The phosphorus connectiona puzzling business
Andreas L. Birkenfeld,
Maik Gollasch,
Ursula Göbel and
Friedrich C. Luft
Franz Volhard Clinic, HELIOS Klinikum-Berlin, Medical Faculty of the Charité, Humboldt University of Berlin, Germany
Correspondence and offprint requests to: Andreas Birkenfeld, Franz Volhard Clinic, Wiltberg Strasse 50, D-13125 Berlin, Germany. Email: birkenfeld{at}fik.charite-buch.de
Keywords: phosphorus
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Case
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A 40 year-old woman was admitted because of profound weakness for the past 4 days. She also claimed to have a severe headache for which she had ingested large doses (
8 g) of aspirin. She steadfastly denied nausea or vomiting and did not complain of abdominal pain. Past medical history revealed generous alcohol consumption and a cardiomyopathy, ostensibly alcohol induced. She had intermittent atrial fibrillation for which she received phenprocoumon; however, her most recent ejection fraction was 48%. On physical examination, her temperature was 38°C, her heart rate was regular at 84 beats/min, her respiratory rate was 20/min, and her blood pressure was 80/60 mmHg. The blood pressure did not fall with upright posture. The neck veins were not distended, the chest was clear, the heart was not appreciably enlarged, and the abdomen was not tender. Bowel sounds were diminished but present. The liver was enlarged at 3 cm below the right costal margin. There was no peripheral oedema.
Her haemoglobin was 11.4 g/dl, and the haematocrit was 36 vol%. The leukocyte count was 11 400/µm3, the INR was 8.4, and C-reactive protein (CRP) was 280 mg/l. Plasma sodium was 132, chloride 87, potassium 5.5, magnesium 1.49, total calcium 1.49 and phosphorus 7.76 (all mmol/l). Plasma creatinine was 1290 µmol/l, urea 66 mmol/l, lipase 131 U/l, amylase 94 U/l, aspartate aminotransferase U/l, alanine aminotransferase 42 U/l,
-glutamyl transferase 150 U/l, total protein 63 g/l and albumin 23 g/l. The urine showed granular casts, erythrocytes and leukocytes with protein +1 without ketones. The urine osmolality was 335 mOsm/kg H2O, Na <10 mmol/l, Cl <10 mmol/l and K 44 mmol/l. The urine creatinine was 17 mmol/l and urea 112 mmol/l. The fractional excretion of Na was <1% and that of urea was 13%. Arterial blood disclosed pH 7.24, PaCO2 29 mmHg, PaO2 105 mmHg, HCO3 12 mmol/l and lactate 0.75 mmol/l. Toxicological studies revealed a plasma salicylate level of 49 mg/dl, while ethanol, methanol and ethylene glycol were undetectable. The electrocardiogram was unremarkable with the exception of a prolonged QT interval attributable to a lengthened ST segment (Figure 1, top).

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Fig. 1. Electrocardiogram on admission (top) showing QTc 520 ms with normal T wave morphology, consistent with hypocalcaemia. With correction of hypocalcaemia, the electrocardiogram reverted to normal (bottom).
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An abdominal ultrasound disclosed an enlarged liver of increased density. The kidneys were normal in size without obstruction. No free abdominal fluid was detected. We then measured creatinine kinase and myoglobin. Both were only slightly elevated. Plasma parathyroid hormone and 25-OH-vitamin D levels were within the low-normal range. We were confronted with a patient who presumably had pre-renal failure, anion gap metabolic acidosis, hypocalcaemia and profound hyperphosphataemia of unknown cause. We did not believe that her salicylate level explained the anion gap, the calcium or the phosphate levels. At the time, we felt we could not rule out a tumour-lysis syndrome and therefore acute haemodialysis coupled with volume expansion was performed. Three dialyses were done on three consecutive days. Thereafter, she had gained 5 kg in weight, her calcium increased to 2.31 and her phosphorus decreased to 1.1 mmol/l. Her electrocardiogram (Figure 1, bottom) now showed a normal QT interval. Her CRP decreased to 145 mg/l. She continued to deny abdominal pain. In the process of pursuing the idea of an occult neoplasm, a magnetic resonance imaging (MRI) study of the abdomen was carried out (Figure 2). Because of the patient's acute renal failure, we did not perform computed tomography (CT) with contrast agents.
To our considerable irritation and surprise, the MRI scan showed clear evidence of acute pancreatitis with secondary haemorrhage. The aetiology of the hypocalcaemia, the hyperphosphataemia and the pre-renal azotaemia suddenly became clear. Less obvious was why her acute pancreatitis failed to present with pain and enzyme elevations. We initially thought that a massive acute phosphate load might have caused hyperphosphataemia in our patient. Since exogenous causes, such as phosphate-containing enemas, could not be identified, we speculated on the tumour-lysis syndrome. However, our patient had no obvious lymphoma and had not received chemotherapy [1]. Rhabdomyolysis may cause hyperphosphataemia [2]. However, our patient had no evidence of that condition. Her renal failure was not pigment induced. Lactic and ketoacidosis can be associated with massive hyperphosphataemia [35]; however, neither was present in our patient. Renal failure is commonly associated with hyperphosphataemia. However, in our patient, renal osteodystrophy was not present and her parathyroid hormone values were low. Hypoparathyroidism is associated with hyperphosphataemia, but generally not to the degree reported here. Salicylate intoxication is not associated with hyperphosphataemia, although hypocalcaemia has been reported with salicylate poisoning after bicarbonate therapy [6]. Our patient had not received bicarbonate.
When hyperphosphataemia is severe, the clinical chemistry laboratory dilutes the patient's serum sample for further accurate determination of the phosphate concentration. There is some evidence that commonly used saline solutions contain phosphorus, and thus lead to further pseudohyperphosphataemia [7]. In our chemistry laboratory, the phosphorus in the saline solution used was out of range (low). Our patient resembles a patient described earlier by Thatte et al. [8]. They also observed a patient with acute pancreatitis and markedly elevated phosphate levels. In their patient, dietary phosphorus supplementation, acute renal failure, ischaemic bowel disease and lactic acidosis were contributing factors. The authors indicated that severe hyperphosphataemia is invariably multifactorial. The conclusion is difficult to dismiss offhand, although we are at a loss to delineate additional factors. Furthermore, we continue to be puzzled about the misleading enzyme values.
When the patient was discharged from our ward, renal function had completely recovered, and phosphorus, as well as lipase and amylase, were within the normal range.
Our diagnosis is occult pancreatitis with secondary haemorrhage, masquerading as profound hyperphosphataemia.
Conflict of interest statement. None declared.
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References
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Received for publication: 28. 8.03
Accepted in revised form: 8. 3.04