What is the diagnosis for a patient with hypercalcemia and elevated Parathyroid Hormone (PTH)

From the Guidelines

Hypercalcemia with elevated parathyroid hormone (PTH) is most likely primary hyperparathyroidism (PHPT), which is typically diagnosed by biochemical testing, specifically serum calcium and serum PTH, as stated in the 2021 study by 1. The diagnosis of PHPT is crucial, as it can lead to various complications, including bone demineralization, fractures, nephrolithiasis, nephrocalcinosis, muscle weakness, or neurocognitive disorders, as mentioned in the study by 1. Some key points to consider in the diagnosis and management of PHPT include:

• PHPT is more common in women, with an incidence of 66 per 100,000 person-years, and 25 per 100,000 person-years in men, as reported by 1.
• The most common cause of PHPT is a single parathyroid adenoma (80%), but it can also occur due to multiple adenomas, parathyroid hyperplasia, or, rarely, parathyroid carcinoma (<1%), as stated in the study by 1.
• Treatment of PHPT is surgical excision of the abnormally functioning parathyroid tissue and is typically indicated even when asymptomatic, given potential negative effects of long-term hypercalcemia, as recommended by 1.
• There are two accepted curative operative strategies for PHPT: bilateral neck exploration (BNE) and minimally invasive parathyroidectomy (MIP), with MIP being less invasive than BNE, as described by 1. The role of imaging in PHPT is to localize the abnormally functioning gland or glands with high accuracy and high confidence to facilitate targeted curative surgery, as emphasized by 1. Initial management includes hydration with normal saline, especially in symptomatic patients or those with calcium levels above 12 mg/dL. While awaiting surgery, medical management may include cinacalcet to lower calcium levels by increasing calcium-sensing receptor sensitivity, as well as bisphosphonates like zoledronic acid or pamidronate for severe hypercalcemia. Patients should maintain adequate hydration, avoid thiazide diuretics, limit calcium intake to 800-1000 mg daily, and ensure sufficient vitamin D levels to prevent secondary hyperparathyroidism, as part of comprehensive management. Regular monitoring of serum calcium, phosphorus, PTH, and renal function is essential to ensure optimal outcomes.

From the FDA Drug Label

Approximately 60% of patients with mild (iPTH ≥ 300 to ≤ 500 pg/mL), 41% with moderate (iPTH > 500 to 800 pg/mL), and 11% with severe (iPTH > 800 pg/mL) secondary HPT achieved a mean iPTH value of ≤ 250 pg/mL. Seventeen patients with severe hypercalcemia due to primary HPT, who had failed or had contraindications to parathyroidectomy, participated in an open-label, single-arm study. At baseline the mean (SE) serum calcium was 12.7 (0.2) mg/dL. At the end of the titration phase the mean (SE) serum calcium was 10.4 (0.3) mg/dL, which is a mean reduction of 2. 3 (0. 3) mg/dL from baseline.

The diagnosis for a patient with hypercalcemia and elevated Parathyroid Hormone (PTH) is likely Primary Hyperparathyroidism (HPT) 2.

• Key features of this condition include:
  • Elevated serum calcium levels
  • Elevated PTH levels
  • Presence of hypercalcemia due to primary HPT
• Treatment may involve cinacalcet, a medication that can help reduce serum calcium levels and PTH levels in patients with primary HPT.

From the Research

Diagnosis of Hypercalcemia with Elevated Parathyroid Hormone (PTH)

The diagnosis of hypercalcemia with elevated PTH is primarily focused on distinguishing between primary hyperparathyroidism (PHPT) and other causes of hypercalcemia.

• Hypercalcemia affects approximately 1% of the worldwide population, with mild hypercalcemia being usually asymptomatic, but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people 3.
• Approximately 90% of people with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy, with PHPT being the most common cause of hypercalcemia in outpatients 3, 4, 5.
• Serum intact parathyroid hormone (PTH) is the most important initial test to evaluate hypercalcemia, distinguishing PTH-dependent from PTH-independent causes 3, 6, 7.
• An elevated or normal PTH concentration in a patient with hypercalcemia is consistent with PHPT, while a suppressed PTH level indicates another cause 3, 4, 6.

Differential Diagnosis

The differential diagnosis of hypercalcemia with elevated PTH includes:

• Primary hyperparathyroidism (PHPT): characterized by elevated PTH levels, often with mild hypercalcemia and few symptoms 3, 4, 5.
• Malignancy: typically presents with rapid onset, high serum calcium levels, and severe symptoms, with suppressed PTH levels 4, 5, 7.
• Other causes: such as granulomatous disease, endocrinopathies, immobilization, genetic disorders, and medications, which can also cause hypercalcemia with elevated or suppressed PTH levels 3, 6.

Diagnostic Approach

The diagnostic approach to hypercalcemia with elevated PTH involves:

• Measurement of intact PTH levels to distinguish between PHPT and other causes of hypercalcemia 3, 6, 7.
• Evaluation of clinical presentation, including symptoms, medical history, and physical examination 3, 4, 5.
• Additional tests, such as parathyroid hormone-related protein (PTH-rP) measurement, may be useful in certain cases, such as malignancy-associated hypercalcemia 7.