Functional Hypoparathyroidism and Parathyroid Hormone End‐organ Resistance in Human Magnesium Deficiency

Abstract

Hypocalcaemia is a well-recognized manifestation of magnesium deficiency. We have studied seventeen patients with this syndrome in an attempt to determine the pathogenesis of the hypocalcaemia. Mean initial serum calcium concentration was 5-6 mg/dl and mean initial serum magnesium concentration was 0-75 mg/dl. Serum immunoreactive parathyroid hormone (IPTH) was measured in sixteen patients in the untreated state. Despite severe hypocalcaemia, serum IPTH was either undetectable (less than 150 pg/ml) or normal (less than 550 pg/ml) in all but two patients. Serial measurements made during the initial 4 days of magnesium therapy in four patients showed an increase in serum IPTH within 24h, but a delayed increase in serum calcium, which required approximately 4 days to reach normal values. The effect of the rapid normalization of serum magnesium on serum IPTH and serum calcium concentration was studied in three patients. Within 1 min after 144-300 mg of elemental magnesium was administered i.v., serum IPTH had risen from undetectable to 3600 pg/ml and 1725 pg/ml in two patients and from 425 pg/ml to 937 pg/ml in the third. Serum calcium concentrations were unchanged after 30-60 min. These data provide evidence for impaired parathyroid gland function in most of the magnesium deficient patients. The rapidity with which serum IPTH rose in response to magnesium therapy indicates that this may reflect a defect in parathyroid hormone (PTH) secretion rather than its biosynthesis. The failure of serum calcium concentration to increase during the initial days of magnesium repletion, at a time when serum IPTH concentrations were normal or elevated, suggests end-organ resistance to PTH in these patients. The renal response to PTH was examined in two magnesium deficient patients by measurement of urinary cyclic AMP excretion following administration of parathyroid extract. In both patients there was a minimal increase in urinary cyclic AMP concentrations. In contrast, when the hepatic response to glucagon was tested on the same patients by measurement of plasma cyclic AMP concentrations following administration of glucagon, normal increases were observed. These results suggest that adenylate cyclase systems of various organs may be affected differentially by a state of magnesium deficiency. It is suggested that magnesium deficiency may result in defective cyclic AMP generation in the parathyroid glands and in the PTH target organs. This could be the principal mechanism operative in both impaired PTH secretion and end-organ resistance to PTH which together contribute to the development of hypocalcaemia.

A Case of Magnesium Deficiency Associated with Insufficient Parathyroid Hormone Action and Severe Osteoporosis

“…Impaired secretion of PTH caused by reduction in serum Mg levels has been thought to be one of the major mechanisms by which hypocalcemia develops in Mg deficiency [3][4][5][6][7]. PTH secretion is known to be affected by extracellular Mg in vitro [24] and in vivo [25,26].…”

“…Previous studies have demonstrated that serum PTH concentration was suppressed in patients with hypomagnesemia [4,5], and Mg substitution therapy enhanced PTH secretion and reversed PTH target-organ resistance, and thus serum calcium concentration returned to normal within several days [4,7]. In addition, Mg deficiency could inhibit the synthesis of 1,25-dihydroxy vitamin D (1,25(OH) 2 D) [9][10][11] as well as its action on bone [11].…”

“…SERUM calcium levels are normally regulated within a relatively narrow range by the parathyroid gland through a negative feedback mechanism: Increased secretion of parathyroid hormone (PTH) by a fall in blood calcium levels enhances the mobilization of calcium, mainly by bone resorption, and then calcium levels are rapidly restored. Chronic magnesium (Mg) deficiency would result in hypocalcemia [1, 2], because of the impairment of PTH secretion [3][4][5][6][7] and/ or resistance of target organ to PTH action [4,6,8].…”

“…SERUM calcium levels are normally regulated within a relatively narrow range by the parathyroid gland through a negative feedback mechanism: Increased secretion of parathyroid hormone (PTH) by a fall in blood calcium levels enhances the mobilization of calcium, mainly by bone resorption, and then calcium levels are rapidly restored. Chronic magnesium (Mg) deficiency would result in hypocalcemia [1, 2], because of the impairment of PTH secretion [3][4][5][6][7] and/ or resistance of target organ to PTH action [4,6,8].Previous studies have demonstrated that serum PTH concentration was suppressed in patients with hypomagnesemia [4,5], and Mg substitution therapy enhanced PTH secretion and reversed PTH target-organ resistance, and thus serum calcium concentration returned to normal within several days [4,7]. In addition, Mg deficiency could inhibit the synthesis of 1,25-dihydroxy vitamin D (1,25(OH) 2 D) [9][10][11] as well as its action on bone [11].…”

Acute effect of high-calcium milk with or without additional magnesium, or calcium phosphate on parathyroid hormone and biochemical markers of bone resorption

“…It has been known for many years that magnesium (Mg) deficiency leads to an increase in serum PTH, which promotes calcium (Ca) release from bone (Rude et al, 1976). More recently Mg deficiency for just 3 weeks in young, growing rats has been shown to lead to decreased bone turnover that could impair bone growth and development (Creedon et al, 1999).…”