From the Guidelines
Low magnesium suppresses parathyroid hormone (PTH) secretion through direct effects on the parathyroid glands, as magnesium is essential for PTH synthesis, secretion, and peripheral action, and its deficiency can lead to paradoxical hypoparathyroidism despite hypocalcemia. Magnesium is a critical cofactor for adenylate cyclase, which generates cyclic AMP needed for PTH secretion, as noted in the study by 1. Additionally, magnesium is required for the activation of G-proteins that couple calcium-sensing receptors to intracellular signaling pathways in parathyroid cells.
When serum magnesium levels fall below 0.8 mmol/L (1.9 mg/dL), the parathyroid glands become dysfunctional, leading to hypoparathyroidism. Severe hypomagnesemia (below 0.4 mmol/L or 1.0 mg/dL) can also cause PTH resistance in target tissues, particularly bone and kidney, further exacerbating hypocalcemia. The importance of magnesium in PTH secretion is highlighted by the fact that magnesium deficiency can impair parathyroid hormone release, as mentioned in the study by 1.
Key points to consider in the management of hypomagnesemia include:
- Correcting the underlying magnesium deficiency, typically with intravenous magnesium sulfate (1-2 g every 6 hours) for severe cases or oral magnesium supplements (magnesium oxide 400-800 mg daily in divided doses) for milder deficiency
- Monitoring serum magnesium levels and adjusting treatment accordingly
- Paying attention to sodium, potassium, and magnesium balance, especially in patients with gastrointestinal losses or renal impairment, as emphasized in the study by 1
- Considering the use of oral rehydration solutions or intravenous supplementation to correct magnesium deficiency, as noted in the study by 1.
Overall, correcting magnesium deficiency is crucial to restore normal PTH secretion and calcium homeostasis, and treatment should be tailored to the individual patient's needs, taking into account the severity of the deficiency and any underlying medical conditions, as supported by the study by 1.
From the Research
Mechanism of PTH Suppression
- Hypomagnesemia (low magnesium) suppresses Parathyroid Hormone (PTH) secretion due to the essential role of magnesium in the normal function of the parathyroid glands 2, 3.
- Magnesium deficit is usually associated with hypoparathyroidism, low production of active vitamin D metabolites, and resistance to PTH and vitamin D 3.
- Intracellular magnesium depletion impairs 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.
Effect of Magnesium on PTH Secretion
- Increasing magnesium concentrations can reduce PTH secretion, especially when parathyroid glands are exposed to moderately low calcium concentrations 4.
- Magnesium can modulate parathyroid gland function through the upregulation of key cellular receptors such as CaR, VDR, and FGFR1/Klotho system 4.
- The rapid increase in serum PTH produced by magnesium infusion suggests an effect of magnesium on hormone secretion rather than an effect on hormone synthesis 5, 6.
Clinical Implications
- Hypocalcemia is a well-recognized manifestation of magnesium deficiency, and impaired parathyroid gland function is a common feature of this condition 5.
- Magnesium deficiency may result in defective cyclic AMP generation in the parathyroid glands and in the PTH target organs, contributing to the development of hypocalcemia 5.
- The level of circulating calcium required for the suppression of parathyroid hormone secretion is lower than that in normal subjects in the presence of magnesium deficiency 6.