Final Diagnosis -- Hypermagnesemia
Hypermagnesemia can cause muscle weakness1,2. Although hypermagnesemia is uncommon, this patient's clinical history is classic3,4. Hypermagnesemia is commonly due to excess intake, and "[t]hose most at risk are the elderly and patients with bowel disorders or renal insufficiency"5. This patient has all of these predisposing factors: increased magnesium consumption, increased age, bowel disorder, and renal insufficiency.
In the body, magnesium is the most prevalent intracellular divalent cation. It is essential for the proper functioning of many cellular processes including enzymatic activities and nucleic acid processes (e.g. transcription, translation, and replication).
Total body magnesium is estimated to be 23g (1 mole). Half of the body's magnesium is in mineralized bone and half is intracellular. Only about 1% of magnesium is in extracellular fluid. Typically, one-third of that 1% is complexed with protein, and two-thirds is free (aka ionized) magnesium. Normal serum concentrations of magnesium are 1.7-2.2 mg/dL (0.75-0.95 mmol/L or 1.5-1.9 mEq/L).
Gastrointestinal absorption plays a part in magnesium balance, and as oral intake increases, the fractional intestinal absorption decreases. Typical oral magnesium intake from green vegetables and other sources is about 300 mg per day, and typically about 100 mg is absorbed per day. Magnesium homeostasis is primarily maintained by renal excretion. Reabsorption of the filtered magnesium ions occurs mainly in the thick ascending loop and the distal tubule and is largely regulated directly by magnesium levels in the blood. Hypomagnesemia is a much more common clinical scenario than hypermagnesemia, but severe hypermagnesemia is associated with morbidity and mortality.
Signs and sypmtoms of hypermagnesemia5,7
Etiology of hypermagnesemia
- Neuromuscular toxicity including loss of deep tendon reflexes, altered mental status, respiratory depression, and flaccid paralysis
- Cardiovacular toxicity including bradycardia, hypotension, and complete heart block
- Decreased PTH resulting in mild hypocalcemia and hyperphosphatemia
Management of hypermagnesemia5
- Impaired renal clearance
Normal dietary intake of magnesium in the setting of severe renal impairment (acute or chronic) has the potential to lead to severe hypermagnesemia6.
- Excess intake or absorption
Excessive magnesium intake due to iatrogenic causes8-12, therapeutic misadventure1,13, or bowel abnormalities3,5 can result in severe hypermagnesemia.
- Elevated parathyroid hormone
Hyperparathyroidism of various etiologies has been associated with hypermagnesemia14-17. PTH affects serum magnesium levels, where increases in PTH result in increases in magnesium, and increases in magnesium result in decreases in PTH15,18,19.
When kidney function is present, hypermagnesemia can often be corrected by simply discontinuing the exogenous source of magnesium. In cases of severe renal impairment, hemodialysis may be needed.
A careful history revealed that the patient was taking 90 ml of milk of magnesia twice per day (?3 times the recommended dose). The patient's decreased oral intake resulted in volume depeltion and subsequent acute renal injury, which impaired the patient's ability to excrete magnesium. The patient's recent bowel surgery and increased age may also have contributed to her hypermagnesemia.
At least some of this patient's other abnormal laboratory values can be explained (at least in part) by her hypermagnesemia. Hypermagnesemia can cause a decrease in parathyroid hormone (PTH) levels15,18,19. Low PTH may result in hyperphosphatemia20, which was present in this patient. Hypermagnesemia can exacerbate hypocalcemia, which was present in this patient3,15,21. The reason for the patient's hyponatremia and hypochloremia is not entirely clear but could be caused by the patient's poor oral intake or metastatic disease22.
Fluid resuscitation enabled the patient's kidney perfusion and function to improve. Return of the patient's kidney function and withholding the patient's exogenous magnesium enabled the patient's plasma electrolyte concentrations to improve over the course of her hospital stay as demonstrated in the figure. The patient was discharged to her home on day 9 of hospitalization.
Hypermagnesemia is a rare condition, but the clinical presentation of this case is classic.
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- Clark, B.A. & Brown, R.S. Unsuspected morbid hypermagnesemia in elderly patients. American journal of nephrology 12, 336-343 (1992).
- Khairi, T., Amer, S., Spitalewitz, S. & Alasadi, L. Severe Symptomatic Hypermagnesemia Associated with Over-the-Counter Laxatives in a Patient with Renal Failure and Sigmoid Volvulus. Case reports in nephrology 2014, 560746 (2014).
- Weisinger, J.R. & Bellorin-Font, E. Magnesium and phosphorus. Lancet 352, 391-396 (1998).
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- Topf, J.M. & Murray, P.T. Hypomagnesemia and hypermagnesemia. Reviews in endocrine & metabolic disorders 4, 195-206 (2003).
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- Garcia, M.C., Byrd, R.P., Jr. & Roy, T.M. Lethal iatrogenic hypermagnesemia. Tennessee medicine : journal of the Tennessee Medical Association 95, 334-336 (2002).
- Witlin, A.G. & Sibai, B.M. Magnesium sulfate therapy in preeclampsia and eclampsia. Obstetrics and gynecology 92, 883-889 (1998).
- Smilkstein, M.J., Steedle, D., Kulig, K.W., Marx, J.A. & Rumack, B.H. Magnesium levels after magnesium-containing cathartics. Journal of toxicology. Clinical toxicology 26, 51-65 (1988).
- Onishi, S. & Yoshino, S. Cathartic-induced fatal hypermagnesemia in the elderly. Internal medicine 45, 207-210 (2006).
- Attie, M.F., et al. Urinary calcium excretion in familial hypocalciuric hypercalcemia. Persistence of relative hypocalciuria after induction of hypoparathyroidism. The Journal of clinical investigation 72, 667-676 (1983).
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- Albert, U., et al. Lithium-associated hyperparathyroidism and hypercalcaemia: a case-control cross-sectional study. Journal of affective disorders 151, 786-790 (2013).
- Ananth, J. & Dubin, S.E. Lithium and symptomatic hyperparathyroidism. Journal of the Royal Society of Medicine 76, 1026-1029 (1983).
- Rodriguez-Ortiz, M.E., et al. Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 29, 282-289 (2014).
- Navarro, J.F., et al. Relationship between serum magnesium and parathyroid hormone levels in hemodialysis patients. American journal of kidney diseases : the official journal of the National Kidney Foundation 34, 43-48 (1999).
- De Sanctis, V., Soliman, A. & Fiscina, B. Hypoparathyroidism: from diagnosis to treatment. Current opinion in endocrinology, diabetes, and obesity 19, 435-442 (2012).
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- Onitilo, A.A., Kio, E. & Doi, S.A. Tumor-related hyponatremia. Clinical medicine & research 5, 228-237 (2007).
Contributed by Daniel D. Rhoads, MD and Octavia M. Peck Palmer, PhD