Cushing’s disease occurs due to excess cortisol production resulting from a malfunctioning pituitary gland. The pituitary gland is present at the base of the brain. In this condition, a non-cancerous tumour on the gland induces it to release excessive adrenocorticotropic hormone (ACTH). ACTH further fuels the adrenal glands to produce more cortisol. Cortisol affects entire organs and tissues in the body, leading to their abnormal growth syndrome called Cushing disease.
Associated Anatomy
Pituitary gland: An organ of the endocrine system
Causes
The following factors can cause Cushing’s disease:
- The long-term high dosage of cortisol (injectable or oral) is the most common cause. Glucocorticoids are examples of cortisols. These medicines treat conditions such as lupus, asthma, and rheumatoid arthritis. One can also find them in asthma inhalers and skin ointments.
- Few people also develop this disease as their bodies produce too much cortisol. Several tumours can accelerate the production of excess cortisol.
- Several tumours can also cause a higher production of cortisol. For instance: pituitary gland tumours, ectopic tumours (they usually occur in the thymus gland, lung, thyroid, or pancreas), and adrenal gland tumours or abnormalities. When it is adrenal tumour , excess production of cortisol is independent of ACTH which are actually low in this condition.
Signs or Symptoms
Common signs and symptoms of cushings disease include:
- Weight gain
- Muscle weakness
- Skin darkening
- Fatty tissue deposits (more around the upper back and midsection), shoulders (buffalo hump), and face (moon face)
- Purple or pink stretch marks on abdominal skin, arms, thighs, and breasts
- More acnes
- Fragile and thin skin prone to bruising
- Rapid bone loss, more prone to fractures
- Slow healing of infections, cuts, and insect bites
- Anxiety, depression, and irritability
- Lesser emotional control
- New episodes of high blood pressure
- Impaired growth (among children)
Signs and symptoms among women:
- An increase in thicker facial or body hair
- Irregular menstrual periods or absent periods
Signs and symptoms among men:
- Erectile dysfunction
- Lower sex drive
- Decreased fertility
Possible Treatment of Cushing s disease
The treatment options for Cushing’s disease focus on lowering the cortisol level in the body. Some of the best treatments are:
Reducing the corticosteroid use
Suppose you suffer from Cushing’s disease due to the long-term usage of corticosteroid medications. In that case, your doctor can reduce the dosage while maintaining your condition. Please Note: Do not start or stop taking these medications without your doctor’s supervision.
Surgery
Your doctor may recommend the removal of tumours through a surgical process. Medical professionals can remove pituitary tumours through a nasal procedure. However, the adrenal glands, pancreas, or lungs require minimally invasive surgical techniques.
Radiation therapy
If the pituitary tumour is not removed even after surgery, the doctor will also prescribe you radiation therapy. Radiation is typically for patients who can’t undergo surgery.
Medications
If both surgery and radiation don’t work, you can be prescribed medications to control cortisol production. Such medicines include:
- Metyrapone (Metopirone)
- Pasireotide (Signifor-injectable)
- Ketoconazole
- Osilodrostat (Isturisa)
- Mitotane (Lysodren)
Surgery of adrenal glands
If all the treatments mentioned above fail, your doctor might recommend bilateral adrenalectomy. It is a surgical process that includes the removal of adrenal glands. While the process cures excessive cortisol production, it requires lifelong replacement medications.
Risk Factors
Factors that can increase the risk of Cushing disease are:
- Long-term use of high doses of corticosteroids
- You are an adult female.
- Your age is between 20 to 50 years.
- You are living with adrenal or pituitary tumours.
Stages
As the changes in appearance and body develop gradually, decoding the early stages of Cushing’s disease is difficult. The hormone elevations appear and disappear. Therefore, one can term them ‘periodic’ or ‘cyclical’ Cushing’s disease, making the diagnosis more difficult.
Diagnosis
If you are not using any corticosteroid medication, the following diagnostic tests may help in identifying Cushing’s disease: Urine and blood tests: You must undergo these tests to determine hormone levels to check if your body produces too much cortisol. The healthcare professional may ask you to take 24-hour urine free cortisol (UFC) measurement. This test collects and examines urine for over 24 hours. Medical professionals also analyse your blood samples to gauge cortisol levels. Saliva test: Cortisol levels keep rising and falling during the day and fall drastically during the evening. Therefore, analysing several saliva samples collected late at night help in decoding the high cortisol levels. Imaging tests: Magnetic resonance imaging (MRI) or computerised tomography (CT) scans help examine tumours and other abnormalities in your adrenal and pituitary glands. Petrosal sinus sampling: Pathologists carry out this sampling test to confirm if the root cause of the disease is in the pituitary gland or somewhere else.
Primary Prevention
Cortisol is integral for carrying out several functions like managing respiration, regulating blood sugar levels, turning food into energy, helping in coping with stress, and more. However, too much cortisol is your body’s enemy. For primary prevention, get your cortisol levels monitored from time to time, especially if you are taking steroids or glucocorticoids. However, there is no way to avoid or prevent tumours causing Cushing’s disease.
Alternative Name
ACTH-Secreting Adenoma, Pituitary Cushing’s Disease
Epidemiology
- Pituitary adenomas (Cushing’s disease) affect about 60 to 70 per cent of adolescents and children and over 70 per cent of adults.
- Cushing’s syndrome is prevalent among women and affects adults in the age group of 20 to 50. They account for around 70 per cent of the total cases.
Expected Prognosis
Cushing’s disease can lead to severe illness and even death if left untreated. However, removing the tumour might help you recover fully, but there are chances of the tumour growing back.
Natural Progression
Cushing’s disease can lead to severe illness and even death if left untreated.
Pathophysiology
The adrenal gland secretes steroid hormones and cortisol stimulated by excessive ACTH. The pituitary gland secretes ACTH, while the hypothalamus secretes the corticotropin-releasing hormone. The latter causes the ACTH to transfer to the petrosal venous sinuses.
Possible Complications
Cushing’s disease can lead to several health problems like:
- Deep vein thrombosis (blood clots in veins)
- Mood swings or related psychiatric problems
- Compression fractures in the spine
- Diabetes
- Frequent infections
- Heart attack or stroke
- Memory loss or trouble concentrating
- High blood pressure
- Kidney stones
- Weight gain
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