In an asymptomatic patient with normal serum calcium and markedly elevated 25‑hydroxyvitamin D (~218 ng/mL), should monitoring be performed by a primary‑care clinician or referred to a specialist?

Who Should Monitor Markedly Elevated Vitamin D in an Asymptomatic Patient?

Primary care can safely monitor this asymptomatic patient with markedly elevated vitamin D (218 ng/mL) and normal calcium, provided the clinician is comfortable with the monitoring protocol and can exclude underlying causes of dysregulated vitamin D metabolism.

Initial Assessment Required

Before deciding on monitoring, the primary care clinician must:

• Measure both 25(OH)D and 1,25(OH)₂D simultaneously to distinguish between exogenous supplementation (high 25(OH)D, normal 1,25(OH)₂D) versus ectopic production from granulomatous disease (low-to-normal 25(OH)D, elevated 1,25(OH)₂D). 1
• Obtain serum calcium, phosphorus, and PTH to confirm the patient is truly normocalcemic and to exclude PTH-independent hypercalcemia that may develop. 2, 3
• Document medication and supplement history to identify the source of vitamin D excess—most commonly over-supplementation with cholecalciferol or ergocalciferol. 1

When Primary Care Monitoring Is Appropriate

Primary care can manage if:

• The patient remains asymptomatic (no nausea, vomiting, confusion, fatigue, constipation, or polyuria). 3
• Serum calcium is consistently normal (<10.2 mg/dL or 2.54 mmol/L). 1, 2
• PTH is not suppressed, indicating no significant calcium dysregulation. 3, 4
• 1,25(OH)₂D is normal, excluding granulomatous disease or other causes of ectopic vitamin D activation. 1, 2
• The clinician can implement the monitoring protocol described below and is comfortable managing potential complications.

When to Refer to Endocrinology

Specialist referral is indicated if:

• Hypercalcemia develops (corrected calcium >10.2 mg/dL), even if mild, because vitamin D levels >100 ng/mL increase toxicity risk. 1, 5
• 1,25(OH)₂D is elevated, suggesting granulomatous disease (sarcoidosis, tuberculosis) requiring specialist evaluation and treatment with glucocorticoids rather than simple vitamin D cessation. 1, 2
• PTH is suppressed (<20 pg/mL), indicating PTH-independent hypercalcemia that may herald malignancy or other serious pathology. 3, 4
• Symptoms of hypercalcemia emerge (confusion, nausea, vomiting, severe fatigue), requiring urgent specialist input. 3
• The primary care clinician is uncomfortable with the monitoring intensity or complexity of the case.

Monitoring Protocol for Primary Care

If primary care assumes monitoring:

• Immediately discontinue all vitamin D supplementation (including multivitamins containing vitamin D) and calcium supplements. 1, 2
• Restrict total elemental calcium intake to ≤2,000 mg/day from all sources (diet plus any remaining supplements). 1
• Measure serum calcium and phosphorus every 2 weeks for the first month, then monthly until vitamin D levels normalize below 100 ng/mL. 1, 2
• Recheck 25(OH)D at 3 months to assess the rate of decline; vitamin D has a long half-life and levels fall slowly. 6
• Do not restart vitamin D supplementation until serum 25(OH)D falls below 100 ng/mL and remains stable for at least 4 weeks, and only if clinically indicated (e.g., documented deficiency risk factors). 1

Critical Pitfalls to Avoid

• Never measure vitamin D levels earlier than 3 months after discontinuation, as levels plateau slowly and premature testing leads to inappropriate management decisions. 6
• Never use active vitamin D analogs (calcitriol, alfacalcidol, doxercalciferol, paricalcitol) in this setting, as they bypass normal regulation and dramatically increase hypercalcemia risk. 1, 5
• Do not assume the patient is safe simply because calcium is normal today—vitamin D levels >100 ng/mL carry ongoing toxicity risk, and hypercalcemia can develop over weeks. 1, 5
• Never supplement vitamin D without measuring both 25(OH)D and 1,25(OH)₂D in any patient with a history of hypercalcemia or markedly elevated vitamin D, as this can worsen occult granulomatous disease. 1, 2

Expected Timeline for Resolution

• Serum 25(OH)D should decline by approximately 50% over 3–6 months after cessation of supplementation, given vitamin D's long half-life. 1, 5
• Calcium should remain normal throughout if the elevation is purely from exogenous supplementation; any rise in calcium mandates immediate specialist referral. 1, 2

Summary Algorithm

1. Measure 1,25(OH)₂D, calcium, phosphorus, and PTH immediately. 1, 2, 3
2. If 1,25(OH)₂D is elevated or PTH is suppressed → refer to endocrinology. 1, 2, 3
3. If calcium rises above 10.2 mg/dL → refer to endocrinology. 1, 2
4. If all parameters are normal and the clinician is comfortable → primary care can monitor with the protocol above.
5. If the primary care clinician is uncertain or uncomfortable → refer to endocrinology for shared management or full transfer of care.