What is the physiological difference between cortisone and cortisol?

What is the physiological difference between cortisone and cortisol?

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There is only hydrogen bond different. Cortisol is synthesized by our body, while cortisone is given to the patient.

Why you cannot give cortisol directly to the patient? I think the reason is metabolism that cortisol will break (probably in liver) and not be useful. Or expansive to produce. Cortisone however can be given.

What is the physiological difference between cortisone and cortisol?

Cortisol is directly given to the patient - it is then called Hydrocortisone. I don't know why this is done but probably to avoid confusion because both names are too similar.

The difference between both forms is one hydrogen atom at the C11 position of the molecule in Cortisol (or Hydrocortison) (image from here):

Otherwise is Cortisol (or Hydrocortisone) the active version, while Cortisone isn't very active in the human body. Both forms can enzymatically turned into the other form (from active to inactive and vice versa). Since Cortisone needs to be activated in the liver, it can only be used for oral uptake. Most of the uses which are colloquially called Cortisone in fact contain Hydrocortisone.

Difference Between Adrenaline and Cortisol

Adrenaline Vs Cortisol

Adrenaline and cortisol have been confused with each other most probably because they come from one source ‘“ the adrenal glands. Immersing further deep into these two hormones would yield various differences.

Adrenaline is the common or layman’s term for epinephrine. As mentioned, it is a hormone but at the same time, it is also classified as a neurotransmitter because they function by carrying the nerve impulses between the neurons towards the target cell. This gives adrenaline its electro-chemical nature.

Adrenaline has been known as one of the most popular hormones because of its effect on the body. A sudden surge in the amount of adrenaline would mean that you are undergoing a period of fight-or-flight. One will experience this when under stress. As a result, the sympathetic nervous system with this hormone (neurotransmitter) speeds up the heart rate and increases blood pressure through blood vessel contraction. There’s also the dilation of air passages.

If you come to think of it, these effects are actually a response mechanism by the body to handle stress. Increasing the heart rate ensures that the body is supplied by ample amounts of blood throughout the circulation. The dilation of the air passages gives more room for air to pass and thus the cells receive more oxygen.

With regard to the chemical nature of adrenaline, it is regarded as one of the most important catecholamines of the body. It is a primitive hormone that was discovered early in the 1900s.

Cortisol is another hormone, particularly a corticosteroid, produced by the adrenal gland gradually throughout the day. It is another stress hormone like adrenaline which is generated more in times of stressful situations like the fight-or-flight response. It has many therapeutic effects in the body like its effect on the liver to hasten the removal of unwanted body toxins. It also heightens STM (short term memory). Perhaps the most common and noteworthy role of cortisol is its anti-inflammatory nature that tends to reduce any form of inflammation.

Nevertheless, there are many downsides to cortisol. This hormone is very difficult to regulate. Hence, if there’s a little abnormality on its serum levels like when there’s too much cortisol then it could end up as Cushing’s syndrome which is characterized by diaphoresis (excessive perspiration), sudden gain of weight and even some psychological disturbances. If there’s a decrease in its blood levels then it will lead to Addison’s disease (the direct opposite). Thus, you would expect weight loss and fatigue in patients suffering from such.

Although both adrenaline and cortisol are hormones involved in the stress response, they still differ because:

1. Adrenaline is a neurotransmitter, a catecholamine and a hormone while cortisol is a corticosteroid hormone.

Social jetlag, circadian disruption, and cardiometabolic disease risk

Susan Kohl Malone , . Freda Patterson , in Sleep and Health , 2019


Cortisol secretions are strongly regulated by the circadian system and, to a lesser extent, behavioral rhythms [70] . Cortisol begins rising 1–2 h after sleep onset, peaks within 1 h of morning waking, and declines thereafter across the 24-h day [70] . Cortisol rhythms parallel those of insulin sensitivity, such that high cortisol levels coincide with increased insulin sensitivity and vice versa [53] . Similarly, postmeal cortisol secretions decline by 33% from morning to evening [48] . These parallel declines in cortisol secretion and insulin sensitivity counter what is known about cortisol's insulin antagonizing effects [128] . Plat et al. reconciled this seeming incongruence by demonstrating that cortisol profoundly decreases insulin sensitivity, however insulin's response lags [129] . Insulin sensitivity begins declining 4–6 h after cortisol's peak and continues declining for > 16 h [129] . This lag between cortisol and insulin sensitivity partially explains morning-to-evening increases in insulin resistance and declines in glucose tolerance. Cortisol rhythms persist with aging, albeit cortisol peaks earlier in the morning and the amplitude of cortisol rhythms are diminished [130] . Cortisol rhythm amplitudes are diminished by irregular and daytime, as opposed to night time sleep [95] . These diminished cortisol amplitudes may be associated with poorer health outcomes [131] .

