Prediction of in vivo function of human parathyroid tissue autografts by in vitro testing

Abstract

In an effort to overcome problems of hypoparathyroidism in patients undergoing reoperation for persistent hyperparathyroidism, a systematic plan has been evolved. All patients who have reoperation and in whom abnormal tissue has been identified have had that tissue removed and portions of it cryopreserved. Following successful reoperation those patients who have prolonged hypoparathyroidism, who cannot be maintained off of vitamin D and calcium, undergo autografting with cryopreserved tissue. Prior to autografting, the parathyroid tissue has been thawed and assessed for the appropriateness of parathyroid hormone suppressibility in response to varying levels of ambient calcium concentration. This report documents that this in vitro test of suppressibility correctly predicts in vivo parathyroid autograft function of both fresh and cryopreserved parathyroid autografts.

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

“…As pointed out previously, it seems favorable to implant tissue with minimal functional disturbances [16][17][18] and graft-dependent recurrence has been observed after insertion of adenomatous tissue with a PTH release insensitive to increments in extracellular calcium [17,18]. This observation has prompted the suggestion that secretion should be routinely assayed in vitro and that autografting should be abolished unless PTH release was found suppressible to calcium [17]. Assessment of parathyroid gland morphology would be another method for discrimination between normal and abnormal tissue [16], but even with certain refinements such as estimation of weight, and intracellular fat of the parathyroid parenchymal cells [7,30], it has been difficult to extrapolate function from such measures.…”

“…The demonstration of variable degrees of secretory disturbance in different parts of the enlarged parathyroid glands suggests a novel possibility for tissue selection in parathyroid autografting in uremic HPT. As pointed out previously, it seems favorable to implant tissue with minimal functional disturbances [16][17][18] and graft-dependent recurrence has been observed after insertion of adenomatous tissue with a PTH release insensitive to increments in extracellular calcium [17,18]. This observation has prompted the suggestion that secretion should be routinely assayed in vitro and that autografting should be abolished unless PTH release was found suppressible to calcium [17].…”

“…Radical parathyroid surgery is advocated in uremic HPT, entailing a subtotal parathyroidectomy or a total parathyroidectomy combined with autotransplantation of fresh or cryopreserved parathyroid tissue [14][15][16]. Recurrent HPT has been reported due to hyperfunction of the grafted tissue [16] and this has been associated with presence of a secretory disturbance within the tissue already at the time of its insertion [17,18]. We have examined the pathophYsiological characteristics of parathyroid glands in uremic patients with hypercalcemic HPT with emphasis on the regulation of PTH release and Ca2+i within large hyperplastic parathyroid nodules, since this may provide a novel basis for tissue selection in the autografting of these patients.…”

Parathyreoidektomie und Autotransplantation beim renalen Hyperparathyreoidismus

“…Nach den Kriterien von Brennan und Brown [2] sind nur jene Driisen optimal zur Autotransplantation geeignet, deren PTH-Sekretion im normocalci/imischen Bereich (1,0-1,/ mmol Ca + ÷) auf zumindest 50% der maximalen PTH-Sekretion supprimierbar ist. Diese Eigenschaften erfiillen am ehesten Fragmente von Typ/a-Driisen oder Typ l a-fihnliche Areale der Typ 2-Drfisen.…”

Invited commentary

“…By definition [3], glands are suitable for grafting only if their PTH secretion can be inhibited by more than 50%, with half of maximum inhibition occurring at calcium concentrations of 1.0-1.1 raM. These very important basic findings [2,3] are vital to all surgeons performing total parathyroidectomy and immediate autotransplantation in uremic patients. A special gland or parts of a gland must be selected for grafting in order to reduce the incidence of graft-dependent recurrence [4,5].…”