Cushing’s syndrome: what is it, causes, symptoms, has a cure?

What is Cushing’s Syndrome?

Cushing’s syndrome appears when there is prolonged and excessive exposure to glucocorticoids, especially cortisol.

The condition is defined as a syndrome, as it refers to a series of symptoms and clinical signs that can be associated with more than one cause. Unlike Cushing’s disease, which is characterized by the presence of tumors that increase cortisol production.

External conditions (exogenous), resulting from the use of corticosteroid medications, or internal conditions (endogenous), resulting from the high production of cortisol, can cause the alteration in the organism.

Listed by ICD-10 (International Classification of Diseases) E24, the condition is also called hypercortisolism or hyperadrenocortisolism.

Data from the World Health Organization (WHO) indicate that approximately 50 thousand people are diagnosed annually with the syndrome, representing an unusual condition.

In general, there is a rapid increase in weight and the main sign is the marked accumulation of fat in the abdominal, face and neck regions . In contrast to the limbs, which are usually more refined, compared to other regions, and may present atrophy of the musculature.

In addition, wide streaks with a marked color, and purple spots (called ecchymoses), can appear on the legs, arms and abdomen. In general, redness on the face, wounds in different regions of the skin, reduced muscle mass and mood swings, such as irritability, may manifest jointly.

The condition still represents a condition that is difficult to diagnose, due to confusion with other diseases, such as obesity itself . When the syndrome is suspected, the diagnosis is confirmed through a series of tests.

About 70% of the syndrome’s cases are caused by the presence of a tumor in the pituitary gland, which is usually benign. In this case, the condition is called Cushing’s disease .

The Pituitary Gland and ACTH

ACTH is produced by the pituitary gland, also known as the pituitary gland, which is located in a central point of the head, just below the brain. The gland makes up the endocrine system, so it performs functions of regulation of the organism and hormonal production.

The pituitary gland can be divided into 2 parts, which comprise the adenohypophysis, responsible for the synthesis and secretion of hormones, and the neurohypophysis, responsible for the storage and secretion of the hormones oxytocin and ADH.

The hormones produced in the adenohypophysis are:

  • STH (somatotrophin or GH) , which acts on growth;
  • TSH (thyrotrophin) , which stimulates the production of hormones T3 and T4;
  • ACTH (adrenocorticotrophic) , which stimulates the production of corticoid hormones;
  • Gonadotrophic Hormone: acts on the gonadotrophic hormones FSH (follicle stimulating hormone) and LH (luteinizing hormone);
  • LTH: called prolactin or lactogenic, which stimulates the production of milk in the female mammary glands.

ACTH, an adrenocorticotropic hormone, also called corticotrophin, is the substance responsible for stimulating the production of cortisol, which regulates various functions in the body.

In the kidney region, just above them, there are the adrenal glands, which are the adrenal cortex (external) and the adrenal medulla (internal). The pituitary adeno then stimulates the release of ACTH which, as a result of the release, causes the region of the cortex to produce steroid hormones, including cortisol.

Cortisol, which is a glucocorticoid, acts on the balance of glucose, proteins and aids lipid metabolism, in addition to keeping blood pressure and immune responses regulated.

The steroid also works by stimulating the glycogen process, in which the body synthesizes nutrients in order to obtain energy for the body’s functions.

Or non-organism cortisol

Cortisol secretion in healthy individuals is higher in the morning, with increased hormonal release in the first 30 minutes after awakening, and tends to decrease over the course of the day.

The amount of the substance is relatively constant throughout adulthood, however, emotional changes, depression or hormonal changes linked to the production of cortisol can change the rates.

Situations stress , physical activities and actions that promote the release of serotonin (popularly known as the happy hormone) can cause variation in cortisol levels during the day.

In general, hormonal marking in the morning is between 5mcg / dL and 23 mcg / dL. At night, the basal cortisol varies between 3mcg / dL and 16 mcg / dL.

When there is an elevation of the substance, symptoms such as changes in blood pressure, edema, concentration of body fat, diabetes or changes in glucose, mood swings and depressive conditions may appear.

Studies indicate that obesity tends to be directly related to the increase in plasma cortisol, which may be a cause or consequence of the condition.

