Cushing’s syndrome is a metabolic disorder that occurs when the body is exposed to excessively high levels of the hormone cortisol over a prolonged period. Cortisol is often referred to as the body’s stress hormone because it helps regulate blood pressure, the immune system, and the way the body converts food into energy. While a certain amount of cortisol is essential for survival, having too much can cause a wide range of physical and psychological symptoms, including weight gain in the torso, a rounded face, and thin skin that bruises easily. Understanding the cause of this hormonal surge is the first step toward effective treatment, as the source of the excess cortisol can originate from either external medications or internal abnormalities within the body’s endocrine system.
What We’ll Discuss in This Article
- The impact of exogenous steroids as the most common cause of high cortisol.
- How pituitary gland tumours lead specifically to Cushing’s disease.
- The role of adrenal gland tumours in direct hormone overproduction.
- Ectopic ACTH production by tumours outside the endocrine system.
- Genetic factors and rare familial conditions that influence cortisol levels.
- Identifying the specific source of excess cortisol through diagnostic testing.
Exogenous Steroid Medication
The most frequent cause of Cushing’s syndrome in the United Kingdom is the long term use of high dose corticosteroid medications. These drugs, such as prednisolone, are chemically similar to the cortisol naturally produced by the adrenal glands and are widely used to treat inflammatory conditions like asthma, rheumatoid arthritis, or lupus. When these medications are taken in large quantities or for a long period, the total amount of “cortisol like” activity in the blood rises far above what the body requires for normal function.
This form of the condition is known as exogenous Cushing’s syndrome because the source of the hormone is outside the body. According to the NHS overview of Cushing’s syndrome, even steroid injections for joint pain or inhaled steroids for respiratory issues can occasionally cause the syndrome if used excessively, though oral tablets carry the highest risk. In these cases, the high levels of artificial steroids signal the brain to stop producing natural cortisol, which can cause the adrenal glands to shrink over time. Managing this cause usually involves a careful, medically supervised reduction of the medication dose to allow the body to return to its natural hormonal balance.
Pituitary Gland Tumours (Cushing’s Disease)
When the cause of the high cortisol levels is internal, it is often due to a non cancerous (benign) tumour in the pituitary gland, a small organ located at the base of the brain. This specific form of the syndrome is known as Cushing’s disease. The pituitary gland is responsible for producing adrenocorticotropic hormone (ACTH), which travels through the bloodstream to signal the adrenal glands to release cortisol. A tumour in the pituitary gland can cause it to produce excessive amounts of ACTH, regardless of how much cortisol is already in the system.
This constant signal forces the adrenal glands to work overtime, resulting in a continuous overproduction of cortisol. Cushing’s disease is the most common cause of endogenous (internal) Cushing’s syndrome, accounting for approximately 70 percent of cases. Because the tumour is usually very small, it does not typically cause headaches or vision problems, but the hormonal impact on the rest of the body is significant. The NICE guidelines on pituitary tumours emphasize that surgical removal of the tumour is generally the most effective way to normalize ACTH and cortisol levels.
Adrenal Gland Tumours
In some cases, the source of the problem lies within the adrenal glands themselves. A tumour in the adrenal cortex, the outer layer of the gland, can start producing cortisol independently of the signals sent by the brain. These tumours are usually benign adenomas, but in very rare instances, they can be cancerous (adrenal cortical carcinomas). Unlike the pituitary cause, these tumours do not rely on ACTH; in fact, ACTH levels in these patients are usually very low because the brain detects the excess cortisol and tries to shut down the signaling system.
| Tumour Type | Hormone Secreted | ACTH Level in Blood |
| Pituitary Adenoma | ACTH | High |
| Adrenal Adenoma | Cortisol | Low |
| Ectopic Tumour | ACTH | Very High |
Adrenal tumours usually only affect one of the two adrenal glands. While the tumourous gland produces too much hormone, the healthy gland on the other side may shrink (atrophy) because it is no longer being stimulated by ACTH. Treatment typically involves the surgical removal of the affected adrenal gland, after which the remaining gland usually takes over the full responsibility for hormone production over several months.
Ectopic ACTH Production
A rarer cause of Cushing’s syndrome is the “ectopic” production of ACTH by tumours located outside the traditional endocrine system. In this scenario, a tumour in another part of the body, most commonly the lungs, begins to produce ACTH. This ectopic ACTH travels to the adrenal glands and triggers them to release massive amounts of cortisol, just as if the signal had come from the pituitary gland.
