Primary and secondary hyperparathyroidism present different expressions of calcium-sensing receptor

Abstract

Background Decreased calcium-sensing receptor (CaSR) has been observed in hyperparathyroidism (HPT) without a known mechanism. The purpose of this study was to evaluate the expression of CaSR in primary (PHPT) and secondary (SHPT) subtypes. Methods Immunohistochemical (IHC) staining and quantitative real-time PCR (qRT-PCR) assay were used to measure the differences in expression of CaSR protein and gene in PHPT and SHPT human samples, compared to matched controls. Results CaSR protein was differentially downregulated in SHPT and PHPT compared to normal parathyroid tissues (2.42 ± 0.5 vs. 3.2 ± 0.62, P < 0.05; 1.8 ± 0.83 vs. 3.2 ± 0.62, P < 0.05, respectively). Furthermore, SHPT tissues exhibited significantly higher levels of CaSR mRNA (0.29 ± 0.23 vs. 0.01 ± 0.12, P < 0.05) and protein (2.42 ± 0.5 vs. 1.8 ± 0.83, P < 0.05) than those in PHPT tissue samples. Conclusion Depressed CaSR expression was a critical pathological hallmark of HPT. We found a differential decline of CaSR, in terms of both mRNA and protein levels, in PHPT and SHPT human samples. We think that CaSR dysregulation occurred at the very beginning of disease onset in PHPT, while a similar pathological scenario appeared at the later stage of SHPT. Future studies should be directed to dissect the mechanistic involvement of CaSR in PHPT and SHPT in order to bring treatment precisions in HPT management.

Tertiary hyperparathyroidism masking an atypical parathyroid tumor

“…Nodular glands have less vitamin D receptor (VDR) and CaSRs compared to diffusely hyperplastic glands and this exacerbates parathyroid gland resistance to calcitriol and calcium 3,7 . In the reported patient THP resulted from prolonged stimulus under SHP 6 . The triad of high serum PTH, calcium and phosphorus levels were indicative 8 …”

“…3,7 In the reported patient THP resulted from prolonged stimulus under SHP. 6 The triad of high serum PTH, calcium and phosphorus levels were indicative. 8 Usually, in THP hyperplasia of the three glands with a single or double adenoma, and in rare cases with a carcinoma coexists.…”

“…In addition, the PTH calcemic effect must be noted, which contributes to hypocalcemia following parathyroid hyperplasia, due to phosphorus, which is the generation of skeletal resistance to that effect. 6 In THP the mechanism is also changed, but it is still unclear. The CaSR expression in not activated, but it acts autonomously, probably due to parathyroid cell monoclonal expansion, where the set point of CaSR protein has been changed.…”

“…Main differences between secondary and tertiary hyperparathyroidism, despite their fundamental common point which is the increased parathyroid hormone secretion by the parathyroid glands, are observed. SHPT is characterized by adapted raised level of PTH, while THPT by non‐adapted raised PTH levels 5,6 . SHPT causes buildup of 25OHVitD deficiency, renal hypercalciuria, kidney failure, malabsorption, and certain medicines, while THP is the result of prolonged stimulus under SHP 5 .…”

“…SHPT is characterized by adapted raised level of PTH, while THPT by non-adapted raised PTH levels. 5,6 SHPT causes buildup of 25OHVitD deficiency, renal hypercalciuria, kidney failure, malabsorption, and certain medicines, while THP is the result of prolonged stimulus under SHP. 5 In addition to their differences, it is important to mention that in SHP the serum calcium levels can be normal, depending on the cause of origin, while in THP the serum calcium levels are increased.…”