Elevated Thyroxine Concentration and Lithium Intoxication—An Analysis Based on the LiSIE Retrospective Cohort Study
Abstract
:1. Introduction
Aims
- Hyperthyroxinaemia is commonly associated with lithium intoxication.
- Hyperthyroxinaemia leads to increased tubular reabsorption of lithium, which increases the risk of lithium intoxication.
2. Materials and Methods
2.1. Study Design
2.2. Lithium—Study into Effects and Side Effects Participants
2.3. Patient Selection and Inclusion Criteria
2.4. Exclusion Criteria
2.5. Outcome Definition
2.6. Exposure Parameters
2.6.1. Lithium Exposure
2.6.2. Hyperthyroxinaemia
2.6.3. Renal Function
2.6.4. Other Variables
2.7. Chart Review, Analysis, and Validation
2.8. Control for Bias and Missing Data
2.9. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Hypothesis 1: Hyperthyroxinaemia Is Commonly Associated with Lithium Intoxication
3.3. Hypothesis 2: Hyperthyroxinaemia Leads to Increased Tubular Reabsorption of Lithium, Which Increases the Risk of Lithium Intoxication
4. Discussion
4.1. Strengths
4.2. Weaknesses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Very Common | ≥1/10 | ≥10% |
---|---|---|
Common (Frequent) | ≥1/100 and <1/10 | ≥1% and <10% |
Uncommon (Infrequent) | ≥1/1000 and <1/100 | ≥0.1% and <1% |
Rare | ≥1/10,000 and <1/1000 | ≥0.01% and <0.1% |
Very Rare | <1/10,000 | <0.01% |
Patients Exposed to Lithium, n | 897 |
---|---|
Sex, n (%) Male Female | 357 (39.8) 540 (60.2) |
Age (years) at study start Mean (SD) Median (min–max) | 45.0 (15.2) 45.0 (18–92) |
Type of diagnosis, n (%) Bipolar disorder Schizoaffective disorder | 768 (85.6) 129 (14.4) |
Time of lithium exposure (person–years) Total Mean (SD) Median (min–max) | 6684 7.5 (6.5) 5.7 (0–21) |
Episode a | fT4 (pmol/L) b | fT3 (pmol/L) c | eGFR (mL/min/1.73m2) | s-Lithium (mmol/L) | NDI | Presumed Main Cause of Lithium Intoxication | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
Before | During | Before | During | Before | During | Before | During | ↑ tubular reabsorption attributable to ↑ fT4 | Alternative explanation: | ||
1 | 22.3 | 84.1 | NA | 17.3 | 51 | 22 | 0.66 | 1.61 | No | Unlikely | Addition of ARB and spironolactone 4 weeks before intoxication leading to ↓ GFR |
2 | 16.1 | 30.1 | 3.1 | 5.7 | 85 | 64 | 0.82 | 1.74 | No | Unlikely | ↓ GFR, reason unclear |
3 | 19.3 | 28.1 | 3.9 | NA | 67 | 15 | 0.81 | 4.20 | No | Unlikely | Infection/pyelonephritis leading to ↓ GFR |
4 | 19.5 | 24.7 | NA | NA | 37 | 6 | 0.83 | 1.50 | No | Unlikely | Postrenal AKI leading to ↓ GFR |
5 | NA | 24.7 | NA | NA | 64 | 42 | 0.62 | 2.59 | No | Unlikely | ACEI and thiazide 11 weeks before leading to ↓ GFR |
6 | 18.9 | 24.1 | 3.9 | 2.7 | 89 | 41 | 0.67 | 1.57 | No | Unlikely | Dehydration and colitis leading to ↓ GFR |
7 | 14.8 | 23.4 | 3.5 | 2.0 | 72 | 62 | 0.62 | 1.56 | Yes | Unlikely | NDI and dehydration leading to ↓ GFR |
8 | 13.7 | 22.6 | 3.4 | 4.9 | 54 | 26 | 0.69 | 2.02 | No | Unlikely | Treatment with amiloride/hydrochlorothiazide 2 weeks before leading to ↓ GFR |
9 | 20.8 | 22.4 | 5.2 | NA | 46 | 5 | 0.31 | 1.81 | No | Unlikely | Sepsis and prerenal AKI leading to ↓ GFR |
Case | Study | Sex | Age (years) | Limax mmol/L | fT4intox pmol/L (Upper Normal Reference) | Creatinine µmol/L (Upper Normal Reference) eGFR a | Presumed Cause of Lithium Intoxication b | |
---|---|---|---|---|---|---|---|---|
Elevation fT4 Mediated (Dehydration/Tubular) | Alternative Explanation | |||||||
Lithium Used as Treatment for an Affective Disorder | ||||||||
1 | [4] | F | 34 | 3.27 | 72.4 (25.0) | 387 (100) 13 | Unlikely | Nephrogenic diabetes insipidus leading to dehydration leading to AKI and ↓ GFR Thioridazine interaction with lithium. Hyperthyroidism mediated dehydration possible |
2 | [6] | F | 64 | 3.81 | 57.3 (19.1) | 226 (71) 20 | Unlikely | Hyperthyroidism mediated dehydration possible AKI due to another reason leading to ↓ GFR cannot be excluded |
3 | [5] | F | 46 | 3.6 | 38.6 (23.2) | Normal | Possible | No |
4 | [7] | F | 36 | 1.6 | FT4I 21.6 (4–12ng/L) c | Not known | Not enough information to rate | |
Lithium Used as a Treatment for Hyperthyroidism | ||||||||
5 | [8] | F | 37 | 3.40 | 103 (23.2) | Normal | Possible | No |
6 | [9] | F | 66 | 1.54 | 31.8 (21.9) | Normal | Possible | No |
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Lieber, I.; Ott, M.; Lundqvist, R.; Eliasson, M.; Sandlund, M.; Werneke, U. Elevated Thyroxine Concentration and Lithium Intoxication—An Analysis Based on the LiSIE Retrospective Cohort Study. J. Clin. Med. 2022, 11, 3041. https://doi.org/10.3390/jcm11113041
Lieber I, Ott M, Lundqvist R, Eliasson M, Sandlund M, Werneke U. Elevated Thyroxine Concentration and Lithium Intoxication—An Analysis Based on the LiSIE Retrospective Cohort Study. Journal of Clinical Medicine. 2022; 11(11):3041. https://doi.org/10.3390/jcm11113041
Chicago/Turabian StyleLieber, Ingrid, Michael Ott, Robert Lundqvist, Mats Eliasson, Mikael Sandlund, and Ursula Werneke. 2022. "Elevated Thyroxine Concentration and Lithium Intoxication—An Analysis Based on the LiSIE Retrospective Cohort Study" Journal of Clinical Medicine 11, no. 11: 3041. https://doi.org/10.3390/jcm11113041