Differential Diagnosis for Pituitary Cushing's

Given the patient's history and failure of the low-dose dexamethasone suppression test (LDDST) 12 years ago, the following differential diagnoses are considered:

• Single Most Likely Diagnosis
  • Pituitary Cushing's Disease: This is the most likely diagnosis given the patient's history of failing the LDDST, which suggests autonomous cortisol production. Pituitary Cushing's disease, caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma, is a common cause of endogenous Cushing's syndrome.
• Other Likely Diagnoses
  • Ectopic ACTH-producing Tumor: Although less common than pituitary Cushing's, ectopic ACTH-producing tumors can also cause Cushing's syndrome by secreting ACTH, leading to bilateral adrenal hyperplasia and excessive cortisol production.
  • Adrenal Cushing's Syndrome: This could be due to an adrenal adenoma or carcinoma that autonomously produces cortisol, leading to Cushing's syndrome. The failure of the LDDST supports the diagnosis of Cushing's syndrome, but further testing would be needed to distinguish between pituitary and adrenal causes.
• Do Not Miss Diagnoses
  • Familial Cushing's Syndrome: This is a rare condition but important to consider, especially if there's a family history. It can be caused by germline mutations affecting the PRKAR1A gene or other genes involved in the cAMP signaling pathway.
  • Pheochromocytoma: Although not directly related to Cushing's syndrome, pheochromocytomas can sometimes present with similar symptoms (e.g., hypertension, weight loss) and can coexist with Cushing's syndrome in the context of multiple endocrine neoplasia (MEN) syndromes.
• Rare Diagnoses
  • McCune-Albright Syndrome: A rare genetic disorder characterized by café-au-lait spots, polyostotic fibrous dysplasia, and several types of endocrine hyperfunction, including Cushing's syndrome due to adrenal nodular hyperplasia.
  • Primary Pigmented Nodular Adrenocortical Disease (PPNAD): A rare cause of Cushing's syndrome, characterized by the presence of small, pigmented nodules in the adrenal glands, often associated with Carney complex, a multiple neoplasia syndrome.