Hypercortisolism in dogs (Cushing's syndrome). Symptoms. Treatment

Description of the disease

Cushing's syndrome is an endocrinological pathology caused by an increased level of one of two hormones in the blood:

• cortisol produced by the adrenal glands;
• ACTH hormone, which is produced by the pituitary gland.

Normally, cortisol is responsible for regulating blood pressure, blood clotting and reducing inflammation. It is often called the stress hormone. In critical situations, a powerful release of cortisol promotes instant mobilization of strength.

The functions of the adrenal glands are closely related to the pituitary gland. It is also a gland, but is located in the brain. For proper functioning of the adrenal glands, the pituitary gland produces adrenocorticotropic hormone (ACTH), which inhibits the concentration of cortisol.

That is, these two glands are closely interconnected and disruption of at least one of them leads to endocrinopathy.

What is Cushing's syndrome

Cushing's syndrome in dogs or hyperadrenocorticism is one of the most common diseases of the endocrine system in dogs (it is rare in cats), which occurs when excessive production of the hormone cortisol by the adrenal glands (located in the abdominal cavity) or adrenocorticotropic hormone by the pituitary gland (located in the brain). Therefore, there are three types of Cushing's syndrome in dogs:

• Pituitary hyperadrenocorticism - associated with increased release of adrenocorticotropic hormone (ACTH) by the pituitary gland and in most cases the cause of this is a neoplasm of this organ (usually a pituitary adenoma);
• Primary adrenal hyperadrenocorticism is caused by a unilateral or bilateral tumor of the adrenal glands, sometimes by a structural change - adrenal hyperplasia, which occurs for an unknown reason;
• Iatrogenic hyperadrenocorticism is a secondary change that results from long-term treatment with large doses of a hormonal drug from the glucocorticoid group.

Cushing's syndrome can occur in middle-aged and older dogs of any breed, but it is more common in poodles, dachshunds, small terriers and boxers. It has also been found that adrenal tumors are more likely to form in large breeds of dogs, weighing more than 20 kg. Both males and females can suffer from Cushing's syndrome.

Sheltie dog with Cushing's syndrome

Risk group

Cushing's disease can occur in dogs of any breed and gender. However, older animals are most often at risk. It has also been established that the breeds most prone to the disease are dachshund, poodle, beagle, boxer, German shepherd, basset hound and the entire group of terriers.

Causes of the disease

We have already learned that Cushing's disease is the result of excess cortisol production, or ACHT. Moreover, only prolonged high levels of hormones in the blood lead to imbalance. But why does cortisol begin to be produced in excess? There are two reasons:

1. The appearance of a tumor (adenoma) in the pituitary gland, which begins to produce excessive amounts of ACTH. Being in close relationship, the adrenal glands begin intensive synthesis of the hormone cortisol. This form of the disease is called “pituitary hyperadrenocorticism” and occurs in 80-90% of dogs. Typically, the tumor develops slowly and does not make itself felt for years.
2. The formation of a hormonally active tumor (glucosteroma) in the adrenal cortex, which leads to the proliferation of glandular tissue and increased production of cortisol. This form of the syndrome is called primary adrenal hyperadrenocorticism and occurs in 10-15% of dogs. As a rule, a tumor in the adrenal glands is malignant and develops quite quickly.

These two causes relate to spontaneous hypercortisolism. However, there is another one that leads to the occurrence of this disease. Iatrogenic syndrome that occurs due to long-term treatment of an animal with hormonal drugs. For example, Dexafort, Prednisolone, Metipred, Dexamethasone, etc.

The acquired form of the syndrome has all the same symptoms as the natural disease.

Treatment

1. Pituitary-dependent Cushing's syndrome: treatment will require taking a drug containing the active element trilostane. Treatment is aimed at suppressing cortisol production. The medications typically require daily administration throughout the dog's life. Symptoms generally decrease fairly quickly, often within the first 2 weeks after starting treatment. The dog will need regular checkups and blood tests to make sure the medication is working and not causing any side effects or complications. Blood tests are usually performed after 10 days of taking the drug, after 4 weeks, and then every 3 months. The prognosis for treatment is usually good.

