How to manage a patient on lithium with hypercalcemia and elevated Parathyroid Hormone (PTH) levels?

Management of Lithium-Associated Hypercalcemia with Elevated PTH

In a patient on chronic lithium therapy presenting with hypercalcemia (calcium 10.6 mg/dL) and elevated PTH (111 pg/mL), the first priority is to determine whether this represents lithium-induced hyperparathyroidism by assessing the duration of lithium therapy, measuring 24-hour urine calcium (which is typically normal or low in lithium-induced disease), and considering a trial of lithium discontinuation if psychiatrically feasible, as this may reverse the biochemical abnormalities in some patients. 1, 2

Diagnostic Evaluation

Confirm lithium-induced hyperparathyroidism by:

• Measure 24-hour urine calcium or spot urine calcium/creatinine ratio - lithium-induced hyperparathyroidism characteristically shows normal or low urinary calcium excretion (fractional excretion <0.026), unlike classic primary hyperparathyroidism which presents with hypercalciuria 1, 2, 3

• Check serum phosphorus levels - typically normal in lithium-induced disease 1

• Measure 25-hydroxyvitamin D levels to exclude vitamin D deficiency as a contributor to elevated PTH, as deficiency causes secondary hyperparathyroidism and must be corrected before making definitive management decisions 4

• Assess kidney function (eGFR) - important for determining monitoring frequency and treatment options 4

Management Algorithm

If Lithium Can Be Discontinued (Psychiatrically Stable or Alternative Available):

• Stop lithium therapy and monitor calcium and PTH levels every 2-4 weeks - hypercalcemia and hyperparathyroidism may normalize within weeks to months in some patients 1, 2

• If calcium and PTH normalize after lithium discontinuation, continue monitoring calcium every 3 months for the first 6 months, then every 3-6 months thereafter 4

• If hypercalcemia persists 3-6 months after lithium discontinuation, the patient has likely developed true primary hyperparathyroidism with parathyroid adenoma or hyperplasia requiring parathyroidectomy 1, 3, 5

If Lithium Must Be Continued (Psychiatric Necessity):

• Initiate cinacalcet hydrochloride 30 mg daily as first-line medical therapy - this calcimimetic has been shown to normalize serum calcium (from 10.8-11.0 mg/dL to 9.9-10.3 mg/dL) and reduce PTH levels (from 138-139 pg/mL to 73-114 pg/mL) in lithium-treated patients with stage 3 CKD and hyperparathyroidism 2

• Monitor serum calcium monthly for 3 months, then every 3 months after initiating cinacalcet 4

• Titrate cinacalcet dose - if calcium remains elevated after 8-11 months on 30 mg daily, increase to 60 mg daily 2

• Consider parathyroidectomy if:

  • Calcium remains >12 mg/dL despite cinacalcet therapy 6
  • PTH exceeds 800 pg/mL with persistent hypercalcemia refractory to medical therapy 4
  • Patient develops symptomatic hypercalcemia (confusion, polyuria, nausea, bone pain) 6, 5
  • Parathyroid adenoma is identified on imaging 3, 5

Immediate Management Considerations

• Discontinue all calcium supplements and vitamin D supplementation immediately - these worsen hypercalcemia 7, 6

• Ensure adequate oral hydration to promote calciuresis 6

• Review and discontinue thiazide diuretics if present - these reduce urinary calcium excretion 6

• Avoid calcium-based phosphate binders if the patient has CKD and requires phosphate management 7, 6

Monitoring Protocol

• During initial evaluation: Check calcium and PTH every 2-4 weeks until stable 7

• After treatment initiation: Monitor calcium monthly for 3 months, then every 3 months 4

• Long-term monitoring: Measure PTH every 3 months for 6 months, then every 3-6 months 4

• If on cinacalcet: Monitor for hypocalcemia and assess QT interval, as cinacalcet can prolong QT and is contraindicated in hypocalcemia 8

Critical Pitfalls to Avoid

• Do not assume hypercalcemia will resolve with lithium discontinuation alone - up to 50% of patients develop permanent parathyroid adenomas requiring surgery even after stopping lithium 1, 3, 5

• Do not delay surgical referral in patients with persistent hypercalcemia >12 mg/dL - this can lead to progressive renal damage, nephrocalcinosis, and bone disease 4, 5

• Do not order parathyroid imaging before confirming biochemical diagnosis - imaging is for surgical planning only, not diagnosis 6

• Do not use low-calcium dialysate (<2.5 mEq/L) if the patient requires dialysis - this can worsen PTH elevation and cause cardiac arrhythmias 8

Surgical Considerations

If parathyroidectomy becomes necessary:

• Obtain preoperative localization with ultrasound and/or 99mTc-sestamibi SPECT/CT 6

• Refer to an experienced parathyroid surgeon - subtotal parathyroidectomy or total parathyroidectomy with autotransplantation are effective options 4

• Monitor ionized calcium every 4-6 hours for 48-72 hours post-operatively, then twice daily until stable, as hungry bone syndrome can occur 4