AR Medford* , AJ France
Department of Respiratory Medicine and Infectious Diseases, King’s Cross Hospital, Clepington Road, Dundee DD3 8EA, Scotland, UK.
*Current address: Department of Respiratory Medicine, Musgrove Park Hospital, Taunton, Somerset TA1 5DA, England, UK.
Correspondence: Dr Andrew Medford, 17 Holden Crescent, Nuthall, Nottingham, NG16 1BW, England, UK.
E-mail: andrewmedford@hotmail.com
SMJ 2006 51(1): 57
Keywords: hypomagnesaemia – pulmonary tuberculosis – hypokalaemia
Abstract
We report a case of persistent hypomagnesaemia in a twenty-year-old girl with pulmonary tuberculosis (TB) despite continuous intravenous magnesium supplementation following nutritional replacement and correction of all other relevant electrolyte deficiencies. Untreated hypomagnesaemia can have serious clinical consequences. Previous associations with TB relate to a combination of the disease itself, TB drugs, malnutrition or alcoholism. It may persist despite treatment of TB, electrolyte abnormalities, removal of offending drugs, and nutritional repletion. In such circumstances, even in the normokalaemic TB patient, it is important to retain a high index of suspicion as it may require ongoing treatment.
Case
history
A twenty year old Pakistani girl was admitted with a two month history of anorexia, weight loss, cough and rigors. She had been increasingly withdrawn and irritable, and had been noted to be twitching. There had been a history of recent TB contact. She was on no regular medication with no history of alcohol dependence.
On examination, she was febrile (38oC), emaciated (weight 45.5kg), tachypnoeic (respiratory rate 28) and tachycardic (pulse 140) with signs of consolidation in the right upper and left lower lobes confirmed on chest x-ray as well as a small left pleural effusion which was exudative but sterile on aspiration.
Investigations confirmed smear positive TB from sputa, profound hypomagnesaemia (0.34 mmol/l), hypocalcaemia (1.66 mmol/l), mild hyponatraemia (130 mmol/l), mild hypokalaemia (3.3 mmol/l), anaemia of chronic disease (haemoglobin 7.6g/dl), mild leucopaenia (3.7 x 109/l) and lymphopaenia (0.6 x 109/l). There was also mild hepatic dysfunction, hypoalbuminaemia (25 g/l), elevated bilirubin (32 mmol/l) and elevated alanine aminotransferase (119 IU/l). Other biochemistry indicated no evidence of hypoadrenalism, diabetes or thyroid disease, pancreatitis or renal dysfunction. A 25-hydroxy-vitamin D level was low (<10 nmol/l) with secondary hyperparathyroidism (PTH 23.4 pmol/l) but there was no radiographic evidence of osteomalacia. There was no evidence of urinary magnesium wasting.
She was commenced on standard quadruple anti-TB chemotherapy (without capreomycin or aminoglycosides) with intravenous calcium, phosphate and potassium replacement as well as enteral feeding followed by calciferol intravenous magnesium supplementation. Her stay was complicated by a left-sided hydropneumothorax requiring drainage and suction for several days and a nosocomial empyema requiring intravenous gentamicin (for five days only), flucloxacillin, metronidazole and cefuroxime. She also received corticosteroids in addition to her anti-TB therapy.
Two months later, she had regained her expected body weight, being nutritionally replete with normal serum electrolytes (including sodium, potassium, calcium and phosphate) except for a persistent low serum magnesium level (0.6 mmol/l), requiring ongoing magnesium supplementation.
Discussion
Hypomagnesaemia is common in inpatients estimated at 7-20% in one study, and clinically important as although it can be asymptomatic it can be associated with a variable severity of clinical features1. The minor complaints include fatigue, cramps, nausea and irritability but more serious adverse effects include tetany, seizures and lethal cardiac arrhythmias and sudden death2. Normal serum magnesium levels can mask a total body magnesium deficit as only a fraction exists in plasma as a physiologically active free form, but a low serum magnesium level is always indicative of magnesium deficiency2.
The neuromuscular effects are thought to relate to calcium antagonism on muscle2. Magnesium deficiency is strongly associated with other electrolyte deficiencies especially potassium and (due to reduced activity of the Na+K+-ATPase) calcium (due to PTH resistance), although phosphate and sodium deficiencies are also described2. In unexplained cases of deficiency, it is important to exclude rarer magnesium wasting disorders by measuring fractional urinary magnesium excretion (usually elevated above 2%)3.
Previous cohort studies have documented the association of hypomagnesaemia with TB (co-existing with hypokalaemia)4,5. This is multifactorial related to the chronic inflammatory disease itself, intestinal side effects of anti-TB treatment, renal wasting related to secondary hyperaldosteronism with capreomycin and aminoglycosides and malnutrition or alcoholism which often coexist. Renal wasting related to drugs is only described with high cumulative doses of aminoglycosides and more common with capreomycin6-9. The largest available cohort study of 115 patients indicated magnesium deficiency presented 2.7 months after detection of hypokalaemia, leading the authors to recommend that a normal serum potassium level avoids the need to check serum magnesium levels.
In the above case, it is likely the magnesium deficiency was a composite of her TB and malnutrition (as evidenced by the other electrolyte deficiencies). The gentamicin was not prolonged, she did not receive capreomycin, she had no history of alcoholism, or intestinal side effects. She had no evidence of a primary magnesium wasting disorder.
The learning point from the above case is, however, that the serum magnesium level was still low despite a normal potassium (and other electrolytes) at subsequent review when she was nutritionally replete. In addition, her magnesium deficiency was detected at the same time as her potassium deficiency unlike previous studies. We therefore suggest it is important to maintain a high index of suspicion of magnesium deficiency in TB patients even when the serum potassium level is normal and that both deficiencies may present simultaneously in TB.
In summary, hypomagnesaemia is common and clinically important with potential serious adverse effects. It should be particularly suspected in TB patients for a variety of reasons and may present simultaneously with hypokalaemia and persist after normokalaemia, unlike previous studies. A high index of suspicion is the key which will prompt the search to exclude other contributory causes and continue replacement.
Learning points:
Hypomagnesaemia is associated with TB for a variety of reasons and should be excluded in such patients.
Hypomagnesaemia may present at the same time as hypokalaemia in TB patients although typically it presents 3 months after
Hypomagnesaemia may persist in TB patients despite resolution of the hypokalaemia. A high index of suspicion is key and a normal serum potassium level is not sufficient.
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