2. Adrenal cortical adenoma or adenocarcinoma: Treatment for dogs with adrenal disease is more complex. Often in these cases it is best to begin treatment with the help of a qualified veterinarian, at least in the initial stages of treatment. There are essentially three treatment options: surgery to remove the adrenal tumor, treatment with mitotane to suppress adrenal function, or treatment with drugs to reduce the symptoms of the disease. The prognosis is quite variable and depends on the extent of the tumor. Your veterinarian should have a frank discussion with you about all treatment options and the pros and cons associated with them.

3. Development of Cushing's syndrome due to medication: in most cases, symptoms disappear after simply stopping the drug. However, it is very important that discontinuation occurs gradually and under veterinary supervision, as abrupt discontinuation can be dangerous and even potentially fatal. Never stop taking the drug without first discussing it with your veterinarian.

Symptoms

The hormone cortisol affects the functions of the dog’s entire body, so Cushing’s syndrome affects almost all systems:

• immune;
• genitourinary;
• musculoskeletal;
• reproductive;
• nervous;
• cardiovascular.

Other glands also change their normal production of hormones, so the kidneys, liver and skin may be affected. The syndrome develops gradually, but the first symptoms you may notice are the following:

• excessive appetite;
• increased thirst and, as a result, frequent urination;
• alopecia (appearance of bald patches in the kidney area).

Hypercortisolism in dogs (Cushing's syndrome). Symptoms. Treatment

Hyperadrenocorticism (Cushing's syndrome) is a disease in which there is a long-term chronic effect on the body of excess amounts of adrenal hormones. This is one of the most common diseases of the endocrine system in dogs and, in rare cases, in cats.

The adrenal cortex produces hormones - glucocorticosteroids, which affect hair growth and pigmentation of hair follicles, acting on specific intracellular receptors of the interfollicular epidermis and basal cells of hair follicles. The main and most active hormone is cortisol; other, less active ones are represented by cortisone, corticosterone, 11-deoxycortisone, 11-dehydrocorticosterone.

Hypercortisolism can be caused by excessively intense formation of cortisol in the adrenal glands (spontaneous hypercortisolism) and after the administration of cortisol to animals in large doses (iatrogenic form). In spontaneous hypercortisolism, the causes of the disease are tumors of the frontal and less commonly the intermediate lobe of the pituitary gland or adrenal glands. The pituitary form of endocrinopathy accounts for 80-85% of all cases of spontaneous hypercortisolism. In such animals, the pituitary gland produces excessive amounts of adrenocorticotropic hormone and causes bilateral hyperplasia of both lobes of the adrenal glands (especially their zona fasciculata and reticularis); in response, the adrenal glands produce excessive amounts of cortisol.

The growth of functional adrenal tumors is the cause of spontaneous hypercortisolism in dogs in 15-20% of cases. These tumors (adenoma and adenocarcinoma) are usually unilateral. Without responding to the control regulatory mechanisms of the hypothalamic-pituitary segment of the endocrine system, they autonomously produce cortisol in large quantities, while the opposite lobe of the adrenal glands usually atrophies.

Iatrogenic hypercortisolism occurs as a result of long-term oral, parenteral and topical cortisone use. This form manifests itself for the most part with the same clinical disorders that are observed in other forms of the disease, as well as signs of suppression of the functional state of the adrenal glands and increased activity of liver enzymes in the blood. For pituitary adrenocorticism, the age range can be from 2 to 16 years. But the disease mainly affects older animals - the average age is 7-12 years.

The disease can occur in animals of any breed. Beagles, poodles, shih tzus, dachshunds, boxers, and various terriers are most susceptible.

The clinical picture of this endocrinopathy is determined by excessive production of cortisol. Symptoms are varied and their severity depends on a number of factors, especially the location of the tumor (in the pituitary gland or adrenal glands), the age of the animal and its breed. In dogs with pituitary adenoma, clinical symptoms appear gradually, while in animals with pituitary carcinoma or adrenal tumors, symptoms develop at an accelerated rate. Aging dogs are more sensitive to the catabolic effects of glucocorticoids, so clinical signs of endocrinopathy appear in them much faster than in young animals. Small breed dogs tend to exhibit more frequent and typical clinical manifestations of the disease than large breed dogs.

