What is the workup for a patient with low vitamin D, hypercalcemia, and hyperparathyroidism (elevated Parathyroid Hormone (PTH))?

Workup for Low Vitamin D, Hypercalcemia, and Elevated PTH

The most appropriate workup for a patient with low vitamin D, hypercalcemia, and elevated PTH should focus on diagnosing primary hyperparathyroidism (PHPT) while ruling out other causes of this biochemical pattern.

Initial Laboratory Evaluation

• Confirm abnormal values:

  • Repeat serum calcium (total and ionized), phosphorus, PTH, and 25-hydroxyvitamin D levels
  • Measure albumin to calculate corrected calcium if total calcium was measured 1

• Additional laboratory tests:

  • 24-hour urinary calcium excretion (to differentiate PHPT from familial hypocalciuric hypercalcemia)
  • Serum creatinine and estimated GFR (to assess kidney function) 1
  • Alkaline phosphatase (to assess bone turnover)
  • Serum bicarbonate (to rule out metabolic acidosis) 1

Imaging Studies

• Parathyroid imaging (once PHPT is biochemically confirmed):

  • Sestamibi scan with SPECT/CT
  • Ultrasound of the neck
  • 4D-CT scan if other imaging is negative or for surgical planning 2

• Bone mineral density testing:

  • Dual-energy X-ray absorptiometry (DXA) scan of lumbar spine, hip, and distal radius 2

Differential Diagnosis Considerations

1. Primary Hyperparathyroidism (PHPT): Most likely diagnosis with elevated calcium, elevated PTH, and low vitamin D 1

2. Secondary Hyperparathyroidism with Vitamin D Deficiency: Usually presents with normal or low calcium, not hypercalcemia 1

3. Tertiary Hyperparathyroidism: Consider in patients with chronic kidney disease 1

4. Familial Hypocalciuric Hypercalcemia: Check calcium/creatinine clearance ratio in 24-hour urine collection 2

5. Parathyroid carcinoma: Consider if calcium is markedly elevated (>14 mg/dL) 3

Management of Vitamin D Deficiency in this Context

The relationship between vitamin D deficiency and primary hyperparathyroidism is complex. Low vitamin D levels are common in PHPT patients and may worsen the hyperparathyroidism 4. However, vitamin D supplementation must be approached cautiously:

• Check 25(OH) vitamin D levels before initiating treatment 1
• For vitamin D insufficiency (serum levels <30 ng/ml), cautious supplementation may be appropriate 1
• Monitor calcium levels closely when supplementing vitamin D in PHPT patients, as some patients may experience worsening hypercalcemia or hypercalciuria 5

Special Considerations

• Chronic Kidney Disease: If GFR <30 ml/min/1.73 m², monitor calcium, phosphorus, and PTH more frequently (every 3 months) 1

• Medication review: Check for medications that can affect calcium levels (thiazide diuretics, lithium, etc.) 6

• Family history: Inquire about family history of hypercalcemia, kidney stones, or endocrine tumors to evaluate for hereditary forms of hyperparathyroidism 2

Pitfalls to Avoid

1. Don't assume vitamin D deficiency is the sole cause of elevated PTH when hypercalcemia is present. In true vitamin D deficiency, calcium is typically normal or low 7

2. Don't miss familial hypocalciuric hypercalcemia (FHH), which can mimic PHPT but doesn't require surgery. The calcium/creatinine clearance ratio is typically <0.01 in FHH 2

3. Don't immediately supplement vitamin D without confirming the diagnosis, as this could worsen hypercalcemia in some PHPT patients 7

4. Don't ignore biotin supplements, which can interfere with PTH assays and cause falsely high or low results 2

5. Don't overlook the possibility of parathyroid carcinoma, especially with markedly elevated calcium and PTH levels 3

The combination of low vitamin D, hypercalcemia, and elevated PTH most commonly indicates primary hyperparathyroidism with coexistent vitamin D deficiency. A thorough workup as outlined above will help confirm the diagnosis and guide appropriate management.