Cushing's Syndrome and Cushing's Disease
Cushing's syndrome is a rare hormonal condition caused by prolonged exposure to too much cortisol. Cortisol is an essential steroid hormone produced by the adrenal glands and is involved in many important functions throughout the body.
When Cushing's syndrome is specifically caused by an ACTH-producing tumour of the pituitary gland, it is called Cushing's disease.
Cushing's can cause significant health problems if left untreated. Symptoms often develop gradually and can resemble those of several much more common conditions, which means diagnosis can sometimes take time.
What is cortisol?
Cortisol is produced by the adrenal glands, which are located above the kidneys.
Production of cortisol is normally controlled by a hormonal pathway involving the hypothalamus, pituitary gland and adrenal glands, known as the hypothalamic-pituitary-adrenal (HPA) axis.
The pituitary gland produces a hormone called adrenocorticotropic hormone (ACTH), which travels through the bloodstream and stimulates the adrenal glands to produce cortisol.
Cortisol has many important functions, including:
- helping the body respond to physical and emotional stress
- helping regulate blood pressure and cardiovascular function
- influencing blood glucose levels and metabolism
- regulating inflammation and immune responses
- influencing the metabolism of proteins, fats and carbohydrates
- contributing to normal bone, muscle and brain function
Although cortisol is essential for life, prolonged exposure to excessive amounts can affect almost every system in the body.
What causes Cushing's syndrome?
There are two broad forms of Cushing's syndrome: exogenous Cushing's syndrome and endogenous Cushing's syndrome.
Exogenous Cushing's syndrome
The most common overall cause of Cushing's syndrome is prolonged exposure to glucocorticoid medicines.
These medicines include corticosteroids such as prednisolone, dexamethasone and hydrocortisone, which may be prescribed to treat inflammatory, autoimmune and other medical conditions.
Corticosteroids can also be given by injection, inhaler, cream or other routes. The likelihood of developing Cushingoid features depends on factors including the medication, dose, route and duration of treatment.
People taking prescribed corticosteroids should never suddenly stop their medication without medical advice, as long-term treatment can suppress the body's natural production of cortisol and sudden withdrawal can cause adrenal insufficiency.
Endogenous Cushing's syndrome
Endogenous Cushing's syndrome occurs when the body itself produces excessive amounts of cortisol.
This is much rarer and can have several different causes.
Cushing's Disease – a pituitary cause
Cushing's disease occurs when a usually benign, non-cancerous tumour of the pituitary gland produces excessive amounts of ACTH.
ACTH stimulates the adrenal glands to produce cortisol. Too much ACTH therefore results in excessive cortisol production.
Cushing's disease is the most common cause of endogenous ACTH-dependent Cushing's syndrome.
Most ACTH-producing pituitary tumours are small and are known as microadenomas.
You may hear healthcare professionals use terms such as:
- pituitary adenoma
- corticotroph adenoma
- ACTH-producing pituitary tumour
- pituitary neuroendocrine tumour (PitNET)
Terminology surrounding pituitary tumours continues to evolve, but these terms describe tumours arising from cells within the pituitary gland.
Other causes of Cushing's syndrome
Ectopic ACTH production
Sometimes ACTH is produced by a tumour located outside the pituitary gland.
This is known as ectopic ACTH syndrome.
These tumours may occur in areas such as the lungs, thymus, pancreas or elsewhere in the body.
The excessive ACTH stimulates the adrenal glands to produce too much cortisol.
Adrenal Cushing's syndrome
Cushing's syndrome can also occur when one or both adrenal glands produce excessive amounts of cortisol independently of ACTH.
Possible causes include:
- an adrenal adenoma
- an adrenal carcinoma, which is rare
- bilateral adrenal hyperplasia
- other uncommon adrenal disorders
Treatment depends upon the underlying cause.
Cushing's Syndrome versus Cushing's Disease
Although the terms are sometimes used interchangeably, they do not mean exactly the same thing.
Cushing's syndrome describes the collection of symptoms and health effects caused by prolonged excessive exposure to cortisol, regardless of the cause.
Cushing's disease is a specific type of endogenous Cushing's syndrome caused by an ACTH-producing pituitary tumour.
Therefore:
All people with Cushing's disease have Cushing's syndrome, but not everyone with Cushing's syndrome has Cushing's disease.
