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Secretory disturbance in hyperplastic parathyroid nodules of uremic hyperparathyroidism: Implication for parathyroid autotransplantation

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Abstract

Pathophysiological characteristics of dispersed parathyroid cells were investigated in vitro with the principal aim of examining dominating hyperplastic parathyroid nodules in uremia. Ten large nodules were macroscopically dissected from the glands of 8 hypercalcemic patients with uremic hyperparathyroidism (HPT). Histologic examination revealed that the remaining parts of these glands were composed of a diffuse or slightly nodular parathyroid hyperplasia. Parathyroid hormone (PTH) concentrations were estimated with a mid-C regional immunoassay and the calcium indicator quin-2 was utilized to measure cytoplasmic calcium concentrations (Ca2+ i) of the parathyroid cells. Ambient calcium control of PTH release and Ca2+ i was significantly more abnormal in cells from the nodules while the less nodular tissue demonstrated a regulation similar to normal bovine parathyroid cells. Since an aberrant secretory regulation of the parathyroid tissue has been shown to greatly influence serum calcium concentrations in HPT, the findings substantiate a functional importance of hyperplastic parathyroid nodules in uremia. The results imply that parathyroid autotransplants should be excised from essentially nonnodular parts of the parathyroid glands since this may reduce the incidence of graft-dependent recurrences after total parathyroidectomy in uremic HPT.

Résumé

Les caractéristiques physiopathologiques des cellules parathyroïdiennes dispersées ont été évaluées in vitro dans le but d'examiner les nodules d'hyperplasie parathyroïdiens de l'hyperazotémie. Dix nodules de volume important ont été disséqués des parathyroïdes chez 8 patients présentant une hyperparathyroïdie urémique (HPT). L'examen histologique a révélé que les portions restantes étaient composées d'hyperplasie parathyroïdienne peu nodulaire ou diffuse. Les concentrations en parathormones (PTH) ont été déterminées par la méthode immunologique C régional moyen; la concentration cytoplasmique en calcium (Ca2+ i) (ionisé) a été mesurée par l'indicateur quin-2. Le contrôle de liberation de PTH par le calcium ambiant Ca2+ i) étaient significativement perturbé dans les cellules provenant des nodules comparés à ceux des tissus peu nodulaires proches de ceux des cellules parathyroïdiennes bovines normales. Puisqu'on a démontré que la régulation sécrétrice aberrante des tissus parathyroïdiens influençait les concentrations en calcium dans HPT, ces données confirment l'importance fonctionnelle des nodules d'hyperplasie dans l'hypeazotémie. Ces résultats impliquent qu'on doit exciser et n'utiliser que les tissus non nodulaires comme implant parathyroïdien, réduisant peut-être ainsi la fréquence de récidives dépendantes du greffon après parathyroïdectomie totale pour HPT urémique.

Resumen

Las características patofisiológicas de células paratiroideas dispersas (preparadas mediante digestión con colagenasa) fueron investigadas in vitro con el propósito principal de analizar los nódulos hiperplásicos paratiroideos dominantes que se observan en la uremia. Diez nódulos grandes fueron disecados macroscópicamente de las glándulas de 8 pacientes hipercalcémicos con hiperparatiroidismo urémico (HPT). El examen histológico reveló que los remanentes de estas glándulas estaban compuestos por una hiperplasia paratiroidea difusa o ligeramente nodular. Las concentraciones de hormona paratiroidea (PTH) fueron determinadas por inmunoanálisis de la región media C de la molécula y se utilizó el indicador de calcio quin-2 para medir las concentraciones citoplásmicas de calcio (Ca2+ i) de las células paratiroideas. El control de la secreción de PTH por el calcio ambiental y el Ca2+ i aparecieron significativamente más anormales en las células de los nódulos, en tan to que el tejido menos nodular demostró una regulación similar a la de las células paratiroideas bovinas normales. Puesto que ha sido demostrado que una regulación secretoria aberrante del tejido paratiroideo influye grandemente sobre las concentraciones séricas de calcio en el HPT, esto hallazgos verifican la importancia funcional de los nódulos hiperplásicos en la uremia. Los resultados implican que los autotrasplantes paratiroideos deben ser tmnados de las porciones esencialmente no nodulares de las glándulas paratiroides ya que ello puede disminuir la incidencia de recurrencias a partir del trasplante después de paratiroidectomía total en el HPT urémico.

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Authors and Affiliations

  1. Departments of Surgery, Medical Cell Biology, and Internal Medicine, University of Uppsala, Uppsala, Sweden

    Chris H. Wallfelt M.D., Rolf Larsson Ph.D., Erik Gylfe Ph.D., Sverker Ljunghall M.D., Jonas Rastad M.D., Ph.D. & Göran Åkerström M.D.

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  1. Chris H. Wallfelt M.D.
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  2. Rolf Larsson Ph.D.
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  3. Erik Gylfe Ph.D.
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  4. Sverker Ljunghall M.D.
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  5. Jonas Rastad M.D., Ph.D.
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  6. Göran Åkerström M.D.
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Supported by the Swedish Medical Research Council, and Förenade Liv Mutual Group Life Insurance Company, Sweden.

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Wallfelt, C.H., Larsson, R., Gylfe, E. et al. Secretory disturbance in hyperplastic parathyroid nodules of uremic hyperparathyroidism: Implication for parathyroid autotransplantation. World J. Surg. 12, 431–436 (1988). https://doi.org/10.1007/BF01655411

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