Neonatal Primary Hyperparathyroidism Research Articles

Idiopathic infantile hypercalcemia with severe nephrocalcinosis, associated with CYP24A1 mutations: a case report

Nephrocalcinosis often occurs in infants and is caused by excessive calcium or vitamin D supplementation, neonatal primary hyperparathyroidism, and genetic disorders. Idiopathic infantile hypercalcemia (IIH), a rare cause of nephrocalcinosis, results from genetic defects in CYP24A1 or SLC34A1. Mutations in CYP24A1, which encodes 25-hydroxyvitamin D 24-hydroxylase, disrupt active vitamin D degradation. IIH clinically manifests as failure to thrive and hypercalcemia within the first year of life and usually remits spontaneously. Herein, we present a case of IIH wih CYP24A1 mutations.An 11-month-old girl visited our hospital with incidental hypercalcemia. She showed failure to thrive, and her oral intake had decreased over time since the age of 6 months. Her initial serum parathyroid hormone level was low, 25-OH vitamin D and 1,25-OH vitamin D levels were normal, and renal ultrasonography showed bilateral nephrocalcinosis. Whole-exome sequencing revealed compound heterozygous variants in CYP24A1 (NM_000782.4:c.376C>T [p.Pro126Ser] and c.1310C>A [p.Pro437His]). Although her hypercalcemia and poor oral intake spontaneously resolved in approximately 8 months, we suggested that her nephrocalcinosis and renal function be regularly checked in consideration of potential asymptomatic renal damage. Hypercalcemia caused by IIH should be suspected in infants with severe nephrocalcinosis, especially when presenting with failure to thrive.

Hereditary syndromal and nonsyndromal forms of primary hyperparathyroidism

Primary hyperparathyroidism is a common disorder of mineral homeostasis, characterized by overproduction of parathyroid hormone and upper normal or elevated calcium levels due to hyperplasia or a tumor of parathyroid gland. 90−95% of cases of primary hyperparathyroidism are sporadic, while hereditary genetic forms occur in 5–10% of all cases. Primary hyperparathyroidism as the component of hereditary syndromes can present in various clinical forms (asymptomatic, symptomatic), can be associated with other endocrine or non-endocrine diseases, and require special approaches to treatment. Given that primary hyperparathyroidism is one of the most common components of these syndromes, it can be used as an important diagnostic tool in identifying affected families. This review is devoted to modern ideas about the clinical course and genetic characteristics of hereditary variants of primary hyperparathyroidism and the diagnostic and treatment algorithms recommended today. The review considers primary hyperparathyroidism as a component of hereditary syndromes including multiple endocrine neoplasias types 1, 2A and 4 and syndrome of hyperparathyroidism with a jaw tumor. Also non-syndromic hereditary forms are descripted, such as familial isolated hyperparathyroidism, familial hypocalciuric hypercalcemia, and severe neonatal primary hyperparathyroidism.

Successful Use of Bisphosphonate and Calcimimetic in Neonatal Severe Primary Hyperparathyroidism

Neonatal primary hyperparathyroidism (NPHT) is associated with an inactivating homozygous mutation of the calcium sensing receptor (CaSR). The CaSR is expressed most abundantly in the parathyroid glands and the kidney and regulates calcium homeostasis through its ability to modulate parathormone secretion and renal calcium reabsorption. NPHT leads to life threatening hypercalcemia, nephrocalcinosis, bone demineralization, and neurologic disabilities. Surgery is the treatment of choice. While waiting for surgery, bisphosphonates offer a good alternative to deal with hypercalcemia. Cinacalcet is a class II calcimimetic that increases CaSR affinity for calcium, leading to parathormone suppression and increased calcium renal excretion. At present, there is little evidence as to whether cinacalcet could improve the function of mutant CaSR in NPHT. We report a case of NPHT, treated successfully with bisphosphonates and cinacalcet after surgery failure. To our knowledge, it is the first time cinacalcet has been used for NPHT.

