His neurological examination is otherwise normal, apart from some weakness in shoulder abduction and hip flexion

A 64-year-old man goes to his general practitioner (GP) because he has become increasingly overweight. He has gained 8kg in weight over the past 6 months. He has noticed that he is constantly hungry. He has found that he is bruising easily. He finds it difficult to get up from his armchair or to climb stairs. He feels depressed and finds himself waking early in the mornings. He has had no previous physical or psychiatric illnesses. He is a retired miner and lives with his wife in a terraced house. He smokes 30 cigarettes per day and drinks 15 units of alcohol per week.
Examination He is overweight particularly in the abdominal region. There are purple stretch marks on his abdomen and thighs. His skin is thin, and there are spontaneous bruises. His pulse is 76/min, regular, and blood pressure 168/104mmHg. There is peripheral oedema. Otherwise, examination of his heart, respiratory and abdominal systems is normal. His neurological examination is otherwise normal, apart from some weakness in shoulder abduction and hip flexion.

Normal Haemoglobin 13.2g/dL 13.3–17.7g/dL Mean corpuscular volume (MCV) 87fL 80–99fL White cell count 5.2 109/L 3.9–10.6 109/L Platelets 237 109/L 150–440 109/L Sodium 138mmol/L 135–145mmol/L Potassium 3.3mmol/L 3.5–5.0mmol/L Urea 6.2mmol/L 2.5–6.7mmol/L Creatinine 113amol/L 70–120amol/L Albumin 38g/L 35–50g/L Glucose 8.3mmol/L 4.0–6.0mmol/L Bilirubin 16mmol/L 3–17mmol/L Alanine transaminase 24IU/L 5–35IU/L Alkaline phosphatase 92IU/L 30–300IU/L Gamma-glutamyl transpeptidase 43IU/L 11–51IU/L
Urinalysis: – protein; – blood; glucose Chest X-ray: normal
INVESTIGATIONS
Questions • What is the likely diagnosis? • How would you investigate and manage this patient?

ANSWER
The symptoms and signs of proximal myopathy, striae and truncal obesity are features of Cushing’s syndrome. The hyperglycaemia and hypokalaemia would fit this diagnosis. In addition psychiatric disturbances, typically depression, may occur in Cushing’s syndrome. Cushing’s disease is due to a pituitary adenoma secreting adrenocorticotrophic hormone (ACTH). The term ‘Cushing’s syndrome’ is a wider one, and encompasses a group of disorders due to overproduction of cortisol.
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• ACTH secretion by a basophil adenoma of the anterior pituitary gland (Cushing’s disease). • Ectopic ACTH secretion, e.g. from a bronchial carcinoma, often causing a massive release of cortisol and a severe and rapid onset of symptoms. • Primary adenoma/carcinoma of the adrenal cortex (suppressed ACTH). • Iatrogenic: corticosteroid treatment. This is the commonest cause in day-to-day clinical practice. Causes of Cushing’s syndrome!
This patient’s primary presenting complaint is rapid-onset obesity. The principal causes of obesity are: • genetic • environmental: excessive food intake, lack of exercise • hormonal: hypothyroidism, Cushing’s syndrome, polycystic ovaries and hyperprolactinaemia • alcohol-induced pseudo-Cushing’s syndrome. This patient should be investigated by an endocrinologist. The first point is to establish is that this man has abnormal cortisol secretion. There should be loss of the normal diurnal rhythm with an elevated midnight cortisol level or increased urinary conjugated cortisol excretion. A dexamethasone suppression test would normally suppress cortisol excretion. It is then important to exclude common causes of abnormal cortisol excretion such as stress/depression or alcohol abuse. Measurement of ACTH levels distinguishes between adrenal (low ACTH) and pituitary/ectopic causes (high ACTH). This patient drinks alcohol moderately and has a normal gamma-glutamyl transpeptidase. His depression seems to be a consequence of his cortisol excess rather than a cause, as he has no psychiatric history. He is having problems with stairs and his social circumstances need to be considered, but his mobility should improve with appropriate treatment. His ACTH level is elevated. Bronchial carcinoma is a possibility as he is a heavy smoker and the onset of his Cushing’s syndrome has been rapid. However his chest X-ray is normal. In this man a magnetic resonance imaging (MRI) scan (T1-weighted coronal image) through the pituitary shows a hypointense microadenoma (Fig. 11.1, arrow). This can be treated with surgery or radiotherapy.