Why are baseline laboratory tests (renal function, thyroid function, electrolytes, complete blood count, pregnancy test, and ECG) required before initiating lithium therapy?

Why Baseline Laboratory Tests Are Required Before Starting Lithium

Baseline laboratory testing before lithium initiation is mandatory to identify contraindications, establish individualized monitoring thresholds, and detect pre-existing organ dysfunction that would increase toxicity risk—specifically renal function (BUN, creatinine, eGFR), thyroid function (TSH), electrolytes, complete blood count, calcium levels, and pregnancy testing in women of childbearing potential. 1

Essential Baseline Tests and Their Rationale

Renal Function Assessment

• Obtain baseline serum creatinine, BUN, eGFR, and urinalysis to establish kidney function before lithium exposure, as lithium is entirely renally eliminated and patients with pre-existing renal impairment are at high risk for toxic accumulation. 1, 2
• Lithium causes progressive renal dysfunction in a significant proportion of patients, with a 1.93-fold increased risk of developing stage 3 chronic kidney disease compared to non-lithium users. 2
• Pre-existing renal failure is a true contraindication to lithium therapy due to accumulation risk and potential for life-threatening toxicity. 3

Thyroid Function Testing

• Measure baseline TSH and thyroid function tests because lithium causes hypothyroidism in approximately 20-30% of patients on long-term therapy, with women under 60 years at particularly high risk (2.31-fold increased hazard ratio). 1, 2
• Establishing baseline thyroid status allows differentiation between pre-existing thyroid disease and lithium-induced dysfunction during maintenance monitoring. 1

Electrolyte Panel

• Obtain complete metabolic panel including sodium, potassium, and other electrolytes to assess baseline status, as lithium affects renal handling of electrolytes and can cause nephrogenic diabetes insipidus. 1
• Baseline electrolyte abnormalities (particularly hypokalemia) may predispose to cardiac complications and require correction before initiating therapy. 4

Calcium and Parathyroid Assessment

• Measure baseline serum calcium because lithium causes hypercalcemia in approximately 25% of long-term patients (1.43-fold increased risk), and parathyroid hormone levels should be considered if calcium becomes elevated during treatment. 1, 2
• Younger women are at higher risk for developing lithium-induced parathyroid dysfunction. 2

Complete Blood Count

• Obtain baseline CBC with differential to document any pre-existing cytopenias and identify contraindications such as severe baseline neutropenia or thrombocytopenia. 1
• This establishes individualized monitoring thresholds for patients who may have baseline hematologic variations. 1

Pregnancy Testing

• Mandatory pregnancy testing in all women of childbearing potential before lithium initiation, as lithium is teratogenic and associated with cardiac malformations (particularly Ebstein's anomaly) when exposed during the first trimester. 1, 3
• A negative pregnancy test must be confirmed as a prerequisite, enabling informed risk-benefit discussion and contraception counseling. 1

Electrocardiogram Considerations

• While not universally required, baseline ECG should be obtained in patients over 40 years, those with cardiac risk factors, or when using other QT-prolonging medications, as lithium can rarely cause cardiac conduction abnormalities. 4

Critical Timing for Initial Post-Baseline Monitoring

• Repeat comprehensive metabolic panel, electrolytes, BUN, and creatinine 2-4 weeks after starting lithium to capture the greatest changes in renal function biomarkers, which typically occur during initial dose escalation. 1
• Check lithium levels 7-8 days after initiation or dose changes, as steady-state concentrations are achieved after approximately 5-7 half-lives (lithium's elimination half-life is 18-36 hours). 1

Common Pitfalls to Avoid

• Do not skip baseline testing even in young, healthy-appearing patients, as undetected renal or thyroid dysfunction dramatically increases toxicity risk and may be asymptomatic. 2
• Always screen for medications that increase lithium levels (NSAIDs, ACE inhibitors, ARBs, thiazide diuretics) before initiation, as these significantly elevate toxicity risk and may require more intensive monitoring or alternative mood stabilizers. 1
• Avoid initiating lithium during acute illness or dehydration, as volume depletion from lithium-induced nephrogenic diabetes insipidus is the most common cause of chronic lithium toxicity. 5
• Document baseline values meticulously, as up to 30% increase in creatinine from baseline is considered acceptable during lithium therapy, but this threshold cannot be applied without knowing the starting point. 1