Parathyroid function and histology in patients with parathyroid adenoma: correlation of clinical and morphologic findings

Serum levels of parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium, creatinine, and vitamin D and the glomerular filtration rate were compared with the histologic properties and expression of PTH and chromogranin A in excised parathyroid adenomas from patients with primary hyperparathyroidism (pHPT). PTH and chromogranin A were detected immunohistochemically, and their mRNA was demonstrated by in situ hybridization with quantification of their mRNA levels by image analysis. There was a positive correlation between the cellular levels of PTH mRNA and the cellular levels of chromogranin A mRNA (r = 4.4; p < 0.05). However, within certain parts of the adenomas, mostly consisting of chief cells, the expression of PTH mRNA and chromogranin A mRNA was heterogeneous and the levels did not correspond to each other. A reduced suppressibility of PTH in patients with pHPT was confirmed. Although cellular levels of PTH and chromogranin A and their mRNAs were low in the oxyphilic parts of the adenomas, there was no correlation between the amount of oxyphilic cells in the adenomas and the suppressibility of PTH by calcium. There was also no association between the cellular levels of PTH mRNA or chromogranin A mRNA as studied by image analysis and "calcium sensitivity." Our results thus demonstrate that although PTH and chromogranin A mRNA levels are in general correlated to each other there are differences in their expression within and between individual parathyroid adenomas. It therefore seems likely that the expression of PTH and chromogranin A are differentially regulated, and that PTH and chromogranin A may not always be co-secreted. This point could be of importance, as chromogranin A and its cleavage products are known to influence PTH secretion.