INTRODUCTION

Cushing disease is an endocrine disorder characterized by increased adrenocorticotropic hormone

(ACTH) production from the anterior pituitary, leading to excess cortisol release from the adrenal
glands.[1] This is often caused by a pituitary adenoma or it is the result of excess production of
corticotropin-releasing hormone (CRH) from the hypothalamus.[2] Symptoms of the disease include
generalized weakness, high blood pressure, diabetes mellitus, menstrual irregularities, or psychiatric
changes.[1] Physical manifestations of excess cortisol levels include moon facies, buffalo hump,
easy bruising, abdominal striae, obesity, facial plethora, and hirsutism.[2]

ETIOLOGY
Patients with Cushing disease almost always have a pituitary adenoma, often not evident by imaging.
However, rare cases may result from diffuse corticotroph cell hyperplasia, even in the absence of
ectopic secretion of corticotropin-releasing hormone (CRH). The tumors are usually microadenomas
(less than 10 mm in size); only about 5 to 10 percent are macroadenomas. Macroadenomas are more
likely to produce abnormally high ACTH concentrations when compared to microadenomas (83
versus 45 percent).[3][4] Several genetic mutations are responsible for these adenomas.[5] The most
common mutation is USP8 (ubiquitin specific peptidase 8). These mutations lead to abnormal
expression of growth factors, which act with ACTH to increase cortisol level.[6]
 FUNCTION OF CORTISOL
Stress Response
The human body is continually responding to internal and external stressors. The body processes
the stressful information and elicits a response depending on the degree of threat. The body's
autonomic nervous system is broken down into the sympathetic nervous system (SNS) and the
parasympathetic nervous system (PNS). In times of stress, the SNS gets activated. The SNS is
responsible for the fight or flight response, which causes a cascade of hormonal and physiological
responses. The amygdala is responsible for processing fear, arousal, and emotional stimuli to
determine the appropriate response. If necessary, the amygdala sends a stress signal to the
hypothalamus.[5] The hypothalamus subsequently activates the SNS, and the adrenal glands
release a surge of catecholamines, such as epinephrine. This results in effects such as increased
heart rate and respiratory rate. As the body continues to perceive the stimuli as a threat, the
hypothalamus activates the HPA axis. Cortisol is released from the adrenal cortex and allows the
body to continue to stay on high