Differential Diagnosis for Elevated PTH with Normal Calcium and Ionized Calcium, and Elevated Alk Phos Bone

• Single Most Likely Diagnosis
  • Primary Hyperparathyroidism with mild or early disease: This condition is characterized by elevated PTH levels, which can sometimes be seen with normal calcium levels, especially in the early stages. The elevated alkaline phosphatase (alk phos) bone isoenzyme suggests bone involvement, consistent with the effects of excess PTH on bone resorption.
• Other Likely Diagnoses
  • Familial Hypocalciuric Hypercalcemia (FHH): Although calcium levels are normal in this case, FHH can sometimes present with normal or slightly elevated calcium levels. The key feature is the elevated PTH with relatively low urinary calcium excretion.
  • Vitamin D deficiency: This condition can lead to secondary hyperparathyroidism, where low vitamin D levels cause decreased calcium absorption, prompting an increase in PTH to maintain calcium homeostasis. Elevated alk phos can be seen due to increased bone turnover.
  • Chronic Kidney Disease (CKD): CKD can lead to secondary hyperparathyroidism due to impaired vitamin D activation, phosphate retention, and decreased calcium levels, all of which can stimulate PTH secretion. Elevated alk phos can occur due to bone disease associated with CKD.
• Do Not Miss Diagnoses
  • Malignancy-associated hypercalcemia: Although the calcium levels are normal, certain malignancies can produce PTH-related protein (PTHrP), leading to elevated PTH levels and hypercalcemia. The absence of hypercalcemia does not rule out this diagnosis entirely, as it can be intermittent or masked by other factors.
  • Multiple Endocrine Neoplasia (MEN) syndromes: These syndromes can include primary hyperparathyroidism and should be considered, especially if there's a family history or other endocrine abnormalities.
• Rare Diagnoses
  • Lithium-induced hyperparathyroidism: Lithium therapy can cause elevated PTH levels, potentially leading to hyperparathyroidism. This would be considered in patients with a history of lithium use.
  • Genetic disorders affecting the calcium-sensing receptor: These disorders can lead to abnormal PTH regulation and calcium homeostasis, presenting with a variety of calcium and PTH level abnormalities.