Cortisol in the context of "Adrenal insufficiency"

Stress, whether physiological, biological or psychological, is an organism's response to a stressor, such as an environmental condition or change in life circumstances. When stressed by stimuli that alter an organism's environment, multiple systems respond across the body. In humans and most mammals, the autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis are the two major systems that respond to stress. Two well-known hormones that humans produce during stressful situations are adrenaline and cortisol.

The sympathoadrenal medullary axis (SAM) may activate the fight-or-flight response through the sympathetic nervous system, which dedicates energy to more relevant bodily systems to acute adaptation to stress, while the parasympathetic nervous system returns the body to homeostasis.

The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which produces steroid hormones and an inner medulla. The adrenal cortex itself is divided into three main zones: the zona glomerulosa, the zona fasciculata and the zona reticularis.

The adrenal cortex produces three main types of steroid hormones: mineralocorticoids, glucocorticoids, and androgens. Mineralocorticoids (such as aldosterone) produced in the zona glomerulosa help in the regulation of blood pressure and electrolyte balance. The glucocorticoids cortisol and cortisone are synthesized in the zona fasciculata; their functions include the regulation of metabolism and immune system suppression. The innermost layer of the cortex, the zona reticularis, produces androgens that are converted to fully functional sex hormones in the gonads and other target organs. The production of steroid hormones is called steroidogenesis, and involves a number of reactions and processes that take place in cortical cells. The medulla produces the catecholamines, which function to produce a rapid response throughout the body in stress situations.

The fight-or-flight or the fight-flight-freeze-or-fawn (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first described by Walter Bradford Cannon in 1914 to which he referred to as "the necessities of fighting or flight" in 1915. His theory states that animals react to threats with a general discharge of the sympathetic nervous system, preparing the animal for fighting or fleeing. More specifically, the adrenal medulla produces a hormonal cascade that results in the secretion of catecholamines, especially norepinephrine and epinephrine. The hormones estrogen, testosterone, and cortisol, as well as the neurotransmitters dopamine and serotonin, also affect how organisms react to stress. The hormone osteocalcin might also play a part.

This response is recognised as the first stage of the general adaptation syndrome that regulates stress responses among vertebrates and other organisms.

Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face due to facial plethora, a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly. Women may have more hair and irregular menstruation or loss of menses, with the exact mechanisms of why still unknown. Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.

Cushing's syndrome is caused by either excessive cortisol-like medication, such as prednisone, or a tumor that either produces or results in the production of excessive cortisol by the adrenal glands. Cases due to a pituitary adenoma are known as Cushing's disease, which is the second most common cause of Cushing's syndrome after medication. A number of other tumors, often referred to as ectopic due to their placement outside the pituitary, may also cause Cushing's. Some of these are associated with inherited disorders such as multiple endocrine neoplasia type 1 and Carney complex. Diagnosis requires a number of steps. The first step is to check the medications a person takes. The second step is to measure levels of cortisol in the urine, saliva or in the blood after taking dexamethasone. If this test is abnormal, the cortisol may be measured late at night. If the cortisol remains high, a blood test for ACTH may be done.

Antiglucocorticoid drugs are a class of medications that act to reduce the effects of glucocorticoids, primarily cortisol, in the body. They include direct glucocorticoid receptor antagonists such as mifepristone and synthesis inhibitors such as metyrapone, ketoconazole, and aminoglutethimide. They are used to treat Cushing's syndrome.

These drugs have also been investigated for their potential therapeutic benefits in various psychiatric disorders, particularly depression and psychosis. The rationale behind using antiglucocorticoids in psychiatry stems from the observed dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in many psychiatric conditions, which often manifests as elevated cortisol levels.

Late onset congenital adrenal hyperplasia (LOCAH), also known as nonclassic congenital adrenal hyperplasia (NCCAH or NCAH), is a milder form of congenital adrenal hyperplasia (CAH), a group of autosomal recessive disorders characterized by impaired cortisol synthesis that leads to variable degrees of postnatal androgen excess.

The causes of LOCAH are the same as of classic CAH, and in the majority of the cases are the mutations in the CYP21A2 gene resulting in corresponding activity changes in the associated P450c21 (21-hydroxylase) enzyme which ultimately leads to excessive androgen production. Other causes, albeit less frequent, are mutations in genes affecting other enzymes involved in steroid metabolism, like 11β-hydroxylase or 3β-hydroxysteroid dehydrogenase. It has a prevalence between 0.1% and 2% depending on population, and is one of the most common autosomal recessive genetic diseases in humans. The pathophysiology is complex and not all individuals are symptomatic.

The zona fasciculata (sometimes, fascicular or fasciculate zone) constitutes the middle and also the widest zone of the adrenal cortex, sitting directly beneath the zona glomerulosa. Constituent cells are organized into bundles or "fascicles".

The zona fasciculata chiefly produces glucocorticoids (mainly cortisol in humans), which regulate the metabolism of glucose. Glucocorticoid production is stimulated by adrenocorticotropic hormone (ACTH), which is released from the anterior pituitary, especially in times of stress as part of the fight-or-flight response. The zona fasciculata also generates a small amount of weak androgens (e.g., dehydroepiandrosterone). The main source of androgens will come from the zona reticularis region. In certain animals such as rodents, the lack of 17alpha-hydroxylase results in the synthesis of corticosterone instead of cortisol.

Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug. Cortisol is converted by the action of the enzyme corticosteroid 11-beta-dehydrogenase isozyme 2 into the inactive metabolite cortisone, particularly in the kidneys. This is done by oxidizing the alcohol group at carbon 11 (in the six-membered ring fused to the five-membered ring). Cortisone is converted back to the active steroid cortisol by stereospecific hydrogenation at carbon 11 by the enzyme 11β-Hydroxysteroid dehydrogenase type 1, particularly in the liver.

The term "cortisone" is frequently misused to mean either any corticosteroid or hydrocortisone, which is in fact cortisol. Many who speak of receiving a "cortisone shot" or taking "cortisone" are more likely receiving hydrocortisone or one of many other, much more potent synthetic corticosteroids.

Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.

Some common naturally occurring steroid hormones are cortisol (C
₂₁H
₃₀O
₅), corticosterone (C
₂₁H
₃₀O
₄), cortisone (C
₂₁H
₂₈O
₅) and aldosterone (C
₂₁H
₂₈O
₅) (cortisone and aldosterone are isomers). The main corticosteroids produced by the adrenal cortex are cortisol and aldosterone.

Stress hormones are secreted by endocrine glands to modify one's internal environment during times of stress. By performing various functions such as mobilizing energy sources, increasing heart rate, and downregulating metabolic processes which are not immediately necessary, stress hormones promote the survival of the organism. The secretions of some hormones are also downplayed during stress. Some of the better known stress hormones are:

• Cortisol, the main human stress hormone
• Catecholamines such as adrenaline and norepinephrine
• Vasopressin
• Growth hormone