Clinical and Molecular Genetics of Primary Hyperparathyroidism

2020 ◽  
Vol 52 (08) ◽  
pp. 578-587
Author(s):  
William F. Simonds
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Tumor Suppressor Genes ◽  
Calcium Concentration ◽  
Systemic Circulation ◽  
Parathyroid Glands ◽  
Serum Calcium Concentration ◽  
Parathyroid Neoplasia ◽  
Excessive Secretion ◽  
Tumor Dna

AbstractCalcium homeostasis is maintained by the actions of the parathyroid glands, which release parathyroid hormone into the systemic circulation as necessary to maintain the serum calcium concentration within a tight physiologic range. Excessive secretion of parathyroid hormone from one or more neoplastic parathyroid glands, however, causes the metabolic disease primary hyperparathyroidism (HPT) typically associated with hypercalcemia. Although the majority of cases of HPT are sporadic, it can present in the context of a familial syndrome. Mutations in the tumor suppressor genes discovered by the study of such families are now recognized to be pathogenic for many sporadic parathyroid tumors. Inherited and somatic mutations of proto-oncogenes causing parathyroid neoplasia are also known. Future investigation of somatic changes in parathyroid tumor DNA and the study of kindreds with HPT yet lacking germline mutation in the set of genes known to predispose to HPT represent two avenues likely to unmask additional novel genes relevant to parathyroid neoplasia.

scholarly journals Persistent Hypercalcemia After Parathyroidectomy in an Adolescent and Effect of Treatment With Cinacalcet HCl

2006 ◽  
Vol 52 (12) ◽  
pp. 2286-2293 ◽  
Author(s):  
Lorin M Henrich ◽  
Alan D Rogol ◽  
Pierre D’Amour ◽  
Michael A Levine ◽  
John B Hanks ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Serum Calcium ◽  
Calcium Concentration ◽  
Case Conference ◽  
Serum Calcium Concentration ◽  
Pharmacodynamic Profile ◽  
Laboratory Results ◽  
Calcium Phosphorus ◽  
Effect Of Treatment

Abstract Background: Hyperparathyroidism is uncommon in adolescence and is more likely to persist after parathyroidectomy than in adults. Cinacalcet HCl is a new calcimimetic that has been used successfully for the treatment of primary and secondary hyperparathyroidism in adults, but its use in adolescents has not been reported. Case: A 16 year-old male presented with hypercalcemia that had persisted for 1.5 years after parathyroidectomy for primary hyperparathyroidism. Parathyroid hormone (PTH) concentrations were nonsupressed despite a mean (SD) serum calcium concentration of 2.82 (0.06) mmol/L. Treatment with cinacalcet HCl was initiated and a pharmacodynamic profile was obtained for serum calcium, phosphorus, and PTH. Cinacalcet HCl normalized serum calcium. The changes in PTH were assay dependent. Issues: We use this case conference to review the evaluation of hypercalcemia in adolescents, examine the changes in relevant laboratory results during treatment with cinacalcet HCl, and discuss differences among assays for PTH. Conclusions: Interpretation of PTH results in patients treated with cinacalcet HCl requires consideration of the pharmacodynamic effects of the drug and the nature of the PTH assay.

scholarly journals Asymptomatic primary hyperparathyroidism

2006 ◽  
Vol 50 (4) ◽  
pp. 647-656 ◽  
Author(s):  
John P. Bilezikian ◽  
Mishaela Rubin ◽  
Shonni J. Silverberg
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Medical Management ◽  
Mineral Metabolism ◽  
Parathyroid Glands ◽  
Parathyroid Cancer ◽  
Diagnostic Features ◽  
Benign Adenoma ◽  
Asymptomatic Primary Hyperparathyroidism ◽  
Excessive Secretion

Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. In adults with the disease, a single, benign adenoma is seen approximately 80 percent of the time, with multiple gland involvement comprising most of the remaining patients. Very rarely, a parathyroid cancer is responsible but it is seen in less than 0.5 percent of patients with primary hyperparathyroidism. In this article, we will review important clinical and diagnostic features of asymptomatic primary hyperparathyroidism as well as considerations for surgical or medical management of the disease.

