Differential Diagnosis of Primary Hyperparathyroidism
The differential diagnosis for primary hyperparathyroidism can be organized into the following categories:
Single Most Likely Diagnosis
- Familial Hypocalciuric Hypercalcemia (FHH): This condition is often considered in the differential diagnosis due to its similarity in presentation to primary hyperparathyroidism, particularly in terms of hypercalcemia and elevated parathyroid hormone (PTH) levels. However, FHH typically has a family history and is characterized by hypocalciuria, which distinguishes it from primary hyperparathyroidism.
Other Likely Diagnoses
- Secondary Hyperparathyroidism: This condition often arises in the context of chronic kidney disease, vitamin D deficiency, or other conditions leading to chronic hypocalcemia, which in turn stimulates parathyroid hormone secretion. Distinguishing features include the underlying cause and typically lower calcium levels compared to primary hyperparathyroidism.
- Tertiary Hyperparathyroidism: Usually develops from long-standing secondary hyperparathyroidism, where the parathyroid glands become autonomously functioning, leading to hypercalcemia. The history of secondary hyperparathyroidism and its underlying cause helps in differentiation.
- Lithium-induced Hyperparathyroidism: Lithium therapy can lead to increased PTH secretion and hypercalcemia, mimicking primary hyperparathyroidism. A history of lithium use is key to this diagnosis.
- Vitamin D intoxication: Although it leads to hypercalcemia, it is typically associated with suppressed PTH levels, unlike primary hyperparathyroidism where PTH is elevated.
Do Not Miss Diagnoses
- Malignancy-associated Hypercalcemia: Various cancers, notably squamous cell lung cancer, breast cancer, and multiple myeloma, can cause hypercalcemia through the production of parathyroid hormone-related protein (PTHrP) or other mechanisms. Missing this diagnosis could delay the treatment of an underlying life-threatening condition.
- Vitamin A intoxication: Can cause hypercalcemia and has serious health implications if not recognized and treated promptly.
- Sarcoidosis: A systemic granulomatous disease that can lead to hypercalcemia due to increased vitamin D conversion to its active form. It's crucial to identify sarcoidosis due to its systemic implications and the availability of specific treatments.
Rare Diagnoses
- Familial Isolated Hyperparathyroidism: A rare genetic condition characterized by hyperparathyroidism without other syndromic features.
- Multiple Endocrine Neoplasia (MEN) syndromes: Specifically MEN1 and MEN2A, which can include primary hyperparathyroidism as part of their syndrome. These are rare but important to diagnose due to their implications for the patient and their family members.
- Parathyroid Carcinoma: A rare cause of primary hyperparathyroidism, often presenting with more severe hypercalcemia and a palpable neck mass.