Differential Diagnosis for Elevated Cortisol and ACTH

Single Most Likely Diagnosis

• Cushing's Disease: This is the most likely diagnosis given the elevated cortisol and ACTH levels. Cushing's disease is caused by an ACTH-producing pituitary adenoma, leading to increased cortisol production by the adrenal glands.

Other Likely Diagnoses

• Ectopic ACTH-producing Tumor: Tumors outside the pituitary gland, such as small cell lung cancer, can produce ACTH, leading to elevated cortisol levels.
• Familial Cushing's Syndrome: A rare genetic disorder that can cause Cushing's syndrome due to mutations affecting the ACTH or cortisol pathways.
• Adrenal Hyperplasia: A condition where the adrenal glands produce excessive cortisol due to hyperplasia (overgrowth) of adrenal cells.

Do Not Miss Diagnoses

• Pituitary Apoplexy: A medical emergency where a pituitary tumor suddenly hemorrhages or infarcts, potentially leading to acute ACTH and cortisol deficiency or excess.
• Adrenal Crisis: A life-threatening condition that occurs when the adrenal glands do not produce enough cortisol, often due to Addison's disease or sudden withdrawal from exogenous steroids.
• Malignant Tumor: Certain malignant tumors, such as adrenal carcinomas or metastatic disease to the adrenal glands, can produce ectopic ACTH or cortisol, leading to Cushing's syndrome.

Rare Diagnoses

• McCune-Albright Syndrome: A rare genetic disorder characterized by precocious puberty, café-au-lait spots, and fibrous dysplasia, which can also lead to Cushing's syndrome due to adrenal nodular hyperplasia.
• Primary Pigmented Nodular Adrenocortical Disease (PPNAD): A rare cause of Cushing's syndrome characterized by multiple small nodules in the adrenal glands, often associated with Carney complex.
• Familial Glucocorticoid Resistance: A rare genetic disorder where the body is resistant to cortisol, leading to elevated ACTH and cortisol levels.