scholarly journals Advances in the diagnosis and the management of primary hyperparathyroidism

2021 ◽  
Vol 12 ◽  
pp. 204062232110159
Author(s):  
Ana Kashfia Islam
Keyword(s):  
Renal Function ◽  
Parathyroid Hormone ◽  
Bone Loss ◽  
Primary Hyperparathyroidism ◽  
Kidney Stones ◽  
Parathyroid Glands ◽  
Definitive Treatment ◽  
Indications For Surgery ◽  
Musculoskeletal Complaints ◽  
Parathyroid Cancer

The parathyroid glands, one of the last organs to be discovered, are responsible for maintaining calcium homeostasis, and they continue to present the clinician with diagnostic and management challenges that are reviewed herein. Primary hyperparathyroidism (PHPT) comprises the vast majority of pathology of the parathyroid glands. The classic variant, presenting with elevated calcium and parathyroid hormone levels, has been studied extensively, but the current body of literature has added to our understanding of normocalcemic and normohormonal variants of PHPT, as well as syndromic forms of PHPT. All variants can lead to bone loss, kidney stones, declining renal function, and a variety of neurocognitive, gastrointestinal, and musculoskeletal complaints, although the majority of PHPT today is asymptomatic. Surgery remains the definitive treatment for PHPT, and advances in screening, evolving indications for surgery, new imaging modalities, and improvements in intra-operative methods have greatly changed the landscape. Surgery continues to produce excellent results in the hands of an experienced parathyroid surgeon. For those patients who are not candidates for surgery, therapeutic advances in medical management allow for improved control of the hypercalcemic state. Parathyroid cancer is extremely rare; the diagnosis is often made intra-operatively or on final pathology, and recurrence is common. The mainstay of treatment is normalization of serum calcium via surgery and medical adjuncts.

scholarly journals Normocalcemic primary hyperparathyroidism

2010 ◽  
Vol 54 (2) ◽  
pp. 106-109 ◽  
Author(s):  
John P. Bilezikian ◽  
Shonni J. Silverberg
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Serum Calcium ◽  
Kidney Stones ◽  
Bone Disease ◽  
Clinical Phenotype ◽  
Mineral Metabolism ◽  
Historical View ◽  
History Of ◽  
Excessive Secretion

Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. The historical view of this disease describes two distinct entities marked by two eras. When primary hyperparathyroidism was first discovered about 80 years ago, it was always symptomatic with kidney stones, bone disease and marked hypercalcemia. With the advent of the multichannel autoanalyzer about 40 years ago, the clinical phenotype changed to a disorder characterized by mild hypercalcemia and the absence of classical other features of the disease. We may now be entering a 3rd era in the history of this disease in which patients are being discovered with normal total and ionized serum calcium concentrations but with parathyroid hormone levels that are consistently elevated. In this article, we describe this new entity, normocalcemic primary hyperparathyroidism, a forme fruste of the disease.

scholarly journals The severe course of hyperparathyroidism in the elderly: Clinical cases

2009 ◽  
Vol 55 (1) ◽  
pp. 33-35
Author(s):  
N G Mokrysheva ◽  
S S Gulyaeva ◽  
L Ya Rozhinskaya ◽  
V N Smorshchok ◽  
M A Lysenko ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Postmenopausal Women ◽  
Endocrine System ◽  
The Elderly ◽  
Phosphorus Metabolism ◽  
Adequate Treatment ◽  
Calcium And Phosphorus ◽  
Excessive Secretion ◽  
Clinical Cases

Primary hyperparathyroidism (PHPT) is a disease of the endocrine system caused by excessive secretion of parathyroid hormone (PTH) and is characterized by a pronounced violation of calcium and phosphorus metabolism. More recently, in Russia, PHPT was detected extremely rarely and often hid under the mask of recurrent urolithiasis, generalized osteoporosis and other pathologies. As a result, patients did not receive adequate treatment, which in a certain percentage of cases led to the development of serious complications.The clinical cases of severe PHPT in postmenopausal women are presented in this article.

