What are the recommended lab investigations for a 75-year-old female (YOF) with elevated Alkaline Phosphatase (ALP) and Chronic Kidney Disease (CKD) if primary hyperparathyroidism is suspected?

Laboratory Investigations for Suspected Primary Hyperparathyroidism in a 75-Year-Old Female with Elevated ALP and CKD

For a 75-year-old female with elevated alkaline phosphatase (ALP) and chronic kidney disease (CKD) with suspected primary hyperparathyroidism, serum intact parathyroid hormone (iPTH), calcium, phosphorus, and 25-hydroxy vitamin D levels are the essential initial laboratory tests to establish diagnosis and guide management.

Initial Laboratory Evaluation

• Serum intact parathyroid hormone (iPTH) - essential for diagnosis of primary hyperparathyroidism 1
• Serum calcium - to assess for hypercalcemia, which is characteristic of primary hyperparathyroidism 1
• Serum phosphorus - often low in primary hyperparathyroidism 1
• Serum alkaline phosphatase (ALP) - already elevated in this patient, helps assess bone turnover 1
• 25-hydroxy vitamin D level - to rule out vitamin D deficiency which can affect PTH levels 1
• Blood urea nitrogen (BUN)/creatinine - to assess kidney function 1
• Estimated glomerular filtration rate (eGFR) - to determine CKD stage 1

Additional Recommended Tests

• Urinary calcium and creatinine - to calculate calcium-to-creatinine ratio and assess for hypercalciuria or hypocalciuria 1, 2
• Serum bicarbonate - to assess acid-base status, particularly important in CKD 1
• Liver function tests - to rule out hepatic causes of elevated ALP 1

Specialized Testing

• Bone scan - recommended in this patient with elevated ALP to assess for bone involvement 1
• Parathyroid imaging studies (if diagnosis is confirmed):
  • SestaMIBI scintigraphy with 99mTechnetium 3
  • Cervical ultrasonography 3

Interpretation Considerations in CKD

• PTH interpretation is challenging in CKD as C-terminal PTH fragments accumulate with declining kidney function 1
• Second-generation PTH assays may overestimate PTH levels in CKD patients 1
• The "gray zone" for PTH interpretation in CKD stage 5D is approximately 2-9 times the upper limit of normal 1
• Consider the patient's vitamin D status, BMI, race, and age when interpreting PTH values 1

Differential Diagnosis Considerations

• Secondary hyperparathyroidism due to CKD 1
• Acquired hypocalciuric hypercalcemia (rare) - consider if hypercalcemia with hypocalciuria is present 2
• Tertiary hyperparathyroidism - autonomous parathyroid function after longstanding secondary hyperparathyroidism 1
• Bone disease related to CKD-mineral and bone disorder (CKD-MBD) 1

When to Consider Bone Biopsy

• If PTH levels are between 100-500 pg/mL with unexplained hypercalcemia, bone pain, or increased bone ALP 1
• Before starting specific treatments when the diagnosis remains unclear 1
• Gold standard for diagnosing renal osteodystrophy, though rarely performed in clinical practice 1

Monitoring Recommendations

• Regular monitoring of iPTH, calcium, phosphorus, and ALP every 1-12 months depending on CKD stage and clinical status 1
• Monitor for progressive renal insufficiency and refer to nephrology if worsening 1
• Annual bone density assessment in elderly women at risk for osteoporosis 4

Pitfalls to Avoid

• Failing to consider normocalcemic primary hyperparathyroidism, which can still cause complications 1
• Not accounting for the effect of CKD on PTH metabolism and interpretation 1
• Overlooking the need for bone scan in patients with elevated ALP and clinical symptoms 1
• Misattributing hypocalciuria solely to CKD when it could indicate other conditions like acquired hypocalciuric hypercalcemia 2