Abstract

85% of sporadic hyperparathyroidism cases have a solitary adenoma. The remainder of cases have multiple tumors. About 95% of all cases achieve a long remission at initial operation. Adverse outcomes are increased in multigland disease. The cause of parathyroid adenoma is believed to be mutation of some gene, with overgrowth of a clone. Mutation of the cyclin D1 (PRAD1) accounts for only 3-4%. Sporadic (nonhereditary) mutation of the MEN1 gene is the most common known mutation, causing 25-30% of adenomas. Of the 15% with multigland disease, 5% (1/3 of 15%) have a familial form. Most have MEN1 or familial hypocalciuric hypercalcemia. About 1% have familial isolated hyperparathyroidism (FIH). When 40 nonsyndromal kindreds with FIH were tested for occult syndromal mutations, there were no MEN1 mutations but about 10% had CASR mutation or HRPT2 mutation. The underlying gene(s)for the remaining majority of FIH are not known, but mutation of a gene on chromosome 2 seems likely, from linkage analysis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK043006-32
Application #
7734118
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
32
Fiscal Year
2008
Total Cost
$473,014
Indirect Cost

  Institution

Name
National Institute of Diabetes and Digestive and Kidney Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Eastell, R; Arnold, A; Brandi, M L et al. (2009) Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab 94:340-50
Ozawa, Atsushi; Agarwal, Sunita K; Mateo, Carmen M et al. (2007) The parathyroid/pituitary variant of multiple endocrine neoplasia type 1 usually has causes other than p27Kip1 mutations. J Clin Endocrinol Metab 92:1948-51
Marx, Stephen J; Simonds, William F (2006) Editorial: Imaging to detect early endocrine cancers. J Clin Endocrinol Metab 91:2861-3
Marx, Stephen J (2005) Molecular genetics of multiple endocrine neoplasia types 1 and 2. Nat Rev Cancer 5:367-75
Marx, Stephen J; Simonds, William F (2005) Hereditary hormone excess: genes, molecular pathways, and syndromes. Endocr Rev 26:615-61
Agarwal, S K; Kennedy, P A; Scacheri, P C et al. (2005) Menin molecular interactions: insights into normal functions and tumorigenesis. Horm Metab Res 37:369-74
Scacheri, Peter C; Crabtree, Judy S; Kennedy, Alyssa L et al. (2004) Homozygous loss of menin is well tolerated in liver, a tissue not affected in MEN1. Mamm Genome 15:872-7
Hao, Wei; Skarulis, Monica C; Simonds, William F et al. (2004) Multiple endocrine neoplasia type 1 variant with frequent prolactinoma and rare gastrinoma. J Clin Endocrinol Metab 89:3776-84
Simonds, William F; Robbins, Christiane M; Agarwal, Sunita K et al. (2004) Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome. J Clin Endocrinol Metab 89:96-102
Crabtree, Judy S; Scacheri, Peter C; Ward, Jerrold M et al. (2003) Of mice and MEN1: Insulinomas in a conditional mouse knockout. Mol Cell Biol 23:6075-85

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