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What is hypercortisolism?

Cortisol: An important hormone for homeostatic well-being

Hypercortisolism, also referred to as Cushing syndrome, occurs when the body is exposed to high levels of the hormone cortisol for a long period of time. Sometimes referred to as the stress hormone, cortisol is naturally produced in the adrenal glands, which are located at the top of the kidneys. Cortisol plays a role in the body's response to stress and affects blood pressure, metabolism, inflammation, and memory formulation. Cortisol also helps to regulate blood sugar and control the amount of water in the body. All of these functions make cortisol crucial for overall health and well-being.1

Cortisol affects many tissues and organs throughout the body

Cortisol regulation and dysregulation

The HPA axis and cortisol production2,3

adrenal and pituitary glands, hypothalamus, and cortisol production

The adrenal and pituitary glands, as well as the hypothalamus, all play a role in cortisol production.1,4 The production of cortisol is controlled by the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis is a feedback loop with 3 steps:

  1. The Hypothalamus stimulates the pituitary gland by releasing corticotropin-releasing hormone (CRH)
  2. The pituitary gland then activates the adrenal glands by secreting adrenocorticotropic hormone (ACTH)
  3. The adrenal glands release cortisol into the bloodstream

A feedback loop ensures that proper levels of cortisol are maintained. When the HPA axis works normally, cortisol in the blood rises and falls regularly over 24 hours.2,5

Cortisol plays a role in a wide range of bodily functions, including4,6

  • Regulation of blood sugar
  • Blood pressure
  • Bone health
  • Weight
  • Metabolism
  • Inflammation
  • Vision and balance
  • Mood and depression

Diurnal rhythm

Unless an individual works the night shift and has an irregular sleep pattern, cortisol production follows a natural rhythm, reaching its lowest levels at night and its highest levels in the morning. This is called a diurnal rhythm.7

Diurnal rhythm is the body’s internal clock, a natural pendulum of approximately 24-hour periods, in which an individual is active during the day and sleeps at night. People who sleep at night and are awake during the day should have peak cortisol levels between 6 and 9 AM. Cortisol levels reach their lowest point between 11 PM and 1 AM.5,7

Cortisol follows this rhythm, which is necessary to restore and maintain homeostasis and to avoid development of a range of conditions within the body.5,8 For people with high cortisol levels, this rhythm can be disrupted. Disruption in the diurnal rhythm of cortisol is associated with increased cardiovascular (CV) mortality.9

Normal vs high cortisol levels 7,8

normal diurnal rhythm vs hypercortisolism

Levels change throughout the day. Cortisol levels peak in the early morning.

What are the signs and symptoms of excess cortisol?

When left untreated over a long period of time, excess cortisol can negatively affect the body and cause multisystemic dysfunction, including increased risk for cardiovascular disease (CVD).5,10 Excess cortisol can produce certain “classic” signs or symptoms such as a fatty hump between the shoulders (dorsocervical fat pad/buffalo hump), weight gain around the mid-section, or pink and purple stretch marks (striae). However, not everyone will display these classic symptoms.3

In fact, many patients present with a constellation of signs and symptoms that are caused by excess cortisol, but that are also common in the general population, such as the following11:

  • Diabetes
  • Hypertension
  • Obesity
  • Depression
  • Menstrual irregularity

These signs and symptoms can be different in every patient. Hypercortisolism occurs when the body is exposed to high levels of the hormone cortisol for a long period of time.1,6

Patient Story

Charsetta's headshot

"The weight gain was very noticeable, and then
I noticed facial hair.
I started to feel less attractive..."

What causes hypercortisolism?

The right level of cortisol activity and proper diurnal rhythm is essential for the body. Hypercortisolism, often referred to as Cushing syndrome, can be caused by taking glucocorticoid medicines such as steroids, or when something inside the body makes too much cortisol on its own.4

Two different types of hypercortisolism


Hypercortisolism can develop from taking glucocorticoid medicines (eg, steroids). This is called exogenous hypercortisolism, meaning it results from something outside the body.12,13


Hypercortisolism can also result from something inside the body and this is called endogenous hypercortisolism. The cause is usually a noncancerous tumor called an adenoma, which is most likely located on the adrenal or pituitary gland. It can also occur elsewhere in the body, which is called an ectopic source.12

Etiology of endogenous hypercortisolism

There are 2 general causes of endogenous hypercortisolism: ACTH-dependent or ACTH-independent.3

ACTH-dependent hypercortisolism can be caused by excess ACTH secretion by a pituitary adenoma or ectopic tumor, which stimulates the adrenal glands to secrete excess cortisol.3

Endogenous ACTH-independent hypercortisolism is caused by autonomous adrenal overproduction of cortisol, usually due to an adrenal adenoma. Autonomous secretion of ACTH from a pituitary adenoma or ectopic tumor, or of cortisol from an adrenal adenoma, disrupts the negative feedback loop that regulates cortisol levels.3,4

pituitary gland and hypothalamus


Pituitary source3

  • Secretion of ACTH from a pituitary adenoma stimulates the adrenal glands to secrete excess cortisol (Cushing disease)


Ectopic source3

  • Secretion of ACTH from an ectopic tumor stimulates the adrenal glands to secrete excess cortisol
adrenal gland and tumor


Adrenal source3

  • Autonomous cortisol secretion

How does hypercortisolism impact the body?

Excess cortisol causes multisystemic dysfunction

The negative effects of hypercortisolism can lead to serious health consequences. Over time, excess cortisol activity can result in the following5,6,11:

  • Diabetes mellitus/Insulin resistance
  • Hypertension/Dyslipidemia
  • Obesity
  • Osteoporosis/Vertebral fracture
  • Insomnia/Concentration difficulties/Psychiatric or mood disturbances
  • Muscle weakness/Atrophy
  • Clotting/Thrombosis
  • Recurrent infection
  • Gonadal dysfunction/Menstrual irregularity
  • Dermatologic manifestations

Learn more about how hypercortisolism impacts the body

Learn the Consequences
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Signs & Symptoms
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