What is the diagnosis and management for a patient with elevated RBC (Red Blood Cell), HGB (Hemoglobin), HCT (Hematocrit), absolute neutrophils, hypercalcemia, elevated albumin, elevated ALT (Alanine Transaminase), and high renin activity?

Diagnostic Approach to Polycythemia with Metabolic Derangements

This constellation of findings—elevated RBC/HGB/HCT, neutrophilia, hypercalcemia, elevated albumin, elevated ALT, and high renin activity—most strongly suggests polycythemia vera with concurrent primary hyperparathyroidism, though secondary polycythemia with dehydration must be excluded first. 1, 2

Initial Diagnostic Priorities

Distinguish True vs. Relative Polycythemia

• Assess hydration status immediately by examining for clinical signs of volume depletion (orthostatic vital signs, skin turgor, mucous membranes, recent fluid losses) 1
• Elevated albumin combined with elevated hematocrit strongly suggests hemoconcentration from dehydration, as plasma volume depletion increases both parameters proportionally 1
• Recheck CBC after ensuring adequate hydration (oral or IV fluids as clinically indicated) to determine if polycythemia persists 1
• If hematocrit normalizes with hydration, this represents relative polycythemia from volume depletion rather than true erythrocytosis 1

Evaluate for Polycythemia Vera

If polycythemia persists after adequate hydration:

• Obtain JAK2 V617F mutation testing as the primary diagnostic test for polycythemia vera 2
• Measure serum erythropoietin level—suppressed EPO supports polycythemia vera, while elevated EPO suggests secondary causes 1
• Assess for splenomegaly on physical examination, which occurs in polycythemia vera 2
• Consider bone marrow biopsy if JAK2 mutation is negative but clinical suspicion remains high 2

Hypercalcemia Evaluation

Primary Hyperparathyroidism Assessment

• Measure intact parathyroid hormone (iPTH) level urgently—the combination of hypercalcemia with elevated or inappropriately normal PTH confirms primary hyperparathyroidism 2
• Check serum phosphorus (typically low in hyperparathyroidism), alkaline phosphatase (often elevated), and 24-hour urinary calcium excretion 2
• Order Tc-99m sestamibi parathyroid scan and neck ultrasound to localize parathyroid adenoma if iPTH is elevated 2
• The rare association between polycythemia vera and primary hyperparathyroidism has been documented, with PTH potentially contributing to erythrocytosis 2

Alternative Hypercalcemia Causes

• If PTH is suppressed, consider malignancy-associated hypercalcemia (check PTHrP, evaluate for solid tumors or hematologic malignancies) 3
• Measure vitamin D levels (25-OH and 1,25-dihydroxy) to exclude vitamin D toxicity 3

Neutrophilia and Elevated ALT Considerations

Neutrophilia Evaluation

• Absolute neutrophilia in polycythemia vera represents part of the myeloproliferative process affecting multiple cell lines 2
• Exclude secondary causes: infection (check inflammatory markers like CRP), corticosteroid use, stress response 3, 4
• In the context of confirmed polycythemia vera, neutrophilia requires no additional specific workup 2

Liver Function Assessment

• Mildly elevated ALT (with normal or mildly elevated AST) suggests hepatic congestion from polycythemia or early liver involvement 3
• Check complete hepatic panel including AST, alkaline phosphatase, GGT, total and direct bilirubin, and albumin 3
• Obtain hepatitis serologies (HBsAg, anti-HCV) to exclude viral hepatitis 3
• Consider abdominal ultrasound with Doppler to assess for hepatosplenomegaly and hepatic vascular patency 3
• If ALT exceeds 5× upper limit of normal, consider drug-induced liver injury and review all medications, over-the-counter products, and herbals 3

High Renin Activity Interpretation

Renin-Angiotensin System Activation

• Elevated renin activity with hypertension suggests secondary hypertension from renal artery stenosis, renin-secreting tumor, or malignant hypertension 5
• Measure blood pressure carefully—severe or malignant hypertension can cause secondary thrombotic microangiopathy 5
• Check for evidence of TMA: examine peripheral smear for schistocytes, measure LDH and haptoglobin, assess for thrombocytopenia 3, 5
• If TMA is present with severe hypertension, consider atypical hemolytic uremic syndrome with complement gene mutations, which can present as malignant hypertension 5
• Obtain renal imaging (renal ultrasound with Doppler or CT angiography) to evaluate for renovascular disease 5

Critical Diagnostic Algorithm

Step 1: Assess hydration and recheck CBC after adequate fluid replacement 1

Step 2: If polycythemia persists, order JAK2 mutation and serum EPO level 1, 2

Step 3: Simultaneously measure iPTH to evaluate hypercalcemia 2

Step 4: Check blood pressure and assess for malignant hypertension features (retinal hemorrhages, acute kidney injury, heart failure) 5

Step 5: If severe hypertension present, examine peripheral smear for schistocytes and measure LDH, haptoglobin to exclude TMA 3, 5

Step 6: Obtain hepatic imaging and complete liver function panel 3

Management Priorities Based on Diagnosis

If Polycythemia Vera Confirmed

• Initiate therapeutic phlebotomy to maintain hematocrit <45% in men, <42% in women 2
• Consider cytoreductive therapy (hydroxyurea) if high-risk features present 2
• Aspirin 81-100 mg daily for thrombosis prevention unless contraindicated 2

If Primary Hyperparathyroidism Confirmed

• Surgical referral for parathyroidectomy is definitive treatment, particularly with symptomatic hypercalcemia 2
• Acute hypercalcemia management: IV hydration with normal saline, furosemide after volume repletion, bisphosphonates, calcitonin if severe 3
• Post-operative monitoring for hungry bone syndrome (hypocalcemia) 2

If Malignant Hypertension Present

• Urgent but controlled blood pressure reduction (avoid precipitous drops that worsen end-organ perfusion) 5
• If TMA confirmed, consider plasma exchange and evaluate for complement gene mutations 5
• Nephrology consultation for potential renal biopsy if diagnosis unclear 5

Common Pitfalls to Avoid

• Do not assume polycythemia is secondary without excluding polycythemia vera—JAK2 testing is essential 2
• Do not attribute hypercalcemia to malignancy without measuring PTH first—primary hyperparathyroidism is more common and treatable 2
• Do not overlook the possibility of multiple concurrent diagnoses—polycythemia vera and primary hyperparathyroidism can coexist 2
• Do not miss malignant hypertension as a cause of microangiopathic hemolytic anemia—check blood pressure and examine for target organ damage 5
• Do not delay treatment of severe hypercalcemia or malignant hypertension—both require urgent intervention 3, 5