How should I manage a patient with a 25‑hydroxy‑vitamin D (25‑OH‑vitamin D) level of 108 ng/mL, normal serum calcium (9.4 mg/dL), and no reported vitamin D supplementation?

Management of Elevated Vitamin D Level Without Supplementation

Stop any inadvertent vitamin D exposure immediately, recheck serum calcium and PTH to rule out alternative causes of elevated vitamin D, and monitor the patient without intervention since the level of 108.2 ng/mL with normal calcium (9.4 mg/dL) represents mild vitamin D excess that will resolve spontaneously over 2-3 months.

Understanding the Clinical Situation

Your patient has a 25-hydroxyvitamin D level of 108.2 ng/mL, which exceeds the upper safety limit of 100 ng/mL established by expert consensus 1. However, the serum calcium remains normal at 9.4 mg/dL, which is reassuring because hypercalcemia caused by excess vitamin D in generally healthy adults has been observed only if the 25(OH)D level exceeded 100 ng/mL 1.

Critical First Steps

• Verify there is truly no vitamin D supplementation by directly reviewing all medications, over-the-counter supplements, multivitamins, calcium preparations (which often contain vitamin D), and fortified foods/beverages 2.
• Check for dispensing errors, as case reports document patients receiving 50,000 IU daily instead of the intended lower dose due to pharmacy mistakes 3.
• Measure serum calcium, ionized calcium, phosphorus, and PTH to assess for hypercalcemia and to rule out alternative diagnoses such as primary hyperparathyroidism or granulomatous disease (sarcoidosis, tuberculosis) that can elevate 1,25-dihydroxyvitamin D independently 4, 5.

Differential Diagnosis for Unexplained Elevation

Exogenous Sources to Investigate

• Hidden supplementation: Many calcium supplements contain 200-400 IU vitamin D per tablet, and patients taking multiple daily doses can accumulate 800-1,600 IU/day without awareness 2.
• Fortified foods: Milk (100 IU per cup), fortified orange juice, cereals, and nutritional shakes can contribute 400-800 IU daily 6, 7.
• Prescription medications: Some formulations of calcium carbonate or phosphate binders contain vitamin D 4.

Endogenous and Pathological Causes

• Excessive sun exposure: Prolonged sunny environment exposure can produce vitamin D equivalent to 20,000 IU/day orally, and measured 25(OH)D concentrations in healthy subjects with prolonged sun exposure rarely exceed 100 ng/mL 1.
• Granulomatous diseases (sarcoidosis, tuberculosis): These conditions cause extrarenal 1α-hydroxylase activity, converting 25(OH)D to active 1,25-dihydroxyvitamin D, which can elevate serum calcium even with normal 25(OH)D levels 4.
• Lymphoma: Certain lymphomas produce 1,25-dihydroxyvitamin D, leading to hypercalcemia 4.
• Primary hyperparathyroidism: Elevated PTH increases 1α-hydroxylase activity, though this typically presents with hypercalcemia and elevated calcium, not isolated 25(OH)D elevation 4.

Management Algorithm

If Calcium is Normal (as in your patient)

• No active intervention is required beyond stopping any identified vitamin D sources 1.
• Reassure the patient that levels between 70-100 ng/mL are considered absolutely safe, and even levels slightly above 100 ng/mL without hypercalcemia do not require aggressive treatment 1.
• Monitor serum calcium and phosphorus every 2-4 weeks for the first 2 months to detect delayed hypercalcemia, as vitamin D has a long half-life (approximately 2-3 months) 2, 4.
• Recheck 25(OH)D in 3 months to confirm the level is declining; expect a decrease of approximately 10-20 ng/mL per month once all sources are eliminated 2, 8.

If Calcium is Elevated (>10.2 mg/dL or 2.54 mmol/L)

• Immediately discontinue all vitamin D and calcium-containing supplements 4, 5.
• Increase oral hydration to promote calciuresis (target 2-3 liters of fluid daily) 4.
• Monitor serum calcium weekly until normalization 4.
• Consider loop diuretics (furosemide 20-40 mg daily) if hypercalcemia is symptomatic or calcium exceeds 11.5 mg/dL, but ensure adequate hydration first 4.
• Hold vitamin D therapy until serum calcium returns to <9.5 mg/dL and remains stable for at least 4 weeks 4.

Expected Timeline for Resolution

• Vitamin D has a half-life of approximately 2-3 months, so levels will decline slowly even after complete cessation of intake 2, 8.
• Serum 25(OH)D should decrease by approximately 10-20 ng/mL per month once all sources are eliminated 8.
• Full normalization to the target range of 30-80 ng/mL may take 4-6 months 1, 2.

Safety Considerations and Reassurance

• Vitamin D toxicity is exceptionally rare and typically only occurs with prolonged daily doses exceeding 10,000 IU or serum 25(OH)D levels persistently above 150 ng/mL 1, 6.
• Your patient's level of 108.2 ng/mL with normal calcium indicates the body's regulatory mechanisms are functioning properly, preventing hypercalcemia despite the elevated 25(OH)D 1.
• No evidence of end-organ damage (hypercalciuria, nephrocalcinosis, renal insufficiency) is expected at this level with normal calcium 1.
• The upper safety limit of 100 ng/mL was established based on observational data showing that healthy subjects with prolonged sun exposure rarely exceed this level, suggesting it represents a physiological ceiling 1.

Common Pitfalls to Avoid

• Do not prescribe calcitriol or other active vitamin D analogs to "balance" the elevated 25(OH)D, as these bypass normal regulatory mechanisms and dramatically increase hypercalcemia risk 4, 5.
• Do not assume the patient is being dishonest about supplementation; instead, systematically review all potential sources including hidden sources in combination products 2, 3.
• Do not order unnecessary imaging (bone density, renal ultrasound) unless hypercalcemia or symptoms develop 4.
• Do not restrict dietary calcium unless hypercalcemia is present, as calcium restriction can paradoxically increase 1,25-dihydroxyvitamin D production 9.

When to Refer or Escalate

• Persistent elevation above 100 ng/mL after 6 months despite eliminating all sources warrants endocrinology referral to investigate granulomatous disease or lymphoma 4.
• Development of hypercalcemia (calcium >10.5 mg/dL) requires urgent evaluation and possible hospitalization if symptomatic 4, 5.
• Suppressed PTH with elevated calcium suggests vitamin D toxicity or alternative diagnosis (malignancy, granulomatous disease) and requires subspecialty evaluation 4.