When obesity precedes hypercortisolism, the condition can trigger an excessive action of the hypothalamus, pituitary and adrenal glands, which results in high cortisol release.

Cortisol, which comes from external sources, is present in antiallergic, immunosuppressive and anti-inflammatory drugs.

Types

Although there is essentially only one type of syndrome, it is differentiated according to the causative factor (tumor in the pituitary gland or not), in addition to the altered hormones involved.

Cushing’s syndrome

It is a condition characterized by various symptoms and responses of the body to excessive and prolonged exposure to cortisol, whether it is ingested (by drugs) or produced by the body itself.

The triggered pathologies are quite diverse, including glycemic, lipid and blood pressure changes.

In addition to the symptoms, the syndrome generally presents physical signs, such as accumulation of adipose tissue in the abdomen and face, in addition to streaks and edema with accentuated tones.

With regard to the endogenous condition, it can be divided according to its physiological link: whether it is dependent on ACTH or not.

When the endogenous condition is ACTH-dependent (related to the hormone), the body tends to have high concentrations of the hormone. In cases where there is no hormonal interaction, ACTH concentrations are low or undetectable.

The term Cushing’s syndrome refers, then, to all causes and manifestations caused by excess cortisol (hypercortisolism).

ACTH-independent Cushing’s syndrome

In this case, excess cortisol is caused by the adrenal glands and ACTH levels remain low. The main occurrences involve adrenal tumors and nodular hyperplasias.

Most diagnoses involve non-cancerous (benign) tumors in the adrenal glands. The tumor, in this case, consists of the abnormal formation of cells in the gland, called adrenal adenoma and promoting the exaggerated release of cortisol into the blood.

Non-cancerous tumors are relatively common, affecting up to 10% of the population up to 70 years of age. However, few cases result in the exaggerated release of cortisol.

The presence of malignant tumors is quite rare and can be accompanied by changes in several hormones together. Therefore, the condition presents a rapid evolution of the symptoms.

Nodular hyperplasias, on the other hand, are rare causes of ACTH-independent Cushing’s syndrome. In summary, there are cellular mutations that regulate the production of a substance called 1-alpha of protein kinase A. They may be related to other tumors.

ACTH-dependent Cushing’s syndrome

The highest prevalence is due to a pituitary adenoma, characterizing Cushing’s disease, or a neuroendocrine tumor, characterizing the ACTH ectopic secretion syndrome.

The condition causes an increase in the adrenal glands, also causing an increase in hormonal production.

Cushing’s disease, in general, presents a small and benign tumor, being called hypophasic adenomas. The condition occurs related to the secretion of ACTH, increasing its quantity, and results in the excessive release of cortisol. Therefore, it is said that the condition is ACTH-dependent.

Cushing’s disease is the most common among reported cases, representing up to 70% of diagnoses.

Ectopic ACTH syndrome

The condition is uncommon, being caused by neuroendocrine tumors that can appear in different regions of the body, other than the pituitary gland. These anomalies alter the production of ACTH and the condition is called ectopic ACTH syndrome.

On average, 50% of diagnoses have lung tumors, but there are also observations of pancreatic islet tumors, thyroid marrow carcinomas and thymomas.

More rarely, there may be changes in the secretion of corticotrophin-releasing hormone (CRH). The substance is responsible for stimulating ACTH.

When there are mutations in its functioning, ACTH changes occur, promoting excess cortisol. In this case, the condition is called CRH Ectopic Secretion Syndrome.

What causes?

The condition is mostly caused by the use of drugs derived from cortisone (endogenous causes).

In addition, diseases of the adrenal gland and dysfunction of the pituitary gland can lead to the syndrome, in addition to tumors in the adrenal and pituitary glands, which are regions involved in hormonal stimulation.

More sporadic cases may present alterations and neuroendocrine tumors.

Exogenous causes

Prolonged use of high doses of corticosteroids can lead to the syndrome of exogenous origin.

Corticosteroids are drugs to treat various diseases and conditions, being administered orally, injectable or inhalable. The most frequent indications are for allergic, inflammatory and autoimmune cases, including:

  • Asthma;
  • Multiple sclerosis;
  • Allergies, mainly anaphylaxis;
  • Lupus;
  • Rheumatoid arthritis;
  • Leukemias and lymphomas;
  • Brain edema;
  • Sarcoidosis;
  • Inflammatory bowel disease;
  • Addison’s disease (adrenal insufficiency);
  • Skin diseases of inflammatory or autoimmune origin;
  • Organ transplantation.

