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

Abstract

(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.

Serious adverse drug events associated with psychotropic treatment of bipolar or schizoaffective disorder: a 17-year follow-up on the LiSIE retrospective cohort study

“…This makes it difficult to derive an incidence rate for lithium intoxications requiring intensive care. Using our own LiSIE cohort with a time frame from 1997 to 2017, we found an incidence rate of 9.7/1,000 PY for unintended lithium intoxications ( 33 ). In previous work exploring the LiSIE cohort from 1997 to 2013, we found that of 91 identified events of lithium intoxication including overdoses, 34% required intensive care.…”

Incidence of hyperthyroidism in patients with bipolar or schizoaffective disorder with or without lithium: 21-year follow-up from the LiSIE retrospective cohort study

“…The current work is the second in series within LiSIE exploring the relationship between hyperthyroid states and lithium. Whereas the first study examined the relationship between hyperthyroxinaemia, that is, increased free thyroxine (fT4) and lithium intoxication, 16 the current work examines the relationship between hyperthyroidism and history of lithium exposure. We have described the method in detail in the first study.…”

“…We have described the method in detail in the first study. 16 To ease understanding, we described the method in detail even here. We have summarised the whole method in a STROBE checklist (Appendix 1).…”

“…This work was the second in series within LiSIE exploring the relationship between hyperthyroid states and lithium. We have described the method in detail in the first study (Lieber 2022, 16 manuscript ID JCM11113041), which has been published as an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) licence (https://creativecommons.org/licenses/by/4.0/). To ease understanding, we described the method in detail even in the current work.…”