Changes in cortisol concentrations in the blood of dogs: diagnostic and clinical aspects. Adrenal gland diseases Adrenal gland disease in dogs symptoms

Introduction
Cushing's syndrome is perhaps the most interesting problem in veterinary endocrinology. The interest lies in overcoming the difficulties associated with the treatment of this endocrinopathy in dogs in our country.
The disease itself and the problems of its treatment will be discussed in this article.

What it is?
Let's start with a definition.
Cushing's syndrome is a pathological condition of the body caused by prolonged excess levels of cortisol in the blood. This means that cortisol is the culprit in Cushing's syndrome. What is this substance?
Cortisol is a steroid hormone that is involved in most metabolic processes.
But, perhaps, its main property is to protect the body from adverse effects. We can say that it is a stress hormone. It allows the body to survive negative influences with minimal losses. How does this happen?
Cortisol helps maintain blood pressure, accelerates blood clotting, and has a powerful anti-inflammatory effect.
But most importantly, it mobilizes the body's energy reserves to combat hostile influences. That is, it stimulates the use of fat reserves and proteins to maintain normal or increased concentrations of glucose (the main source of energy) in the blood.

Cortisol is secreted by the adrenal glands. These are two small endocrine glands, which, as the name implies, are located near each kidney.
The adrenal glands are not normally independent organs; their activity is regulated by the pituitary gland, a structure of the brain.
The pituitary gland releases adrenocorticotropic hormone (ACTH) into the blood, which, acting on the adrenal glands, stimulates their work. Without going into details, we can say that there is something like a vertical “pituitary gland - adrenal glands”. In this vertical there is a so-called negative feedback mechanism, which allows you to keep the concentration of cortisol in normal values. When the concentration of cortisol reaches a certain level required by the body, it interacts with the pituitary gland and inhibits the release of ACTH into the blood. The ACTH concentration decreases, which means the adrenal glands stop being stimulated and produce less cortisol.

With Cushing's syndrome, this mechanism is disrupted, and cortisol begins to be released excessively and uncontrollably into the blood. This can happen for two reasons:

• if one or both adrenal glands are affected by a tumor capable of uncontrolled hormone secretion
• if the pituitary gland has a tumor (usually an adenoma) that secretes excess amounts of ACTH.

In both cases, the concentration of cortisol in the blood will be constantly increased. That is, the biochemical picture that occurs during stress will be simulated.
A situation arises in which the body spends months and years fighting against adverse effects that actually do not exist. Of course, this will deplete the body’s energy reserves, which will lead to disruption of metabolic processes, and therefore disruption of the functioning of a variety of organ systems. As a result, Cushing's syndrome leads to “burnout” of the body.

Who is sick?
If we talk about small pets, Cushing's syndrome is extremely rare in cats and, at the same time, is one of the most common endocrine diseases of dogs.
Dogs older than middle age get sick.
Cushing's syndrome can occur in any breed of dog, but is more common in dachshunds, terriers, small poodles and boxers.

What does it look like?
Cushing's syndrome begins unnoticed and develops gradually, symptom by symptom.
With a detailed clinical picture, the usual complaints voiced by the owners of an animal with Cushing's syndrome look something like this.

• the most common complaints are excessive thirst and urination
• in second place in popularity is the deterioration of the quality of the coat and the appearance of extensive bald patches. Hairless areas are distributed symmetrically, localized in the body, tail and neck.
• quite soon after the first signs of the disease appear, bitches go into estrus
• animals become less mobile
• the physique changes: fat loss from subcutaneous fat occurs, muscles atrophy. Due to weakness of the abdominal wall muscles, the abdomen increases in volume and sags.

The result is a thin dog with a voluminous belly and extensive bald spots.
A doctor who has an understanding of Cushing's syndrome can most often suspect this disease based on the patient's appearance.
But only the appearance and history told by the animal owner are not enough to make a diagnosis, even if everything is obvious.
Why? Because treatment for Cushing's syndrome is not easy, not cheap and not safe. This means that before starting treatment, taking into account these three “Ns”, we need to be sure that we are treating Cushing’s syndrome.

Diagnostics
As soon as Cushing's syndrome is suspected, we begin to conduct additional diagnostic methods, which include clinical and biochemical blood tests.
These studies provide additional indirect evidence of Cushing's syndrome. And when enough evidence has been collected, we resort to specific tests, that is, tests that prove the presence of the disease.
Basically, if you think about it, the first thing that comes to mind when we suspect Cushing's syndrome is to measure the concentration of cortisol in the patient's blood. In theory, it should be higher than normal, because, as we remember, Cushing’s syndrome develops precisely due to a long-term persistent increase in the concentration of cortisol in the blood.
But cortisol levels can increase not only when the pituitary gland or adrenal glands are damaged. It can also increase against the background of some other diseases and under some other conditions. Therefore, simply measuring baseline cortisol levels in the blood is not an appropriate test.