How rare is Cushing's?
Endogenous Cushing's syndrome is considered a rare condition.
International studies have historically estimated that approximately 2–3 new cases of endogenous Cushing's syndrome occur per million people each year, although reported rates vary between studies, populations and methods of diagnosis.
Cushing's disease represents the majority of cases of endogenous ACTH-dependent Cushing's syndrome.
Cushing's in Ireland
There is currently no dedicated national pituitary disease or Cushing's patient registry in the Republic of Ireland from which reliable Irish incidence or prevalence figures can be established.
For this reason, statistics quoted by Pituitary Ireland are based on international published research and should not be interpreted as representing the exact number of people living with Cushing's syndrome or Cushing's disease in Ireland.
Cushing's can occur at any age, including childhood, although it is more commonly diagnosed in adults. Endogenous Cushing's syndrome, particularly Cushing's disease, is diagnosed more frequently in women than men.
Most cases occur sporadically and are not inherited. However, some rare genetic conditions can predispose people to particular pituitary or adrenal disorders associated with Cushing's syndrome.
Cyclical Cushing's
In some people, cortisol production is not continuously elevated.
Instead, periods of excessive cortisol production may alternate with periods during which cortisol levels are normal or lower.
This is known as cyclical or cyclic Cushing's syndrome.
The cycles may occur over weeks, months or longer.
Because cortisol levels can be normal when testing takes place, cyclical Cushing's can be particularly difficult to diagnose. Repeated testing over time may therefore be necessary when there is strong clinical suspicion.
Symptoms of Cushing's Syndrome and Cushing's Disease
Cushing's affects people differently, and not everyone will experience every symptom.
Symptoms often develop gradually and may initially be attributed to other conditions.
A combination of several characteristic symptoms may increase clinical suspicion.
Changes in body composition
Possible symptoms include:
- weight gain, particularly around the abdomen and trunk
- comparatively thinner arms and legs
- increased fat around the neck and upper back
- a fuller or rounder face
- loss of muscle mass
- muscle weakness, particularly around the hips and thighs
Skin changes
People may experience:
- thin or fragile skin
- easy bruising
- slow wound healing
- wide reddish-purple stretch marks, particularly on the abdomen, thighs, breasts or arms
- acne
- increased facial or body hair in some women
- changes in skin pigmentation in some forms of Cushing's
Bones and muscles
Prolonged cortisol excess can weaken bones and muscles and may cause:
- muscle weakness
- reduced muscle mass
- osteoporosis or reduced bone density
- back pain
- increased risk of fractures
Blood pressure and metabolism
Cushing's can contribute to:
- high blood pressure
- insulin resistance
- raised blood glucose
- type 2 diabetes
- abnormal cholesterol or other blood lipid levels
These complications can increase cardiovascular risk.
Reproductive and hormonal symptoms
Women may experience:
- irregular menstrual periods
- periods stopping altogether
- increased facial or body hair
- reduced fertility
Men may experience:
- reduced testosterone
- erectile difficulties
- reduced fertility
Both men and women may experience reduced libido.
Psychological and cognitive symptoms
Cortisol excess can also affect emotional and psychological wellbeing.
Symptoms may include:
- depression
- anxiety
- irritability
- mood changes
- difficulty concentrating
- memory problems
- disturbed sleep
- severe psychological symptoms in some cases
These symptoms are genuine effects of the condition and can significantly affect quality of life.
Other symptoms
People may also experience:
- severe or persistent fatigue
- headaches
- increased susceptibility to infection
- swelling of the legs
- increased thirst and urination
- slow recovery from illness or injury
Cushing's in children
Cushing's syndrome is particularly rare in children.
One important warning sign is weight gain occurring at the same time as slowing or stopping of normal height growth.
Children with suspected Cushing's should be assessed by specialist paediatric endocrine services.
Diagnosing Cushing's Syndrome
Diagnosing Cushing's can be complex.
Many symptoms associated with Cushing's — including weight gain, hypertension, diabetes, depression, fatigue and menstrual changes — are common in the general population and can have many other causes.
No single symptom confirms Cushing's.
Diagnosis normally takes place in stages.
The first step is determining whether the body is genuinely being exposed to excessive cortisol. If hypercortisolism is confirmed, further investigations are undertaken to determine why it is occurring.
