A critically ill alcoholic patient has corrected hypokalaemia but serum calcium remains 6.8 mg/dL despite repeated intravenous calcium gluconate infusions. Serum magnesium is 1.0 mg/dL (normal 1.7 to 2.2). What is the mechanism of the refractory hypocalcaemia?

• A Magnesium deficiency accelerates 24-hydroxylation of calcidiol to inactive metabolites
• B Magnesium competes with calcium at the renal distal tubular TRPV5 channel, increasing calciuria
• C Magnesium activates the calcium-sensing receptor in the parathyroid, mimicking hypercalcaemia
• D Magnesium depletion suppresses parathyroid hormone secretion and induces end-organ PTH resistance ✓

Explanation

Severe hypomagnesaemia impairs both the release of PTH from the parathyroid gland and the adenylate cyclase-coupled action of PTH in target tissues such as bone and kidney. Intravenous calcium alone fails because the hormonal axis is defective; correction requires magnesium repletion. Option C is wrong because cinacalcet-like activation would suppress PTH, but the dominant examined mechanism in Mg depletion is impaired PTH secretion and action. This combination is a classic exam scenario.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.