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
The biochemical basis for clinical variability in primary hyperparathyroidism (PHPT) is poorly understood.
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.
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.
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.
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.
We provide our journal authors with a variety of resources for increasing the discoverability and citation of their published work. Use these tools and tips to broaden the impact of your article.
Read our special collections of Endocrine Society journal articles, curated by topic, Altmetric Attention Scores, and Featured Article designations.