Hyperparathyroidism, neonatal severe primary

Neonatal Severe Primary Hyperparathyroidism (NSPHT) is a rare endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) from the parathyroid glands, leading to severe hypercalcemia and bone demineralization in newborns. This condition is typically evident shortly after birth and is considered a life-threatening genetic disorder.

Etiology[edit | edit source]

NSPHT is primarily caused by mutations in the CASR gene, which encodes the calcium-sensing receptor (CaSR) on the surface of parathyroid and kidney cells. Mutations in this gene lead to decreased sensitivity of the parathyroid glands to calcium levels in the blood, resulting in excessive production of PTH.

Pathophysiology[edit | edit source]

The pathophysiology of NSPHT revolves around the deregulation of calcium homeostasis. Under normal conditions, the CaSR in the parathyroid glands responds to high calcium levels by inhibiting PTH secretion. However, mutations in the CASR gene reduce the sensitivity of these receptors, leading to uninhibited PTH release despite high calcium levels. The excessive PTH acts on the bones, causing their demineralization and releasing calcium into the bloodstream, and increases calcium reabsorption in the kidneys, further exacerbating hypercalcemia.

Clinical Presentation[edit | edit source]

Infants with NSPHT present with severe hypercalcemia, poor feeding, vomiting, dehydration, and failure to thrive. Bone demineralization may lead to fractures and neonatal rickets. Without prompt treatment, NSPHT can result in severe complications, including nephrocalcinosis, renal failure, and potentially fatal cardiovascular issues.

Diagnosis[edit | edit source]

Diagnosis of NSPHT involves clinical evaluation and laboratory tests showing significantly elevated PTH levels and hypercalcemia. Genetic testing can confirm mutations in the CASR gene. Imaging studies, such as X-rays, may show bone demineralization and fractures.

Treatment[edit | edit source]

The primary treatment for NSPHT involves surgical removal of the hyperactive parathyroid glands (parathyroidectomy). This procedure usually results in the normalization of calcium levels. In cases where surgery is not immediately possible, medical management to lower calcium levels may be necessary, including hydration, diuretics, and bisphosphonates.

Prognosis[edit | edit source]

With early diagnosis and treatment, the prognosis for infants with NSPHT can be favorable. However, delays in treatment can lead to significant morbidity and mortality due to the complications of severe hypercalcemia.