Cushing's syndrome: What is it and how is it manifested?

Cushing's syndrome: What is it and how is it manifested?
Photo source: Getty images

Cushing's syndrome is caused by excessive levels of glucocorticoids in the body. This disease is relatively rare. It is the cause of hypertension, weight gain, skin changes, or even a mental disorder. An endocrine disorder can be caused centrally in the brain or peripherally when there is a problem in the adrenal cortex.


Cushing's syndrome is a rare disease that affects approximately 1 to 2 people in 500,000 people a year. It is also known as  hypercortisolism, which means excessive production of cortisol. Cortisol, or hydrocortisone, is a steroid hormone. It plays a very important role in the body's metabolism and in the stress response.

The disease is an endocrine disease.

Frequently asked questions: 
What is the disease and why does it arise? 
How does it manifest, diagnose and treat? 

Cushing's syndrome is the result of long-term and excessive production of this hormone. Its production can be triggered by several mechanisms. Accordingly, it is further determined and marked. The origin can be exogenous as well as endogenous.

The difference between the exogenous and endogenous origin of the disease:

  1. exogenous when the hormone is delivered to the body in a higher dose, i.e. iatrogenic. For example, in the treatment of glucocorticoid drugs
  2. endogenous originates in a production disorder, i.e. in overproduction 

The issue of the endogenous form is more complex. This type can be caused by overproduction:

  • ACTH, an adrenocorticotropic hormone, is made up of the anterior lobe of the pituitary gland
  • cortisol, in the adrenal gland
  • CRH stands for corticotropin releasing hormone, or corticoliberin, is a rarer form
  • pseudocushingoid conditions when the error is at a different level of the hypothalamic-pituitary-adrenocortical axis, which is a rare condition

What is cortisol?

Cortisol is a steroid hormone that is classified as a glucocorticoid. These are produced in the adrenal glands, and thus more precisely in the adrenal cortex. The synthesis of steroid hormones requires fats, ie cholesterol, plasma lipoproteins, also known as LDL and HDL.

Cortisol has an irreplaceable role in the body's metabolism, it affects the supply of energy, ie sugars to the brain and the stimulation of the cardiovascular system. It is an essential stress hormone.

Cortisol production is affected by the secretion of another hormone, which is controlled centrally, that is, from the CNS (central nervous system). More precisely from the pituitary gland. According to its function, it also has a derived name, ie the adrenocorticotropic hormone ACTH. It is formed in the anterior lobe of the pituitary gland.

Kidney, adrenal gland - anatomical view
The adrenal gland on the kidney. Photo source: Getty images

To make matters worse, ACTH excretion is controlled by the hypothalamus. More specifically through another hormone, and that is corticoliberin. Also referred to as CRH, from the English corticotropin-releasing hormone. It increases its secretion in the pituitary gland.

Cortisol affects and affects:

  • metabolism
  • energy management
  • is important in stress response and acts under stress:
    • in the muscles
    • baked
    • pancreas
    • and also acts on adipose tissue as an energy store
    • acts catabolically and antianabolically
  • sugar metabolism, especially their intake during the stress response to the brain
  • fat metabolism releases energy from the body's fat stores
  • protein metabolism, ie amino acids
  • cardiovascular system, increasing blood pressure and cardiac output
  • suppresses immune responses, reduces the production of eosinophils, leukocytes, lymphocytes, but increases the level of erythrocytes
  • has an anti-inflammatory effect, which is used, for example, in allergic reactions and inflammation
  • psychic

Interesting information:  The opposite of increased, is the production of adrenal hormones, ie
Addison's disease. The article also contains brief information about adrenals .

Hypothalamus - pituitary - adrenocortical axis in brief

The hypothalamic-pituitary-adrenocortical axis is also technically called HPA and is an important neuroendocrine system. It plays a major role in energy management and participates in the stress response. Its components interact with each other and affect the body and hormonal, nervous, and immune processes.

This system consists of three components, namely:

  1. hypothalamus where CRH is formed
  2. the pituitary gland, more specifically the adenohypophysis, which produces ACTH
  3. the adrenal cortex, where glucocorticoids are excreted in the blood, and thus cortisol

The whole issue is complex and unnecessary for the average person, of course, also uninteresting. This basic information is only to suggest that the problem with cortisol production can have a variety of causes. This is important in the diagnosis of the underlying cause and in the treatment of Cushing's syndrome.


The cause of the disease is increased cortisol production. It can have various reasons. Disorders during HPA are rare, similar to the less common cause in CRH production. The problem with the secretion of ACTH or cortisol alone is initially estimated.