To confirm Cushing's syndrome, so-called functional tests are recommended.
Tests that evaluate adrenal function (whether it is excessive or normal).
The most common are the low-dose dexamethasone test and the ACTH test. The essence of the tests is that in addition to determining the base level of cortisol, its concentration is also determined after the administration of dexamethasone or the drug ACTH. And by how its concentration in the blood changes after the use of these drugs, one judges whether there is pathological excess work of the adrenal glands or not.

Once Cushing's syndrome is confirmed, you should try to find out where the pathological focus is localized - in the pituitary gland or in the adrenal glands.
A small dose of dexamethasone test (small dexamethasone test) can provide some information on this issue. But more valuable are visual diagnostic methods (methods that allow you to see the adrenal glands and pituitary gland in one way or another).
We have an ultrasound scan of the adrenal glands at our disposal. We can evaluate the ultrasound structure of the organ, compare the right and left adrenal glands and suggest, in conjunction with other additional studies, how likely it is that one of the adrenal glands is affected by a tumor.
Unfortunately, computed tomography and magnetic resonance imaging are not yet available to us. These are quite informative types of organ visualization, which make it possible to accurately identify neoplasms in the pituitary gland or adrenal glands and assess the extent of their spread.
I think that after some time such research will be easily accessible to domestic veterinary medicine.

Treatment
The choice of treatment for Cushing's syndrome primarily depends on the location of the pathological focus - the pituitary gland or the adrenal glands.
If the tumor affects one of the adrenal glands and no metastases are found in the lungs and liver, then the method of choice is to remove the affected adrenal gland. In this case, the approach is relatively simple.

The situation is somewhat more complicated when the cause of Cushing's syndrome is a pituitary adenoma.
That is, formally everything is not complicated. For this form of Cushing's syndrome, the use of drugs that suppress the production of cortisol by the adrenal glands is recommended. But in reality, purchasing these drugs is a big problem. They are not supplied to the domestic market, and their price is very high. Therefore, in order to choose drug treatment, you need to be able to purchase the drug abroad (Germany, USA, Canada) and have enough money to purchase it. Several patients are treated this way in our clinic. But, unfortunately, not everyone can purchase the drugs mentioned above.
There are two ways left. Use alternative methods of drug treatment or resort to surgery.
Alternative treatment methods refer to the use of drugs whose effectiveness is low or unproven. It seems wrong to me to recommend drugs with low effectiveness and a high probability of side effects or simply zero effectiveness. Therefore, I resort to using these drugs extremely rarely.

Surgical treatment for Cushing's syndrome caused by damage to the pituitary gland involves removing both adrenal glands.
Considering that the adrenal glands synthesize vital hormones, namely mineralo- and glucocorticoids, their removal should involve further replacement therapy. That is, you will need to take some of the missing hormones for life. These hormones include mineralcorticoids and glucocorticoids, which are easy to take.
It appears that surgical removal of both adrenal glands (adrenalectomy) may today become the most suitable treatment for Cushing's syndrome in our country. That is why we are trying to practice adrenalectomy (removal of the adrenal glands).
This operation is not indicated for every animal suffering from Cushing's syndrome. Before recommending surgical treatment, the benefits of it and the degree of risk of complications are weighed. And the choice is not always made in favor of surgical treatment. This is due to the fact that, as a rule, animals suffering from Cushing’s syndrome are very old and by that time have some diseases that are more important than Cushing’s syndrome.

In conclusion, it should be said that the treatment of Cushing's syndrome in small domestic animals in our country faces certain difficulties, quite serious, but completely surmountable.
And finding the optimal solution to existing problems is one of the priority tasks facing us.

The endocrine system is one of the biggest mysteries of our body. Almost all biochemical processes occurring in the body are tied to the endocrine glands, and the slightest change in hormone levels often leads to irreversible consequences. If we talk about the field of veterinary medicine, the most common disorder is Cushing's syndrome. In dogs, this disorder most often occurs in old age, and today we will look in detail at what it is and how it can be dealt with. This article is for informational purposes only; in any case, you should consult a doctor to make a diagnosis and choose a treatment regimen.

What is it in dogs

This is a pathology that is not as rare as we would like. The violation consists in the fact that the animal’s pituitary gland begins to secrete cortisol in excessively increased quantities. This is a very important hormone, which is a powerful natural remedy for resisting stress. We will not dwell on the mechanism of action of this hormone on the body; we will only say that this substance mobilizes all reserves to withstand the negative influences of the external environment.

