What are the treatment options for Hyperparathyroidism (HPP) or Hereditary Pyropoikilocytosis (HPP)?

Treatment of HPP (Hyperparathyroidism vs. Hereditary Pyropoikilocytosis)

Critical Clarification Required

The acronym "HPP" refers to two completely different conditions requiring entirely different management approaches. You must first determine which condition is being addressed:

If HPP = Hereditary Pheochromocytoma/Paraganglioma Syndromes

Begin tumor surveillance at 6-8 years of age with annual biochemical screening (plasma-free metanephrines) and biennial imaging for all SDHx variant carriers. 1

Surveillance Protocol

• Blood pressure monitoring at all medical visits starting at age 2 years 1
• Annual plasma-free metanephrines starting at age 2 years, collected ideally from indwelling venous catheter after 30 minutes supine to limit false positives 1
• Biennial MRI brain and spine with contrast starting at age 8 years to detect CNS hemangioblastomas 1
• Annual MRI abdomen starting at age 10 years for renal cell carcinoma and pancreatic NET surveillance 1

Treatment Approach

• Surgical resection remains the definitive treatment for localized pheochromocytomas and paragangliomas 1
• SDHB-related tumors carry particularly high malignant potential and require aggressive early detection, as metastatic potential correlates with tumor size at diagnosis 1
• There is currently no established medical therapy to prevent tumor development in asymptomatic carriers 1

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If HPP = Hereditary Pyropoikilocytosis

Hereditary pyropoikilocytosis requires chronic transfusion support for severe hemolytic anemia, as there is no curative medical therapy. 2, 3

Management Strategy

• Regular red blood cell transfusions to maintain adequate hemoglobin levels and prevent complications of severe anemia 2
• Folic acid supplementation to support increased erythropoiesis (standard practice for chronic hemolytic anemias, though not specifically cited in provided evidence)
• Monitor for transfusion-related iron overload and initiate chelation therapy when indicated 2
• Intrauterine transfusions may be necessary for severe fetal anemia presenting as hydrops fetalis 2

Special Considerations

• Homozygous SPTA1 mutations (such as SPTA1c.6154delG) cause severe disease with transfusion dependence from birth 2
• Neonates require aggressive management of hyperbilirubinemia 2
• Parents and siblings should undergo genetic testing, as heterozygous carriers may have hereditary elliptocytosis 3
• Red blood cells show characteristic extreme thermal sensitivity and membrane skeleton instability 3

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If HPP = Hyperparathyroidism (Primary or Secondary)

For primary hyperparathyroidism, parathyroidectomy is the definitive treatment; for secondary hyperparathyroidism in CKD patients on dialysis, increase active vitamin D and/or decrease phosphate supplements. 4, 5

Primary Hyperparathyroidism Management

• Parathyroidectomy is indicated when serum calcium >11.3 mg/dL, particularly in hereditary forms (MEN1, MEN2A, HPT-JT) which require identification of all four glands and subtotal parathyroidectomy 6, 7
• Cinacalcet is FDA-approved for hypercalcemia in primary HPT patients unable to undergo parathyroidectomy, though surgery remains preferred 8
• Hereditary forms present earlier (average age 25-35 years) and require genetic testing of family members 6, 9

Secondary Hyperparathyroidism Management

• Increase active vitamin D (calcitriol 20-30 ng/kg/day or alfacalcidol 30-50 ng/kg/day) and/or decrease phosphate supplements as first-line therapy 1, 5
• Cinacalcet is FDA-approved for secondary HPT in adult CKD patients on dialysis, but NOT indicated for CKD patients not on dialysis due to hypocalcemia risk 8
• Monitor serum calcium and phosphorus every 2 weeks for 1 month after dose changes, then monthly 1, 5
• Monitor PTH monthly for 3 months, then every 3 months once target achieved 1, 5

Managing Elevated PTH with Hypercalciuria

• First evaluate for vitamin D deficiency (target 25-OH vitamin D >20 ng/mL) and dietary calcium adequacy 5
• Reduce phosphate supplements and/or increase active vitamin D to prevent nephrocalcinosis 1, 5
• Implement measures to decrease urinary calcium: regular water intake, potassium citrate administration, limited sodium intake 1

Critical Pitfall

Calcimimetics (cinacalcet) are NOT indicated in pseudohypoparathyroidism, as the problem is PTH resistance, not excess PTH production 4