) retrospective cohort study. Of 1562 patients included in the study, 897 patients had been exposed to lithium at any time between 1997 and 2017 with 6684 person-years of observation. (3) Results: There were 65 episodes of unintentional lithium intoxication in 53 patients. There were nine episodes with hyperthyroxinaemia at the time of lithium intoxication, yielding an incidence of 1.3 episodes/1000 person-years. For all nine episodes, we could identify alternative, more plausible, explanations for the observed lithium intoxications. (4) Conclusions: We conclude that hyperthyroxinaemia-associated unintentional lithium intoxication is an uncommon event. A direct causal link between hyperthyroxinaemia and altered tubular renal function remains elusive. Increasing the frequency of routine thyroid function tests seems unlikely to decrease the risk of lithium intoxication.

Automated summary

This study investigated the relevance of hyperthyroxinaemia as a risk factor for lithium intoxication and found that hyperthyroxinaemia was associated with a low incidence of unintentional lithium intoxication. There was no direct causal link between hyperthyroxinaemia and altered tubular renal function. Therefore, increasing the frequency of thyroid function tests may not reduce the risk of lithium intoxication.