Cushing’s Syndrome vs Addison’s Disease

Pathophysiology
Cushing’s Syndrome- Is the clinical manifestation of pathologic hypercortisolism. Can be caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumors (termed Cushing disease), by autonomous adrenal cortisol overproduction, and, rarely, by ectopic ACTH-secreting tumors.
Addison’s Disease- Primary adrenal insufficiency resulting in glucocorticoid and mineralocorticoid insufficiency. Low levels of cortisol secretion by the adrenal glands. Can result from inadequate stimulation from the anterior pituitary by adrenocorticotropic hormone (ACTH). Caused by autoimmune destruction of the adrenal cortex in 80% of cases.

Incidence
Cushing’s Syndrome- Relatively uncommon in the general population. However, high-risk groups report a significantly greater prevalence. Incidence greater among women.
Addison’s Disease- Most common between ages 30 – 60 years. Incidence greater among women and children. 

Signs and SymptomsCushing’s Syndrome- Weight gain with central obesity, facial rounding and plethora, proximal muscle weakness, and thinning of the skin, hyperglycemia.
Addison’s Disease- Fatigue, Weakness, Anorexia, Weight Loss, Nausea, Abdominal Pain, Diarrhea.

Labs/Diagnostic Testing
Cushing’s Syndrome

• CBC, Serum Glucose Levels, CMP
• urine pregnancy test
• late-night salivary cortisol
• 1 mg overnight dexamethasone suppression test
• 24-hour urinary free cortisol
• 48-hour 2 mg (low-dose) dexamethasone suppression test

Addison’s Disease

• CBC, CMP, BUN, GFR
• Rapid ACTH test (establishes adrenal insufficiency, but does not differentiate between primary and secondary adrenal insufficiency) 
• Plasma ACTH level

Management (Non-Pharmacologic)
Cushing’s Syndrome

• Transsphenoidal resection of the causative pituitary adenoma
• Resection or ablation of ectopic tumors producing ACTH or CRH
• Unilateral adrenalectomy or tumor resection
• Bilateral adrenalectomy

Addison’s Disease

• Adrenal CT scan- if the cause of primary adrenal insufficiency is not apparent

Management (Pharmacologic) 
Cushing’s Syndrome- A somatostatin analog (pasireotide), steroidogenesis inhibitor, or glucocorticoid receptor antagonist (mifepristone) is occasionally used for mild hypercortisolism, or short term for severe hypercortisolism before other therapies are undertaken. Exogenous Glucocorticoid Therapy (Hydrocortisone, Prednisone, Dexamethasone).
Addison’s Disease- Hydrocortisone is the drug of choice. Can also use prednisone. Mineralocorticoid (Fluddrocortisone).

References
Cash, J. C., & Glass, C. A. (2017). Family practice guidelines. New York: Springer Publishing Company, LLC.

Dunphy, L.M., Winland-Brown, J.E., Porter, B.O. & Thomas, D.J. (2015). Primary Care: The Art and Science of Advanced Practice Nursing, 4th Edition, Philadelphia: F.A. Davis Company

Fleseriu, M. (2018). Cushing syndrome. Epocrates. Retrieved from https://online.epocrates.com/diseases/20511/Cushing-syndrome/Key-Highlights