From the Guidelines
Yes, hypomagnesemia can both inhibit Parathyroid Hormone (PTH) secretion and block its effect in the kidneys. Magnesium plays a crucial role in calcium homeostasis by regulating PTH secretion from the parathyroid glands and influencing PTH action at target tissues, as noted in the 2018 Clinical Nutrition guidelines 1. When serum magnesium levels are low, the parathyroid glands become less responsive to low calcium levels, resulting in reduced PTH secretion.
Key points to consider:
- Magnesium is essential to the activity of the Mg-dependent adenyl-cyclase involved both in the PTH release and activity on bone, as highlighted in the study 1.
- In Mg deficiency, there is both deficient PTH release and peripheral resistance to PTH with subsequent hypocalcaemia 1.
- The concentration of magnesium in red blood cells represents a better indicator of Mg content in tissues, and total blood Mg concentration is not the best estimate of the biologically active fraction (ionized Mg) 1.
The dual inhibition of PTH secretion and action often leads to hypocalcemia that is resistant to PTH treatment until the magnesium deficiency is corrected. Treatment typically involves magnesium replacement, and the underlying mechanism involves magnesium's role as a cofactor for adenylate cyclase and its influence on the calcium-sensing receptor in parathyroid cells, highlighting the interconnected nature of magnesium and calcium metabolism.
From the Research
Hypomagnesemia and PTH Secretion
- Hypomagnesemia can inhibit Parathyroid Hormone (PTH) secretion, as evidenced by studies that show a close association between chronic hypomagnesemia and hypocalcemia, which is caused by impaired PTH secretion or the refractoriness of bone and renal tubules to PTH 2.
- Additionally, magnesium depletion can impair the ability of the parathyroid to secrete PTH, resulting in a fall in serum PTH levels and subsequently a fall in serum calcium concentration 3.
Effect of Hypomagnesemia on PTH in the Kidneys
- Hypomagnesemia can block the effect of PTH in the kidneys, as shown in a study where a patient with hypomagnesemia-induced hypocalcemia had elevated PTH levels, but the renal tubular maximal reabsorption rate of phosphate to GFR (TmP/GFR) was elevated, indicating refractoriness of the renal tubules to PTH 2.
- Another study suggests that hypomagnesemia can lead to inhibition of PTH secretion and hypocalcaemia resistant to calcium supplementation, due to the dissociation of magnesium from the alpha subunit of G protein caused by hypomagnesemia, which increases the activity of the calcium-sensitive receptor (CASR) 4.
Mechanism of Hypomagnesemia-Induced PTH Secretion Inhibition
- The paradoxical block of PTH secretion under magnesium deficiency is mediated through a novel mechanism involving an increase in the activity of G alpha subunits of heterotrimeric G-proteins 5.
- The mechanism of hypomagnesemia-induced PTH secretion inhibition is complex and involves multiple pathways, including the calcium-sensing receptor (CaSR) and the G-protein signaling pathway 5.