Parathyroid hormone is 75.3 pg/mL; is this elevated and what evaluation and management steps are indicated?

Evaluation and Management of PTH 75.3 pg/mL

A PTH of 75.3 pg/mL is elevated above the normal range (typically 10–65 pg/mL), and you must immediately measure serum calcium, phosphorus, 25-hydroxyvitamin D, and creatinine/eGFR to distinguish primary hyperparathyroidism from secondary causes. 1

Initial Diagnostic Workup

The interpretation of this PTH level depends entirely on the calcium level, which determines whether this represents autonomous parathyroid disease or a physiologic response to an underlying metabolic disturbance.

Measure these labs simultaneously:

• Serum calcium (total and ionized): If calcium is >10.2 mg/dL with elevated PTH, this confirms primary hyperparathyroidism. 1 If calcium is normal or low, this suggests secondary hyperparathyroidism. 2

• Serum phosphorus: Typically low-normal (often <2.5 mg/dL) in primary hyperparathyroidism due to PTH-mediated renal phosphate wasting. 1, 2 Normal or elevated phosphorus suggests secondary hyperparathyroidism from CKD. 3

• 25-hydroxyvitamin D: Vitamin D deficiency (levels <20 ng/mL) is the most common cause of secondary hyperparathyroidism and must be excluded before diagnosing primary hyperparathyroidism. 1, 4 PTH reference values are 20% lower in vitamin D-replete individuals. 1

• Creatinine and eGFR: PTH rises when eGFR falls below 60 mL/min/1.73 m², making CKD a key differential. 1, 4 Impaired renal function (eGFR <60) with elevated PTH and hypercalcemia requires urgent specialist referral. 2

• 24-hour urine calcium or spot urine calcium/creatinine ratio: Hypercalciuria (>300 mg/24hr) indicates renal calcium wasting and helps differentiate causes. 1, 5

Interpretation Algorithm

If Calcium is Elevated (>10.2 mg/dL):

This is primary hyperparathyroidism. 1 The parathyroid glands autonomously secrete PTH despite elevated calcium, which is the hallmark of this disease. 1

Immediate actions:

• Discontinue all calcium supplements, vitamin D supplements, and thiazide diuretics. 1
• Ensure adequate oral hydration. 1
• Refer to endocrinology and an experienced parathyroid surgeon for surgical evaluation. 1, 2

Surgical indications include: 1

• Corrected calcium >1 mg/dL above upper limit of normal (>11.2 mg/dL)
• Age <50 years
• eGFR <60 mL/min/1.73 m²
• Osteoporosis (T-score ≤-2.5 at any site)
• History of nephrolithiasis or nephrocalcinosis
• 24-hour urine calcium >300 mg/day

If Calcium is Normal (8.6–10.2 mg/dL):

You must systematically exclude all causes of secondary hyperparathyroidism before considering normocalcemic primary hyperparathyroidism. 6

Rule out these secondary causes in order:

1. Vitamin D deficiency (most common): If 25-OH vitamin D is <20 ng/mL, supplement with cholecalciferol or ergocalciferol to achieve levels >30 ng/mL. 4, 2 Recheck PTH after 3 months of repletion. 4

2. Inadequate dietary calcium intake: Confirm the patient consumes 1,000–1,200 mg/day of elemental calcium. 1 Low urinary calcium (<100 mg/24hr) suggests calcium deprivation. 5

3. Chronic kidney disease: Even mild CKD (eGFR 45–59) causes PTH elevation. 1, 4 If eGFR is <60, this is secondary hyperparathyroidism from CKD. 4

4. Medications: Lithium salts, loop diuretics, and bisphosphonates can elevate PTH. 5

5. Renal calcium leak: Hypercalciuria (>300 mg/24hr) with normal calcium suggests renal phosphate wasting. 5 A thiazide challenge test can help differentiate this from normocalcemic primary hyperparathyroidism. 5

6. Malabsorption syndromes: Celiac disease, inflammatory bowel disease, and bariatric surgery impair calcium absorption. 5

If all secondary causes are excluded and PTH remains elevated with persistently normal calcium over 3–6 months, this is normocalcemic primary hyperparathyroidism (NPHPT). 1, 6 This is not a benign entity and carries risks comparable to hypercalcemic primary hyperparathyroidism. 1

Critical Pitfalls to Avoid

• Do not assume PTH elevation alone indicates primary hyperparathyroidism—the calcium level is essential for proper classification. 4

• Do not order parathyroid imaging (ultrasound or sestamibi scan) before confirming the biochemical diagnosis—imaging is for surgical planning, not diagnosis. 1

• PTH assays vary by up to 47% between different assay generations—always use assay-specific reference ranges. 1, 7 Second-generation "intact" PTH assays detect inactive fragments and overestimate bioactive PTH. 3, 7

• Biological variation of PTH is substantial (20% in healthy individuals)—a change >54% is required to be clinically meaningful. 1

• PTH is most stable in EDTA plasma at 4°C, not serum—improper sample handling can yield falsely low results. 1

• Biotin supplementation interferes with PTH immunoassays—instruct patients to discontinue biotin 72 hours before testing. 1

• PTH increases with age, higher BMI, and is 20% higher in Black individuals—interpret results in demographic context. 1

Management Based on Calcium Level

For Primary Hyperparathyroidism (Elevated Calcium):

Parathyroidectomy is the definitive treatment and is recommended even in asymptomatic patients because prolonged disease produces adverse metabolic effects. 1 Refer to a high-volume parathyroid surgeon, as outcomes are significantly better with specialized expertise. 1

Medical management for non-surgical candidates: 1

• Maintain normal calcium intake (1,000–1,200 mg/day)—avoid high or low calcium diets
• Ensure 25-OH vitamin D >20 ng/mL with supplementation if needed
• Avoid calcitriol or active vitamin D analogs, as they increase intestinal calcium absorption and worsen hypercalcemia 1
• Monitor serum calcium every 3 months 4

For Secondary Hyperparathyroidism (Normal/Low Calcium):

Treat the underlying cause:

• Vitamin D deficiency: Supplement with cholecalciferol 50,000 IU weekly for 8–12 weeks, then 1,000–2,000 IU daily to maintain 25-OH vitamin D >30 ng/mL. 4 Monitor calcium and phosphorus every 2 weeks for the first month, then monthly. 4

• CKD-related: If eGFR <60 and phosphorus is elevated, restrict dietary phosphate to 800–1,000 mg/day. 4 Do not start active vitamin D (calcitriol) if calcium is >10.2 mg/dL or phosphorus is >6.5 mg/dL. 4

• Renal calcium leak: Consider thiazide diuretics to reduce urinary calcium losses. 5

Recheck PTH every 3 months for 6 months after correcting vitamin D deficiency. 4 If PTH remains elevated despite correction of all secondary causes, refer to endocrinology for evaluation of normocalcemic primary hyperparathyroidism. 2, 6