When the whole-body scan shows no abnormality

Abstract

In September, 2006, a 66-year-old man was admitted to our hospital with a 6-week history of nausea, dysphagia to solids, and abdominal discomfort after eating. His appetite was much reduced, and he reported that he felt sated after eating little food; he had lost 10 kg in weight, and was constantly tired. His past medical history included hypertension, dyslipidaemia, and coronary artery disease; his regular medications were enalapril, atenolol, simvastatin, and aspirin. Other than epigastric tenderness, nothing of note was found on physical examination. The blood tests showed no abnormality. Nor did ultrasonography of the abdomen; upper gastrointestinal endoscopy; a barium swallow test; endoscopic ultrasonography of the upper gastrointestinal tract; colonoscopy; CT of the chest, abdomen, and head; CT of the neck; oesophageal manometry; ear, nose, and throat examination; neurological and psychiatric assessments; or further blood tests, including thyroid function tests and an extensive autoantibody screen. Eventually, a whole-body gallium-67 scan was done. This too showed no abnormality (fi gure). Meanwhile, the patient developed joint pains, and continued to lose weight. Repeated blood tests showed a low serum albumin concentration (29 g/L), as well as normocytic anaemia (haemoglobin 113 g/L), and eosinophilia (0·6×109/L). The combination of unexplained gastrointestinal symptoms, weight loss, arthralgia, and eosinophilia caused the possibility of cortisol defi ciency to be considered. After an overnight fast, the serum cortisol concentration was found to be only 14 nmol/L (normal 190–690 nmol/L). The short corticotropin-stimulation test elicited an impaired response, with a serum cortisol concentration of 308 nmol/L after 60 min. The baseline serum concentration of corticotropin was extremely low (<2·2 pmol/L), indicating dysfunction of the pituitary gland or hypothalamus. Concentrations of luteinising hormone, follicle-stimulating hormone, testosterone, and insulin-like growth factor 1 were all normal; the prolactin concentration was slightly increased. MRI of the brain and pituitary showed no abnormality. There was no evidence of head trauma or of sarcoidosis, which can aff ect the hypothalamus and pituitary. Urine testing, by highperformance liquid chromatography (HPLC), ruled out covert steroid ingestion. The patient was prescribed prednisolone, at a dose of 5 mg daily. When last seen, in May, 2007, his gastrointestinal symptoms had long disappeared, his haemoglobin concentration was 143 g/L, his eosinophil count was normal, and he had regained his former weight. Unintentional weight loss is common in elderly people, and is associated with signifi cantly increased morbidity and mortality. In up to a quarter of patients, no defi nitive aetiology can be established. The possibility of cortisol defi ciency should be considered in all patients with unexplained weight loss or abdominal symptoms. Eosinophilia and anaemia can also be caused by cortisol defi ciency, as can arthralgia. Unusually, our patient’s cortisol defi ciency was secondary to dysfunction of the pituitary or hypothalamus. Chronic understimulation of the adrenal cortex by corticotropin causes an impaired response on the short corticotropin-stimulation test, which does not necessarily indicate Addison’s disease. Since there was no evidence of generalised hypopituitarism, and no evidence of hypothalamic damage on MRI, we made a diagnosis of isolated corticotropin defi ciency—a rare disorder, sometimes caused by lymphocytic hypophysitis, which may be of autoimmune aetiology. Our patient’s recovery strikingly illustrated the diagnostic usefulness of Occam’s razor.