What could cause a 25‑hydroxyvitamin D (25‑OH vitamin D) level of 117 ng/mL to be elevated?

Causes of Elevated Vitamin D (117 ng/mL)

Understanding the Elevation

A vitamin D level of 117 ng/mL exceeds the established upper safety threshold of 100 ng/mL and indicates vitamin D toxicity (hypervitaminosis D), which is almost always caused by excessive supplementation rather than dietary intake or sun exposure alone. 1

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Primary Causes of Vitamin D Elevation

1. Excessive Supplementation (Most Common)

• High-dose daily intake: Taking more than 10,000 IU daily for prolonged periods can push levels above 100 ng/mL 1, 2
• Accidental overdosing: Taking a weekly dose (e.g., 50,000 IU) daily instead of weekly is a common error that rapidly produces toxic levels 1
• Cumulative effect from multiple sources: Combining prescription vitamin D, over-the-counter supplements, fortified foods, and multivitamins without accounting for total intake 1
• Ultra-high loading doses: Single doses exceeding 300,000–540,000 IU or repeated high-dose regimens (e.g., 120,000 IU weekly) predictably produce supra-physiologic levels 1

2. Dysregulated Vitamin D Metabolism (Hypersensitivity)

• Vitamin D hypersensitivity: Some individuals develop hypercalcemia even with doses considered safe for the general population (600–2,000 IU daily), reflecting abnormal metabolism 3
• Genetic polymorphisms: Variations in vitamin D binding protein, receptor genes, or metabolic enzymes (24-hydroxylase deficiency) can cause excessive accumulation 3, 4
• Saturation of vitamin D binding protein: When binding capacity is exceeded, free (active) vitamin D increases disproportionately 3

3. Endogenous Overproduction (Rare)

• Granulomatous disorders: Sarcoidosis, tuberculosis, and other granulomatous diseases produce excessive 1,25(OH)₂D locally through unregulated 1α-hydroxylase activity in macrophages 3
• Lymphomas: Certain lymphomas (especially Hodgkin's) can produce active vitamin D metabolites autonomously 3
• Williams-Beuren syndrome: This congenital disorder causes excessive production of both 25(OH)D and 1,25(OH)₂D 3
• Idiopathic infantile hypercalcemia: Reduced degradation of active vitamin D metabolites leads to accumulation 3

4. Iatrogenic Causes

• Inappropriate use of active vitamin D analogs: Calcitriol, alfacalcidol, doxercalciferol, or paricalcitol prescribed for nutritional deficiency (rather than advanced kidney disease) bypass normal regulation and cause rapid elevation 1
• Compounding pharmacy errors: Incorrect formulation concentrations have caused toxicity 3

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Clinical Assessment Algorithm

Step 1: Medication Reconciliation

• Document all vitamin D sources: prescription, over-the-counter, multivitamins, calcium+D combinations, fortified foods
• Calculate total daily vitamin D intake from all sources
• Identify any recent changes in dosing or frequency (e.g., weekly dose taken daily)
• Check for active vitamin D analogs (calcitriol, etc.) that should never be used for nutritional deficiency 1

Step 2: Check for Hypercalcemia

• Measure serum calcium immediately – vitamin D toxicity manifests primarily as hypercalcemia 1, 3
• Also check serum phosphorus and PTH (PTH will be suppressed if hypercalcemia is vitamin D-mediated) 1
• Symptoms of hypercalcemia include confusion, nausea, vomiting, weakness, polyuria, polydipsia, and dehydration 3

Step 3: Evaluate for Endogenous Causes (if supplementation doesn't explain the level)

• Screen for granulomatous disease: chest X-ray, ACE level, consider sarcoidosis workup
• Evaluate for lymphoma if clinically indicated (lymphadenopathy, B symptoms)
• Consider genetic testing for 24-hydroxylase deficiency if family history or recurrent hypercalcemia

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Immediate Management

Discontinue All Vitamin D

• Stop all vitamin D supplementation and calcium-containing supplements immediately 1
• Hold therapy until serum 25(OH)D falls below 100 ng/mL and serum calcium normalizes for at least 4 weeks 1

Monitor Closely

• Check serum calcium and phosphorus every 2 weeks for the first month, then monthly until vitamin D levels normalize 1
• If calcium exceeds 10.2 mg/dL (2.54 mmol/L), increase oral hydration and monitor weekly 1
• Severe hypercalcemia (>11.0 mg/dL) may require hospitalization, IV fluids, and calciuresis 1

Expected Timeline

• Vitamin D has a long half-life; levels decline slowly over 3–6 months after discontinuation 1
• Re-measure 25(OH)D approximately 3 months after stopping supplementation 1

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When to Resume Supplementation (If Needed)

• Do not restart until serum 25(OH)D is <100 ng/mL (preferably <50 ng/mL) and calcium has been normal for ≥4 weeks 1
• Reassess whether ongoing supplementation is truly indicated based on risk factors (dark skin, limited sun exposure, malabsorption, osteoporosis, etc.) 1
• If supplementation is warranted, restart at a maintenance dose of 800–1,000 IU daily (not high-dose therapy) 1
• Re-check serum 25(OH)D 3 months after restarting to ensure levels remain in the optimal range (30–44 ng/mL) without overshoot 1

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Critical Pitfalls to Avoid

• Never assume dietary intake or sun exposure alone caused this elevation – levels >100 ng/mL almost always result from supplementation 1, 5
• Do not ignore asymptomatic hypercalcemia – vitamin D toxicity can be present without symptoms initially 3
• Do not restart vitamin D prematurely – wait for documented normalization of both 25(OH)D and calcium 1
• Do not use active vitamin D analogs (calcitriol, etc.) to treat nutritional deficiency – they dramatically increase toxicity risk 1