Editing Hypercortisolism (section)

== Pathophysiology ==

* '''Definition of Cushing's syndrome: hypercortisolism secondary to excessive production of glucocorticoids by the adrenal cortex'''
* '''<span style="color:#ff0000">Causes of Cushing's syndrome</span>''' 
** '''<span style="color:#ff0000">Categorized into 3 main groups: exogenous vs. ACTH-dependent vs. ACTH-independent</span>'''
**# '''<span style="color:#ff0000">Exogenous</span>'''
**#* '''Most common cause of hypercortisolism in patients of the Western world</span>'''
**#* Can cause virilization, including hirsutism, but should not elevate ketosteroid levels
**# '''<span style="color:#ff0000">ACTH-dependent (endogenous)</span>'''
**#* '''85% of cases of endogenous Cushing syndrome'''
**#* '''Results from an increased serum ACTH level'''
**#* '''Caused by pathology extrinsic to the adrenal gland:'''
**#*# '''Primary pituitary pathology (also known as Cushing disease)'''
**#*#* '''Most common (80%) cause of ACTH-dependent hypercortisolism'''
**#*# '''Ectopic ACTH production'''
**#*#* '''Nearly always malignant;''' the most common associated malignancies are bronchial carcinoid, small cell lung cancer, and less often pheochromocytoma
**#*# '''Ectopic CRH syndrome'''
**#*#* Extremely uncommon; bronchial carcinoma is the most common cause
**# '''<span style="color:#ff0000">ACTH-independent (endogenous)</span>'''
**#* '''15% of cases of endogenous Cushing syndrome; relatively rare'''
**#* '''Cause by pathology intrinsic to the adrenal gland'''
**#* '''Results from unregulated overproduction of glucocorticoids by the adrenal(s), either unilateral neoplasm or rarely, bilateral disease'''
* '''Subclinical Cushing syndrome'''
** '''Hypercortisolemia in the absence of an overt cushingoid phenotype'''
** '''Surgical indications for subclinical Cushing syndrome are still a matter of debate'''.
*** Some argue that adrenalectomy should be performed only in patients who are potentially symptomatic and exhibit clinical signs, such as hypertension, obesity, glucose intolerance, or osteopenia. Others argue that surgery must be offered to all patients to prevent the sequelae of hypercortisolism.
* '''Other conditions can stimulate the Hypothalamus-Pituitary-Adrenal axis and mimic Cushing’s syndrome'''
** '''Causes of hypercortisolism in the absence of Cushing’s syndrome:'''
*** Some features of Cushing syndrome may be present:
**** Morbid obesity
**** Glucocorticoid resistance
**** Poorly controlled diabetes mellitus
**** Pregnancy
**** Depression
**** Alcohol dependence
*** Unlikely to have any clinical features of Cushing syndrome
**** Physical stress (hospitalization, surgery, pain)
**** Malnutrition, anorexia nervosa
**** Intense chronic exercise
**** Hypothalamic amenorrhea
**** Corticosteroid-binding globulin excess (increased serum but not in urine cortisol)