It seems like a complete benefit, why, when describing this mechanism, do we talk about Cushing’s syndrome in dogs? The fact is that the amounts of the hormone that begin to be released into the blood are excessive even for an elephant. And the pituitary gland, which is supposed to control the amount of hormone produced, is completely switched off from this process. Because of this, your pet faces extremely unpleasant consequences.

Negative consequences

Cushing's syndrome in dogs leads to changes in the animal's behavior. Mental disorders are clearly manifested. The dog is tormented by constant, exhausting thirst. This creates a high load on the kidneys, and in addition, leads to excess urine production. This disorder can easily lead to death, and quite quickly. The reason for this is easily explained from a physiological point of view. The body is in a mobilized state, which means it wears out several times faster. In veterinary practice, there are examples when the state of the body of a three-year-old dog suffering from this disease is identical in wear and tear to the body of a 13-15 year old dog.

Main symptoms

Let's now talk about how you can suspect Cushing's syndrome in dogs. First of all, owners pay attention to the increased appetite. The animal begins to gain weight very quickly. At the same time, you may notice extreme thirst and very frequent urination. The animal cannot tolerate it for long and, despite the increased number of walks, still pees at home.

In fact, this disease does not appear out of nowhere, but gradually develops, and the symptoms get worse. The dog becomes weak and lethargic, drowsy, but shows an excellent appetite. The abdomen sags due to weakness of the abdominal muscles. Very rapid fatigue is observed. Baldness is gradually added. Large areas of skin remain completely hairless. Most often these are areas on the body, but not on the head or paws. There is no itching. Without treatment, diabetes mellitus develops very quickly against the background of this disease.

Causes of the disease

In fact, veterinarians have several theories as to why dogs suffer from this hormonal disorder. However, the main cause is a tumor affecting the adrenal glands. Most often, doctors try to correct this condition with surgery or medications, which also have their side effects. However, this is not the only reason that can cause Cushing's syndrome in dogs. The photo shows us the external changes that occur in sick animals, but below we will return to the symptoms.

Another cause may be a pituitary adenoma. Therefore, both the pituitary gland and the adrenal glands will need to be examined. However, having discovered a tumor, the doctor is only beginning his work. It is also necessary to determine whether we are dealing with a benign or malignant lesion, and only then predict the course of treatment.

Predisposition

There are certain breeds in which this disease occurs more often than in others. Thus, boxers and terriers of all types are at risk. This also includes dachshunds, beagles, poodles and basset hounds. Most often, adults who are 7-10 years old are susceptible to this disease. At this age, doctors can only maintain the condition of the body as much as possible. However, Cushing's syndrome is also diagnosed at a fairly young age - in dogs less than two years old. The disease is very dangerous because it affects all organs and systems at once, and therefore, without proper treatment, there is a high probability of death of the animal, as well as a serious reduction in life expectancy with adequate treatment.

Survey

It is essential to reliably confirm Cushing's syndrome in dogs. Diagnosis of this disease is very difficult; not all clinics are able to provide the necessary conditions for this. First of all, the doctor must examine the animal and take the necessary tests. A clinical and biochemical blood test, as well as a urine test, in which it is important to check protein levels, will be indicative.

To clarify the picture, the doctor may prescribe an x-ray, which will show enlargement of the liver or mineralization of the adrenal glands. It is necessary to perform an ultrasound to exclude an adrenal tumor. Correct diagnosis should not only confirm Cushing's syndrome in dogs. The symptoms that will be treated in the next stage may be vague, which means it is extremely important to find the source of the problem.

Treatment

This is a difficult and responsible moment. At this stage, the doctor must choose the most appropriate therapy. Restoring cortisol levels and supporting the functioning of all organs and systems is the main task that has faced him since he was diagnosed with Cushing's syndrome. In dogs, treatment can be done in two ways.

The first way is surgical. It is not indicated for all animals, but only for those who have an adrenal tumor. In the case of the animal, everything is even more complicated, and the adrenal glands are simply removed and the animal is prescribed lifelong hormonal treatment.

The second way is medication. In this case, hormone therapy is used to normalize cortisol levels. This is the drug "Mitotane". Reception begins with a dosage of 50 mg per day per 1 kg of weight. The daily dose is divided into 2-3 doses. Treatment lasts two weeks. The animal's condition is monitored using a blood test. When cortisol in the blood decreases to acceptable levels, you need to switch to a dosage of the drug 50 mg/kg once a week.

The second option, which is often prescribed by doctors, is First of all, it is prescribed to those animals who also develop fungal skin damage against the background of Cushing's syndrome. Take this drug in the first week - 10 mg per 1 kg of weight (in two doses). The second week, increase the dosage to 20 mg per 1 kg of weight (also in two doses). Finally, the third week of treatment involves a daily dosage of 30 mg per 1 kg of weight.

