Differential Diagnosis for Elevated Cortisol and ACTH Levels

The patient's presentation of elevated fasting AM cortisol, 24hr urinary cortisol, and failure to suppress cortisol levels after dexamethasone testing, along with an elevated morning ACTH level, suggests a diagnosis related to excessive cortisol production. The differential diagnosis can be categorized as follows:

• Single Most Likely Diagnosis
  • Cushing's Disease: This condition, caused by an ACTH-producing pituitary adenoma, leads to elevated ACTH levels, which in turn cause the adrenal glands to produce excessive cortisol. The elevated morning ACTH level and the failure of dexamethasone to suppress cortisol production are consistent with this diagnosis.
• Other Likely Diagnoses
  • Ectopic ACTH-producing Tumor: Tumors outside the pituitary, such as small cell lung cancer, can produce ACTH, leading to elevated cortisol levels. The high ACTH level in this patient could suggest an ectopic source, although this is less common than Cushing's disease.
  • Familial Cushing's Syndrome: Although rare, familial cases due to genetic mutations affecting the pituitary or adrenal glands can present similarly.
• Do Not Miss Diagnoses
  • Pheochromocytoma: While primarily known for causing hypertension due to excessive catecholamine production, some pheochromocytomas can co-secrete ACTH, leading to Cushing's syndrome. Missing this diagnosis could be catastrophic due to the potential for severe hypertension and cardiovascular complications.
  • Adrenal Carcinoma: Although rare, adrenal carcinomas can produce both cortisol and ACTH, leading to a similar clinical presentation. The failure to diagnose and treat an adrenal carcinoma could result in significant morbidity and mortality.
• Rare Diagnoses
  • McCune-Albright Syndrome: A rare genetic disorder that can lead to Cushing's syndrome due to adrenal nodular hyperplasia. It is characterized by café-au-lait spots, polyostotic fibrous dysplasia, and various endocrine disorders.
  • Primary Pigmented Nodular Adrenal Disease (PPNAD): A rare cause of Cushing's syndrome, often associated with Carney complex, characterized by multiple small nodules in the adrenal glands producing cortisol autonomously.