• Cortisol is a steroid hormone of the glucocorticoid family that plays a vital role in the response to stress. In particular, cortisol
  • Stimulates gluconeogenesis
  • Suppresses inflammation
  • Maintains vascular responsiveness to catecholamines
• Cortisol is synthesized secreted by the adrenal cortex. It is regulated by adrenocorticotropic hormone (ACTH) produced by the anterior pituitary. ACTH is, in turn, regulated by corticotropin-releasing hormone (CRH) produced by the hypothalamus. Cortisol exerts negative feedback control by inhibiting the secretion of CRH ACTH.
• A 24-hour circadian rhythm causes oscillatory release of CRH, ACTH, cortisol. for those who sleep at night, cortisol levels are highest just before waking lowest in the evening.
• Disease states include Cushing's syndrome (glucocorticoid excess) Addison's disease (adrenocortical insufficiency).

• Cortisol is a steroid hormone that enters cells binds to an intracellular cytoplasmic receptor. This bound complex stimulates DNA transcription resulting in protein production that mediates the effects of cortisol.
• Cortisol stimulates gluconeogenesis:
  • Increases protein catabolism decreases protein synthesis in the muscle, thereby providing more amino acids to the liver for gluconeogenesis.
  • Decreases insulin sensitivity decreases glucose utilization in adipose tissue.
  • Lipolysis is increased, providing more substrate for gluconeogenesis.
• Cortisol suppresses inflammation:
  • Inhibits the production of interleukin-2 proliferation of T lymphocytes.
  • Inhibits release of histamine serotonin from mast cells platelets.
  • Decreases prostaglin leukotriene synthesis by inhibiting the formation of arachidonic acid.

• CRH-containing neurons are located in the paraventricular nuclei of the hypothalamus. CRH is released into the hypothalamic–hypophysial portal blood delivered to the anterior pituitary where it stimulates ACTH secretion.
• The anterior lobe of the pituitary synthesizes secretes ACTH into the bloodstream under CRH stimulation.
• Cortisol is produced by cells within the zona fasciculata of the adrenal cortex.
• The adrenal gl is composed of the inner medulla that produces catecholamines the outer cortex that is divided into three histological zones. Going from outside inwards: The outer most zona glomerulosa is the source of aldosterone production. Just beneath is the zona fasciculata, the source of glucocorticoids production. The inner most layer of the cortex is the zona reticularis; responsible for the production of rogens.

• Cortisol excess states (Cushing's syndrome):
  • Caused by endogenous oversecretion or iatrogenic treatment with glucocorticoids at supraphysiologic doses.
  • Endogenous oversecretion. The majority of instances involve ACTH overproduction (80%). These disease states include ACTH producing pituitary adenoma ectopic ACTH production from tumors such as small cell carcinoma of the lung pancreatic carcinoma. ACTH-independent processes such as cortisol secreting adrenal adenoma or carcinoma make up the remainder of endogenous cortisol oversecretion (20%).
  • When the source of endogenous cortisol is caused by overproduction of ACTH by the pituitary, the condition is known as Cushing's disease.
  • Chronic excess of glucocorticoids results in physical changes. These include central obesity, moon facies, purple striae, muscle wasting, osteopenia, hirsutism, hyperpigmentation. Clinical signs include glucose intolerance hypertension, hypokalemic alkalosis, leukocytosis.
  • Treatment of endogenous sources of excess glucocorticoid entails surgical resection.
• Cortisol-deficient states:
  • Primary adrenocortical insufficiency is caused by the inability of adrenal gls to produce both glucocorticoids mineralocorticoids (Addison's disease).
    • Most common cause is autoimmune destruction of the adrenal cortex resulting in acute adrenal crisis. Other causes of adrenocortical insufficiency include metastatic disease to the adrenal cortex, adrenal hemorrhage, infection of the adrenal gl (tuberculosis, opportunistic infections with HIV, fungemia), amyloid infiltration [1].
    • Characterized by elevated ACTH levels but decreased levels of glucocorticoids mineralocorticoids.
    • Clinical features are related to the adrenocortical hormone deficiency. Hypoglycemia is caused by cortisol deficiency. Hypotension, postural hypotension, hyperkalemia, metabolic acidosis, volume contraction are caused by mineralocorticoid deficiency. Hyperpigmentation is caused by elevated ACTH secretion. Other signs symptoms include weakness, fatigue, lethargy, anorexia, nausea, abdominal pain, prerenal azotemia, hypercalcemia, convulsions, fever, syncope.
    • Treatment: Replacement of glucocorticoids (hydrocortisone, prednisone, methylprednisolone) mineralocorticoids (fludrocortisone).
  • Secondary adrenocortical insufficiency is caused by decreased ACTH production by the anterior pituitary gl.
    • Most common cause of secondary adrenocortical insufficiency is withdrawal of corticosteroid therapy. Other causes include pituitary tumor, pituitary surgery or radiation, postpartum hypopituitarism (Sheehan's syndrome), sarcoid infiltration of the pituitary gl.
    • Chronic corticosteroid therapy suppresses the hypothalamus anterior pituitary resulting in decreased production of CRH ACTH, respectively. Decreased levels of CRH ACTH cause atrophy of the zona fasciculata, resulting in glucocorticoid deficiency. During times of physiologic stress, the patient is unable to acutely increase cortisol production, resulting in acute secondary adrenocortical insufficiency.

• Cortisol excess states:
  • Patients with Cushing's syndrome must have their diabetes, BP, intravascular volume status, electrolytes optimized prior to surgery.
  • The body habitus of Cushingoid patients (central obesity, moon facies, buffalo hump) may present an airway challenge.
  • A high cortisol state causes immunosuppression poor wound healing. Sterile technique is vital for all procedures line placements to minimize iatrogenic infections.
  • Careful positioning is vital as severe osteopenia increases risk of fractures.
  • Patients with adrenal Cushing's syndrome presenting for adrenalectomy should receive hydrocortisone at the time of surgery as they are at risk of developing acute glucocorticoid deficiency postoperatively. Hydrocortisone can then be tapered as the previously quiescent contralateral adrenal gl resumes corticosteroid production.
• Cortisol-deficient states:
  • Patients with adrenocortical insufficiency should continue their mineralocorticoid glucocorticoid replacement therapy up until their time of surgery. Clinical features of overt deficiency include hyperkalemia, hyponatremia, metabolic acidosis, myocardial conduction defects.
  • Hydrocortisone has both glucocorticoid mineralocorticoid activity. Therefore, it is an ideal agent to use for the management of adrenocortical insufficiency.
  • Additional perioperative stress dose of glucocorticoids may be necessary as these patients may not be able to mount an adequate stress response. Traditional recommendation is 200 mg hydrocortisone per 70 kg body weight per day [2]. However, smaller doses of 100 mg per 70 kg body weight per day have been used with success [3,4].
  • The amount of perioperative hydrocortisone supplementation is based on the anticipated stress of the procedure, relative degree of trauma, the depth of anesthesia [5].

• Aldosterone
• Acute Adrenal Insufficiency

Joe C. Hong , MD