Hyperparathyroidism in hereditary syndromes

Special expressions and special managements

Stephen J. Marx, William F. Simonds, Sunita K. Agarwal, A. Lee Burns, Lee S. Weinstein, Craig Cochran, Monica C. Skarulis, Allen M. Spiegel, Steven K. Libutti, H. Richard Alexander, Clara C. Chen, Richard Chang, Settara C. Chandrasekharappa, Francis S. Collins

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

Hyperparathyroidism (HPT) in its hereditary variants assumes special forms, has special associations, and requires special managements. Familial hypocalciuric hypercalcemia (FHH or FBHH) and neonatal severe primary hyperparathyroidism (NSHPT) reflect heterozygous or homozygous mutations, respectively, in the calcium-sensing receptor. FHH and NSHPT represent the mildest and severest variants of HPT. Both cause hypercalcemia from birth and atypical HPT that always and uniquely persists after subtotal parathyroidectomy. Their HPT is likely polyclonal and nonneoplastic. In contrast, mono- or oligo-clonal parathyroid neoplasia underlays most other HPT variants: multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and hyperparathyroidism-jaw tumor syndrome (HPT-JT). Familial-isolated HPT combines several diagnoses, including occult forms of the above syndromes. Each neoplastic variant has tumors in multiple parathyroids and a delayed, but still early age of onset for HPT (average age, 25-35 years). Each justifies special and similar approaches to parathyroidectomy: typically, identification of four glands, subtotal parathyroidectomy, rapid intraoperative parathyroid hormone (PTH) assays, and parathyroid cryopreservation. Outcomes of parathyroidectomy remain suboptimal in each. Each syndrome of parathyroid neoplasia associates with characteristic cancer(s): enteropancreatic neuroendocrine or foregut carcinoid tissues (MEN1), thyroidal C cells (MEN2A), or parathyroid (HPT-JT). HPT has promoted gene discovery more through its rare hereditary variants than through common adenoma; the main genes causing four of six hereditary variants are known. The RET mutation test became essential in management of MEN2A. The MEN1 test is less urgent, because it rarely guides a major patient benefit. The CASR test, perhaps least urgent, has largely been unavailable. Further progress in molecular genetics will enhance understandings, diagnosis, and therapy of HPT.

Original languageEnglish (US)
JournalJournal of Bone and Mineral Research
Volume17
Issue numberSUPPL. 2
StatePublished - Nov 1 2002
Externally publishedYes

Fingerprint

Hyperparathyroidism
Parathyroidectomy
Multiple Endocrine Neoplasia Type 2a
Multiple Endocrine Neoplasia Type 1
Neoplasms
Calcium-Sensing Receptors
Mutation
Cryopreservation
Carcinoid Tumor
Hypercalcemia
Genetic Association Studies
Parathyroid Hormone
Age of Onset
Adenoma
Molecular Biology
Parturition

Keywords

  • Calcium-sensing receptor
  • FHH
  • HRPT2
  • MEN1
  • MEN2
  • Oncogene
  • RET

ASJC Scopus subject areas

  • Surgery

Cite this

Marx, S. J., Simonds, W. F., Agarwal, S. K., Burns, A. L., Weinstein, L. S., Cochran, C., ... Collins, F. S. (2002). Hyperparathyroidism in hereditary syndromes: Special expressions and special managements. Journal of Bone and Mineral Research, 17(SUPPL. 2).

Hyperparathyroidism in hereditary syndromes : Special expressions and special managements. / Marx, Stephen J.; Simonds, William F.; Agarwal, Sunita K.; Burns, A. Lee; Weinstein, Lee S.; Cochran, Craig; Skarulis, Monica C.; Spiegel, Allen M.; Libutti, Steven K.; Alexander, H. Richard; Chen, Clara C.; Chang, Richard; Chandrasekharappa, Settara C.; Collins, Francis S.

In: Journal of Bone and Mineral Research, Vol. 17, No. SUPPL. 2, 01.11.2002.

Research output: Contribution to journalArticle

Marx, SJ, Simonds, WF, Agarwal, SK, Burns, AL, Weinstein, LS, Cochran, C, Skarulis, MC, Spiegel, AM, Libutti, SK, Alexander, HR, Chen, CC, Chang, R, Chandrasekharappa, SC & Collins, FS 2002, 'Hyperparathyroidism in hereditary syndromes: Special expressions and special managements', Journal of Bone and Mineral Research, vol. 17, no. SUPPL. 2.
Marx SJ, Simonds WF, Agarwal SK, Burns AL, Weinstein LS, Cochran C et al. Hyperparathyroidism in hereditary syndromes: Special expressions and special managements. Journal of Bone and Mineral Research. 2002 Nov 1;17(SUPPL. 2).
Marx, Stephen J. ; Simonds, William F. ; Agarwal, Sunita K. ; Burns, A. Lee ; Weinstein, Lee S. ; Cochran, Craig ; Skarulis, Monica C. ; Spiegel, Allen M. ; Libutti, Steven K. ; Alexander, H. Richard ; Chen, Clara C. ; Chang, Richard ; Chandrasekharappa, Settara C. ; Collins, Francis S. / Hyperparathyroidism in hereditary syndromes : Special expressions and special managements. In: Journal of Bone and Mineral Research. 2002 ; Vol. 17, No. SUPPL. 2.
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