Before testing, your healthcare team will also need to know about all steroid medications you are taking or using, including tablets, injections, inhalers, nasal sprays and creams.
Tests for Cushing's Syndrome
Depending upon your individual circumstances, an endocrinologist may recommend one or more of the following.
Overnight dexamethasone suppression test
You are given a small dose of dexamethasone, usually late in the evening, and your cortisol level is measured the following morning.
In people without Cushing's syndrome, dexamethasone normally suppresses cortisol production.
Failure to suppress cortisol appropriately can indicate that further investigation is necessary.
24-hour urinary free cortisol
All urine produced during a 24-hour period is collected in a special container and analysed for cortisol.
Because cortisol production varies, more than one collection may be required.
Late-night salivary cortisol
Cortisol levels normally fall to very low levels late at night.
A saliva sample collected late in the evening can therefore help determine whether the normal daily cortisol rhythm has been disrupted.
Repeated samples may be requested.
Why tests sometimes need repeating
Cortisol levels naturally vary throughout the day and can also be influenced by illness, stress, sleep patterns, medications and other factors.
Cyclical Cushing's can make diagnosis particularly challenging.
For these reasons, endocrinologists often use more than one test and may repeat testing before confirming or excluding Cushing's syndrome.
Finding the cause
Once endogenous Cushing's syndrome has been confirmed, further tests are used to determine where the excessive cortisol or ACTH is coming from.
A blood test measuring ACTH is an important part of this process.
If ACTH is low, an adrenal cause may be suspected.
If ACTH is normal or elevated despite excessive cortisol, an ACTH-producing pituitary tumour or ectopic ACTH source may be investigated.
Pituitary MRI
If Cushing's disease is suspected, an MRI scan of the pituitary gland is usually performed.
However, ACTH-producing pituitary tumours can be extremely small and may not always be visible on MRI.
Equally, small incidental pituitary abnormalities are relatively common in the general population. Finding a small pituitary lesion on MRI does not automatically prove that it is causing Cushing's.
The results therefore need to be interpreted alongside hormone tests and the overall clinical picture.
Inferior Petrosal Sinus Sampling – IPSS
When biochemical tests suggest ACTH-dependent Cushing's but it remains unclear whether ACTH is coming from the pituitary gland or somewhere else in the body, a specialist procedure called inferior petrosal sinus sampling (IPSS) may be considered.
During IPSS, blood samples are taken from veins that drain the pituitary gland and compared with ACTH levels in blood from elsewhere in the circulation.
The procedure is performed in specialist centres and can help distinguish a pituitary source of ACTH from an ectopic source.
Additional imaging such as CT scanning may be required if an ectopic source is suspected.
Treatment of Cushing's Disease
Treatment aims to bring cortisol levels back into a safe range, treat the underlying cause and manage complications caused by prolonged cortisol excess.
Treatment is individualised and may involve:
- surgery
- medication
- radiotherapy
- adrenal surgery
- or a combination of treatments
Pituitary Surgery
For most people with Cushing's disease caused by an ACTH-producing pituitary tumour, pituitary surgery is the preferred first-line treatment when appropriate.
The aim is to remove the tumour while preserving as much normal pituitary function as possible.
The operation is usually performed using a transsphenoidal approach, where the surgeon reaches the pituitary gland through the nose and sphenoid sinus.
Endoscopic techniques are commonly used in modern pituitary surgery.
The likelihood of remission depends on several factors including:
- tumour size
- tumour location
- whether the tumour has invaded surrounding structures
- previous treatment
- the experience of the specialist pituitary surgical team
Some people achieve remission following their first operation, while others may have persistent or recurrent disease requiring further treatment.
After successful pituitary surgery
Following successful treatment, cortisol levels may become very low.
This is often expected because prolonged exposure to excessive cortisol suppresses the body's normal hypothalamic-pituitary-adrenal axis.
People may therefore require temporary glucocorticoid replacement, usually hydrocortisone, while normal ACTH and cortisol production recovers.
Recovery can take months and sometimes longer.
During this period, patients who are glucocorticoid-dependent should receive education about adrenal insufficiency, Sick Day Rules and emergency steroid treatment.
Hydrocortisone or other prescribed glucocorticoid replacement must never be stopped suddenly unless specifically instructed by the treating endocrine team.
Recovery after treatment
Recovery from Cushing's is often gradual.
