A patient has a 25‑hydroxyvitamin D level of 15 ng/mL, an intact parathyroid hormone level of 89.7 pg/mL, and a serum phosphate of 5.3 mg/dL. What is the most likely diagnosis and how should it be managed?

Diagnosis: Secondary Hyperparathyroidism Due to Vitamin D Deficiency

This patient has secondary hyperparathyroidism driven by severe vitamin D deficiency (15 ng/mL), as evidenced by the elevated PTH (89.7 pg/mL) and elevated phosphate (5.3 mg/dL), requiring immediate high-dose vitamin D repletion with cholecalciferol 50,000 IU weekly for 12 weeks. 1

Understanding the Clinical Picture

Vitamin D Status Classification

• A 25-hydroxyvitamin D level of 15 ng/mL represents severe deficiency (< 20 ng/mL), falling well below the minimum threshold of 30 ng/mL required to suppress PTH and prevent skeletal complications 1, 2
• Levels below 15 ng/mL are associated with greater severity of secondary hyperparathyroidism, even in patients on dialysis 3
• At this level, approximately 65% of patients demonstrate elevated PTH, confirming the strong inverse relationship between vitamin D and parathyroid hormone 3

PTH Elevation Explained

• The PTH of 89.7 pg/mL is elevated (normal typically < 65–70 pg/mL) and represents a physiologic response to inadequate vitamin D 1
• Serum PTH is inversely correlated with free 25-hydroxyvitamin D levels, though only 30–40% of patients with vitamin D deficiency will have elevated PTH 4
• This patient falls into the subset with overt secondary hyperparathyroidism requiring aggressive repletion 1

Phosphate Interpretation

• The phosphate of 5.3 mg/dL is elevated (normal 2.5–4.5 mg/dL) and likely reflects increased PTH-mediated bone resorption and renal phosphate retention 5
• Critically, the elevated phosphate does NOT contraindicate vitamin D therapy in this setting—it is a consequence of the vitamin D deficiency, not a contraindication to treatment 1
• The K/DOQI guideline threshold of 4.6 mg/dL for holding active vitamin D steroids (calcitriol) does not apply to nutritional vitamin D replacement with cholecalciferol 5

Evidence-Based Treatment Protocol

Loading Phase (Weeks 1–12)

• Administer cholecalciferol (vitamin D₃) 50,000 IU once weekly for 12 weeks to rapidly correct severe deficiency 1, 2
• Cholecalciferol is strongly preferred over ergocalciferol (vitamin D₂) because it maintains serum levels longer and has superior bioavailability 1, 2
• The 12-week duration (rather than 8 weeks) is appropriate for severe deficiency < 15 ng/mL 1, 2

Essential Co-Intervention: Calcium Supplementation

• Ensure adequate calcium intake of 1,000–1,500 mg daily from diet plus supplements 1, 2
• Vitamin D therapy requires adequate dietary calcium for optimal bone response and PTH suppression; without sufficient calcium, the PTH may not normalize despite vitamin D repletion 1
• Divide calcium supplements into doses ≤ 600 mg for optimal absorption 1

Maintenance Phase (After Week 12)

• Transition to maintenance dosing of 2,000 IU daily (or 50,000 IU monthly, equivalent to ~1,600 IU daily) 1, 2
• Target serum 25-hydroxyvitamin D ≥ 30 ng/mL for anti-fracture efficacy and PTH suppression 1, 2
• Some experts recommend targeting 30–40 ng/mL for optimal health benefits 1

Monitoring Protocol

Initial Monitoring (First 3 Months)

• Recheck 25-hydroxyvitamin D level at 3 months after completing the loading phase to confirm adequate response 1, 2
• Monitor serum calcium and phosphorus every 3 months during the first 6 months to detect hypercalcemia early 5, 1
• Measure PTH every 3 months for the first 6 months to assess treatment response 1

Long-Term Monitoring

• Once target 25-hydroxyvitamin D ≥ 30 ng/mL is achieved and stable, recheck annually 1, 2
• Continue monitoring serum calcium every 3 months if on maintenance therapy 5, 1

Safety Thresholds

• Discontinue all vitamin D immediately if serum calcium rises above 10.2 mg/dL (2.54 mmol/L) 5, 1
• The upper safety limit for 25-hydroxyvitamin D is 100 ng/mL 1, 2

Expected Clinical Outcomes

PTH Response

• In patients with elevated PTH at baseline, the PTH decreases significantly as 25-hydroxyvitamin D increases to ≥ 30 ng/mL, though only 44% reach a completely normal PTH 4
• The PTH should begin to decline within 3 months of starting therapy 1
• If PTH remains elevated after achieving 25-hydroxyvitamin D ≥ 30 ng/mL, evaluate for other causes of secondary hyperparathyroidism (e.g., chronic kidney disease, malabsorption) 1

Phosphate Response

• The elevated phosphate should normalize as PTH suppression occurs and bone turnover decreases 5
• If phosphate remains elevated despite vitamin D repletion, consider underlying renal impairment 5

Bone Health Benefits

• Achieving 25-hydroxyvitamin D ≥ 30 ng/mL reduces non-vertebral fractures by 20% and hip fractures by 18% 1, 2
• Anti-fall efficacy begins at 25-hydroxyvitamin D ≥ 24 ng/mL, with optimal fall prevention at 30–40 ng/mL 1, 2

Critical Pitfalls to Avoid

Do NOT Use Active Vitamin D Analogs

• Never use calcitriol, alfacalcidol, doxercalciferol, or paricalcitol to treat nutritional vitamin D deficiency 5, 1, 2
• These active vitamin D steroids bypass normal regulatory mechanisms and dramatically increase hypercalcemia risk 5, 1
• They are reserved for advanced chronic kidney disease with impaired 1α-hydroxylase activity, not nutritional deficiency 5, 1

Do NOT Underdose

• Standard 400 IU daily supplements are grossly inadequate for correcting deficiency and should be avoided 1
• The loading dose of 50,000 IU weekly is necessary because standard daily doses would take many weeks to normalize low vitamin D levels 1

Do NOT Delay Treatment Due to Elevated Phosphate

• The elevated phosphate in this setting is a consequence of vitamin D deficiency, not a contraindication to nutritional vitamin D replacement 1
• The K/DOQI threshold of phosphate > 4.6 mg/dL applies only to active vitamin D steroids (calcitriol), not cholecalciferol 5

Do NOT Ignore Calcium Intake

• Vitamin D therapy without adequate calcium intake is less effective for bone health and PTH suppression 1
• Ensure total calcium intake reaches 1,000–1,500 mg daily from all sources 1

Special Considerations

If Chronic Kidney Disease Is Present

• For CKD stages 3–4 (GFR 20–60 mL/min/1.73 m²), use the same nutritional vitamin D replacement protocol with cholecalciferol or ergocalciferol 5, 6
• CKD patients are at particularly high risk for vitamin D deficiency due to reduced sun exposure, dietary restrictions, and urinary losses 5, 6
• Monitor calcium and phosphorus more frequently (every 2 weeks initially) in CKD patients 5, 6

If Malabsorption Is Suspected

• For patients with documented malabsorption (post-bariatric surgery, inflammatory bowel disease, celiac disease), consider intramuscular cholecalciferol 50,000 IU as the preferred route 1, 2
• IM administration results in significantly higher 25-hydroxyvitamin D levels and lower rates of persistent deficiency compared with oral supplementation in malabsorptive conditions 1, 2