Lesson of the Week: Addison's disease

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Abstract
Case reports CASE 1 A 26 year old man was admitted to hospital with a history of two to three days of nausea and vomiting and increasingly frequent watery stools. He had also complained of a sore throat for two to three days, for which his family doctor had prescribed pivampicillin. He had not travelled overseas nor had he eaten any food outside his own home. He worked as a security officer near the Thames but never swam there. He had no previous history of weight loss, abdominal pain, or cardiovascular symptoms nor any important past medical history. Initial examination showed him to be dehydrated with a temperature of 37.5°C, a pulse rate of 120 beats a minute, and blood pressure of 85/60 mm Hg (with no postural drop). No hyperpigmentation of skin creases or mucous membranes was noted. His tonsillar bed was inflamed. Examination of his abdomen was unremarkable. Haematological investigations gave normal results, in particular sodium 135 mmol/l (normal range 135-150 mmol/l), potassium 5.9 mmol/l (normal range 3.5-5.3 mmol/l), creatinine 233 µmol/l, urea 15.4 mmol/l, and glucose 3.9 mmol/l (normal range 3.0-8.0 mmol/l). His electrocardiogram showed a sinus tachycardia with a normal axis, voltage, and T waves. A chest x ray picture revealed a normal heart with normal lung fields. Urine analysis and microscopy were normal. Paracetamol and salicylate were not detected. Blood, urine, and stool cultures gave negative results, as did a monospot test and virology serology (results obtained after death). An autoantibody screen and a test for antineutrophil cytoplasmic antibodies were negative. A provisional diagnosis of viral infection complicated by acute renal failure was made. The diagnosis of Addison's disease was considered but was thought unlikely. Rehydration was started. A central venous pressure line was inserted, and renal dopamine infusion was started when his urine output was measured as less than 30 ml/hour. An urgent abdominal ultrasound scan revealed normal kidneys and ureters and no other intra-abdominal abnormality. Over the next few hours he became increasingly ill, with deteriorating oxygenation, and he was transferred to the intensive care unit, where he was ventilated on admission with an inspired oxygen concentration of 60% and positive end expiratory pressure of 5 cm water. Infusion with dobutamine 10 µg/kg/min was also started. A pulmonary artery catheter was inserted, revealing pulmonary arterial wedge pressure of 13 mm Hg, cardiac index of 6.7 l/min/m2, and systemic vascular resistance of 260 dyn.s.cm-5. Infusions of adrenaline and noradrenaline were started, as were broad spectrum antibiotics (metronidazole, benzylpenicillin, erythromycin, and cefotaxime). He gradually deteriorated over the next 24 hours, with rising blood urea and creatinine concentrations and increasing metabolic acidosis. His cardiac index fell despite increasing ionotropic support, and electrocardiography revealed a left axis shift and the development of an intraventricular conduction defect. His creatinine kinase and alanine transferase concentrations rose to 639 U/l and 953 U/l respectively. An echocardiogram revealed acute cardiac dilatation with poor systolic function. Urgent transfer was arranged to the nearby cardiology unit. Unfortunately, just before transfer he suffered a cardiac arrest from which he could not be resuscitated. At necropsy, the changes in most organs were nonspecific: petechial haemorrhages in the pericardium, intense acute congestion and oedema of both lungs, mild fatty change in the liver, and some swelling of the renal cortices. The heart was moderately dilated, but its weight (340 g) was normal. No adrenal gland tissue could be identified with certainty on macroscopic examination. Multiple blocks for histology were prepared from the adrenal sites. Microscopy revealed minute remnants of the glands infiltrated with lymphocytes (fig 1), and there were a few tiny nodules of cortical cells showing acute coagulative necrosis. There was no fibrous scarring. In view of the absence of fibrosis, the histological changes had probably developed quite rapidly. Both macroscopic and microscopic appearances were entirely different from the acute haemorrhagic destruction of the adrenal glands that occurs in some cases of septicaemia (Waterhouse-Friderichsen syndrome) and many other conditions (reviewed by Rao4). A random cortisol test of 30 nmol/l (result obtained after death) was consistent with the findings at necropsy. View larger version: In this window In a new window Fig 1 Low power micrograph of left adrenal from case one showing greatly thinned adrenal parenchyma between wall of central vein (top left) and part of capsule (bottom right). Cells are shrunken and are separated by oedema and lymphocyte infiltrate (haematoxylin and eosin stain)