Even after cortisol levels have returned to a safe range, the body needs time to recover from prolonged cortisol exposure.
Some people initially feel worse following successful treatment because the body has become accustomed to high cortisol levels.
During recovery people may experience:
- fatigue
- muscle and joint pain
- weakness
- low mood
- reduced stamina
- changes in weight and body composition
Improvements in muscle strength, bone health, blood pressure, diabetes, appearance and psychological wellbeing can occur gradually over many months.
Some health effects may persist and require ongoing treatment.
Other treatments for Cushing's Disease
If surgery does not result in remission, if Cushing's later returns, or if surgery is not appropriate, additional treatments may be considered.
Medication
Several types of medication can be used.
Some medicines reduce cortisol production by the adrenal glands.
Others act on the pituitary tumour to reduce ACTH production, while some treatments reduce the effects of cortisol on tissues.
The most appropriate medication depends on the individual patient, severity of cortisol excess, other medical conditions, previous treatment and availability of particular medicines.
People receiving medical treatment require regular endocrine monitoring.
Radiotherapy
Radiotherapy or stereotactic radiosurgery may be considered when pituitary disease persists or recurs following surgery.
The effects of radiotherapy can take time to develop, so medication may be required to control cortisol while waiting for treatment to become fully effective.
Long-term monitoring of pituitary hormone function is necessary because radiotherapy can cause hypopituitarism.
Bilateral adrenalectomy
In selected people with severe or persistent Cushing's disease that cannot be adequately controlled by other treatments, surgical removal of both adrenal glands may be considered.
This immediately prevents the adrenal glands from producing excessive cortisol.
However, removing both adrenal glands causes permanent adrenal insufficiency.
Lifelong glucocorticoid replacement — and usually mineralocorticoid replacement — is therefore required, together with Sick Day Rules and emergency steroid precautions.
People with Cushing's disease who undergo bilateral adrenalectomy also require long-term monitoring of their pituitary tumour and ACTH levels.
Other pituitary hormone problems
Cushing's disease itself, pituitary surgery and radiotherapy can sometimes affect the production of other pituitary hormones.
This is known as hypopituitarism.
Depending upon which hormones are affected, long-term hormone replacement may be required.
Temporary or permanent Arginine Vasopressin Deficiency (AVP-D), previously known as diabetes insipidus, can also occur following pituitary surgery.
AVP-D causes excessive production of dilute urine and significant thirst and can usually be treated with desmopressin when required.
Long-term follow-up
Even after successful treatment, people who have had Cushing's disease require long-term endocrine follow-up.
Cushing's disease can recur, sometimes years after apparently successful treatment.
Follow-up may therefore include:
- cortisol testing
- assessment of pituitary hormone function
- monitoring blood pressure
- monitoring blood glucose and diabetes risk
- assessment of cardiovascular risk
- bone health and bone density assessment where appropriate
- monitoring psychological wellbeing and quality of life
- repeat pituitary imaging where clinically indicated
Long-term follow-up is an important part of Cushing's care.
Living with Cushing's
Cushing's can affect almost every aspect of a person's life.
The physical changes caused by cortisol excess can be distressing, while fatigue, muscle weakness, sleep disturbance, anxiety, depression and cognitive difficulties can significantly affect everyday life.
Recovery does not always occur immediately after cortisol levels normalise.
Support from family, friends, healthcare professionals and other people who understand pituitary disease can therefore be extremely valuable.
Pituitary Ireland provides information, awareness and peer support for people affected by pituitary conditions throughout the Republic of Ireland.
Important Information
The information provided by Pituitary Ireland is intended for general information and patient education and should not replace individual medical advice.
Diagnosis and treatment of Cushing's syndrome and Cushing's disease should be undertaken by healthcare professionals with appropriate expertise in endocrinology and pituitary disease.
If you are concerned that you may have symptoms of Cushing's syndrome, speak with your GP or healthcare professional. Where clinically appropriate, you may be referred to an endocrinologist for further assessment.
Never start, stop or alter prescribed corticosteroid medication without medical advice.
Sources and further information
This information has been developed with reference to internationally recognised clinical guidance and patient information, including:
Because Ireland currently has no dedicated national Cushing's or pituitary patient registry, epidemiological figures presented by Pituitary Ireland are based on published international data.
Last reviewed: 2026