How should a low parathyroid hormone (PTH) level be interpreted when serum calcium is normal or at the upper limit of normal?

Interpretation of Low PTH with Normal or High-Normal Calcium

A low PTH level in the setting of normal or upper-limit-normal calcium is physiologically appropriate and indicates PTH-independent hypercalcemia—the parathyroid glands are correctly suppressing in response to adequate or elevated calcium. 1

Diagnostic Framework

This biochemical pattern represents PTH-independent hypercalcemia, where calcium elevation occurs through mechanisms that do not involve parathyroid hormone. 1 The suppressed PTH (typically <20 pg/mL) confirms that the parathyroid glands are functioning normally by shutting down in response to the calcium level. 1

Key Principle: Inappropriately Normal vs. Appropriately Low PTH

• In primary hyperparathyroidism, PTH is elevated OR inappropriately normal (fails to suppress below 20 pg/mL) despite hypercalcemia. 1 This represents autonomous PTH secretion. 1
• When PTH is truly suppressed (<20 pg/mL) with elevated calcium, this is appropriate physiology and excludes primary hyperparathyroidism. 1
• Even PTH values in the "normal range" (e.g., 20-65 pg/mL) are inappropriate when calcium is elevated and should prompt evaluation for primary hyperparathyroidism. 1, 2

Essential Diagnostic Workup

When you encounter low PTH with normal-to-high calcium, immediately obtain:

First-Tier Laboratory Tests

• Measure PTH-related protein (PTHrP) to evaluate for malignancy-associated hypercalcemia, which presents with suppressed PTH and elevated PTHrP. 3
• Obtain both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels simultaneously before any vitamin D supplementation, as their relationship provides critical diagnostic information. 1
• Measure ionized calcium (normal: 4.65-5.28 mg/dL) for definitive assessment, as total calcium can be misleading if albumin is abnormal. 1

Interpretation of Vitamin D Metabolites

The pattern of vitamin D metabolites distinguishes the underlying cause:

• Vitamin D intoxication: Markedly elevated 25-OH vitamin D with elevated 1,25-(OH)₂ vitamin D 1
• Granulomatous disease (sarcoidosis): Low 25-OH vitamin D but elevated 1,25-(OH)₂ vitamin D due to increased 1α-hydroxylase activity in granulomas 1
• Malignancy-associated hypercalcemia: Both 25-OH and 1,25-(OH)₂ vitamin D are typically low because suppressed PTH reduces conversion to active vitamin D 1

Common Etiologies by PTH Level

PTH Suppressed (<20 pg/mL) with Hypercalcemia

Malignancy (most common in hospitalized patients):

• Elevated PTHrP with suppressed PTH defines humoral hypercalcemia of malignancy (HHM), with median survival approximately 1 month after detection. 1
• Most frequent PTHrP-secreting tumors: squamous cell carcinoma of lung, head-and-neck squamous carcinoma, renal cell carcinoma, breast carcinoma, and neuroendocrine tumors 1
• Immediate comprehensive imaging (chest CT, abdominal/pelvic CT or MRI, PET-CT) must proceed simultaneously with calcium-lowering measures due to poor prognosis. 1

Vitamin D-mediated hypercalcemia:

• Vitamin D intoxication: Excessive supplementation or ingestion 1
• Granulomatous disease: Sarcoidosis, tuberculosis, fungal infections 1
• Glucocorticoids are the primary treatment when hypercalcemia results from excessive intestinal calcium absorption. 3

Other causes:

• Hyperthyroidism
• Immobilization
• Thiazide diuretics
• Milk-alkali syndrome

PTH in "Normal Range" (20-65 pg/mL) with Hypercalcemia

This represents inappropriately normal PTH and suggests primary hyperparathyroidism. 1, 2

• PTH should suppress below 20 pg/mL when calcium is elevated; failure to do so indicates autonomous parathyroid function. 1
• Primary hyperparathyroidism can occur with PTH levels as low as 5 pg/mL in rare cases, though this represents an unusual phenotype. 2
• Cure rates after parathyroidectomy are similar whether PTH is frankly elevated or inappropriately normal. 1

Critical Management Pitfalls

Do NOT Supplement Vitamin D in Active Hypercalcemia

• Discontinue all vitamin D therapy and calcium supplementation immediately when serum calcium exceeds 10.2 mg/dL. 1
• Avoid calcitriol or active vitamin D analogs in primary hyperparathyroidism, as they increase intestinal calcium absorption and exacerbate hypercalcemia. 1
• Do not resume vitamin D until serum calcium is consistently below 9.5 mg/dL and the underlying cause is identified. 1

Recognize Parathyroid Insufficiency Post-Thyroidectomy

• Normal PTH levels do not exclude permanent hypoparathyroidism after thyroid surgery. 4
• Patients can have persistent hypocalcemia with PTH in the normal range when remaining parathyroid tissue is maximally stimulated but insufficient to restore normocalcemia. 4
• This represents "parathyroid insufficiency" rather than true hypoparathyroidism. 4

Adjust PTH Interpretation for Chronic Kidney Disease

• PTH concentrations rise when eGFR falls below 60 mL/min/1.73 m², making CKD a key differential for elevated PTH. 1
• In CKD, measure 1,25-(OH)₂ vitamin D together with 25-OH vitamin D: both are typically low in CKD-related secondary hyperparathyroidism. 1

Immediate Actions for Moderate-to-Severe Hypercalcemia

When total calcium ≥12 mg/dL or ionized calcium ≥10 mg/dL with suppressed PTH:

• Initiate aggressive IV crystalloid hydration with normal saline to restore intravascular volume and promote calciuresis. 3
• Administer loop diuretics (furosemide) only after adequate volume repletion to enhance calcium excretion. 3
• Give IV bisphosphonates (zoledronic acid or pamidronate) as primary therapy for PTH-independent hypercalcemia. 3
• Consider calcitonin as a temporizing measure for rapid calcium reduction while awaiting bisphosphonate effect. 3
• For severe symptomatic hypercalcemia (total calcium ≥14 mg/dL), initiate hypertonic 3% saline IV in addition to aggressive hydration. 3

Monitoring Strategy

• Monitor serum calcium and ionized calcium every 1-2 weeks until stable. 3
• Measure serum calcium, phosphorus, and electrolytes closely during acute treatment. 1
• Recheck calcium, phosphorus, and PTH in 3 months if etiology remains unclear after initial workup. 5