Small cell lung cancer is the most frequent source of ectopic ACTH, though it can also be produced by carcinoid tumours in the chest or thymus. These cases are often more severe and develop more rapidly than those caused by pituitary tumours. Patients with ectopic Cushing’s may also experience electrolyte imbalances, such as very low potassium levels, which require urgent medical management. Identifying the location of these hidden tumours often requires advanced imaging techniques like CT or MRI scans of the chest and abdomen.
Rare Genetic and Familial Causes
Although most cases of Cushing’s syndrome are sporadic, meaning they occur by chance, there are rare genetic conditions that can increase the risk. One such condition is Multiple Endocrine Neoplasia type 1 (MEN1), a hereditary disorder that causes tumours to grow in various endocrine glands, including the pituitary and adrenals. Another rare genetic cause is Carney complex, which can lead to small, pigment producing tumours in the adrenal glands that secrete excess cortisol.
In children, a rare condition called primary pigmented nodular adrenocortical disease (PPNAD) can cause the adrenal glands to develop multiple small, dark nodules that produce cortisol. These genetic forms of the syndrome are often suspected if the patient is very young or if multiple family members have endocrine problems. Genetic counseling and screening are often recommended for families affected by these conditions to ensure early detection and management of hormonal imbalances.
Identifying the Cause Through Testing
Because the symptoms of Cushing’s syndrome are the same regardless of the cause, doctors must use specific diagnostic tests to find the source of the excess cortisol. The first step is usually to confirm that cortisol levels are indeed high, often using a 24 hour urine collection or a late night saliva test. Once high cortisol is confirmed, an ACTH blood test is performed to see if the brain is involved.
If the ACTH is high, doctors may perform a “dexamethasone suppression test” or a “corticotropin releasing hormone (CRH) test” to distinguish between a pituitary source and an ectopic source. Imaging the pituitary and adrenal glands is also a standard part of the process. In complex cases, a procedure called inferior petrosal sinus sampling (IPSS) may be used, where blood is taken directly from the veins draining the pituitary gland to measure ACTH levels at the source. This meticulous testing ensures that the patient receives the correct treatment, whether it be surgery, radiotherapy, or medication to block hormone production.
Conclusion
Cushing’s syndrome is caused by an excess of cortisol that can stem from various sources, most commonly the long term use of steroid medications. When the cause is internal, it is typically due to a tumour in the pituitary gland, the adrenal glands, or more rarely, an ectopic tumour in the lungs. Identifying the exact cause through specialized blood tests and imaging is essential for restoring hormonal balance and preventing long term health complications. If you experience severe, sudden, or worsening symptoms, call 999 immediately.
Is Cushing’s syndrome the same as Cushing’s disease?
Cushing’s syndrome is the general term for high cortisol, while Cushing’s disease refers specifically to high cortisol caused by a pituitary tumour.
Can stress alone cause Cushing’s syndrome?
While stress raises cortisol temporarily, it does not cause the sustained, dangerously high levels seen in Cushing’s syndrome.
Will the symptoms go away if I stop my steroid medication?
The symptoms usually improve, but you must never stop steroids suddenly; they must be tapered slowly under medical supervision.
Is Cushing’s syndrome more common in men or women?
Endogenous Cushing’s syndrome (caused by tumours) is significantly more common in women than in men.
Can a high sugar diet cause Cushing’s syndrome?
No, while the condition can cause high blood sugar and weight gain, it is not caused by diet or lifestyle choices.
How long does it take to recover after surgery?
Recovery is a gradual process that can take several months to a year as your body’s natural hormone production stabilizes.
Are the tumours that cause Cushing’s usually cancerous?
Most pituitary and adrenal tumours associated with the syndrome are benign (non cancerous), although ectopic tumours can be malignant.
Authority Snapshot (E-E-A-T Block)
This article provides clear, factual information about the causes of cortisol overproduction to assist in patient education. It has been authored and reviewed by Dr Rebecca Fernandez and Dr Stefan, who hold extensive experience in UK internal medicine and acute care settings. All content is strictly aligned with current NHS and NICE clinical guidelines to ensure medical accuracy and reliability.
