The secretion of parathyroid hormone (PTH) by the parathyroid gland is directly regulated by extracellular calcium ions (Ca2+) via the Ca2+-sensing receptor. However, there are reports of magnesium (Mg) effect on PTH secretion: acute hypermagnesemia can suppress PTH. It is suggested that the mechanism of suppression is similar to that of hypercalcemia. We investigated the relationship between Ca, Mg, and inorganic phosphorus (Pi) in patients with hyperparathyroidism (HrPT, n=62) and hypoparathyrodism (HoPT, n=27). We measured the serum concentrations of total Ca (TCa), ionized Ca (iCa), total Mg (TMg) and ionized Mg (iMg) and, by calculating the ionized fraction (i.e., ionized/total), indirectly determined the bound fraction (i.e., bound to albumin and complexed with anions) of these cations.The relationship between the concentrations of TCa and iCa, and of TMg and iMg, for both groups of patients was significant (p is less than 0.0001). However, there was a major difference in the relationship of Ca and Mg forms (i.e., total, ionized, and ionized fraction) and Pi. For HrPT patients there was a positive relationship between iCa and iMg (p is less than 0.0001) indicating simultaneous increase of both ions. The iCa fraction was not affected by TMg (p is greater than 0.1) but the iMg fraction decreased as the TCa increased (p=0.04). The bound fractions of Ca and Mg were not affected by albumin (p is greater than 0.1). However, the bound fraction of Ca increased (p equals 0.004), and that of Mg decreased (p equals 0.009), with the increasing concentrations of Pi, (i.e., the concentration of Ca-phosphate increased and of Mg-phospate decreased). This indicates that for HrPT patients the equilibrium between the free and bound Ca and Mg is mainly determined by the concentration of Pi. In contrast, for HoPT patients, no significant relationship was found between Ca and Mg forms (p is greater than 0.1), and the bound fractions of Ca and Mg were not affected by Pi (p equals 0.8). Additional studies need to be performed to establish the full clinical usefulness of iMg determinations for HrPT patients.We compared the analytical performance of the three currently available Mg ion-selective electrodes. We also determined the effect of freezing and of pH change on the iMg results. Fresh and frozen (-20 degrees C) serum samples from volunteers and patients were analyzed at NIH (AVL and NOVA) and at the Academic Medical Center (AMC) in Amsterdam, Netherlands (AVL, KONE). The best correlation was found between the AVL and KONE analyzers (slope 0.964, intercept -0.01). Freezing affected only the KONE and the NOVA results. There was a significant decrease in NOVA results and the extent of this decrease was related to the pH change that occurred during storage of samples. For KONE, some results were increased while some were decreased, and these changes were not pH dependent. Theoretically, such pattern would be observed if interfering factors (e.g., drugs) were themselves affected by freezing. This difference in the analytical response of the three Mg electrodes is important because freezing is often used, especially in research, to preserve the samples for later batch-analysis.The apparent dissociation constant of the magnesium-ATP complex, KDMgATP, is used for determination of intracellular free magnesium with 31P NMR spectroscopy. We determined the constant experimentally by measuring the chemical shift difference between a- and b-ATP in the phosphorus (P) spectrum with 31P NMR spectroscopy and by determining the concentration of free magnesium using the fluorescence indicator, Mag-fura-2. The value of KDMgATP = 8.2 ' 0.5 mM at 37 degrees C, pH=7.2, and ionic strength 0.15 were verified by calculation using the concentration of total magnesium that was determined with the atomic absorption spectroscopy.
