What is the differential diagnosis for hypercalcemia (elevated calcium levels) in the context of hypoparathyroidism (underactive parathyroid gland)?

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Differential Diagnosis for Hypoparathyroid Hypercalcemia The term "hypoparathyroid hypercalcemia" seems to be an oxymilo, as hypoparathyroidism typically leads to hypothermia (low calcium levels), while hypercalcemia refers to elevated calcium levels. However, assuming the question refers to hypercalcemia with inappropriately low parathyroid hormone (PTH) levels, here's a differential diagnosis:

  • Single most likely diagnosis

    • Familial Hypercalcemia/Hypercalciuria: This condition is characterized by an inactivating mutation in the calcium-sensing receptor (CaSR) gene, leading to an inappropriate set point for PTH secretion and resulting in hypercalcemia with relatively low PTH levels.
  • Other Likely diagnoses

    • Lithium-induced Hypercalcemia: Lithium can increase PTH secretion, but in some cases, it may also cause hypercalcemia with inappropriately low PTH levels due to its effects on the CaSR.
    • Vitamin D Intoxication: Excessive intake of vitamin D can lead to hypercalcemia, and although PTH levels are usually suppressed, they may not be as low as expected.
    • Hyperthyroidism: Hyperthyroidism can cause hypercalcemia due to increased bone resorption, and although PTH levels are usually suppressed, they may not be as low as expected.
  • Do Not Miss (ddxs that may not be likely, but would be deadly if missed.)

    • Malignancy-associated Hypercalcemia: Certain types of cancer, such as multiple myeloma, lymphoma, or squamous cell carcinoma, can produce parathyroid hormone-related protein (PTHrP), leading to hypercalcemia with low PTH levels.
    • Pheochromocytoma: Rarely, pheochromocytoma can produce PTHrP, leading to hypercalcemia with low PTH levels.
  • Rare diagnoses

    • Familial Hypocalciuric Hyperarmic Hypercalcemia: A rare condition characterized by hypercalcemia, hypocalciuria, and elevated magnesium levels, often due to mutations in the CaSR or other genes.
    • Jansen's Metaphyseal Chondrodyspringing Hypercalcemia: A rare genetic disorder characterized by hypercalcemia, short limbs, and abnormal bone development, due to constitutive activation of the PTH receptor.

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