A 74 year old smoker presents with cough and pigmentation of the oral mucosa. What is the most probable diagnosis?

In this scenario, the symptoms of cough and pigmentation of the oral mucosa are significant. The pigmentation, particularly of the mucosal surfaces, is often associated with an excess of adrenocorticotropic hormone (ACTH) production. This can occur in conditions such as ectopic ACTH syndrome, where ACTH is produced by a tumor outside of the pituitary gland, frequently originating from lung tumors, which can explain the patient’s cough.

In ectopic ACTH syndrome, excessive ACTH leads to overproduction of cortisol by the adrenal glands, resulting in symptoms of Cushing's syndrome, such as weight gain, hypertension, and distinctly, skin changes including pigmentation. The link between the patient's smoking history and the potential for an underlying malignancy, such as a lung cancer, further supports the idea that an ectopic source of ACTH could be the cause of these signs.

Other conditions such as Cushing’s disease—where ACTH is overproduced by a pituitary adenoma—would typically also cause these features, but the specific combination of a cough (suggesting a pulmonary cause) and oral mucosal pigmentation strongly points towards an ectopic source being responsible for the adrenal stimulation, confirming the diagnosis of ectopic ACTH secretion.