Unusually severe phenotype of neonatal primary hyperparathyroidism due to a heterozygous inactivating mutation in the CASR gene

We present a male patient with neonatal severe primary hyperparathyroidism, whose manifestation was exceptionally serious for the heterozygous inactivating mutation he carried in the CASR gene. The patient presented soon after birth with respiratory distress requiring long-term mechanical ventilation, bone and chest deformities, feeding problems, and hypotonia. He had hypercalcaemia, hypophosphataemia, and hyperparathyroidism. There was no known history of calcium metabolism disorders in the family. As the impact on calcaemia of a rescue therapy with bisphosphonates was only transient, a subtotal and subsequently total parathyroidectomy were performed in the fourth month of life. Afterwards his clinical status improved and the fractures healed, but his neuropsychological development is delayed due to cerebral atrophy. Genetic analysis revealed a heterozygous missense CASR mutation R185Q, and an approximately equal expression of the mutated and wild-type RNA in the parathyroid tissue. The mother of the child was homozygous for the wild-type allele; the father is unknown. In conclusion, this patient demonstrates how serious neonatal hyperparathyroidism can be when caused by a heterozygous mutation. This may be attributable to a combination of dominant-negative action of the mutant allele with an intrauterine foetal hyperparathyroidism developed in the mother's normocalcaemic environment, further aggravated by a putative maternal vitamin D deficiency during pregnancy.

Intrathyroid parathyroid gland and neonatal primary hyperparathyroidism

Neonatal hyperparathyroidism (NPHP) is exceedingly rare and often fatal. A neonate is presented with a serum calcium concentration of 33 mg/dL, an intrathyroid parathyroid gland, and a family history of hypocalciuric hypercalcemia (FHH). She underwent successful total parathyroidectomy. Six years later, the child is normocalcemic and developmentally normal, requiring calcium and calcitrol replacement. The results of this case support the concept that NPHP is associated with parathyroid hyperplasia and is part of a continuum that includes FHH. J Pediatr Surg 35:1517-1519. Copyright © 2000 by W.B. Saunders Company.

The ineffectiveness of Technetium-99m-sestamibi for the pre-operative localization of parathyroid glands in neonatal primary hyperparathyroidism: case report

OBJECTIVE: To present the case of a child with neonatal primary hyperparathyroidism submitted to preoperative image studies that couldn't localize the parathyroid glands. METHODS: Report of clinical and laboratory evaluation of neonatal primary hyperparathyroidism in a two-and-a-half-monthold child submitted to preoperative cervical ultrasonography and parathyroid scintigraphy with Technetium-99m-Sestamibi, and subtotal parathyroidectomy at the age of four-and-a -half months. RESULTS: The preoperative images suggested an erroneous diagnosis of parathyroid adenoma. After surgery and pos-operative histopathological exams, hyperplasia of parathyroid glands was confirmed. After two years and a half the child has normal parathyroid function. CONCLUSIONS: The cervical ultrasonography and the parathyroid scintigraphy with Technetium-99m-Sestamibi were not useful for preoperative localization of hyperplasied parathyroid glands in the neonatal primary hyperparathyroidism in this case. The subtotal parathyroidectomy has been a successful method for the maintenance of normocalcemy in the patient.

Neonatal primary hyperparathyroidism masked by vitamin D deficiency

Neonatal primary hyperparathyroidism is a life threatening disorder that is associated with severe hypercalcaemia, hypotonia, bone demineralization, fractures and respiratory distress. Treatment consists of total parathyroidectomy and without this affected infants will usually die by the age of three months. We report a patient with neonatal primary hyperparathyroidism who survived without fractures or parathyroidectomy to an age of nine months, and in whom the hypercalcaemia became masked by vitamin D deficiency. At surgery, four-gland hyperplasia was demonstrated and total parathyroidectomy followed by oral calcitriol treatment has restored well-being and normocalcaemia. An absence of skeletal complications, a survival beyond three months of age without parathyroidectomy and the masking of the hypercalcaemia by vitamin D deficiency represents a unique combination of metabolic abnormalities in a patient with neonatal primary hyperparathyroidism.

Self limiting neonatal primary hyperparathyroidism associated with familial hypocalciuric hypercalcaemia.

A boy is described who presented aged 7 weeks with severe biochemical and radiological neonatal hyperparathyroidism that had completely resolved by the age of 6 months. His mother had a normal serum calcium concentration but his father, paternal aunt, and paternal cousin all had a raised serum calcium due to familial hypocalciuric hypercalcaemia.

Neonatal primary hyperparathyroidism—a case report and review of the literature : J.W. Blair and R. Carachi. Eur J Pediatr Surg 1:110–114, (April), 1991

Neonatal primary hyperparathyroidism—a case report and review of the literature : J.W. Blair and R. Carachi. Eur J Pediatr Surg 1:110–114, (April), 1991

Neonatal Primary Hyperparathyroidism - A Case Report and Review of the Literature

Primary Hyperparathyroidism in the neonate is exceptionally rare and is almost invariably fatal unless a prompt diagnosis is made and urgent surgical intervention instituted. The first case was reported in 1947 by Prat et al (30) and since then 35 cases have been published. The true number is probably greater due to the diagnosis being missed both clinically and at autopsy and it has been suggested as a possible contributor to a small number of cases of the Sudden Infant Death Syndrome (17). The authors report on a case presenting in a female neonate, review the world literature and discuss the clinical manifestations, investigators findings and the management options available.

