Causes of Hypercalcemia and PTH-Mediated vs Non-PTH-Mediated Hypercalcemia

Hypercalcemia refers to elevated levels of calcium in the blood. It can result from various underlying conditions and can be classified based on its association with parathyroid hormone (PTH).

Causes of Hypercalcemia

PTH-Mediated Hypercalcemia

• Primary Hyperparathyroidism: Excessive secretion of PTH due to parathyroid adenoma or hyperplasia.
• Secondary Hyperparathyroidism: Occurs in response to chronic kidney disease (CKD), leading to compensatory PTH secretion.
• Tertiary Hyperparathyroidism: Seen in prolonged CKD cases where parathyroid glands become autonomous.

Non-PTH-Mediated Hypercalcemia

• Malignancy: Tumors producing parathyroid hormone-related peptide (PTHrP), osteolytic bone metastases, or cytokine-mediated bone resorption.
• Vitamin D Toxicity: Excessive intake leading to increased calcium absorption.
• Granulomatous Diseases: Such as sarcoidosis, which leads to increased vitamin D production.
• Endocrine Disorders: Thyrotoxicosis and adrenal insufficiency contribute to calcium imbalance.

Clinical Presentation and Symptoms of Hypercalcemia

Mild Hypercalcemia (Serum Calcium: 10.5–12 mg/dL)

• Fatigue
• Constipation
• Mild cognitive impairment

Severe Hypercalcemia (Serum Calcium > 14 mg/dL)

• Polyuria and polydipsia
• Abdominal pain and vomiting
• Cardiac arrhythmias
• Confusion or coma

Management and Treatment

Treatment depends on the underlying cause and severity of hypercalcemia. Hydration, bisphosphonates, calcitonin, and corticosteroids may be utilized based on etiology.