The Importance of the Adrenal Cortex Hormones Cortisol and Aldosterone

The adrenals, small glands located above each kidney, produce a number of important hormones. The adrenals’ inner medulla produces epinephrine and norepinephrine (adrenaline). The adrenals also contain an outer cortex, which produces hormones such as cortisol, aldosterone, testosterone, DHEA, DHEAS, androstenedione and estrogens.

Cortisol and aldosterone are two of the most important hormones the body makes. Excesses or deficiencies of these hormones result in important clinical problems. Cortisol, a glucocorticoid, is the stress hormone and is involved in weight control, infection fighting, quality of skin and bones, and heart function. Its levels are the highest in the morning, and are increased by stress and severe illness. Too much cortisol from any cause leads to Cushing’s syndrome the symptoms and signs of which include redistribution of fat to the face, upper back and abdomen, weight gain, stretch marks, bruising, extra hair growth, irregular periods in women, loss of muscle, trouble sleeping and emotional problems, such as depression. Too little cortisol is part of the syndrome called Addison’s disease, often marked by low energy, joint and abdominal pain, weight loss, diarrhea, fever, and electrolyte disturbances. If the adrenals are making too little cortisol, the pituitary compensates and makes more of the hormone, ACTH. If the pituitary is not working, both ACTH and cortisol levels may be low.

Aldosterone is the salt-retaining hormone and is a mineralocorticoid. Excesses of aldosterone leads to high blood pressure and low potassium. Deficiencies of aldosterone are much less appreciated than deficiencies of cortisol, and lead to low blood pressure and high pulse, especially on standing, the desire to eat salt (salt-craving), dizziness or lightheadedness on standing, and palpitations. Severe cases may lead to high potassium and low sodium in blood tests. When the adrenal is not making aldosterone, renin, a kidney hormone, increases. Excesses of cortisol and aldosterone may occur independently, that is a patient may have only excess aldosterone, only excess cortisol, or excesses of both. Similarly, deficiencies of cortisol and aldosterone deficiencies may be independent.

Many patients with symptoms of fatigue and often salt-craving, “cognitive fuzziness”, dizziness or lightheadedness on standing, or palpitations have low blood levels of aldosterone. The connection between low aldosterone levels and fatigue is as follows: with low aldosterone, the kidney loses salt, leading to low blood volume. This coupled with the idea that the leg veins don’t constrict properly, leads to lower blood volume to the brain and fatigue and other symptoms. These patients often have a drop in their blood pressure and an increase in their pulse when standing. They may also have decreased blood flow to the brain when measured by SPECT scan. Aldosterone deficiency may be made worse if patients restrict their salt intake.

Soon-to-be-published research (Friedman, T., et al., in preparation) shows a few patterns of abnormalities in the renin-aldosterone axis. A little more than half the patients with fatigue had low blood levels of both renin and aldosterone. This is called hyporeninemic hypoaldosteronism and is probably due to dysfunction of what is called the autonomic nervous system, which sends messages from the brain to the kidneys. Other aspects of the autonomic nervous system have been found to be deficient in chronic fatigue syndrome. About one-third of the patients studied were found to have low aldosterone and high renin. This indicates a deficiency in the aldosterone production in the adrenals themselves, with a compensatory rise in the renin coming from the kidney. The aldosterone defect can either be an isolated problem, or part of Addison’s disease (often early Addison’s disease), in which both cortisol and aldosterone production are diminished. The remaining patients (about one-sixth) had both high renin and high aldosterone. This is likely to be a compensatory rise in both of these hormones as a reaction to a low blood volume, most likely due to an inability of the kidney to retain salt.