The most commercialized drugs indicated for the treatment of these diseases are prednisone , prednisolone , hydrocortisone , dexamethasone , methylprednisolone and beclomethasone .

Endogenous causes

Daily factors, when they are extremely pronounced, can trigger changes in cortisol levels. For example, stress and irregular sleep for long periods.

However, the condition does not represent prevalence in cases of Cushing’s syndrome, in which the most common causes tend to be tumors or renal gland disorders .

In ACTH-dependent syndrome (responsible for up to 85% of diagnoses), pituitary adenoma is the major cause of the disorder. The condition is defined by lesions or irregular cellular formations, usually benign in the pituitary region, which lead to neurological and hormonal dysfunctions.

In addition to adenoma, ACTH-secreting ectopic tumors may be responsible for cortisol dysfunctions. These tumors can affect several regions and tissues of the organism more frequently in the lungs (about 70% of diagnoses).

When the syndrome is independent of the ACTH hormone, the causes come from benign or malignant lesions, also characterized as adrenal tumors, and from nodular hyperplasias.

These tumors can be unilateral lesions of the adrenal glands (affecting only one adrenal gland), or bilateral lesions (affecting both glands), which stimulate the excessive production of cortisol.

While adenomas account for about 95% of diagnoses, bilateral lesions are considerably less frequent.

However, the condition tends to be associated with other conditions, such as pigmented nodular disease of the adrenals, bilateral macronodular hyperplasia and, even more rarely, bilateral adenomas.

These cases, in general, are reported equally among men and women, with a higher prevalence after 50 years of age.

occurrences

According to the World Health Organization (WHO), approximately 50 thousand people a year are affected by the syndrome. This indicates an estimated 12 cases for every 1 million people.

Pituitary adenomas, which are classified as Cushing’s disease, account for more than 70% of cases in adults. In children, the syndrome with the presence of a tumor occurs between 60% and 70% of diagnosed cases.

The prevalence, in Cushing’s disease, in general, affects more women than men (about 70% of cases), and prevails in the age group of 20 to 50 years.

When adrenal adenomas are the cause of excess cortisol, the condition affects 4 women for each man. In cases of adrenal carcinomas, 2 women are diagnosed for each man.

Groups of risk

The conditions that make people more susceptible to the syndrome are quite broad. Genetic and environmental factors can favor changes in cortisol, but generally attention should be focused on:

  • Patients using corticosteroids;
  • Obese patients;
  • Diabetes patients;
  • Patients with high and constant stress levels.

Signals and symptons

Patients with hypercortisolism, resulting from Cushing’s syndrome, may present several physical and organic signs and symptoms.

It is possible to compile the signs with a play on words, making it easier to symptomatic association:

  • C Purple icatrizes neck or abdomen, less resistant collagen risk of kidney stones and concentration of fat;
  • U rina with high concentrations of cortisol and glucose;
  • S ensibilidade skin and bones, with slow healing and bone degeneration;
  • H ipertensão and hyperglycemia;
  • I inhibited immunity, irregular menstrual cycle in women or impotence in men;
  • N oplasms in the condition if it is endogenous;
  • G lamb weight and excess fat on the face, neck, belly and back.

When the syndrome is endogenous, not due to the use of corticosteroids and there is no suspicion of tumors in the pituitary gland (Cushing’s disease), the diagnosis tends to take longer, due to the amplitude of the symptoms.

Body and external signs

Patients with Cushing’s syndrome tend to have accumulation of fat in the regions of the face and abdomen. The characteristic is defined as one of the morphological signs, being called classic cushingoid appearance .

The swelling and accumulation of fat make the face more rounded and promote obesity of the trunk, with a marked accumulation of fat in the region close to the collarbone and on the back (below the neck, in the central region of the spine).

Usually, the most finely tuned extremities in patients are identified, such as the arms, legs and fingers. There are also reports of weakness and decreased muscle mass, which tend to make up the first symptoms associated with the syndrome.

