The Journal of Clinical Endocrinology and Metabolism Journal Article

Calcium Sensing in Human Parathyroid Tumors

November 23, 2021
 

James Koh, Run Zhang, Sanziana Roman, Quan-Yang Duh, Jessica Gosnell, Wen Shen, Insoo Suh, Julie A Sosa
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 11, November 2021, Pages 3168–3183
https://doi.org/10.1210/clinem/dgab524

Abstract

Context

The biochemical basis for clinical variability in primary hyperparathyroidism (PHPT) is poorly understood.

Objective

This study aimed to define parathyroid tumor biochemical properties associated with calcium-sensing failure in PHPT patients, and to relate differences in these profiles to variations in clinical presentation.

Methods

Preoperative clinical data from a sequential series of 39 patients undergoing surgery for PHPT at an endocrine surgery referral center in a large, public university hospital were evaluated for correlation to parathyroid tumor biochemical behavior. An intact tissue, ex vivo interrogative assay was employed to evaluate the calcium-sensing capacity of parathyroid adenomas relative to normal donor glands. Tumors were functionally classified based on calcium dose-response curve profiles, and clinical parameters were compared among the respective classes. Changes in the relative expression of 3 key components in the calcium/parathyroid hormone (PTH) signaling axis — CASR, RGS5, and RCAN1 — were evaluated as potential mechanisms for calcium-sensing failure.

Results

Parathyroid adenomas grouped into 3 distinct functional classes. Tumors with diminished calcium sensitivity were the most common (18 of 39) and were strongly associated with reduced bone mineral density (P = 0.0009). Tumors with no calcium-sensing deficit (11 of 39) were associated with higher preoperative PTH (P = 0.036). A third group (6/39) displayed a nonsigmoid calcium/PTH response curve; 4 of these 6 tumors expressed elevated RCAN1.

Conclusion

Calcium-sensing capacity varies among parathyroid tumors but downregulation of the calcium-sensing receptor (CASR) is not an obligate underlying mechanism. Differences in tumor calcium responsiveness may contribute to variations in PHPT clinical presentation.

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