Multi-organ failure after a glucagon test

In November, 2005, a glucagon test (1 mg intravenously) was done in a lean 43-year-old man to measure his insulin reserve as part of the assessment of recently diagnosed type 2 diabetes mellitus. He was taking glimepiride 2 mg daily and metoprolol 50 mg daily for mild hypertension. 12 h after the test he presented to the emergency department with dyspnoea and haemoptysis. On examination, he was pale, tachypnoeic, and hypoxic (oxygen saturation 86% on room air). Blood pressure was 140/100 mm Hg, heart rate was 160 beats per min, and temperature was 35∙4°C. General examination showed no abnormalities. Chest radiography suggested consolidation in the right lower lobe. Blood tests showed a raised white-cell count of 24∙4×10/L with neutrophilia (86·3%), lactic acidosis (pH 7·22, pCO2 3·4 kPa, pO2 10·6 kPa, bicarbonate 11 mmol/L, and lactate 9·1 mmol/L), and high creatinine concentration (268 μmol/L). He was admitted to the intensive care unit with a presumed diagnosis of respiratory failure due to pneumonia. Benzylpenicillin and ciprofl oxacin were initiated. His condition deteriorated, and he developed hypotension, anuric renal failure, shock liver, rhabdomyolysis, and widespread bilateral lung infi ltrates. Dobutamine and norepinephrine were started, and activated protein C was administered. He was ventilated in the prone position and continuous venovenous ultrafi ltration was initiated. 2 days after admission, inotropes and vasopressors were withdrawn. He then developed hypertension (with blood pressure up to 250/140 mm Hg) and microangiopathic haemolytic anaemia (platelets 52×10/L); blood test results showed fragmented red cells (8%) and high lactate dehydrogenase (5190 IU/L). The hypertension in combination with negative blood and sputum cultures raised our suspicion of a phaeochromocytoma. Abdom inal ultrasonography showed a mass measuring 9·4×7·9×8·3 cm above the right kidney—this was confi rmed by CT (fi gure). We deduced that the phaeochromocytoma crisis was triggered by the glucagon test. Plasma catecholamine concentrations measured in samples obtained during the glucagon test were very high, confi rming the diagnosis (norepinephrine and epinephrine each >100 000 nmol/L). Our patient’s condition improved after administration of intravenous labetalol (up to 2400 mg daily), doxazosin 16 mg daily, and phentolamine (up to 1440 mg daily). 31 days after admission an uncomplicated adrenal extirpation was done, after which he remained normotensive and normoglycaemic. Histological examin ation of the tumour confi rmed the diagnosis of phaeochromocytoma. He was discharged from the hospital 3 months after admission. When seen in September, 2006, our patient remained well—no urinary catecholamine excess was found and MRI of the abdomen showed no remaining tumour. Multi-organ failure is a rare initial presentation of a phaeochromocytoma, but in most cases is fulminant. In this case, the phaeochromocytoma crisis was precipitated by a glucagon test, which stimulates the phaeochromocytoma to secrete catecholamines—lactic acidosis ensued as a result of the metabolic and vascular eff ects of catecholamine excess. Haemolytic anaemia was probably the result of extreme hypertension and resulting endothelial injury. The increase in catecholamines in such patients is the basis on which the glucagon test was used as a provocative test in the diagnosis of a phaeochromocytoma—because of the unpredictable response and the danger of a hypertensive crisis, its use for this purpose is almost obsolete. In our patient, the glucagon test was used to measure the C-peptide response to fi nd out whether his diabetes was caused by a secretory defect of insulin and to assess the effi cacy of treatment with oral antidiabetic drugs. Hyperglycaemia is a common fi nding in patients with phaeochromocytoma owing to insulin defi ciency and resistance. The glucagon test is often used in patients with diabetes mellitus; however, it rarely leads to a hypertensive crisis due to an undiscovered phaeochromocytoma. Although the incidence of phaeochromocytoma is low, we suggest that it is prudent to be aware of the signs leading to a phaeochromocytoma crisis in lean diabetic and hypertensive patients undergoing a glucagon test.