title: Progression of uremic hyperparathyroidism involves allelic loss on chromosome 11.
abstract: In occasional cases of secondary hyperparathyroidism, long term stimulation of the parathyroid glands leads from compensatory to autonomous hyperfunction, and thus, hypercalcemia develops. This clinical entity, named tertiary hyperparathyroidism, is possibly due to the formation of an adenoma in one of the hyperplastic glands. Previous studies have shown that parathyroid adenomas may arise with allelic loss on chromosome 11. We tested for allelic loss at several loci on chromosome 11 in 12 enlarged parathyroid glands from 6 uremic patients and found loss of heterozygosity in 2 of the glands from 2 different patients with higher serum calcium levels (11.3 +/- 0.29 vs. 9.8 +/- 0.28 mg/dL; P < 0.004) and, therefore, ascribable to the so-called tertiary hyperparathyroidism. The 2 glands with allelic loss were significantly greater in mass than those without loss (3.42 +/- 0.37 vs. 1.60 +/- 0.54 g; P < 0.001). These data offer new evidence that autonomous parathyroid proliferation in uremic patients can develop through overgrowth by a monoclonal tumor, presumably with inactivation of a tumor suppressor gene(s) on chromosome 11.
authors.affiliation: Department of Clinical Physiopathology, University of Florence, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Falchetti
authors.forename: A E
authors.initials: AE
authors.lastname: Bale
authors.forename: A
authors.initials: A
authors.lastname: Amorosi
authors.forename: C
authors.initials: C
authors.lastname: Bordi
authors.forename: P
authors.initials: P
authors.lastname: Cicchi
authors.forename: S
authors.initials: S
authors.lastname: Bandini
authors.forename: S J
authors.initials: SJ
authors.lastname: Marx
authors.forename: M L
authors.initials: ML
authors.lastname: Brandi
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000483:Alleles; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002881:Chromosomes, Human, Pair 12; D005260:Female; D017353:Gene Deletion; D006801:Humans; D006961:Hyperparathyroidism / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006965:Hyperplasia; D008875:Middle Aged; D010280:Parathyroid Glands / Q000473:pathology*; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D006435:Renal Dialysis; D014511:Uremia / Q000150:complications* / Q000473:pathology / Q000628:therapy