Cellular Proliferation and Secretion in Secondary Hyperparathyroidism during Renal Failure

Abstract

Secondary hyperparathyroidism is one of the severe complications of chronic renal failure. In this study, we investigated the cellular components of parathyroid tissue, with measurements of various serum parathyroid hormone (PTH) types in the circulation, and evaluated their clinical significance in hemodialysis patients. Thirty-eight patients who underwent both subtotal parathyroidectomy and autotransplantation in Tokai University Hospital from 1979 to 1994 were divided into two groups. Group 1 (G-1) was not administered active-type vitamin D₃ (VD; 19 patients; 15 males and 4 females), and group 2 (G-2) was administered VD (19 patients; 10 males and 9 females). The parathyroid tissues which were obtained from G-1 and G-2 patients were classified into three classes based on the size of the oxyphilic cell area (class I < 25%, class II25-50% and class III > 50%). Our results showed that the proliferation index of parathyroid tissues in the oxyphilic cell area was higher in G-2 than that in G-1. Immunohistochemically, MIB-1 staining was more intense than that in the chief cell area in G-2 patients. Moreover, the proliferative index in the same specimen was also higher in the oxyphilic cell area than in the chief cell area. It was suggested that the oxyphilic cells proliferated independently. Furthermore, synthesis of PTH in the oxyphilic cell area was revealed immunohistochemically by the presence of PTH and was confirmed by positive staining of PTH mRNA in the oxyphilic cell area with in situ hybridization. HS(M-terminal)- and C-PTH levels in the serum were significantly higher in class III than in class I (p < 0.01). No significant difference of HS- and C-PTH levels between class II and class III was noted. Moreover, no significant difference of intact-PTH levels was found in all three classes. From the above findings, it was suggested that proliferation of the parathyroid tissues or secretory state of PTH in hemodialysis-maintained patients with secondary hyperparathyroidism, which was closely related to the proliferation of oxyphilic cells, can be more accurately reflected by HS- and C-PTH levels than by the intact-PTH level. Therefore, it was suggested that HS- and C-PTH levels in the serum are important indices for accurate evaluation of the pathology and suitable therapy of secondary hyperparathyroidism, as well as observation of the clinical course.

Frequency of Ectopic and Supernumerary Intrathymic Parathyroid Glands in Patients with Renal Hyperparathyroidism: Analysis of 461 Patients Undergoing Initial Parathyroidectomy with Bilateral Cervical Thymectomy

“…Renal hyperparathyroidism (rHPT) is defined as inappropriate and uncontrolled hypersecretion of parathyroid hormone (PTH) in response to vitamin D deficiency, hypocalcemia, and hyperphosphatemia [1][2][3]. Associated hypertrophy and hyperplasia usually affect all parathyroid glands [4,5].…”

Supernumerary Parathyroid Glands: Frequency and Surgical Significance in Treatment of Renal Hyperparathyroidism

“…In patients with chronic renal failure, parathyroid cells are stimulated by vitamin D deficiency, hyperphosphatemia, and decreased serum calcium levels [1]. With time, progressive alteration of the parathyroid cell calcium and vitamin D receptors leads to inappropriate and uncontrolled hypersecretion of parathyroid hormone, causing renal hyperparathyroidism (HPT) [2,3]. When surgical excision of hyperplastic parathyroid tissue becomes necessary, correct identification of all parathyroid tissue is mandatory prior to determining the optimal surgical strategy [4].…”

Cell Biology of Parathyroid Gland Hyperplasia in Chronic Renal Failure

“…However, detailed morphologic examination including electron microscopy frequently showed heterogeneous aspects of cellular and nuclear size and mitotic features not seen in purely hyperplastic tissue, in glands re-moved from the neck as well as in parathyroid tissue fragments removed from the forearm following parathyroid autotransplantation (72). Two groups observed an enrichment in oxyphilic cells in nodular areas with higher proliferative activity than in diffusely hyperplastic areas (73,74).…”