When investigating a patient with suspected Cushing's syndrome, two stages are necessary: confirmation of the presence of Cushing's syndrome and, if present, differential diagnosis of the precise cause.
The diagnosis of Cushing's syndrome relies upon the demonstration of excessive cortisol secretion and abnormal feedback regulation of the hypothalamic-pituitary-adrenal axis.
No clinical features provide uniformly reliable differentiation between the causes of the syndrome, but unequivocal pigmentation, clinical diabetes mellitus, and especially unprovoked hypokalaemia strongly suggest the presence of ectopic ACTH secretion. Virilisation may be indicative of androgen secretion by an adrenal tumour.
