What is the appropriate management for a 19-year-old patient with memory loss and lab results indicating hypercalcemia, elevated total protein, erythrocytosis, and increased hemoglobin and hematocrit levels?

Evaluation and Management of a 19-Year-Old with Memory Loss and Laboratory Abnormalities

The most appropriate next step for this 19-year-old patient with memory loss and laboratory abnormalities is to evaluate for polycythemia vera with JAK2 mutation testing, serum erythropoietin level, and peripheral blood smear.

Laboratory Interpretation and Diagnostic Considerations

The patient presents with concerning laboratory abnormalities that require immediate attention:

• Elevated calcium (10.8 mg/dL, normal high 10.5 mg/dL)
• Elevated total protein (8.5 g/dL, normal high 8.3 g/dL)
• Elevated RBC count (6.35 million/μL, normal high 6.10 million/μL)
• Elevated hemoglobin (19.5 g/dL, normal high 17.0 g/dL)
• Elevated hematocrit (54.7%, normal high 51.0%)

These findings strongly suggest polycythemia vera (PV), a myeloproliferative disorder characterized by increased red blood cell production 1. The constellation of erythrocytosis, elevated hemoglobin and hematocrit, along with hypercalcemia and memory loss, creates a clinical picture that requires urgent hematologic evaluation.

Diagnostic Approach

1. First-line testing for suspected PV:

   • JAK2 V617F mutation testing (present in >95% of PV cases)
   • Serum erythropoietin level (typically low in PV)
   • Complete peripheral blood smear examination 1

2. Hypercalcemia workup:

   • Intact parathyroid hormone (PTH) level
   • 25-hydroxyvitamin D level
   • Parathyroid hormone-related protein (if PTH is suppressed)
   • 24-hour urine calcium 2, 3

3. Neurological evaluation:

   • MRI of the brain to evaluate for structural causes of memory loss
   • Consider EEG if seizure activity is suspected 2

Clinical Correlation and Pathophysiology

The memory loss in this young patient is concerning and may be related to hyperviscosity syndrome from polycythemia vera. Elevated blood viscosity can impair cerebral blood flow and cause neurological symptoms including memory disturbances 1.

The hypercalcemia could be:

• A paraneoplastic phenomenon associated with the myeloproliferative disorder 4, 5
• Primary hyperparathyroidism (which has been reported to co-occur with PV) 4
• Related to increased bone turnover from the myeloproliferative process 6

Management Algorithm

1. Immediate management:

   • If symptomatic hypercalcemia (confusion, lethargy):
     • IV hydration with normal saline
     • Consider bisphosphonate therapy if calcium >12 mg/dL or symptomatic 3

2. For suspected polycythemia vera:

   • Urgent hematology consultation
   • Therapeutic phlebotomy to maintain hematocrit <45%
   • Low-dose aspirin (81-100 mg daily) unless contraindicated 1

3. Further management based on confirmed diagnosis:

   • If PV is confirmed: cytoreductive therapy (hydroxyurea, interferon-α, or ruxolitinib) for high-risk patients
   • If primary hyperparathyroidism is confirmed: consider parathyroidectomy 7
   • If secondary cause of hypercalcemia: treat underlying condition

Monitoring and Follow-up

• Regular CBC monitoring every 2-3 months initially, then every 3-6 months once stable
• Serial calcium measurements until normalized
• Neurological reassessment to monitor memory symptoms
• Long-term monitoring for disease progression, thrombotic complications, and transformation to myelofibrosis 1

Pitfalls and Caveats

1. Don't attribute memory loss solely to hypercalcemia - While hypercalcemia can cause cognitive symptoms, the combination with polycythemia requires comprehensive neurological evaluation.

2. Avoid excessive phlebotomy - While therapeutic phlebotomy is indicated, overly aggressive phlebotomy can lead to iron deficiency and paradoxically increase stroke risk 1.

3. Don't miss rare associations - The combination of hypercalcemia and polycythemia has been reported with parathyroid adenomas 4 and as a complication of interferon therapy 5.

4. Consider age-appropriate differential - In a 19-year-old, congenital causes of polycythemia and genetic causes of hypercalcemia should be considered alongside acquired causes.

This patient requires urgent hematology consultation for management of what appears to be polycythemia vera with associated hypercalcemia and neurological symptoms.