Immediate Management: Stop Vitamin D Supplementation
You have iatrogenic hypercalcemia from vitamin D supplementation in a patient who likely has an underlying calcium regulation disorder—stop all vitamin D immediately and investigate the primary cause of hypercalcemia. 1, 2
Understanding the Clinical Picture
Your patient presents with a paradoxical constellation of findings that reveals vitamin D supplementation has unmasked or worsened an underlying hypercalcemic disorder:
- Persistent hypercalcemia (10.7 mg/dL) despite suppressed PTH (14 pg/mL) 2
- Suppressed PTH indicates PTH-independent hypercalcemia, ruling out primary or secondary hyperparathyroidism 2, 3
- Elevated 24-hour urinary calcium (346 mg/24hr) confirms true hypercalcemia with inappropriate renal calcium handling 2
- Normal 1,25-OH vitamin D and PTHrP helps narrow the differential but doesn't explain the persistent hypercalcemia 2
The low PTH (14 pg/mL) is appropriately suppressed in response to hypercalcemia, which excludes hyperparathyroidism as your patient correctly suspected. 2, 3
Immediate Actions Required
1. Stop All Vitamin D Supplementation Immediately
Discontinue all forms of vitamin D therapy when serum calcium exceeds 10.2 mg/dL. 1, 2 The K/DOQI guidelines explicitly state that if corrected total calcium exceeds 10.2 mg/dL (2.54 mmol/L), all vitamin D therapy must be stopped. 1
Vitamin D supplementation in this patient has caused or exacerbated hypercalcemia by increasing intestinal calcium absorption in someone with impaired calcium regulation. 4, 3
2. Ensure Adequate Hydration
Encourage generous oral fluid intake to promote renal calcium excretion and prevent nephrocalcinosis. 4, 5 Hypercalcemia impairs renal concentrating ability, leading to polyuria and risk of volume depletion. 6, 7
3. Discontinue Calcium Supplements
Stop any calcium-containing supplements or calcium-based medications immediately. 2 Total elemental calcium intake should not exceed 2000 mg/day, and in hypercalcemia, calcium supplementation is contraindicated. 2
Diagnostic Workup for PTH-Independent Hypercalcemia
With suppressed PTH and hypercalcemia, you must investigate alternative causes:
Measure 25-hydroxyvitamin D levels
Although you supplemented vitamin D, you need to know the current 25-OH vitamin D level to assess for vitamin D intoxication. 2, 4 Vitamin D toxicity typically occurs when 25-OH vitamin D exceeds 100 ng/mL and causes hypercalcemia through increased intestinal calcium absorption. 8, 4
Consider granulomatous disease (especially sarcoidosis)
Sarcoidosis causes hypercalcemia with low 25-OH vitamin D but elevated 1,25-(OH)2 vitamin D due to extrarenal 1α-hydroxylase activity in granulomas. 2, 3 However, you reported normal 1,25-OH vitamin D, making this less likely but not excluded if measured during active supplementation.
Evaluate for malignancy
Although PTHrP is normal, malignancy-associated hypercalcemia can occur through local osteolytic mechanisms without elevated PTHrP. 3, 7 Consider age-appropriate cancer screening, particularly for multiple myeloma (serum protein electrophoresis, free light chains) and solid tumors. 6, 7
Screen for other endocrinopathies
Thyrotoxicosis, adrenal insufficiency, and immobilization can cause hypercalcemia. 3 Check TSH and consider cortisol if clinically indicated. 3
Review medications
Thiazide diuretics, lithium, and excessive calcium or vitamin A supplementation can cause hypercalcemia. 3 Sodium-glucose cotransporter 2 inhibitors and immune checkpoint inhibitors are emerging causes. 3
Monitoring Strategy
Recheck calcium in 2-4 weeks after stopping vitamin D
Serum calcium should be measured 2-4 weeks after discontinuing vitamin D to assess whether hypercalcemia resolves. 1, 2 If calcium normalizes, vitamin D supplementation was the primary culprit.
Monitor for hypercalcemia complications
Check serum creatinine to assess renal function, as hypercalcemia can cause nephrocalcinosis and irreversible renal damage. 2, 6 Consider renal ultrasonography to evaluate for nephrocalcinosis or kidney stones. 2
Measure PTH again after calcium normalizes
Once calcium normalizes, remeasure intact PTH to determine if the patient has underlying parathyroid dysfunction that was masked by hypercalcemia. 2 If PTH remains suppressed with normal calcium, consider familial hypocalciuric hypercalcemia (FHH) by calculating calcium/creatinine clearance ratio. 2
When to Resume Vitamin D (If Ever)
Do not resume vitamin D supplementation until:
- Serum calcium is consistently below 9.5 mg/dL 1
- The underlying cause of hypercalcemia is identified and treated 1, 2
- 24-hour urinary calcium normalizes (below 300 mg/24hr) 2
- You have ruled out conditions where vitamin D supplementation is contraindicated 1, 8
If vitamin D deficiency persists after calcium normalizes and no contraindication exists, restart at a much lower dose (800-1000 IU daily) with monthly calcium monitoring for the first 3 months. 1, 8
Critical Pitfalls to Avoid
Never assume hypercalcemia is "due to vitamin D deficiency"—this is physiologically incorrect. 2, 3 Vitamin D deficiency causes secondary hyperparathyroidism with normal or low calcium, not hypercalcemia. 2 Your patient was right to question this explanation.
Do not continue vitamin D supplementation hoping it will "correct" the calcium. 1, 4 Vitamin D increases intestinal calcium absorption and will worsen hypercalcemia in patients with impaired calcium regulation. 4, 3
Do not ignore mild hypercalcemia (10.7 mg/dL). 3 While mild hypercalcemia may be asymptomatic in 80% of patients, it can cause long-term complications including nephrolithiasis, nephrocalcinosis, and bone demineralization. 3, 5
Recognize that "normal" PTH in the setting of hypercalcemia is abnormal. 2, 3 PTH should be suppressed (below 20 pg/mL) when calcium is elevated; a "normal" PTH suggests autonomous parathyroid function (primary hyperparathyroidism). 2, 3 In your case, PTH is appropriately suppressed at 14 pg/mL, confirming PTH-independent hypercalcemia. 2