title: Persisted/recurrent hyperparathyroidism associated with development of multi-drug resistance phenotype and proliferation of parathyroid transplants.
abstract: The surgical treatment of secondary hyperparathyroidism (HPTH) requires sub-total excision of parathyroid glands or total excision with their autotransplantation. Although this approach has been considered as a safe method of treatment, in this report we describe persisted/recurrent HPTH after parathyroid transplantation. Due to parathormone (PTH) hypersecretion and uncontrolled proliferation, the parathyroid grafts were removed and used for generation of cell cultures, which further have been subjected to in vitro studies. As a control we used parathyroid tissue, obtained during multiorgan harvesting. We found increased proliferation and up-regulated PTH production by the graft-derived, but not control in vitro cultured cells. Moreover, due to decrease of in vivo radiotracer uptake by parathyroid grafts, the expression of multi-drug resistance-involved factors, including P-glycoprotein (P-gp/mdr1), multi-drug resistance-associated protein (mrp) and bcl-2 have been investigated using RT-PCR. The analysis revealed increased expression of both, mdr1 and mrp in graft-derived cells, in contrast to control cells, which did not express P-gp/mdr1 or mrp. However, we did not observe any difference in expression of bcl-2 between analyzed cells. The up-regulated expression of P-gp/mdr1 on graft-derived cells was further confirmed by immunofluorescence studies. The described case indicates potential risk associated with transplantation of parathyroid tissue. Our results confirm a role of MDR phenomenon in occurrence of false negative results in parathyroid tissue scintigraphy studies. Moreover, they indicate that standard histological examination of transplanted material could not be sensitive enough to exclude any potential danger of abnormal graft progression. Thus, they could support the concept to use encapsulated parathyroid transplants.
authors.affiliation: Department of Histology and Embryology, Warsaw Medical University, 5 Chalubinskiego Str., PL 02 004 Warsaw, Poland. tgrzela@ib.amwaw.edu.pl
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grzela
authors.forename: Witold
authors.initials: W
authors.lastname: Chudzinski
authors.forename: Maciej
authors.initials: M
authors.lastname: Lazarczyk
authors.forename: Justyna
authors.initials: J
authors.lastname: Niderla
authors.forename: Piotr
authors.initials: P
authors.lastname: Dziunycz
authors.forename: Lukasz
authors.initials: L
authors.lastname: Milewski
authors.forename: Robert
authors.initials: R
authors.lastname: Samaha
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kobylecka
authors.forename: Joanna
authors.initials: J
authors.lastname: Miskiewicz
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Bogacka-Zatorska
authors.forename: Barbara
authors.initials: B
authors.lastname: Gornicka
authors.forename: Pawel
authors.initials: P
authors.lastname: Swiercz
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jelenska
authors.forename: Leszek
authors.initials: L
authors.lastname: Krolicki
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D018432:Drug Resistance, Multiple; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D010280:Parathyroid Glands / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation*; D010281:Parathyroid Hormone / Q000096:biosynthesis / Q000378:metabolism; D010641:Phenotype; D012008:Recurrence
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010281:Parathyroid Hormone