How to determine the effectiveness of treatment

The primary guidelines will be blood tests, ultrasound and x-rays. However, there are indicators that the owner himself can evaluate. This is primarily a reduction in the amount of water consumed by the dog. However, it must be taken into account that the animal may develop complications during the therapy. This is vomiting and increased weakness, lethargy and refusal to eat. Such symptoms may indicate concomitant disorders and diseases. Therefore, to get a clearer picture, it is necessary to conduct laboratory tests.

Treatment results

What can we hope for if such patients are diagnosed with Cushing's syndrome? These questions are often asked by owners and veterinarians. It must be said that the described disease is only partially treatable. Most often, life expectancy, even after successful therapy, does not exceed 2-3 years. This is due to the fact that Cushing's syndrome is a systemic disease that affects all organs and systems and causes a number of irreversible changes. These are the musculoskeletal, cardiovascular and nervous systems. At the same time, this disease reduces the body's resistance to various infections, and also provokes a significant increase in blood pressure.

Hormonal system In dogs, the structure is no less complex than in humans. It also reacts sensitively to any changes in the body and, under certain circumstances, can lead to serious pathologies.

The most common disease associated with the hormonal system is hyperadrenocorticism in dogs, or Cushing's syndrome. This pathology develops due to an excess of a hormone such as cortisol in the animal’s plasma. This substance slows down metabolic processes, which leads to intestinal disorders, increased blood pressure and other complications in the dog.

Description of the pathology

This disease appears in dogs after they have been The pituitary gland begins to produce cortisol in excess. This hormone is very important. Normally, it is a means of protection against stress. In emergency situations, thanks to it, the animal’s body is fully mobilized to protect itself from the external environment.

That is, the body needs cortisol, but not in the quantities produced by the gland in Cushing's syndrome. The pituitary gland ceases to control the process of hormone production. As a result, the animal develops various disorders:

• Mental and behavioral disorders.
• Constant thirst and frequent urination. At the same time, urine has such a pungent odor that it is almost impossible to be near it.

In severe cases, this disease can lead to the death of the pet. The cause of death lies in the wear and tear of the body, which has been in a state of complete mobilization for a long time.

When autopsying young animals that died from Cushion's syndrome, veterinarians note that the condition of the internal organs is equivalent to dogs that died of old age.

Reasons for development and varieties

Despite the fact that scientists have been trying for many years to identify possible causes of the disease, their complete clarification is still far away. In some cases, veterinarians simply cannot determine the cause that caused malfunction of the pituitary gland.

Nevertheless, scientists have identified several of the most common causes of pathology:

• Hormonally active tumors in the pituitary gland.
• Glandular tumors affecting the adrenal cortex.
• Incorrect drug treatment using steroid drugs.
• Significant age of the animal.
• Overweight.
• Genetic reasons.

Scientists have also identified several forms of this disease. The division into forms is determined by the reasons for the development of pathology.

• Cushing's disease. In dogs, symptoms of this pathology appear when tumors appear in the pituitary gland: adenoma or hyperplasia. This form of the disease is the most common and is detected in 80% of cases.
• Cushing's syndrome. It is also often called glucosteroma. The cause of this pathology is dysfunction of the adrenal cortex caused by a tumor. Because of it, a large amount of glucocorticoids are released into the blood, which disrupt the functioning of the pituitary gland.
• Iatrogenic Itsenko-Cushing syndrome. This form of pathology develops as a reaction to the excessive introduction of hormonal agents such as prednisolone and dexamethasone into the animal’s body. Typically, these medications are prescribed to dogs for serious colds and allergic reactions. This type of disease goes away quickly after stopping the medications.

If symptoms of Cushing's disease appear after starting treatment with hormonal drugs, then the supply of these drugs should not be abruptly interrupted. It is necessary to gradually reduce the daily dosage of the drug until the symptoms disappear completely.

Symptoms

Hyperadrenocorticism develops slowly, so it may not manifest itself for a long time. In this case, the disease can only be detected through a laboratory blood test to determine the level of cortisol in the blood.

Clinical manifestations appear in the later stages of the disease. The following symptoms appear:

• The dog develops extreme thirst.
• The dog urinates frequently but little by little.
• The coat becomes dry and brittle. Increased loss is observed. First, the hair falls out in clumps in the abdominal area, and later it can become completely bald.
• The animal is depressed and tries to move less.
• The abdominal muscles weaken, causing it to sag.
• The fat layer becomes thinner. At the same time, muscle atrophy occurs.
• The cyclical nature of sexual behavior is disrupted. Males don’t want to mate, and females go out of heat.

Dogs with Cushing's disease may experience mental health problems, but this is rare. Much more often, sick pets get tired quickly and move little. They have a significant decrease in reflexes.

Sometimes animals exhibit involuntary convulsive movements. