Cushing’s Syndrome

Diagnosis

• The physical examination
• Laboratory Diagnosis
  • Demonstration of cortisol hypersecretion
  • The determination of 24-hour urinary excretion of cortisol is the most direct and reliable index of cortisol secretion
  • Concurrent measurement of both plasma ACTH (corticotrophin) and plasma cortisol
    • If the plasma ACTH is greater than 50 pg/mL, the cortisol secretion is ACTH-dependent (the patient a111rafywWaarr~laraal. has Cushing's disease or ectopic ACTH or CRH secretion).
    • If the ACTH is low, the patient has adrenal disease, adenoma, or carcinoma
  • If corticotrophin/cortisol assay is not available, the dexamethasone suppression test is utilized
    • Low-dose dexamethasone 0.5 mg QID causes plasma cortisol suppression to normal in patients with pseudoCushing's and normal patients
    • High-dose dexamethasone 2.0 mg QID causes plasma cortisol suppression in patients with pituitary Cushing's (Cushing's disease)
    • Patients with adrenal adenoma and carcinoma do not suppress plasma cortisol with high-dose dexamethasone
    • Patients with ectopic ACTH are often also resistant to high-dose dexamethasone The most direct way to demonstrate pituitary ACTH hypersecretion is with petrosal venous sinus sampling
• Radiographic Localization
  • In patients with Cushing's disease, CT or MRI of the sella turcica often identifies pituitary adenoma
  • Adrenal lesions are defined by adrenal CT
    • Patients with bilateral hyperplasia show diffuse thickening and elongation of the adrenal rami
    • Adrenal adenomas are usually larger than 2 cm and solitary with atrophy of the opposite gland
    • Adrenal carcinomas are characteristically greater than 5 em, irregular, and nonhomogeneous with necrosis and calcification. However, they may be indistinguishable from adenomas
  • Adrenal MRI may be useful
    • Adenomas have low signal intensity
    • Adrenal carcinomas may show high signal intensity
    • Metastatic tumors to the adrenal show high signal intensity
    • Medullary tumors show high signal intensity

Treatment

• Cushing's disease
  • Trans-sphenoidal pituitary adenomectomy
  • Pituitary radiation
• Ectopic CRH/ACTH secretion
  • Removal of the primary tumor
• Adrenal adenoma/carcinoma
  • Unilateral adrenalectomy
    • Small-laparoscopic removal
    • Carcinoma or size greater than 6-cm open surgical removal
  • Mitotane (OP-DDD) is utilized for patients with metastatic adrenal carcinoma.
• Preoperative/postoperative management
  • Preoperative steroid suppression with metyrapone to reduce symptoms.
  • Intraoperative glucocorticoid administration.
  • Postoperative steroid replacement with dexamethasone.
  • Patients are at increased risk for infection, hemorrhage, and fractures.

References

• Blumenfeld JD, Schlusse, Sealey JE, et al: Diagnosis and treatment of primary hyperaldosteronism. Ann Intern Med, 121:877-885, 1994.
• Blumenfeld JD, Vaughan ED Jr.: The adrenals. In: Campbell's Urology. 7th Ed. Philadelphia, Saunders, 1998, pp. 2915-2971.
• Manger WM, Gifford RW Jr.: Pheochromocytoma. A clinical review. In: Hypertension Pathophysiology, Diagnosis, and Management. Laragh JH, Brenner BM, eds. 1995, pp. 2225-2246.
• Orth DN: Cushing syndrome. N Eng J Med 332:791-795, 1995.
• Ulchaker JC, Goldfarb DA, Bravo EL, Novick AC: Successful outcomes in pheochromocytoma surgery in the modern era. J Urol 161:764-767, 1999. Vaughan ED Jr.: Adrenal surgery. F. F. Marshall, Ed. In: Textbook of Operative Surgery. Philadelphia, Saunders, 1996, p 220-230.
• Vaughan ED Jr., (ed): Diagnosis and treatments of adrenal disorders. World J Urol 17:1064, 1999.