How does low magnesium (Mg) affect Parathyroid Hormone (PTH) levels?

From the Guidelines

Low magnesium levels can lead to an increase in parathyroid hormone (PTH) levels in the body, as magnesium is essential for the normal functioning of the parathyroid glands and the sensing of calcium levels by the calcium-sensing receptors on parathyroid cells. When magnesium becomes deficient, it can impair the release of PTH and also cause peripheral resistance to PTH, leading to hypocalcemia 1. This is because magnesium is necessary for the activity of the Mg-dependent adenyl-cyclase involved in PTH release and activity on bone.

Key Points to Consider

• Magnesium deficiency can cause both deficient PTH release and peripheral resistance to PTH, leading to hypocalcemia 1.
• The biologically active fraction of magnesium, represented by the concentration in red blood cells, is a better indicator of magnesium content in tissues than total blood magnesium concentration 1.
• Magnesium is essential for proper calcium homeostasis, and its deficiency can lead to secondary hyperparathyroidism or functional hypoparathyroidism in some cases.
• Clinically, patients with hypomagnesemia often present with hypocalcemia that is resistant to calcium supplementation alone, requiring magnesium repletion to restore normal calcium and PTH balance.

Clinical Implications

• It is crucial to monitor and maintain adequate magnesium levels, especially in patients at risk of magnesium deficiency, such as those with certain medical conditions or taking certain medications.
• Magnesium repletion is necessary to restore normal calcium and PTH balance in patients with hypomagnesemia, and it should be done under the guidance of a healthcare professional.
• The most recent and highest quality study on this topic, published in 2018, highlights the importance of magnesium in pediatric parenteral nutrition and its effects on PTH levels 1.

From the Research

Effect of Low Magnesium on PTH Hormone

• Low magnesium (Mg) levels can affect Parathyroid Hormone (PTH) levels, as Mg is involved in numerous biological processes, including the regulation of PTH secretion 2.
• Studies have shown that intracellular Mg 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 2, 3.
• Mg deficiency can lead to hypocalcemia, and impaired PTH secretion is a significant factor contributing to this condition 4.
• The administration of Mg can stimulate PTH secretion in Mg-deficient patients, but not in normal individuals or those with hyperparathyroidism 4, 3.
• The relationship between serum PTH and Mg levels is complex, and serum Mg levels can be inversely correlated with serum PTH levels in certain patient populations, such as those on continuous ambulatory peritoneal dialysis (CAPD) 5.

Mechanisms of Mg-PTH Interaction

• Mg is essential for the secretion of PTH, and its deficiency can impair the release of PTH 3.
• The level of circulating calcium required for the suppression of PTH secretion is lower in Mg-deficient patients than in normal subjects 3.
• Mg plays a critical role in energy-requiring metabolic processes, including protein synthesis and anaerobic phosphorylation, which can affect PTH secretion 6.

Clinical Implications

• Hypomagnesemia can lead to a wide range of clinical presentations, including neuromuscular irritability, cardiac arrhythmias, and increased sensitivity to digoxin 6.
• Refractory hypokalemia and hypocalcemia can be caused by concomitant hypomagnesemia and can be corrected with Mg therapy 6.
• The detection of Mg deficiency can be increased by measuring Mg concentration in the urine or using the parenteral Mg load test 6.