Treatment of patients with such symptoms requires an individualized combination of increased salt consumption, a synthetic form of aldosterone called Florinef (fludrocortisone), or Midodrine (proamantine), a drug used to raise blood pressure. Salt is the most benign of the treatments. Salt tablets can be purchased in a drug store or a patient can add an extra teaspoon of salt to their food per day. Florinef comes in 0.1 mg pills and the usual recommended starting dose is 1/2 pill in the morning for a week or two. If no side effects occur, the dose can be increased to 1 pill in the morning if needed. The main side effects are headache and swelling in legs (edema). Midodrine comes in 5 mg pills and Dr. Friedman usually starts with one 5 mg pill in the morning and another at noon. This may be increased up to 2 pills three times a day. Sometimes both Florinef and Midodrine, as well as extra salt are needed. The side effects of Midodrine include high blood pressure, itching, goosebumps, numbness and the feeling of writing on your skin or scalp. Many of these side effects go away with use and both drugs are unlikely to cause long term damage. Most patients taking Florinef and Midodrine, as well as extra salt report an improvement in their symptoms of palpitations and dizziness/lightheadedness on standing, and many report an improvement in fatigue and cognitive dysfunction. Licorice, available as a tea from Alvita, may help with mild cases.

Author: Dr.Ted Friedman MD PhD (Fall, 2003)

Editor’s Note: Dr. Friedman is Associate Professor of Medicine-UCLA, Endocrinology Division, Charles R. Drew University in Los Angeles, CA. Dr. Friedman has ongoing clinical research studies on the renin-aldosterone axis in chronic fatigue syndrome (CFS) and testosterone replacement in hypopituitary women. He also has a private clinic in Los Angeles where he sees patients with pituitary, adrenal and thyroid disorders.

Functions of Cortisol & DHEA

Cortisol is a primary stress hormone produced by the adrenals, and is also a potent anti-inflammatory hormone. Cortisol’s action can suppress immune function. Another of its primary functions is to raise blood sugar through gluconeogenesis. High amounts of glucocorticoids can suppress thyroid function, chiefly the inhibition of the conversion of T4 into the active T3. CRH (cortico-tropin releasing hormone), which is a hypothalamus precursor to cortisol can inhibit thyroid function as well, suppressing TSH.

DHEA (dehydroepiandrosterone) is called an androgenic hormone. It is a precursor for testosterone and the estrogens. DHEA antagonizes the effects of cortisol. DHEA is a very powerful anti-aging hormone. Low levels of DHEA are found among those with Cancer, CVD, Alzheimer’s, Diabetes, Depression, Hypothyroidism and Adrenal Fatigue.

Since cortisol and DHEA have opposing effects, they should be viewed together as a ratio. Like with every major control system in the body, cortisol and DHEA work through their alternating, dualistic balance.

The ratio between cortisol and DHEA has numerous effects in the body. When cortisol is elevated disproportionately to DHEA, the ratio is higher. When the cortisol to DHEA ratio is elevated, the numerous biological effects that this ratio has in the body is augmented. Here are some of the major effects of the Cortisol to DHEA ratio:

  • The balance of pro/anti-inflammatory stasis
  • Immune Regulation. Remeber that cortisol suppresses immune function
  • Protein, Fat and Glucose metabolism. Evidence suggests that hyperglycemia, which can result in diabetes, in many cases can be caused specifically from imbalanced cortisol and DHEA levels
  • Thyroid, Pancreas and ovarian function
  • Detoxification capacity. Since the body needs energy to properly deal with toxic metals, the hormones produced by the adrenal glands are considered to be the cornerstone to heavy metal and xenobiotic elimination.
  • Skeletal health. High levels of cortisol can cause breakdown of bone as well as the collagen matrix that holds bone together.
  • Memory. DHEA is a critical component for brain function and cognition.
  • Cortisol and DHEA have intrinsic relationships with numerous other steroidal hormones such as progesterone and aldosterone. If adrenal function is compromised, the body may bypass the pregnenelone > progesterone > cortisol pathway and “steal” pregnenelone. This can cause numerous complications including the transference of progesterone into androgenic testosterone.

Before taking this medicine

You should not use this medication if you are allergic to cortisone, or if you have a fungal infection anywhere in your body.

Steroid medication can weaken your immune system, making it easier for you to get an infection. Steroids can also worsen an infection you already have, or reactivate an infection you recently had. Before taking this medication, tell your doctor about any illness or infection you have had within the past several weeks.