scholarly journals Relationship between parathyroid calcium-sensing receptor expression and potency of the calcimimetic, cinacalcet, in suppressing parathyroid hormone secretion in an in vivo murine model of primary hyperparathyroidism

2005 ◽  
Vol 153 (4) ◽  
pp. 587-594 ◽  
Author(s):  
Takehisa Kawata ◽  
Yasuo Imanishi ◽  
Keisuke Kobayashi ◽  
Takao Kenko ◽  
Michihito Wada ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Secondary Hyperparathyroidism ◽  
Murine Model ◽  
Hormone Secretion ◽  
Suppressive Effect ◽  
Receptor Expression ◽  
Parathyroid Glands ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

Cinacalcet HCl, an allosteric modulator of the calcium-sensing receptor (CaR), has recently been approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, due to its suppressive effect on parathyroid hormone (PTH) secretion. Although cinacalcet’s effects in patients with primary and secondary hyperparathyroidism have been reported, the crucial relationship between the effect of calcimimetics and CaR expression on the parathyroid glands requires better understanding. To investigate its suppressive effect on PTH secretion in primary hyperparathyroidism, in which hypercalcemia may already have stimulated considerable CaR activity, we investigated the effect of cinacalcet HCl on PTH-cyclin D1 transgenic mice (PC2 mice), a model of primary hyperparathyroidism with hypo-expression of CaR on their parathyroid glands. A single administration of 30 mg/kg body weight (BW) of cinacalcet HCl significantly suppressed serum calcium (Ca) levels 2 h after administration in 65- to 85-week-old PC2 mice with chronic biochemical hyperparathyroidism. The percentage reduction in serum PTH was significantly correlated with CaR hypo-expression in the parathyroid glands. In older PC2 mice (93–99 weeks old) with advanced hyperparathyroidism, serum Ca and PTH levels were not suppressed by 30 mg cinacalcet HCl/kg. However, serum Ca and PTH levels were significantly suppressed by 100 mg/kg of cinacalcet HCl, suggesting that higher doses of this compound could overcome severe hyperparathyroidism. To conclude, cinacalcet HCl demonstrated potency in a murine model of primary hyperparathyroidism in spite of any presumed endogenous CaR activation by hypercalcemia and hypo-expression of CaR in the parathyroid glands.

BIOASSAY OF PARATHYROID HORMONE IN RATS BY DETERMINATION OF PLASMA CALCIUM, URINARY 32P EXCRETION AND SERUM ALKALINE PHOSPHATASE

1966 ◽  
Vol 35 (3) ◽  
pp. 229-238 ◽  
Author(s):  
R. J. TREACHER
Keyword(s):  
Alkaline Phosphatase ◽  
Parathyroid Hormone ◽  
Serum Calcium ◽  
Calcium Concentration ◽  
Serum Alkaline Phosphatase ◽  
Plasma Calcium ◽  
Significant Alteration ◽  
Good Precision ◽  
Serum Calcium Concentration

SUMMARY Methods for assay of parathyroid hormone based on an increase in serum calcium concentration, urinary 32P excretion and serum alkaline phosphatase elevation in parathyroidectomized rats have been compared and modifications introduced to improve sensitivity, precision, speed and ease of manipulation. Both the serum calcium and urinary 32P assay gave good precision (mean λ = 0·23 and 0·29, respectively) but by the serum calcium method less than 10 USP units of parathyroid hormone could not be detected, whereas the phosphaturic assay detects as little as 0·5 USP unit. Both assays are simple to perform and each requires only 2 days to complete. They can be combined in a single design using the same animals. Assays based on serum alkaline phosphatase levels in parathyroidectomized rats were not successful since it was impossible to produce a significant alteration in serum alkaline phosphatase by the administration of parathyroid hormone.

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