Evidence for suppression of parathyroid gland activity by hypermagnesemia Shaul G. Massry, … , Jack W. Coburn, Charles R. Kleeman J Clin Invest. 1970;49(9):1619-1629. https://doi.org/10.1172/JCI106379. Research Article The effect of hypermagnesemia, produced by MgCl2 infusion, on the activity of parathyroid glands, as assessed by changes in levels of serum calcium (SCa) and in the fraction of filtered phosphate excreted (CP/CCr), was studied in 11 intact and 4 thyroparathyroidectomized (T-PTX) dogs. To exclude the effect of diurnal variation in CP/CCr on the results, studies were initiated in both morning and afternoon hours and each study with MgCl2 infusion was paired with a control experiment in the same dog not receiving MgCl2. During MgCl2 infusion, serum phosphorus rose progressively. Despite this rise, the levels of CP/CCr fell in all experiments and were significantly different from values observed at the same time of the day in the paired control experiments. The concentrations of total SCa fell by 1.0-2.4 mg/100 ml with a proportional decrease in the levels of the diffusible and ionized fractions. The pattern of the fall in CP/CCr during MgCl2 resembled that observed after CaCl2 infusion (seven dogs) and that which acutely followed thyroparathyroidectomy (seven dogs). When parathyroid extract was given to dogs receiving MgCl2 infusion both CP/CCr and SCa rose, and MgCl2 infusion did not affect CP/CCr and SCa in T-PTX dogs. These results indicate that hypermagnesemia suppresses the activity of the parathyroid glands, probably, by inhibiting production and (or) release of the hormone, without interfering with […] Find the latest version: https://jci.me/106379/pdf Evidence for Suppression of Parathyroid Gland Activity by Hypermagnesemia SHAuL G. MASSRY, JACK W. COBURN, and CHARLEs R. KLEEMAN From Cedars-Sinai Medical Research Institute and the Departments of Medicine, Cedars-Sinai Medical Center, Veterans Administration Center, and the University of California at Los Angeles School of Medicine, Los Angeles, California 90048 A B S T R A C T The effect of hypermagnesemia, pro- of simultaneous modest hypocalcemia and hypermag- duced by MgCla infusion, on the activity of parathyroid nesemia suggests that a decrease in the level of serum glands, as assessed by changes in levels of serum cal- calcium is more potent than an increase in the concen- cium (Sca) and in the fraction of filtered phosphate tration of serum magnesium in the regulation of para- excreted (CP/Ccr), was studied in 11 intact and thyroid activity. 4 thyroparathyroidectomized (T-PTX) dogs. To ex- clude the effect of diurnal variation in CP/Ccr on the re- sults, studies were initiated in both morning and after- INTRODUCTION noon hours and each study with MgCL infusion was Although it is well documented that the concentration paired with a control experiment in the same dog not of ionized calcium in the plasma is of primary impor- receiving MgCl2. During MgCL infusion, serum phos- tance in regulating parathyroid hormone secretion (1- phorus rose progressively. Despite this rise, the levels 3), evidence exists suggesting that the level of blood of CP/Ccr fell in all experiments and were significantly magnesium may also play a role in the regulation of the different from values observed at the same time of the activity of the parathyroid glands. In the rat, magnesium day in the paired control experiments. The concentra- deficiency and hypomagnesemia may stimulate the para- tions of total Sca fell by 1.0-2.4 mg/100 ml with a pro- thyroid glands (4-6). Gitelman, Kukolj, and Welt portional decrease in the levels of the diffusible and (7) reported data in nephrectomized rats compatible ionized fractions. The pattern of the fall in CP/Cc, with the concept that hypermagnesemia may suppress the during MgCl2 resembled that observed after CaClh in- activity of the parathyroid glands in the rat; their stud- fusion (seven dogs) and that which acutely followed ies, however, do not exclude the possibility that the hy- thyroparathyroidectomy (seven dogs). When parathy- pocalcemic effect of magnesium injections could have roid extract was given to dogs receiving MgCla infu- been produced by mechanism(s) other than the inhibi- sion both CP/CCr and Sc. rose, and MgClh infusion did tion of the parathyroid glands. In four experiments not affect CP/Ccr and Sc. in T-PTX dogs. These results utilizing the in vivo perfusion of isolated parathyroid indicate that hypermagnesemia suppresses the activity glands in goats and sheep with perfusate containing high of the parathyroid glands, probably, by inhibiting pro- concentration of magnesium, there was an inverse cor- duction and (or) release of the hormone, without inter- relation between the level of parathyroid hormone in the fering with end-organ response. An increase in serum affluent blood and the