Abstract

To the Editor,
Srivastava et al. 1 addressed the efficiency and effectiveness of the common practice of added-on tests. Among the five examples given was the wise addition of serum magnesium measurement in patients with significant hypokalaemia (<2.5 mmol/L) and hypocalcaemia (<1.8 mmol/L albumin-adjusted). Reflex added-on serum magnesium (automatically initiated by the analyser) revealed low concentrations (<0.7 mmol/L) in 46% and 38% of patients with hypokalaemia and hypocalcaemia, respectively. The corresponding data for reflective added-on magnesium, which took into account wider clinical judgement by experienced laboratorians, were similar, with low serum magnesium of ∼42% in both conditions. Although these results may be considered reasonable and useful in patients with hypocalcaemia, it can be highly misleading in patients with hypokalaemia because magnesium deficiency coexists in almost all cases with significant hypokalaemia, irrespective of serum magnesium concentration. 2
Magnesium in the circulation does not represent total body magnesium, being only 1% or less of the total body content. 2,3 In addition, magnesium in the serum is subdivided into three heterogeneous fractions: magnesium bound to albumin (∼30%); a fraction loosely complexed with anions such as phosphate, citrate and bicarbonate (∼20%); and a free ionized fraction (∼50%) mistakenly regarded by some to be the biologically active moiety. 2,3 A large amount of body magnesium is in the bone, the bulk of which is an integral part of the bones'crystal lattice, forming the bone scaffolding together with the two more abundant minerals, calcium and phosphorus. A smaller fraction of magnesium is on a surface limited pool present either within the hydration shell or else on the crystal surface. 3,4 Based largely on animal studies, it has been speculated that this form of bone surface magnesium may represent a limited buffering capacity.
Added-on serum magnesium is useful because low serum concentrations indicate deficiency warranting replacement. However, normal serum magnesium (total or ionized) concentration must not be used to exclude deficiency since magnesium is predominantly an intracellular moiety. Magnesium is necessary for cellular potassium homeostasis and plays a role in the aetiology of hypokalaemia, being necessary for the activity of cellular membrane ATP/ATPase pumps such as Na+/K+ pump. Latent magnesium deficiency can impede the efficacy and activity of Na+/K+ pump, leading eventually to potassium depletion and hypokalaemia.
The perception that ‘normal’ serum magnesium concentration excludes deficiency is common among clinicians and this may be reinforced by added-on tests which signify ‘abnormal’ results. A health warning may therefore be warranted in add-on magnesium testing regarding the misuse of ‘normal’ results in general and among patients with significant hypokalaemia in particular.
DECLARATIONS