Clinical symptoms are associated with the multifaceted influence of cortisol on almost all vital systems of the body - cardiovascular, genitourinary, reproductive, nervous, immune and musculoskeletal. Polyuria, more often than other clinical disorders (80-90% of cases), occurs at an early stage of endocrinopathy - typical skin manifestations usually appear 6-12 months later. Skin lesions (such as loss of shine in the coat, the appearance of dry dandruff and mild hypotrichosis) may occur in the early stages of endocrinopathy, but over time, other dermatological disorders begin to come to the fore - changes in skin pigmentation and the appearance of bilateral symmetrical alopecia.

The skin of dogs affected by hypercortisolism becomes thin, hypotonic and inelastic; affected dogs may exhibit phlebectasia, ecchymotic and petechial hemorrhages (even after minor injuries), skin peeling and dandruff formation, acne and cutaneous calcification (especially in the iatrogenic form). Cutaneous calcification usually affects the upper neck, axilla, and groin areas; it is manifested by the appearance of dense whitish papules and plaques. Over time, the plaques become ulcerated and dogs experience severe itching where they are located. As complications, pyoderma and demodicosis often develop.

Pyoderma in dogs with hypercortisolism in typical cases is manifested by the appearance of elongated non-follicular pustules and mild inflammation in the affected areas of the skin. Secondary infections in such cases are difficult to treat with antibiotics.

The main signs are severe thirst and frequent urination with urinary incontinence, increased appetite, drowsiness, sagging belly, muscle weakness and atrophy, noisy and rapid breathing, obesity.

Concomitant manifestations include secondary diabetes mellitus, genitourinary tract infections, and pulmonary embolism. Disorders of the reproductive cycle and atrophy of the testes occur. The kidneys, liver and other endocrine glands are also affected. Determination of basal cortisol in blood serum has low diagnostic value. Therefore, certain screening tests are performed to confirm the diagnosis. For primary diagnosis, you can use the cortisol/creatinine ratio in the urine (if the result is negative, this diagnosis is unlikely).

A small dexamethasone test and a stimulation test with ACTH can accurately detect hyperadrenocorticism. A large dexamethasone test makes it possible to differentiate hyperadrenocorticism of adrenal and pituitary origin. Ultrasound and radiography of the abdominal cavity can reveal the presence of adrenal tumors; in addition, Cushing's syndrome is characterized by liver enlargement. To more accurately confirm the diagnosis, humane medicine uses CT and MRI of the pituitary gland and adrenal glands.

For adrenal tumors, treatment consists of surgery to remove the adrenal gland (adrenalectomy). For conservative treatment, the drug of choice for many veterinarians is mitotane (it affects the middle and deep layers of the adrenal cortex). Alternative treatment methods include drug therapy with ketoconazole (nizoral), L-deprenyl, cyproheptadine (peritol).

The prognosis for many animals is good, especially if the animal survives 16 weeks after starting mitotane drug therapy. The average period is about 2 years. Poor prognosis for pituitary macroadenoma, adrenal adrenocarcinoma with metastases and in animals with neurological manifestations.

Diagnostics

To establish a diagnosis, the veterinarian uses several examination methods:

• inspection;
• blood and urine tests;
• functional tests;
• Ultrasound, MRI and radiography.

The first study is an examination. It can be used to detect areas of fat deposition, myopathy, characteristic signs of alopecia and changes in the skin (dryness, thinning, calcification, coldness).

You can also visually determine signs of osteoporosis and the presence of a bone fracture.

The second stage is general and biochemical tests of the animal’s blood and urine. Laboratory tests determine the content of ACTH and cortisol, which indicate changes in the pituitary gland, hypothalamus and adrenal cortex. A general blood test establishes hypokalemia, red blood cell content, lymphocytopenia, hemoglobin level, neutrophilic leukocytosis, eosinopenia. A biochemical study determines changes in protein fractions, an increase in alkaline phosphatase and liver transaminases.

