Normocalcemic Hyperparathyroidism

Normocalcemic primary hyperparathyroidism (NHPT) is a relatively new classification of primary hyperparathyroidism (PHPT). The definition of NHPT is a disorder in which elevated parathyroid hormone (PTH) levels are the result of autonomous hypersecretion from 1 or more parathyroid glands, and the albumin-adjusted and ionized serum calcium levels are consistently within the normal range when measured at least twice over 6 months. Before establishing a diagnosis of NHPT, all causes of secondary hyperparathyroidism (SHPT) must be excluded.

In SHPT, the PTH elevation and parathyroid gland hyperplasia develop in response to a low serum calcium stimulus from diverse causes such as low vitamin D or chronic renal failure. The PTH remains elevated as long as the low calcium stimulus persists and returns to normal as soon as it is corrected. Patients with chronic SHPT typically develop hyperplasia of all 4 parathyroid glands, which can lead to tertiary hyperparathyroidism. Excluding SHPT by a thorough history, physical examination, and directed laboratory investigations is essential before diagnosing NHPT. In those with SHPT, medical treatment is directed at correcting the causes of the reduced serum calcium, which increases PTH. In contrast, the treatment of NHPT is focused on the abnormal parathyroid gland(s), which may include surgical parathyroidectomy.

In addition to differentiating NHPT from SHPT, there is a significant overlap between NHPT and PHPT, with the latter characterized by elevated serum calcium. Many patients with NHPT go on to develop PHPT, suggesting that NHPT may be an early presentation of PHPT in some cases. Predicting which patients will develop the hypercalcemia associated with PHPT is impossible. Therefore, clinicians must continue to monitor serum calcium levels. Diagnosis and treatment of NHPT and PHPT are very similar. See StatPearls' companion reference, "Primary Hyperparathyroidism," for more information.