concentration of magnesium in magnesium of 1.7-2.0 mg/100 ml was capable of pro- the perfusate in three experiments; this correlation was ducing the suppressive effect. Evaluation of the effect highly significant in only one study (8). The relation between magnesium metabolism and the This work was presented in part before the Western Sec- activity of parathyroid glands in the dog and man has tion of the American Federation for Clinical Research, not been delineated. Magnesium deficiency in the dog Carmel, Calif., 2 February 1968. may be associated with normal or low levels of serum Dr. Massry is an Established Investigator of the American the effect of acute Heart Association. calcium (9-12); hypermagnesemia Received for publication 18 February 1970 and in revised on the activity of the parathyroid glands has not been form 23 April 1970. studied in the species. In man, magnesium deficiency The Journal of Clinical Investigation Volume 49 1970 1619 may be accompanied by hypocal- and hypomagnesemia CONTROL INFUSION ; -itott MgCI2 cemia (13), which cannot be corrected by the adminis- I M tration of parathyroid extract, suggesting that the skele- I I 0 a 0 5' ton is rendered resistant to the action of parathormone. V- _ and U The repeated injections of magnesium salts (14) utE oral magnesium loading (15) to humans were associated 0)J------- - with a decrease in phosphate excretion; these results Di 911 were not attributed to inhibition of parathyroid glands. 0 Furthermore, the relative importance of simultaneous gm.UE a changes in the concentration of serum calcium and mag- %A E 9L nesium in the regulation of the activity of parathyroid .E _ 6. glands is not known. 0 The present study was undertaken to evaluate the ef- fect of acute hypermagnesemia on the activity of the parathyroid glands in the dog as assessed by changes in the concentration of serum calcium and in the fraction T of filtered phosphate excreted. The influence of a simul- E4J0 UNO., ,.T-' -T. l-rlT-17 taneous hypermagnesemia and hypocalcemia on the ac- 10 tivity of these glands was also studied. Qz so 4: METHODS 52 experiments were carried out during pentobarbital anes- thesia in 18 intact and 11 thyroparathyroidectomized (T-PTX) mongrel dogs weighing 16-25 kg. An oral water TIME (p.m.) load of 500 ml was given to the animals in each experiment FIGURE 2 Afternoon studies. The changes in mean levels of serum magnesium (Mg), calcium (Ca), and phosphorus ( P) and in the fraction of filtered phosphate excreted CONTROL INFUSION 0 without MgC12 (Cp/Cc,) in four intact dogs with and without the infusion a E 10 of MgCl2 (100,ug Mg'+/kg per min). The changes in CP/Cc, 0 are expressed as in Fig. 1. Ut £L~- :1-~ - ZuE I hr before the induction of anesthesia. Respiration was controlled by a Harvard respiratory pump, which was adjusted initially with a stroke volume of 10 ml/kg body weight and at a rate of 30 strokes/min. Blood pH was mea- sured several times during each study with a Radiometer pH meter (London Co., Westlake, Ohio), and the stroke volume of the respirator was adjusted thereafter to maintain 150. blood pH within normal range; usually, little adjustment 0 was necessary. Glomerular filtration rate was measured by B.- .r1/ exogenous creatinine clearance. Urine was collected from w 100. a retention catheter, and the bladder was washed with air vO at the end of each period. Blood was obtained at the mid- V Z k.., point of each clearance period from an indwelling needle in 50. the femoral vein. The studies were ma I L I T . following performed. .0 _ Experiments zedth the infussion of magnesium chloride (15 dogs, 38 experiments). After three control clearance pe- O. T ---r- I" riods, each of 20 min duration, magnesium chloride was 10 11 12 1 2 3 4 5 added to 0.45%o saline, and this solution was infused at I ml/ a.m. TIME p.m. min for 6 hr to deliver 100 gug Mg'+/kg per min in each experiment unless noted otherwise; clearance collections of FIGURE 1 Morning studies. The changes in mean levels of 30 min duration were obtained throughout. To exclude the serum magnesium (Mg) and phosphorus (P) and in the effect of the diurnal variation in phosphate excretion on the fraction of filtered phosphate excreted (CP/CC,) in seven results, experiments were initiated in both morning (morn- intact dogs with and without the infusion of MgClz (100 ing studies) and afternoon (afternoon studies) hours, and Ag Mg'+/kg per min). In order to reduce the variability in each experiment with infusion of MgCl2 was paired with absolute fraction of CP/CCr from one experiment to another, a control study in which the same animal received only the changes in CP/Cc, are expressed as the per cent of the 0.4517o saline at 1 ml/min for 6 hr over the same period of mean of the three control clearances in each individual ex- the day during which the MgCl2 infusion was given.