Affected patients usually have thinned and atrophic skin, with difficulty in healing. Due to the sensitivity of the tissue, purple spots and lesions are quite common.

The abdominal region usually presents wide streaks and in purplish tones.

However, there are cases in which excess cortisol resulting from malignant or benign tumors (ectopic ACTH) has a very marked evolution and does not show the stigmatized cushingoid appearance .

But, even though patients do not have the classic morphology of the syndrome, there is a high prevalence of obesity, high blood pressure, diabetes and changes in bone constitution.

Some may still have excessive hair, especially on the facial region, and darkening of the skin, which makes up difficult to recover stains or swelling.

Internal symptoms

About 60% of the cases show muscle weakness, especially in the lower limbs, and weakening of the bones, resulting in the action of cortisol in the bone tissue.

Hypertensive conditions, renal dysfunction, glycemic alterations, low immunity and osteoporosis are very common in the reported cases.

The syndrome can also have neuropsychiatric effects, which affect about 80% of patients, promoting irritability, depression, reduced ability to concentrate and memory.

There are occurrences of infertility, amenorrhea, osteoporosis, erectile dysfunction and decreased libido are also associated with the syndrome, which can affect men and women equally.

Also noteworthy is the reduction of potassium (which affects kidney functions), cardiovascular problems and difficulty with weight loss.

Diagnosis

The physical characteristics point to the need to investigate the presence of Cushing’s syndrome, which is done through laboratory tests, such as urine and blood tests help in the measurement of cortisol levels.

In addition, saliva tests can assist in the measurement of rates during the day, composing a panoramic picture of hormonal rates.

Imaging exams may indicate the presence of tumors or abnormalities in the hypophic and adrenal glands.

The condition must be accompanied by an endocrinologist .

Concentration of free urinary cortisol

The procedure is a simple method and, in general, it is the most used for the evaluation of cortisol, as soon as the majority of patients with Cushing’s syndrome present high levels of cortisol in the urine.

However, urinary change can also be present in patients with obesity, polycystic ovary syndrome or depression, without configuring the syndrome.

The urine is accumulated for a period of 24 hours and must comprise at least 3 collections.

Dexamethasone suppression test

The test is usually requested when there is a change in the concentration of free urine.

False positive cases have been reported in a patient with psychiatric illness, alcoholism , stress, pregnancy, use of estrogen, resistance to glucocorticoids, reduced absorption of dexamethasone, in addition to the use of drugs such as phenobarbital and phenytoin.

The exam consists of the administration of 1mg to 2mg of dexamethasone at night, at approximately 11 pm, subsequently followed by the measurement of plasma cortisol at 9 am.

In healthy patients, the administration of the substance suppresses cortisol, reducing it drastically. In the case of those affected by the syndrome, even if there is a reduction in levels, it presents itself in a very subtle way, still remaining high.

Saliva test

Through the collection and evaluation of small salivary samples, it is possible to measure cortisol rates. The method has been shown to be quite efficient, being a recent procedure, but facilitated for the diagnosis of Cushing’s syndrome.

ACTH concentration

After identifying the presence of changes in cortisol rates, the ACTH rate test is performed in order to define the origin of the syndrome (dependent or independent of ACTH).

Normal or elevated levels of ACTH indicate the presence of secretory tumors, whereas adrenal cases have low levels of the substance.

Imaging exams

They are used in the suspicion of tumors or adrenal, polyphasic and ectopic abnormalities. The exams that can be ordered are:

  • Computed tomography;
  • Magnetic resonance imaging;
  • Ultrasonography.

However, tumors are usually small and difficult to locate. Therefore, imaging studies should not be used as the sole source of diagnosis.

Studies indicate that up to 50% of Cushing’s disease cases can present negative imaging results for the anomaly, making up a false negative.

Is there a cure?

In most cases, yes . In exogenous cases, it is possible to stop the excessive supply of cortisol quickly by stopping the medication.

In endogenous cases, surgery can eliminate the cause of cortisol dysfunction and eliminate symptoms. However, surgical treatment cannot always be performed or is completely efficient.

In such cases, diseases that persist to treatment (such as diabetes or hypertension) must be treated continuously.

