Calcitriol pulse therapy and histology of parathyroid glands in hemodialysis patients

Abstract

Background: Calcitriol pulse therapy (CPT) is considered the most appropriate treatment of secondary hyperparathyroidism (sHPTH). This treatment inhibits parathyroid hormone (PTH) synthesis and secretion, suppresses parathyroid cell proliferation and controls parathyroid gland growth. However, not much is known about the effect of such therapy on parathyroid morphology.

Methods: To investigate this, we studied all first parathyroidectomies (PTx, either total or subtotal) effected in 30 hemodialysis (HD) patients referred to our surgery department by five regional dialysis units in 2000-2001. Six patients were excluded from the study because of either the persistence or the precocious relapse (in the 1st 6 months post-operation) of sHPTH. Twenty-four HD patients were considered eligible as four parathyroid glands were ablated in each patient; 96 glands were then examined histologically. The cohort consisted of 16 males and 8 females with a mean age of 54 +/- 13 SD yrs (range 20-73) and a dialysis duration of 142 +/- 71 months (range 14-289). Data concerning calcitriol treatment (doses, administration route and treatment duration) were collected for each patient. The patients were subdivided into two groups according to the treatment effected in the months preceding PTx: group A (n=13), treated by either intravenous (i.v.) (n=12) or per os (n=1) CPT, and group B (n=11), not treated at all with calcitriol or vitamin D sterols. Parathyroid gland morphology and the parenchymal cell distribution of the parathyroid glands were evaluated by a semiquantitative assessment. Serum intact PTH (iPTH), alkaline phosphatase (AP), calcium (Ca) and phosphate (P) levels were studied pre- and post-PTx.

Results: Chief cells (CC) were found in all glands, either alone or associated with oxyphil cells (OC). OC were present in 13 of 24 patients (54%); however, it must be underlined that they were present 12 times in group A parathyroid glands (92%), and only once in group B (9%) (p<0.01). Nodular hyperplasia was found in 71% (17/24) of patients: 92% (12/13) in group A, and 45% (5/11) in group B (p<0.05). There were no significant differences in age, gender, dialysis duration, serum levels of iPTH, AP, Ca and P levels between the two groups.

Conclusions: There was a strong association between OC presence in parathyroid glands and CPT. Furthermore, nodular hyperplasia appeared to be associated significantly with CPT. There is still speculation regarding the meaning of these CPT effects on parathyroid gland histology and consequently on sHPTH pathophysiology.