A patient taking venlafaxine 37.5 mg daily and vitamin D 4000 IU daily has normal renal function, normal electrolytes, low‑grade CRP, calcium 2.57 mmol/L (high‑normal), phosphate 0.79 mmol/L (low), and hemoglobin 174 g/L (elevated). What is the likely cause of the elevated hemoglobin and high‑normal calcium, and how should these abnormalities be managed?

Evaluation of Elevated Hemoglobin and High-Normal Calcium with Low Phosphate

The elevated hemoglobin (174 g/L) is most likely due to hemoconcentration or a physiologic variant unrelated to the metabolic abnormalities, while the high-normal calcium (2.57 mmol/L) combined with low phosphate (0.79 mmol/L) in the setting of high-dose vitamin D supplementation (4000 IU daily) raises concern for vitamin D-mediated increased calcium absorption that requires immediate dose reduction and close monitoring to prevent hypercalcemia. 1

Primary Concern: Vitamin D Supplementation and Calcium-Phosphate Balance

Immediate Management of Vitamin D Dosing

• Reduce vitamin D supplementation from 4000 IU to 1000-2000 IU daily to prevent progression to overt hypercalcemia, as doses above 400 IU daily are associated with increased hypercalcemia risk in patients with normal renal function. 1, 2
• The current calcium level of 2.57 mmol/L (approximately 10.3 mg/dL) is at the upper limit of normal and warrants intervention before frank hypercalcemia develops. 1
• Discontinue all calcium supplements immediately if the patient is taking any, as combined calcium and vitamin D supplementation significantly increases hypercalcemia risk. 1

Phosphate Evaluation and Management

• The low phosphate (0.79 mmol/L or approximately 2.4 mg/dL) requires comprehensive evaluation to distinguish between decreased intake, increased renal losses, or vitamin D-mediated redistribution. 3
• Obtain a spot urine sample for phosphate, calcium, and creatinine to calculate tubular maximum reabsorption of phosphate per GFR (TmP/GFR) and assess for renal phosphate wasting. 3
• Measure intact parathyroid hormone (PTH), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D levels to determine if the low phosphate is PTH-mediated or related to vitamin D excess. 3, 4
• If TmP/GFR shows fractional phosphate excretion >15% in the presence of hypophosphatemia, this confirms renal phosphate wasting. 3

Venlafaxine Considerations

• Venlafaxine at 37.5 mg daily is a low dose and is not directly associated with calcium or phosphate disturbances. 5
• However, monitor for hyponatremia (current sodium 138 mmol/L is low-normal), as SNRIs including venlafaxine can cause SIADH, particularly in combination with volume depletion that may accompany hypercalcemia. 4

Hemoglobin Elevation Assessment

Likely Causes of Elevated Hemoglobin

• The hemoglobin of 174 g/L with normal RDW-CV (11.4%) suggests hemoconcentration rather than true polycythemia, as the RDW would typically be elevated in primary bone marrow disorders. 5
• Mild dehydration from hypercalcemia-induced polyuria is the most likely explanation, as calcium levels approaching 2.6 mmol/L can impair renal concentrating ability. 2
• Assess hydration status clinically and consider repeating hemoglobin after ensuring adequate fluid intake for 48-72 hours. 1

When to Pursue Further Hematologic Workup

• If hemoglobin remains >170 g/L after correcting hydration status, measure serum erythropoietin level to distinguish between appropriate and inappropriate erythrocytosis. 4
• The normal renal function (creatinine 72 μmol/L, approximately 0.8 mg/dL) makes secondary polycythemia from chronic hypoxia or renal disease unlikely. 5, 6
• Consider sleep apnea screening if the patient has risk factors, as nocturnal hypoxemia can drive erythropoietin production. 4

Monitoring Protocol

Short-Term Surveillance (First 2-4 Weeks)

• Recheck serum calcium, phosphate, creatinine, and albumin within 1 week after reducing vitamin D dose to assess response. 4, 1
• Measure 25-hydroxyvitamin D level to determine current vitamin D status and guide ongoing supplementation needs. 3, 7
• If calcium rises above 2.6 mmol/L (10.4 mg/dL), discontinue vitamin D supplementation entirely until calcium normalizes. 1

Long-Term Management (Beyond 4 Weeks)

• Target 25-hydroxyvitamin D level of 50-75 nmol/L (20-30 ng/mL) with maintenance vitamin D 1000-2000 IU daily once calcium and phosphate normalize. 7, 8
• Monitor calcium and phosphate every 3-6 months while on vitamin D supplementation to detect early trends toward hypercalcemia. 4
• Maintain dietary calcium intake at 1000-1200 mg/day from food sources rather than supplements. 1

Critical Pitfalls to Avoid

• Do not normalize phosphate with oral phosphate supplements while calcium is elevated, as this increases the calcium-phosphate product and risk of soft tissue calcification. 4
• Avoid assuming the low phosphate is purely dietary without measuring urinary phosphate excretion, as renal phosphate wasting requires different management. 3
• Do not continue high-dose vitamin D supplementation (>2000 IU daily) in patients with calcium levels >2.5 mmol/L, even if 25-hydroxyvitamin D is low. 1, 7
• Recognize that corrected calcium may underestimate true hypercalcemia if albumin is low; consider measuring ionized calcium if albumin is <35 g/L. 1