The exogenous cause is caused by an excessive supply of hormones from the outside. Most often in pharmacological treatment. When glucocorticoids are given to a person. The endogenous form is caused by a disorder in the production of the hormones CRH, ACTH or cortisol.

For example, a pseudocushingoid condition is associated with obesity, alcoholism, long-term stress, or even depressive disorder. Endogenous Cushing's syndrome is further divided into two types.

The table shows the distribution of Cushing's syndrome according to the root cause

Title Description The most common cause
ACTH dependent secondary
ACTH-dependent Cushing's syndrome ACTH
overproduction subsequently stimulates higher cortisol production
75-80% of cases
increased production in the pituitary gland
central pituitary tumor
most often adenoma 80%
pituitary carcinoma is rare also
referred to as Cushing's disease
ectopic about 20%
small cell lung cancer
bronchial carcinoid
ACTH independent primary Cushing's syndrome
independent of ACTH
cortisol overproduction, without influence of ACTH
20 - 25% of cases
increased production in the adrenal cortex
peripheral Cushing's syndrome mostly unilateral adrenal tumor
adenoma 50 - 60%
carcinoma 40 - 50%
bilateral adrenal disease
rare tumor of both adrenal glands
bilateral hyperplasia
primary pigmented nodular adrenocortical disease
macronodular adrenal hyperplasia


Cushing's syndrome affects several body systems and organs. This is due to the broad spectrum of activity of cortisol. It is involved in the metabolic, hormonal and immune processes of the body. It is also an important hormone involved in managing the stress response.

The symptoms of Cushing's syndrome are listed in the table below

Area of ​​operation Description
sugars causes diabetes, ie type 2 diabetes mellitus
fats affects deposition and lipolysis
protein protein catabolism
steroid myopathy
muscle atrophy
muscle weakness
muscle pain
mainly affects the muscles of the limb girdle
Cardiovascular system is the cause of secondary hypertension
increases the risk of cardiovascular disease
frequent thrombosis of the lower extremities
Leather is thin, fragile
so-called parchment skin
prone to injury
frequent skin infections
poor wound healing
increased formation of bruises, blood bruises, hematomas
are typical pink to purple, purple stretch 
marks can be wider than 1 cm,
characteristic mainly on the abdomen
but also on the thighs, calves or breast
Bones affects bone density
is the cause of osteoporosis
back pain pathological fractures
are common
Body weight body weight increases
overweight and obesity
arises so-called central obesity
spider appearance
large abdomen and lean limbs (also for muscle atrophy)
places where fat is preferentially stored:
  • belly
  • face, ie crescent face, facies lunata
  • neck, a hump or gibbus is formed, or a bull neck (buffalo hump)
  • at the top of the chest, above the collarbones, like a collar
  • fat is also stored in the mediastinum and epidural, ie in the spinal canals,
    which can result in neurological problems
Psyche memory
disorder concentration disorder
depressive disorder
mental emotional lability
Gynecological menstrual disorders
decreased libido
Metabolic syndrome Cushing's syndrome increases the risk of its occurrence
, it is a set of diseases and symptoms
together leading to health complications
, such as:
  • sugar metabolism disorder, diabetes
  • insulin resistance
  • central obesity
  • dyslipidemia
  • arterial hypertension
  • ischemic heart disease
  • nephropathy
  • hyperfibrinogenemia

Less typical symptoms of the disease include swelling, especially of the limbs, headache or frequent urination. It causes androgenic changes in women, such as hair loss. But also hirsutism, which is the increased growth of hair in atypical places. It is also hyperpigmentation of the skin and increased acne. Infertility is a serious complication. In children, this disease can cause retardation or even cessation of growth and sexual development.

Interesting information:  What are the blood pressure values and how does hypertension typically manifest ?


Diagnosis of Cushing's syndrome is performed in two steps. This is by confirming hypercotisolism and determining the cause of overproduction of hormones, ACTH or cortisol. What is important is history and clinical pictureBiological material is collected. It is necessary that the man does not use any corticoids and the women hormonal contraception for at least 6 weeks before collection.

Blood and urine are tested in the laboratory. Serum cortisol, ACTH or CRH are determined in the blood. Specifically, a so-called dexamethasone suppression test is also  performed. One method is to administer dexamethrazone to the blood, which is a glucocorticoid analogue. The amount of cortisol in the blood is then measured. Blood is also collected for the determination of leukocytes, erythrocytes and also biochemical parameters, glycemic value, pH determination .

