Abstract
Basal parathyroid hormone (PTH) levels measured by a chemiluminescent immunoassay for intact PTH showed good discrimination between normal, n=82 (1.2–9.4 pmol/l), and hyperparathyroid subjects, n=55 (9–200 pmol/l). In malignant hypercalcemia, all PTH levels were within the normal range or suppressed (0.8–5.2 pmol/l). Dynamic studies of PTH release in response to intramuscular salmon calcitonin (100 u) showed no significant rise out of the normal range in controls, but adenoma patients demonstrated a mean rise at 120, 180, and 240 minutes of 22%, 22%, and 35%, respectively, and hyperplasia patients a mean rise of 44%, 63%, and 46%, respectively. The mean absolute rise in PTH concentration was 10.6±7.2 pmol/g parathyroid adenoma and 26.6±19.2 pmol/g hyperplastic parathyroid tissue; this difference being significant (p <0.01). In vitro studies were performed in which dispersed cells prepared from both parathyroid adenomas and hyperplastic tissue were exposed to low (0.5 mM) and high (2.5 mM) extracellular calcium. Intact PTH secretion was measured under these conditions and compared with the results obtained by a mid-region (44–68) specific immunoassay for PTH. There was parallel secretion of intact and mid-region hormone under all conditions, the secretion rate of hyperplastic cells being greater than that of adenomas. Suppressibility of PTH release by high extracellular calcium was significantly greater in hyperplasia than in adenomas. These differences in the behavior of adenomatous and hyperplastic tissues both in vivo, in response to calcitonin, and in vitro, in response to changes in extracellular calcium concentration, suggest that the underlying pathogenesis of hyperparathyroidism may be heterogenous at the cellular level.
Résumé
Mesurés par la méthode de chimioluminescence, les taux de parathormone (PTH) intacte se sont montrés discriminants entre les sujets normaux (n=82; 1.2–9.4 pmol/l) et les sujets hyperparathyroïdiens (n=55; 9–200 pmol/l). Dans l'hypercalcémie maligne, les taux de parathormone étaient tous dans la limite de la normale ou supprimés (0.8–5.2 pmol/l). A l'etude dynamique en réponse à l'injection intramusculaire de calcitonine de saumon (100 u), les concentrations en PTH n' ont pas augmenté au-delà des limites normales chez les témoins, alors qu'elles se sont élevées chez les sujets porteurs d'adénome par 22%, 22%, et 35% et chez les sujets porteurs d'hyperplasie parathyroïdienne par 44%, 63%, et 46% à 120, 180, et 240 mn, respectivement. L'elévation moyenne de la concentration en PTH était de 10.6±7.2 pmol/g poids d'adénome et de 26.6±19.2 pmol/g tissus hyperplasiques: cette différence était significative àp < 0.01. Les cellules dispersées préparées à partir d'adénome et d'hyperplasie ont été exposés in vitro au calcium extracellulaire à des concentrations basse (0.5 mM) ou haute (2.5 mM). On a comparé les résultats des dosages de PTH intacte avec l'immunodosage spécifique de la région moyenne (44–68). La sécrétion de PTH intacte et de la région moyenne était parallèle dans ces conditions, le taux de sécrétion dans l'hyperplasie étant plus important que pour les adénomes. La sécrétion de PTH était supprimée davantage par le calcium extracellulaire en cas de cellules hyperplasiques par rapport aux cellules d'adénomes. Ces différences de comportement des tissus adénomateux et hyperplasiques in vivo en réponse de calcitonine et in vitro, en réponse aux changements de concentration en calcium extracellulaire, suggèrent que la pathogenèse d'hyperparathyroïdie est peut-être différente selon l'anomalie cellulaire, hyperplasie ou adénome.
Resumen
Los niveles basales de hormona paratiroidea (PTH) medidos por inmunoanálisis quimioluminiscente de la PTH mostró una buena discriminacíon entre el individuo normal, n = 82 (1.2–9.4 pmol/l) y el paciente hiperparatiroideo, n=55 (9–200 pmol/l). En la hipercalcemia maligna, todos los niveles de PTH aparecieron dentro del rango normal o en niveles de supresión (0.8–5.2 pmol/l). Los estudios dinámicos de secreción de PTH en respuesta a la calcitonina de salmón administrada por vía intramuscular (100 u) no mostró un ascenso significativo sobre el valor normal en los controles, pero los pacientes con adenoma demostraron un aumento promedio de 22%, 22%, y 35% a los 120, 180, y 240 minutes, y los pacientes con hiperplasia de 44%, 63%, y 46%, respectivamente. El aumento promedio absoluto en la concentración de PTH fue de 10.6±7.2 pmol/g adenoma paratiroideo y de 26.6±19.2 pmol/g tejido paratiroideo hiperplásico; esta diferencia es estadísticamente significativa (p < 0.01). Se realizaron estudios in vitro con células dispersas preparadas a partir de adenoma y de tejido hiperplásico expuestas a bajas (0.5 mM) y altas (2.5 mM) concentraciones de calcio extracelular. La secreción de PTH intacta fue medida bajo estas condiciones y comparada con los resultados obtenidos mediante inmunoanálisis específico para la regíon media (44–68) de la molécula de PTH. Se encontró una secreción paralela de la hormona intacta y de la región media bajo todas las condiciones, con una demonstrada secreción mayor de las células hiperplásicas que la de los adenomas. La supresión de la secreción de PTH por la alta concentración de calcio extracelular fue significativamente mayor en la hiperplasia que en los adenomas. Estas diferencias en el comportamiento de los tejidos adenomatosos e hiperplásicos tanto in vivo en respuesta a la calcitonina como in vitro en respuesta a los cambios en la concentración de calcio extracelular sugieren que la patogénesis del hiperparatiroidismo puede ser de carácter heterogéneo en el nivel celular.
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Aston, J.P., Wheeler, M.H., Brown, R.C. et al. Studies on in vivo and in vitro release of intact parathyroid hormone using a new two-site immunochemiluminometric assay. World J. Surg. 12, 454–461 (1988). https://doi.org/10.1007/BF01655419
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DOI: https://doi.org/10.1007/BF01655419