Treatment

The treatment must be initiated aiming, above all, to resolve the primary cause of the alteration. But it is also necessary to restore normal levels of cortisol, minimize the damage caused by the syndrome and, finally, recover the patient’s well-being.

Surgical intervention

Endogenous causes are mostly treated with surgical procedures. The indication of the type of surgery depends on the location of the tumor.

Radiotherapy

If it is not possible to perform the surgery or remove the tumor completely, radiotherapy treatments are indicated. They are often indicated after surgery.

The procedure uses the application of radiation in order to destroy tumor cells and prevent the proliferation of cancer .

Stereotaxic Radiosurgery

While radiotherapy treatments involve an average of 40 sessions, radiosurgery has been shown to be quite efficient in some types of tumor. Despite the name, the method is not invasive, that is, there are no incisions or perforations.

The technique consists of administering high doses of radiation at specific and well-defined points. In general, the procedure lasts up to 5 sessions and can be designed for tumors in the brain, lungs, liver, pancreas and kidneys.

Studies indicate the effectiveness of treatment in cases of ACTH-secreting adenoma. The results show a reduction in tumors in 54% of cases, in addition to controlling or stabilizing tumor growth in 96% of patients with Cushing’s disease.

Medicines

In general, medications are indicated to stabilize the condition and reduce the damage from exposure to cortisol.

Thus, it is possible to indicate medications before surgery, in order to make the procedure more effective, or even to associate them afterwards with chemotherapy treatment.

If the syndrome is of exogenous origin, caused by the use of cortisol derivatives, the treatment consists of the gradual withdrawal of the medication.

The conditions for decreasing and replacing the compound should be determined by the doctor, who will take into account the patient’s clinical condition.

Surgery

Surgical indication is the most frequently used in cases where malignant tumors are present or not. Usually, laparoscopic procedures are more indicated in cases of adrenal adenomas, while open surgery is preferable in cases of carcinomas.

If the patient is unable to perform the operation, treatment through radiotherapy can be made possible, usually associated with medications that inhibit cortisol levels.

Transsphenoidal or Transcranial Surgery

They perform the removal of tumors in the pituitary region (skull).

Incisions can be made through the nose, configuring a minimally invasive operation, or through the skull, which is more indicated in malignant tumors, with marked volume or difficult to access through the nasal region.

In the second case (transcranial), the operation consists of a more invasive and delicate method, in which the cut is made on the top or side of the head, depending on the location of the tumor.

Laparoscopy

If the tumor is located in the region close to the adrenal glands, the most recurrent surgery is laparoscopy.

The method is minimally invasive, as it consists of the incision of extremely thin tubes and instruments in the abdominal region. Through microperforations, the surgeon removes the tumor and investigates the conditions of nearby tissues.

Medicines

Cortisol inhibitors can be administered concurrently with chemotherapy, prior to surgery, or even be administered when surgical treatment is not completely effective.

For Cushing’s disease, pasireotide diaspartate has good results when pituitary surgery is not effective or cannot be performed.

In cases where the patient has inoperable adrenal tumors in the cortex, the indication for mitotane is quite recurrent.

Ketoconazole is also administered to control cortisol secretion, being another medication option.

In some cases, after surgery, hormone replacement is necessary. The drugs that are generally most recommended include:

  • Predinison ;
  • Deflazacort;
  • Hydrocortisone .

Attention!

NEVER self-medicate or stop using a medication without first consulting a doctor. Only he will be able to tell which medication, dosage and duration of treatment is the most suitable for his specific case. The information contained in this website is only intended to inform, not in any way intended to replace the guidance of a specialist or serve as a recommendation for any type of treatment. Always follow the instructions on the package insert and, if symptoms persist, seek medical or pharmaceutical advice.

Living together

After the diagnosis of the syndrome, it is necessary to adopt measures that aim to stabilize cortisol levels and, consequently, reduce the complications and symptoms of the alteration.

Patients are recommended to practice physical activities, aiming to stabilize diabetes, obesity and hypertension.

In addition, food can be planned in order to bring better results in weight loss, blood glucose, cholesterol and hypertension rates, in addition to contributing to several associated symptoms, such as joint pain (which is accentuated with overweight), poor circulation, muscle weakness, among others.

food

Food can help to reduce plasma cortisol levels (present in the blood). However, it is necessary to emphasize that dietary changes should only be carried out with the indication and monitoring of health and nutrition professionals.