Urine testing may also be used for diagnosis, as it also excretes cortisol. Waste cortisol is determined in the urine in 24 hours. Imaging methods are used to confirm a tumor on the pituitary gland or adrenal gland, such as  CT  or  MRI. X-rays,  in turn, to rule out osteoporosis or to diagnose a pathological fracture.


The course of the disease also depends on the primary cause. It can have a long-term but also a fast course. Typically, there is a change in figure, ie weight gain. Characteristic is the deposition of fat on predilection sites and the formation of the so-called spider figure or bull hump. The limbs are poor, which is due to muscle atrophy.

Muscle weakness and pain apply to weakened muscles. The skin is thin, fragile, easily damaged. The wounds heal poorly, the skin is prone to inflammation. Increased bruising is formed. In falls, there is an increased risk of fractures for osteoporosis, however, cushing's syndrome is also the cause of pathological fractures. .

Among cardiovascular problems, hypertension and the risk of other cardiovascular problems are at the forefront. This risk is multiplied by a disorder of lipid and sugar metabolism, increased blood sugar levels. In general, the disease predisposes to the development of metabolic syndrome.

Magazine article:  Diet in diabetes .

The person may also develop mental disorders and emotional lability. In children, the reason is growth arrest and retardation of sexual development. With the onset of difficulty, a typical clinical picture may not appear. Differential diagnosis, differentiation and treatment are important.

How it is treated: Cushing's syndrome

Treatment for Cushing's syndrome: medications or surgery?

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How Cushing's syndrome manifests?

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Interesting resources

  • Celik O, Niyazoglu M, Soylu H, Kadioglu P (August 2012). "Iatrogenic Cushing's syndrome with inhaled steroid plus antidepressant drugs". Multidisciplinary Respiratory Medicine7 (1): 26. doi:10.1186/2049-6958-7-26. PMC 3436715. PMID 22958272.
  • "What are the symptoms of Cushing's syndrome?". 2012-11-30. Archived from the original on 2 April 2015. Retrieved 16 March 2015.
  • "Cushing syndrome". Mayo Clinic. Retrieved June 5, 2022.
  • "Cushing's Syndrome". National Endocrine and Metabolic Diseases Information Service (NEMDIS). July 2008. Archived from the original on 10 February 2015. Retrieved 16 March 2015.
  • "How do health care providers diagnose Cushing's syndrome?". 2012-11-30. Archived from the original on 2 April 2015. Retrieved 16 March 2015.
  • "What are the treatments for Cushing's syndrome?". 2012-11-30. Archived from the original on 2 April 2015. Retrieved 16 March 2015.
  • "Is there a cure for Cushing's syndrome?". 2012-11-30. Archived from the original on 27 March 2015. Retrieved 16 March 2015.
  • "How many people are affected by or at risk for Cushing's syndrome?". 2012-11-30. Archived from the original on 2 April 2015. Retrieved 16 March 2015.
  • Forbis P (2005). Stedman's medical eponyms (2nd ed.). Baltimore, Md.: Lippincott Williams & Wilkins. p. 167. ISBN 9780781754439. Archived from the original on 2017-09-08.
  • Sharma ST, Nieman LK (June 2011). "Cushing's syndrome: all variants, detection, and treatment". Endocrinology and Metabolism Clinics of North America40 (2): 379–91, viii–ix. doi:10.1016/j.ecl.2011.01.006. PMC 3095520. PMID 21565673.
  • "What causes Cushing's syndrome?". 2012-11-30. Archived from the original on 2 April 2015. Retrieved 16 March 2015.
  • Nieman LK, Ilias I (December 2005). "Evaluation and treatment of Cushing's syndrome". The American Journal of Medicine118 (12): 1340–1346. doi:10.1016/j.amjmed.2005.01.059. PMID 16378774.
  • "Cushing syndrome - Diagnosis and treatment - Mayo Clinic". Retrieved 2019-04-21.
  • Graversen D, Vestergaard P, Stochholm K, Gravholt CH, Jørgensen JO (April 2012). "Mortality in Cushing's syndrome: a systematic review and meta-analysis". European Journal of Internal Medicine23 (3): 278–282. doi:10.1016/j.ejim.2011.10.013. PMID 22385888.
  • Steffensen C, Bak AM, Rubeck KZ, Jørgensen JO (2010). "Epidemiology of Cushing's syndrome". Neuroendocrinology. 92 Suppl 1: 1–5.