title: Hyperparathyroidism in hereditary syndromes: special expressions and special managements.
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.
authors.affiliation: Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-1802, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Marx
authors.forename: William F
authors.initials: WF
authors.lastname: Simonds
authors.forename: Sunita K
authors.initials: SK
authors.lastname: Agarwal
authors.forename: A Lee
authors.initials: AL
authors.lastname: Burns
authors.forename: Lee S
authors.initials: LS
authors.lastname: Weinstein
authors.forename: Craig
authors.initials: C
authors.lastname: Cochran
authors.forename: Monica C
authors.initials: MC
authors.lastname: Skarulis
authors.forename: Allen M
authors.initials: AM
authors.lastname: Spiegel
authors.forename: Steven K
authors.initials: SK
authors.lastname: Libutti
authors.forename: H Richard
authors.initials: HR
authors.lastname: Alexander
authors.forename: Clara C
authors.initials: CC
authors.lastname: Chen
authors.forename: Richard
authors.initials: R
authors.lastname: Chang
authors.forename: Settara C
authors.initials: SC
authors.lastname: Chandrasekharappa
authors.forename: Francis S
authors.initials: FS
authors.lastname: Collins
mesh_terms: D002118:Calcium / Q000652:urine; D029721:Drosophila Proteins; D030342:Genetic Diseases, Inborn / Q000150:complications*; D006579:Heterozygote; D006801:Humans; D006934:Hypercalcemia / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D006961:Hyperparathyroidism / Q000209:etiology* / Q000628:therapy*; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases; D007573:Jaw Neoplasms / Q000150:complications / Q000235:genetics; D018761:Multiple Endocrine Neoplasia Type 1 / Q000150:complications / Q000235:genetics; D018813:Multiple Endocrine Neoplasia Type 2a / Q000150:complications / Q000235:genetics; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D016105:Parathyroidectomy; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D002118:Calcium