In most cases, food is not able to restore adequate levels of cortisol, but it can help treatment later and avoid health risks.

Food, therefore, can mitigate the elevation and impacts on the substance in the body. Nutritional indications may involve:

  • Reduce sodium;
  • Maintain hydration;
  • Consume foods rich in phenylalanine (chicken, eggs, brown rice, broccoli, pumpkin);
  • Consume foods rich in tryptophan (brown rice, soy, oilseeds, meat, eggs);
  • Reduce caffeine;
  • Eat foods rich in vitamin B5 (apricot, almond, milk, salmon);
  • Control the consumption of potassium.

Physical activities

Resuming or starting activities helps the treatment and recovery of the patient. It is important that the exercises are performed gradually and provide well-being and satisfaction.

The whole organism benefits from the practice of activities, because in addition to reducing anxiety and stress, it promotes the proper functioning of the organism, eases symptomatic conditions, such as diabetes and high blood pressure , and improves the patient’s emotional conditions.

Take care of mental health

All pathological changes and dysfunctions can cause mental and psychological impacts. The suffering caused by diagnosis and treatment can therefore manifest itself in different ways, affecting emotional aspects.

It is also necessary to take care of the mental condition and, if necessary, carry out therapeutic monitoring with a professional.

Depression, irritability, anxiety, panic attacks and mild paranoia resulting from Cushing’s syndrome can be reduced or stopped through mental health care .

Look for alternatives to discomfort

There are innumerable palliative resources to control possible pain and discomfort, such as relaxing massages and hot baths to soothe pain, moisturizing creams for dry skin, in addition to adopting facilitating measures in cases of obesity, such as means of locomotion at home or on the street.

Do mental activities

The syndrome can lead to changes in memory, learning and concentration. Although it is generally a more delicate aspect to be treated, neural changes can be mitigated through stimulating measures.

Reading, writing, playing word games and memorizing, learning new activities and exercising cognitive activities on a daily basis, such as logical reasoning and mathematical accounts, can greatly favor routine and well-being.

Prognosis

Mortality rates in patients with Cushing’s syndrome are high, representing a risk 4 times higher than in healthy people.

The chronic condition predisposes the patient to complications related to high blood pressure, diabetes, obesity and cardiovascular diseases. In these cases, mortality is more associated due to cardiovascular risks.

Follow-up studies indicate that patients who stabilize excessive cortisol, even after 5 years of treatment, may still be at risk of developing cardiac, glycemic and arterial changes.

Complications

Complications are diverse and, in general, the most serious are related to the development of diseases, including diabetes, hypertension and obesity.

Patients may experience cardiovascular changes, kidney and bone problems.

Mortality is high due to the complications of the resulting diseases, especially in patients with obesity and morbid obesity.

A study carried out in Denmark followed 166 patients for 11 years. Among them, the mortality rate in the first 8 years was 16%, with the majority running within 1 year after diagnosis, before surgical treatment was performed.

How to prevent

Prevention of the syndrome occurs through medical monitoring and attention to the body’s signals. For patients using cortisol-based drugs, caution should be emphasized, especially if administration is prolonged.

Cushing’s syndrome in dogs

The condition was initially diagnosed in humans, but it has been found that the incidence in dogs is quite common. However, the condition is rarely reported in cats or other animals.

The syndrome presents itself in the same way: through the excessive release of cortisol in the animal’s body.

Dogs, which need very small amounts of the hormone, are especially affected by stress.

In general, the canine organism cannot differentiate between good and bad stress. For example, the dog’s euphoria at seeing a cat or the nervousness of going to the vet also causes an increase in cortisol.

Over time, constant excess can lead to Cushing’s syndrome. Treatment consists of administering medications that inhibit high cortisol production.


Cushing’s syndrome is a condition that is often difficult to be properly diagnosed, especially due to the diverse symptoms that present themselves. Medical follow-up, preventive and investigative exams help the diagnosis and refer to the correct treatment of the condition.

So it is important to be well informed and talk to your doctor about doubts and suspicions.

On our blog you will find lots of information about health, prevention and treatments!

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