Differential Diagnosis for ACTH-Dependent Cyclic Cushing's with Normal UFC but Huge Volumes

• Single Most Likely Diagnosis
  • Cyclic Cushing's Disease: This condition is characterized by periodic episodes of cortisol hypersecretion, which can lead to variable UFC (urine free cortisol) levels. The huge volumes (3 and 4L) could indicate polyuria, a symptom sometimes associated with Cushing's syndrome due to the effects of cortisol on glucose metabolism and subsequent osmotic diuresis. The ACTH-dependent nature points towards a pituitary source, making Cushing's disease a prime consideration.
• Other Likely Diagnoses
  • Ectopic ACTH-Producing Tumor: Although less common than Cushing's disease, ectopic ACTH-producing tumors can cause cyclic Cushing's syndrome. These tumors can lead to intermittent hypercortisolism, which might result in normal UFC levels at times but significant clinical symptoms during periods of high cortisol production.
  • Familial Cushing's Syndrome: Rare familial cases can present with cyclic or variable cortisol production. This could be due to genetic mutations affecting the pituitary or adrenal glands, leading to ACTH-dependent Cushing's syndrome.
• Do Not Miss Diagnoses
  • Pheochromocytoma with Ectopic ACTH Production: A rare but potentially deadly condition if missed. Pheochromocytomas can occasionally produce ACTH, leading to Cushing's syndrome. The cyclic nature and huge volumes could be indicative of episodic catecholamine and cortisol release.
  • Medullary Thyroid Carcinoma with ACTH Production: Another rare but critical diagnosis to consider. Some medullary thyroid carcinomas can produce ACTH, leading to Cushing's syndrome. Early diagnosis is crucial due to the aggressive nature of this cancer.
• Rare Diagnoses
  • McCune-Albright Syndrome: A rare genetic disorder that can lead to Cushing's syndrome due to adrenal nodular hyperplasia. It's characterized by café-au-lait spots, polyostotic fibrous dysplasia, and various endocrine disorders, including cyclic Cushing's syndrome.
  • Carney Complex: A rare multiple neoplasia syndrome that includes Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). It can present with cyclic cortisol production and is associated with other tumors and skin abnormalities.