Familial Benign (Hypocalciuric) Hypercalcemia: A Troublesome Mimic of Mild Primary Hyperparathyroidism

Familial benign hypercalcemia, or hypocalciuric hypercalcemia, may be defined as a dominantly inherited disorder of calcium and magnesium metabolism, characterized by lifelong hypercalcemia and hypermagnesemia (both of variable degree), that usually is not associated with any symptoms, physical signs, reduced vitality, or ill health. Chondrocalcinosis, pancreatitis, gallstones, and neonatal primary hyperparathyroidism are possible rare associations, but findings differ among various studies. The biochemical findings are bland, with "normal" values for serum PTH by many techniques, modest hypophosphatemia, and other findings usually normal. A low calcium:creatinine clearance ratio is suggestive of, but not diagnostic for, FBH; urinary calcium excretion less than 100 mg per day may be just as helpful. The diagnosis should not be made casually or without family screening, because the findings in a given patient may be identical to those in mild primary hyperparathyroidism. The major rationale for careful evaluation is to diagnose the syndrome of FBH and to help affected family members avoid needless expense and the risk of further evaluation and treatment.

Neonatal Primary Hyperparathyroidism: Total Parathyroidectomy with Autotransplantation of Cryopreserved Parathyroid Tissue

Primary neonatal hyperparathyroidism is a life threatening disease because of severe hypercalcemia. The best therapy is early total parathyroidectomy which requires permanent replacement therapy. We describe the first case treated by total parathyroidectomy and late autotransplantation of cryopreserved parathyroid tissue. Twenty months after transplantation, serum calcium and phosphate levels are normal in the absence of any supplementary treatment.

Primary Hyperparathyroidism in German Shepherd Dogs: A Disorder of Probable Genetic Origin

Primary hyperparathyroidism was diagnosed in two German shepherd pups from a litter of four females. Clinical signs were apparent by two weeks of age and included stunted growth, muscular weakness, and polydipsia/polyuria. Radiography revealed diffuse reduction in bone density. Both pups had marked hypercalcemia, hypophosphatemia, increased plasma immunoreactive parathyroid hormone concentrations and increased fractional clearance of inorganic phosphate in the urine. Intravenous infusion of one affected pup with calcium gluconate failed to suppress the plasma concentration of immunoreactive parathyroid hormone, suggesting autonomous secretion of parathyroid hormone. Necropsy of the other pup at eight weeks of age revealed diffuse hyperplasia of parathyroid chief cells, nodular hyperplasia of thyroid C-cells, skeletal alterations consistent with fibrous osteodystrophy, hypercalcemic nephropathy, and extensive mineralization of the lungs and gastric mucosa. The dam and sire were half sibs. One male pup from a previous litter of six had developed similar clinical signs and radiographic lesions, suggesting autosomal recessive inheritance. This is the first report of hereditary primary hyperparathyroidism in domestic animals, a disease which may be analogous to hereditary neonatal primary hyperparathyroidism in children.

Post-parathyroidectomy restoration of normal calcium homeostasis in neonatal primary hyperparathyroidism.

Total parathyroidectomy is required to cure neonatal primary hyperparathyroidism (NPH) as any parathyroid remnant quickly becomes hyperplastic, causing recurrent hypercalcaemia. We present a patient with NPH who had total removal of his eutopic parathyroid glands but continued to have parathyroid hormone secretion from presumed ectopic parathyroid tissue. Hypercalcaemia initially recurred but normal calcium homeostasis was established as the child grew older. We postulate that the underlying defect in NPH is decreased sensitivity to the serum ionic calcium feedback inhibition at the parathyroid receptor level and that this sensitivity can improve with age.

Neonatal primary hyperparathyroidism with autosomal dominant inheritance

PRIMARY HYPERPARATHYROID ISM in infancy is a rare and sometimes life-threatening disease. Prominent features of the 15 reported cases include anorexia, hypotonia, bony demineralization, hypercalcemia, and hyperplasia of the parathyroid. 1-~ Hillman and associates 1 reported two cases in brothers and termed the disease familial primary hyperparathyroid ism. Subsequently Goldbloom and associates-' described two sisters with similar findings and suggested that the disease was inherited as an autosomal recessive trait. In the process of testing a large kindred with familial hyperparathyroidism, we encountered a case of severe neonatal hyperparathyroidism with features similar to those of the 15 previously reported cases. This case indicates clearly that the disease may be inherited in autosomal dominant fashion.