How does lithium affect laboratory tests in patients with bipolar disorder?

How Lithium Affects Laboratory Tests

Lithium therapy requires comprehensive baseline and ongoing laboratory monitoring due to its well-established effects on renal, thyroid, and parathyroid function, with the most clinically significant impacts being hypothyroidism (2-fold increased risk), stage 3 chronic kidney disease (1.35-2.11-fold increased risk), and hypercalcemia. 1, 2, 3

Baseline Laboratory Requirements Before Initiating Lithium

Before starting lithium, obtain the following mandatory tests 4, 5:

• Complete blood count 4
• Thyroid function tests (TSH, free T4) 4, 5
• Renal function: Blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), urinalysis 4, 5
• Serum calcium levels 4
• Pregnancy test in females of childbearing age 4, 5

Ongoing Monitoring Schedule

Lithium Levels

• During acute phase: Check lithium levels twice weekly until stabilized 6
• Maintenance phase: Monitor lithium levels every 3-6 months 4, 5
• Therapeutic range for acute mania: 1.0-1.5 mEq/L 6
• Therapeutic range for maintenance: 0.6-1.2 mEq/L 6
• Blood samples must be drawn 8-12 hours after the previous dose (trough levels) for accurate interpretation 6

Renal Function Monitoring

• Check BUN, creatinine, eGFR, and urinalysis every 3-6 months during maintenance therapy 4, 5
• Lithium increases risk of stage 3 chronic kidney disease by 35-93% (HR 1.35-1.93) 1, 2, 3
• Women younger than 60 years are at higher risk for renal dysfunction 1
• Higher lithium serum levels (>0.5865 mEq/L mean) are associated with increased CKD3+ risk 3
• Creatinine levels progressively increase and eGFR progressively decreases over time with lithium treatment 2

Thyroid Function Monitoring

• Check TSH and free T4 every 3-6 months during maintenance therapy 4, 5
• Lithium increases risk of hypothyroidism by 100-131% (HR 2.00-2.31) 1, 3
• Women are at significantly greater risk than men for developing thyroid disorders 1
• Younger women (<60 years) face higher risk than older women 1
• TSH levels progressively decrease over time with lithium treatment 2
• Higher lithium serum levels (>0.5028 mEq/L mean) are associated with increased hypothyroidism risk 3
• Lithium can also cause hyperthyroidism, though less commonly (HR 1.81 with higher lithium levels) 3

Parathyroid and Calcium Monitoring

• Check serum calcium levels every 3-6 months during maintenance therapy 4
• Lithium increases risk of hypercalcemia by 43% (HR 1.43) 1
• Calcium levels progressively increase over time with lithium treatment 2
• PTH levels remain relatively stable during lithium treatment 2

Mechanism of Laboratory Abnormalities

Thyroid Effects

• Lithium is concentrated by the thyroid gland and inhibits thyroidal iodine uptake 7
• Lithium inhibits iodotyrosine coupling and alters thyroglobulin structure 7
• Most critically, lithium inhibits thyroid hormone secretion, leading to compensatory TSH elevation and potential goiter/hypothyroidism 7
• Goiter occurs in 0-60% of patients (wide variation in reported incidence) 7
• Lithium causes exaggerated TSH and prolactin response to TRH in 50-100% of patients 7

Renal Effects

• Adverse renal effects occur early in treatment (HR <1 for length of treatment) 1
• Greater number of lithium toxicity episodes is associated with increased CKD3+ risk 3
• Severely adverse renal outcomes (e.g., CKD stage 4+, ESKD) remain rare during lithium treatment 2

Critical Risk Factors for Laboratory Abnormalities

Patients at highest risk for adverse laboratory changes include 1, 3:

• Women, particularly those younger than 60 years 1
• Patients with lithium concentrations higher than median therapeutic levels 1
• Patients with mean lithium levels >0.5028 mEq/L (hypothyroidism threshold) 3
• Patients with mean lithium levels >0.5034 mEq/L (hyperthyroidism threshold) 3
• Patients with mean lithium levels >0.5865 mEq/L (CKD3+ threshold) 3
• Patients experiencing multiple episodes of lithium toxicity 3

Prevention Strategies

To minimize laboratory abnormalities 8:

• Temporarily suspend lithium during intercurrent illness, planned IV radiocontrast administration, bowel preparation, or prior to major surgery 8
• Avoid concomitant NSAIDs, which increase lithium levels 8
• Maintain adequate hydration, especially during illness 8
• Educate patients on early signs of toxicity: fine tremor, nausea, diarrhea, polyuria-polydipsia 8

Common Pitfalls to Avoid

• Do not rely solely on serum lithium levels—accurate patient evaluation requires both clinical assessment and laboratory analysis 6
• Elderly patients often exhibit signs of toxicity at serum levels ordinarily tolerated by other patients (1.0-1.5 mEq/L) 6
• Observational studies of long-term lithium treatment are prone to detection bias, as lithium users undergo substantially more frequent laboratory testing than non-lithium-treated patients (e.g., 2.5 vs 1.4 creatinine tests per year) 2
• The absolute number of severe adverse outcomes remains low despite increased hazard ratios (e.g., chronic kidney disease occurred in only 10 patients, 0.6% of lithium users in one large cohort) 2