Differential Diagnosis for Malignancy Causing High Intact PTH

• Single Most Likely Diagnosis
  • Parathyroid carcinoma: This is a rare but well-known cause of primary hyperparathyroidism, characterized by elevated intact PTH levels. It is a malignancy of the parathyroid glands that can lead to severe hypercalcemia.
• Other Likely Diagnoses
  • Metastatic disease to the parathyroid glands: Although rare, metastasis from other cancers (like breast, lung, or kidney cancer) can involve the parathyroid glands, potentially causing hyperparathyroidism.
  • Parathyroid hyperplasia associated with MEN syndromes: Multiple Endocrine Neoplasia (MEN) syndromes, particularly MEN1 and MEN2A, can involve parathyroid hyperplasia leading to elevated PTH levels. While not a malignancy per se, these conditions can have malignant potential and are associated with other endocrine tumors.
• Do Not Miss Diagnoses
  • PTHrP-producing tumors: Certain malignancies, such as squamous cell lung cancer, can produce parathyroid hormone-related protein (PTHrP), leading to humoral hypercalcemia of malignancy. This condition mimics primary hyperparathyroidism with elevated calcium levels but typically has low or normal intact PTH levels. However, in some cases, the assay might cross-react, or there could be co-existing primary hyperparathyroidism, making it crucial not to miss.
  • Lymphoma: Some lymphomas can cause hypercalcemia through various mechanisms, including the production of PTHrP or osteoclast-activating factors. Although intact PTH might not be elevated in these cases, the clinical presentation could mimic that of a PTH-producing malignancy.
• Rare Diagnoses
  • Tertiary hyperparathyroidism due to malignancy-associated renal disease: Chronic kidney disease, which can be a consequence of certain malignancies or their treatment, can lead to secondary hyperparathyroidism. In rare cases, this can progress to tertiary hyperparathyroidism, characterized by autonomous parathyroid function and elevated intact PTH levels.
  • Ectopic PTH-producing tumors: Extremely rare cases of tumors producing intact PTH have been reported, such as ovarian or lung cancers. These are exceptionally uncommon causes of elevated intact PTH.