What is the management approach for an adult patient with elevated parathyroid hormone (PTH) levels, normal calcium levels, and normal phosphorus levels?

Management of Elevated PTH with Normal Calcium and Normal Phosphorus

The first priority is to assess kidney function (eGFR) and measure 25-hydroxyvitamin D levels, as vitamin D deficiency is the most common and most frequently missed reversible cause of secondary hyperparathyroidism and must be corrected before considering any other diagnosis or intervention. 1

Initial Diagnostic Workup

The evaluation requires three essential laboratory tests to distinguish between secondary hyperparathyroidism (SHPT) and normocalcemic primary hyperparathyroidism (NPHPT):

• Measure serum creatinine and calculate eGFR to assess kidney function, as PTH rises early in chronic kidney disease, often before calcium or phosphorus abnormalities become apparent 1, 2

• Check 25-hydroxyvitamin D levels, as deficiency (<30 ng/mL) is the most common reversible cause of elevated PTH with normal calcium 1, 2

• Confirm serum phosphorus is truly normal, as low phosphorus suggests primary hyperparathyroidism while elevated phosphorus points toward CKD-related secondary hyperparathyroidism 1, 2

Treatment Algorithm Based on Underlying Cause

If Vitamin D Deficiency is Present (25-OH vitamin D <30 ng/mL):

Supplement with cholecalciferol or ergocalciferol to achieve levels ≥30 ng/mL before considering any other diagnosis or therapy. 1, 2 This is the first intervention and must be completed before proceeding with further evaluation, as vitamin D deficiency causes physiologic PTH elevation that mimics other conditions 3.

• Recheck PTH levels 3-6 months after achieving vitamin D repletion 1
• If PTH normalizes, the diagnosis was secondary hyperparathyroidism due to vitamin D deficiency 3
• If PTH remains elevated despite vitamin D repletion and normal kidney function, consider normocalcemic primary hyperparathyroidism 3

If Chronic Kidney Disease is Present (eGFR <60 mL/min/1.73m²):

Correct all modifiable factors before considering PTH-lowering therapy: 1, 2

• Ensure vitamin D sufficiency (≥30 ng/mL) with cholecalciferol or ergocalciferol 1
• Consider dietary phosphate restriction if phosphorus trends toward upper normal range 1, 2
• Maintain adequate calcium intake (1000-1200 mg/day) but avoid excessive supplementation 4
• Avoid routine use of calcitriol or vitamin D analogs in CKD stages 3a-5 not on dialysis, as this increases risk of adynamic bone disease and hypercalcemia 1

If Vitamin D is Replete and Kidney Function is Normal:

This scenario suggests normocalcemic primary hyperparathyroidism (NPHPT), but diagnosis should only be made after careful exclusion of all secondary causes 3:

• Review medications that can increase PTH: thiazide diuretics, lithium, loop diuretics 3
• Assess dietary calcium intake—both deficiency and high phosphorus/low calcium ratios can elevate PTH 5
• Consider 24-hour urine calcium or spot urine calcium/creatinine ratio to exclude familial hypocalciuric hypercalcemia if urinary calcium is low 4, 6
• Measure 1,25-dihydroxyvitamin D if granulomatous disease is suspected 4

If NPHPT is confirmed after excluding all secondary causes, refer to endocrinology and consider surgical evaluation only if there is evidence of end-organ damage: 3

• Osteoporosis (T-score ≤-2.5 at any site) 4
• History of nephrolithiasis or nephrocalcinosis 4
• Impaired kidney function (eGFR <60 mL/min/1.73m²) 4
• Age <50 years 4

Critical Monitoring Parameters

For patients with CKD (not on active treatment): 1

• Measure calcium and phosphorus every 6-12 months for CKD G3a-G3b
• Every 3-6 months for CKD G4
• Every 1-3 months for CKD G5

During active vitamin D supplementation: 1

• Check serum calcium and phosphorus monthly for the first 3 months, then every 3 months
• Measure PTH levels every 3 months for 6 months, then every 3-6 months thereafter
• Discontinue all vitamin D therapy immediately if serum calcium exceeds 10.2 mg/dL 4, 1

Common Pitfalls to Avoid

• Do not diagnose normocalcemic primary hyperparathyroidism without first correcting vitamin D deficiency and excluding all secondary causes 3. Many patients labeled with NPHPT actually have unrecognized SHPT.

• Do not use calcitriol or active vitamin D analogs in CKD patients not on dialysis, as this can cause hypercalcemia and adynamic bone disease 1. Use native vitamin D (cholecalciferol/ergocalciferol) instead.

• Do not rush to surgery in normocalcemic primary hyperparathyroidism—these patients have smaller adenomas, less sensitive imaging, and outcomes of surgery are less well-established than in hypercalcemic PHPT 3, 7. A conservative approach is warranted.

• Recognize that high phosphorus/low calcium diets can elevate PTH even with normal vitamin D levels 5. Dietary assessment and modification may be therapeutic.