The third stage is conducting functional tests that allow you to assess the function of the adrenal cortex. Their essence is simple: first, the basic level of cortisol in the blood is determined, and then a small dose of ACTH or dexamethasone is administered. Next, doctors monitor changes in the concentration of the hormone.

After confirming Cushing's syndrome, the doctor needs to accurately determine the source of the pathology - the pituitary gland or adrenal glands. To do this, an ultrasound of the abdominal cavity is performed. It will show the structure of organs, help compare the left and right adrenal glands, and see tumors. X-ray reveals mineralization of organs, enlarged liver, and bone lesions due to osteoporosis, which are characteristic of the syndrome.

MRI and CT are used to detect pituitary adenoma. But this device is not always available in veterinary clinics.

Diagnosis of Cushing's disease in dogs

Ishchenko-Cushing's disease has two different forms:

• Pituitary hyperadenocorticism – PDH (pituitary disease). It involves the release of the hormone ACTH by the pituitary gland, which stimulates the adrenal glands to produce glucocorticoids. In most cases of diagnosing this disease, it is the pituitary tumor that provokes overproduction of the hormone ACTH. This form of PDH disease accounts for up to 80% of cases of Cushing's disease in dogs.
• Hyperadenocorticism due to adrenal disease. Typically, this form of the disease is a consequence of a tumor of the adrenal cortex, which causes an overproduction of glucocorticoids. Adrenal tumors account for 20% of cases of Cushing's disease in dogs.

There is an "iatrogenic" form of Cushing's disease that occurs from high-dose steroid use. In this form of the disease, the symptoms of the disease disappear after stopping the use of steroids.

For each dog suspected of having Cushing's disease (as part of the diagnosis), it is recommended that a complete and biochemical blood test and urinalysis be performed.

Common common abnormalities of these standard tests are increased alkaline phosphatase and ALT (liver enzymes), increased cholesterol levels, decreased urea nitrogen (renal function test) and low urine specific gravity. However, a definitive diagnosis can never be made based on standard laboratory tests alone.

To make a diagnosis of hyperadenocorticism, the following tests and methods are used:

• Urine test for cortisol, creatine. To perform this test, the animal's urine is collected at home and sent to a laboratory. Most dogs have an abnormal result, but based on the fact that similar deviations from the norm are characteristic of other diseases, the need for the following tests is urgent.
• LDDST test (small dexamethasone test). When low doses of dexamethasone are administered, cortisol levels in healthy dogs decrease markedly after 8 hours. Most dogs with Cushing's disease (up to 90%) do not have this indicator. Sometimes the results of this test help determine the form of the disease.
• ACTH test. This is a functional specific test in the diagnosis of Cushing's disease. And although it is problematic to distinguish the type of disease based on its results, in particularly difficult cases it helps in diagnosing the assessment of adrenal function. Its principle is based on measuring the concentration of cortisol in the dog's blood serum before and after the administration of a synthetic analogue of ACHT, which stimulates the adrenal glands. Dogs with Cushing's syndrome have a significant increase in cortisol levels. It is also used to evaluate the effectiveness of therapy.
• Ultrasound of the abdominal cavity. These studies are useful in all cases because they allow a realistic assessment of the condition of all internal organs of a sick animal, their size, tumors, and metastases.
• LDDST test (high dexamethasone test). Not often used, but its results help distinguish between two forms of Cushing's disease - pituitary hyperadenocorticism and hyperadenocorticism based on adrenal disease.

Forecast

Cushing's syndrome is an insidious disease that weakens all body systems. It disrupts the functioning of vital organs and reduces immunity to parasitic and bacterial infections. Therefore, doctors do not often give an optimistic prognosis. The average life expectancy of a dog after detection of the syndrome is about 3 years. But good care and care can extend the life of a pet for several more years.

Prevention

There is no prevention for spontaneous Cushing's syndrome. Veterinarians advise regularly examining their pets. Only in this case can primary signs of pathology be detected even before symptoms become apparent.

To prevent the development of an iatrogenic type of disease, do not self-medicate, especially with hormonal drugs. Carefully study the information about the composition of the medicine. Do not neglect consultation with a veterinarian, even if you want to cure the simplest disease of your dog.