To make sure you can safely take cortisone, tell your doctor if you have any of these other conditions:

Adrenal Cortex

The adrenal cortex, or the outer layer of the adrenal gland, is divided, in turn, into three additional layers, called zones (Figure (PageIndex<3>)). Each zone has distinct enzymes that produce different hormones from the common precursor molecule cholesterol, which is a lipid.

  1. Zona glomerulosa is the outermost layer of the adrenal cortex. It lies immediately under the outer fibrous capsule that encloses the adrenal gland.
  2. Zona fasciculata is the middle layer of the adrenal cortex. It is the largest of the three zones, accounting for nearly 80 percent of the adrenal cortex.
  3. Zona reticularis is the innermost layer of the adrenal cortex. It is directly adjacent to the medulla of the adrenal gland.

Types of Adrenal Cortex Hormones

Hormones produced by the adrenal cortex are called corticosteroids. As steroid hormones, corticosteroids are endocrine hormones that are made of lipids and exert their effects on target cells by crossing the plasma membrane and binding with receptors within the cytoplasm. A steroid hormone and its receptor form a complex that enters the cell nucleus and affects gene expression. There are three types of corticosteroids synthesized and secreted by the adrenal cortex. Each type is produced by a different zone of the adrenal cortex, as shown in Figure (PageIndex<3>).


Mineralocorticoids are produced in the zona glomerulosa and include the hormone aldosterone. These hormones help control the balance of mineral salts (electrolytes) in the body. In the kidneys, aldosterone increases the reabsorption of sodium ions and the excretion of potassium ions. Aldosterone also stimulates the retention of sodium ions by cells in the colon and by the sweat glands. The amount of sodium in the body affects the volume of extracellular fluids including the blood and thereby affects blood pressure. In this way, mineralocorticoids help control blood volume and blood pressure.


Glucocorticoids are produced in the zona fasciculata and include the hormone cortisol, which is released in response to stress and is considered the primary stress hormone. Glucocorticoids help control the rate of metabolism of proteins, fats, and sugars. In general, they increase the level of glucose and fatty acids circulating in the blood. Cells rely primarily on glucose for energy, but they can also use fatty acids for energy as an alternative to glucose. Glucocorticoids are also involved in the suppression of the immune system, having a potent anti-inflammatory effect. In addition, cortisol reduces the production of new bone and decreases the absorption of calcium from the gastrointestinal tract.


Androgens are produced in the zona reticularis and include the hormone DHEA (dehydroepiandrosterone). Androgens are a general term for male sex hormones, although this is somewhat misleading as adrenal cortex androgens are produced by both males and females. In adult males, they are converted to more potent androgens such as testosterone in the male gonads (testes). In adult females, they are converted to female sex hormones called estrogens in the female gonads (ovaries).

Regulation of Adrenal Cortex Hormones

Steroid hormone production by the three zones of the adrenal cortex is regulated by hormones secreted by the anterior lobe of the pituitary gland as well as by other physiological stimuli. For example, the production of glucocorticoids such as cortisol is stimulated by adrenocorticotropic hormone (ACTH) from the anterior pituitary, which in turn is stimulated by corticotropin releasing hormone (CRH) from the hypothalamus. When levels of glucocorticoids start to rise too high, they provide negative feedback to the hypothalamus and pituitary gland to stop secreting CRH and ACTH, respectively. This negative feedback mechanism is illustrated in Figure (PageIndex<4>). The opposite occurs when levels of glucocorticoids start to fall too low.

Figure (PageIndex<4>): The negative feedback loop that controls the production of glucocorticoids includes the pituitary gland and hypothalamus in addition to the adrenal cortex.

The body usually produces the right amount of cortisol. In a condition such as Cushing’s syndrome, it produces too much. In a condition such as Addison’s disease, it produces too little.

Symptoms of too much cortisol include:

  • weight gain, particularly around the abdomen and face
  • thin and fragile skin that is slow to heal
  • for women, facial hair and irregular menstrual periods

Symptoms of not enough cortisol include:

If you experience any of these symptoms, your doctor may suggest you have a blood test to measure your cortisol levels.


