What is the significance of a parathyroid hormone level of 75 pg/mL and what work‑up and management should be pursued?

Evaluation and Management of PTH 75 pg/mL

A PTH level of 75 pg/mL requires immediate measurement of serum calcium (both total corrected for albumin and ionized), phosphorus, 25-hydroxyvitamin D, and kidney function (creatinine/eGFR) to distinguish primary hyperparathyroidism from secondary causes—the calcium level is the critical determinant of your next steps. 1

Initial Diagnostic Algorithm

Step 1: Measure Concurrent Calcium and Complete Metabolic Panel

• If calcium is elevated (>10.2 mg/dL corrected): This confirms primary hyperparathyroidism, as the PTH is inappropriately elevated when it should be suppressed by hypercalcemia. 1, 2
• If calcium is normal (8.6-10.2 mg/dL): You must exclude all secondary causes before diagnosing normocalcemic primary hyperparathyroidism. 1, 3
• If calcium is low or low-normal: This indicates secondary hyperparathyroidism from vitamin D deficiency, CKD, or calcium malabsorption. 1

Step 2: Essential Laboratory Work-Up

Obtain the following tests simultaneously:

• Serum calcium (total corrected for albumin AND ionized calcium 4.65-5.28 mg/dL) 2
• Serum phosphorus (expect low-normal 2.7-4.6 mg/dL in primary hyperparathyroidism) 4, 2
• 25-hydroxyvitamin D (must be >30 ng/mL to exclude vitamin D deficiency as cause of elevated PTH) 1
• Creatinine and eGFR (PTH rises when eGFR falls below 60 mL/min/1.73 m²) 1, 2
• 24-hour urine calcium or spot urine calcium/creatinine ratio (to assess for hypercalciuria >300 mg/24hr) 1, 2

Step 3: Interpret PTH in Context

Critical caveat: PTH assays vary by up to 47% between different generations—always use your laboratory's assay-specific reference ranges, not generic cutoffs. 1, 2 The "normal" range for healthy individuals (typically 15-65 pg/mL) differs from target ranges in CKD patients (150-300 pg/mL for dialysis). 4, 5

Management Based on Calcium Status

If Hypercalcemic (Calcium >10.2 mg/dL): Primary Hyperparathyroidism

Refer to endocrinology AND an experienced high-volume parathyroid surgeon for evaluation. 1, 2 Parathyroidectomy is indicated if ANY of the following criteria are met:

• Corrected calcium >1 mg/dL above upper limit of normal (>11.2 mg/dL) 1, 2
• Age <50 years 1, 5
• eGFR <60 mL/min/1.73 m² 1, 5
• Osteoporosis (T-score ≤-2.5 at any site) 1
• History of kidney stones or nephrocalcinosis 1, 5
• 24-hour urine calcium >300 mg 1
• Symptomatic disease (bone pain, fractures, neurocognitive symptoms, depression, "brain fog") 5

Before surgery: Obtain preoperative localization with ultrasound and/or 99mTc-sestamibi SPECT/CT to enable minimally invasive parathyroidectomy. 1, 5 Do NOT order imaging before confirming biochemical diagnosis—imaging is for surgical planning only. 2

If Normocalcemic (Calcium 8.6-10.2 mg/dL): Exclude Secondary Causes First

You must systematically rule out every secondary cause before diagnosing normocalcemic primary hyperparathyroidism:

1. Vitamin D deficiency (most common cause):

   • If 25-OH vitamin D <30 ng/mL, supplement with cholecalciferol or ergocalciferol to achieve levels ≥30 ng/mL 1
   • Recheck PTH every 3 months for 6 months, then every 3-6 months 1
   • Do NOT supplement vitamin D if calcium is already >10.2 mg/dL 1, 2

2. Chronic kidney disease:

   • If eGFR <60 mL/min/1.73 m², the elevated PTH represents secondary hyperparathyroidism from CKD 1, 2
   • Target PTH 150-300 pg/mL in dialysis patients; attempting to normalize PTH causes adynamic bone disease 4

3. Inadequate dietary calcium:

   • Confirm intake meets 1,000-1,200 mg/day for adults 1, 2
   • Low urinary calcium (<100 mg/24hr) suggests calcium deprivation 1

4. Medications:

   • Review for thiazide diuretics, lithium, calcium supplements, vitamin D supplements 2

If all secondary causes are excluded and PTH remains elevated with persistently normal calcium: This is normocalcemic primary hyperparathyroidism. 1, 3 These patients are NOT benign—they carry comparable risk to hypercalcemic primary hyperparathyroidism and often present with kidney stones, osteoporosis, or neurocognitive symptoms. 1, 3

Monitoring Protocol

For Confirmed Primary Hyperparathyroidism (Not Surgical Candidate)

• Serum calcium and phosphorus every 3 months 1, 2
• Annual bone density scan 2
• Annual renal ultrasound to assess for stones/nephrocalcinosis 2
• Maintain 25-OH vitamin D >20 ng/mL with supplementation 1, 5
• Ensure dietary calcium 1,000-1,200 mg/day (not exceeding 2,000 mg/day total) 2

For Secondary Hyperparathyroidism on Treatment

• Calcium and phosphorus every 2 weeks for 1 month after starting/adjusting vitamin D, then monthly 1, 5
• PTH monthly for 3 months, then every 3 months once stable 1, 5
• Stop all vitamin D immediately if calcium exceeds 10.2 mg/dL 1, 2

Critical Pitfalls to Avoid

• Never assume elevated PTH alone means primary hyperparathyroidism—the calcium level is essential for proper classification. 1
• Never start active vitamin D (calcitriol) if phosphorus >6.5 mg/dL or calcium >10.2 mg/dL—this risks vascular calcification. 1
• Never over-suppress PTH in CKD patients below 150 pg/mL—this causes adynamic bone disease. 4, 1
• Never order parathyroid imaging before confirming biochemical diagnosis—imaging is for surgical planning, not diagnosis. 2
• Never use generic PTH reference ranges—assays differ by up to 47% between methods; use your lab's specific values. 1, 2
• Never measure PTH in serum stored at room temperature—use EDTA plasma kept at 4°C for stability. 2, 6
• Never ignore biotin supplementation—it interferes with PTH immunoassays and causes spurious results. 2

When to Refer Urgently

Immediate endocrinology and surgical referral is warranted for:

• Calcium >12 mg/dL (severe hypercalcemia requiring urgent treatment) 2
• Symptomatic hypercalcemia (confusion, nausea, polyuria, weakness) 2
• eGFR <45 mL/min/1.73 m² with hypercalcemia (high risk for acute kidney injury) 1
• Severe hypercalciuria (>400 mg/24hr) with risk of irreversible nephrocalcinosis 1
• Disabling neurocognitive symptoms (depression, memory loss, inability to function) 1