Inactivating calcium-sensing receptor mutations in patients with primary hyperparathyroidism

Area of Science:

• Endocrinology
• Medical Genetics

Background:

• Primary hyperparathyroidism (HPT) involves autonomous parathyroid hormone (PTH) secretion causing hypercalcaemia.
• Familial hypocalciuric hypercalcaemia (FHH) is an inherited disorder due to calcium-sensing receptor (CaSR) gene mutations, also causing hypercalcaemia.
• Differentiating HPT from FHH is critical as surgery cures HPT but is ineffective for FHH.

Purpose of the Study:

• To investigate the role of CaSR gene mutations in patients with suspected HPT.
• To evaluate clinical and biochemical parameters in differentiating HPT and FHH.
• To assess the impact of parathyroid surgery in patients with coexisting HPT and FHH.

Main Methods:

• Analysis of CaSR gene mutations in 139 outpatients with hypercalcaemia.
• Evaluation of clinical and biochemical profiles.
• Histological confirmation of parathyroid tissue post-surgery.

Main Results:

• Six different CaSR gene mutations were identified in eight patients.
• Four patients had confirmed FHH due to CaSR mutations.
• Four patients diagnosed with HPT, confirmed by parathyroid adenomas, benefited from surgery despite carrying CaSR mutations.

Conclusions:

• CaSR gene mutations may play a role in the pathogenesis of HPT.
• Parathyroid surgery can be beneficial for HPT even in the presence of CaSR mutations.
• Accurate diagnosis through genetic testing is essential for appropriate patient management.