What is the appropriate management for an asymptomatic patient with normal serum calcium (9.3 mg/dL) and a markedly elevated 25‑hydroxyvitamin D level (~218 ng/mL)?

Management of Asymptomatic Patient with Normal Calcium (9.3 mg/dL) and Markedly Elevated Vitamin D (218 ng/mL)

Immediate Action: Stop All Vitamin D Supplementation

Discontinue all vitamin D supplementation immediately—including cholecalciferol, ergocalciferol, multivitamins, and any calcium-containing supplements—because a serum 25-hydroxyvitamin D level of 218 ng/mL is more than double the upper safety threshold of 100 ng/mL and poses significant risk for vitamin D toxicity. 1

• The optimal therapeutic range for vitamin D is 30–44 ng/mL; concentrations above 50 ng/mL confer no additional clinical benefit, and levels exceeding 100 ng/mL markedly increase toxicity risk. 1
• Vitamin D toxicity manifests primarily as hypercalcemia, which can cause nausea, vomiting, weakness, confusion, and renal impairment. 1
• Although the patient's current serum calcium is normal at 9.3 mg/dL, continued vitamin D intake at this supra-physiologic level will eventually overwhelm calcium homeostasis and precipitate hypercalcemia. 2

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Assess for Current Hypercalcemia and Renal Function

Measure serum corrected total calcium, ionized calcium, phosphorus, creatinine, and parathyroid hormone (PTH) immediately to detect subclinical hypercalcemia or early renal impairment. 3

• If corrected total calcium exceeds 10.2 mg/dL (2.54 mmol/L), hold all vitamin D therapy and initiate aggressive hydration to promote calciuresis. 3, 2
• A suppressed PTH in the setting of elevated vitamin D confirms vitamin D–mediated excessive intestinal calcium absorption. 2, 4
• Check serum phosphorus; if it rises above 4.6 mg/dL, add or increase non-calcium-containing phosphate binders to prevent calcium-phosphate product accumulation. 3, 2
• Elevated creatinine or reduced estimated glomerular filtration rate (eGFR) may indicate nephrocalcinosis from chronic hypercalciuria, a complication of prolonged vitamin D excess. 4, 5

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Monitoring Protocol During Washout Phase

Re-measure serum 25-hydroxyvitamin D and serum calcium every 3 months until the vitamin D level falls below 100 ng/mL and remains stable. 1

• Vitamin D has a long half-life; serum concentrations require approximately 3 months to plateau after cessation, so earlier testing will not accurately reflect the washout trajectory. 1
• Continue monitoring serum calcium monthly during the first 3 months to detect delayed hypercalcemia, which can emerge as stored vitamin D is mobilized from adipose tissue. 2, 6
• Once the 25-hydroxyvitamin D level drops below 100 ng/mL and serum calcium has remained normal for at least 4 weeks, the acute toxicity risk is resolved. 1, 2

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Criteria for Resuming Vitamin D Supplementation (If Indicated)

Do not restart vitamin D supplementation until serum 25-hydroxyvitamin D is below 50 ng/mL, preferably within the 30–44 ng/mL target range, and serum calcium has been normal for at least 4 weeks. 1, 2

• Before restarting, evaluate whether ongoing supplementation is truly necessary by assessing risk factors such as dark skin pigmentation, limited sun exposure, obesity, malabsorption syndromes, osteoporosis, autoimmune disease, or chronic kidney disease. 1
• If supplementation is warranted, initiate a maintenance dose of 800–1,000 IU daily (or 50,000 IU monthly, equivalent to approximately 1,600 IU daily) to maintain levels within the 30–44 ng/mL range. 1
• Re-check serum 25-hydroxyvitamin D 3 months after restarting to verify achievement of the target range without overshoot. 1

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Critical Pitfalls to Avoid

• Never use active vitamin D analogs (calcitriol, alfacalcidol, doxercalciferol, paricalcitol) to treat nutritional vitamin D deficiency or insufficiency, as they bypass normal regulatory mechanisms and dramatically increase hypercalcemia risk. 3, 1
• Avoid single ultra-high loading doses (>300,000 IU), which are inefficient and may paradoxically increase fall and fracture risk. 1
• Do not measure serum 25-hydroxyvitamin D earlier than 3 months after stopping supplementation, as levels need time to plateau and earlier testing may lead to inappropriate dose adjustments. 1
• Ensure total elemental calcium intake from all sources (diet plus supplements) does not exceed 2,000 mg/day, as excessive calcium combined with elevated vitamin D accelerates vascular calcification and nephrocalcinosis. 3, 2

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Special Considerations

• If the patient has chronic kidney disease (CKD stages 3–4, eGFR 20–60 mL/min/1.73 m²), use standard nutritional vitamin D (cholecalciferol or ergocalciferol) when restarting, never active analogs, and monitor calcium and phosphorus every 3 months. 3, 1
• In CKD patients with persistent hypercalcemia despite medication adjustments, consider dialysis using low-calcium dialysate (1.5–2.0 mEq/L) for 3–4 weeks. 2
• For patients with granulomatous disease (e.g., sarcoidosis), simultaneously measure both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D before any supplementation, as granulomatous macrophages produce excessive 1α-hydroxylase, converting 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D independent of normal regulation. 2

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Expected Timeline for Resolution

• Serum 25-hydroxyvitamin D should decline by approximately 50% over 3–6 months after cessation of supplementation, depending on baseline adipose stores and renal function. 1
• Serum calcium should normalize within 2–4 weeks if hypercalcemia develops, provided all vitamin D and calcium supplements are stopped and hydration is maintained. 2, 5