Main findings

In this systematic review we included 37 studies examining basal cortisol levels in adults with current PTSD in comparison with adults without psychiatric disorders published between 1980 and March 2005. Combining all available data for meta-analysis we found no systematic difference in basal cortisol levels between people with PTSD and controls. However, results were highly heterogeneous, indicating that differences between subgroups might be present. Subsequent explanatory subgroup analyses revealed that studies assessing plasma or serum reported significantly lower cortisol levels in people with PTSD compared with controls when compared with controls with no previous exposure to trauma. Lower cortisol levels were also found in people with PTSD compared with controls in studies including only females, in studies on physical or sexual abuse and in afternoon samples. Although the general assumption is that cortisol levels are low in PTSD, we could not confirm this hypothesis even though we used homogeneous groups as a result of strict exclusion criteria. This study shows that low cortisol levels do not relate to PTSD in general, but rather seem to mirror trauma exposure and PTSD subgroups.

Adrenaline, Cortisol, Norepinephrine: The Three Major Stress Hormones, Explained

Thanks to the work of our sympathetic nervous system, the "fight or flight" system that takes over when we're stressed, when you see your boss's name in your inbox late at night, your body reacts like there's a lion on the loose.

Behind the wide range of both physical and mental reactions to stress are a number of hormones that are in charge of adding fuel to the fire.

What It Is: Commonly known as the fight or flight hormone, it is produced by the adrenal glands after receiving a message from the brain that a stressful situation has presented itself.

What It Does: Adrenaline, along with norepinephrine (more on that below), is largely responsible for the immediate reactions we feel when stressed. Imagine you're trying to change lanes in your car, says Amit Sood, M.D., director of research at the Complementary and Integrative Medicine and chair of Mayo Mind Body Initiative at Mayo Clinic. Suddenly, from your blind spot, comes a car racing at 100 miles per hour. You return to your original lane and your heart is pounding. Your muscles are tense, you're breathing faster, you may start sweating. That's adrenaline.

Along with the increase in heart rate, adrenaline also gives you a surge of energy -- which you might need to run away from a dangerous situation -- and also focuses your attention.

What It Is: A hormone similar to adrenaline, released from the adrenal glands and also from the brain, says Sood.

What It Does: The primary role of norepinephrine, like adrenaline, is arousal, says Sood. "When you are stressed, you become more aware, awake, focused," he says. "You are just generally more responsive." It also helps to shift blood flow away from areas where it might not be so crucial, like the skin, and toward more essential areas at the time, like the muscles, so you can flee the stressful scene.

Although norepinephrine might seem redundant given adrenaline (which is also sometimes called epinephrine), Sood imagines we have both hormones as a type of backup system. "Say your adrenal glands are not working well," he says. "I still want something to save me from acute catastrophe."

Depending on the long-term impact of whatever's stressing you out -- and how you personally handle stress -- it could take anywhere from half an hour to a couple of days to return to your normal resting state, says Sood.

What It Is: A steroid hormone, commonly known as the stress hormone, produced by the adrenal glands.

What It Does: It takes a little more time -- minutes, rather than seconds -- for you to feel the effects of cortisol in the face of stress, says Sood, because the release of this hormone takes a multi-step process involving two additional minor hormones.

First, the part of the brain called the amygdala has to recognize a threat. It then sends a message to the part of the brain called the hypothalamus, which releases corticotropin-releasing hormone (CRH). CRH then tells the pituitary gland to release adrenocorticotropic hormone (ACTH), which tells the adrenal glands to produce cortisol. Whew!

In survival mode, the optimal amounts of cortisol can be life saving. It helps to maintain fluid balance and blood pressure, says Sood, while regulating some body functions that aren't crucial in the moment, like reproductive drive, immunity, digestion and growth.

But when you stew on a problem, the body continuously releases cortisol, and chronic elevated levels can lead to serious issues. Too much cortisol can suppress the immune system, increase blood pressure and sugar, decrease libido, produce acne, contribute to obesity and more.

"Ducks walk out of a lake, flap their wings and they fly off," says Sood. "When you face something stressful, particularly if it's not likely to repeat or doesn't have a huge long-term impact, you want to be able to shake it off and move on with life."

Of course, he adds, estrogen and testosterone are also hormones that affect how we react to stress, as are the neurotransmitters dopamine and serotonin. But the classic fight-or-flight reaction is mostly due to the three major players mentioned above. How do you react to stress? Let us know in the comments.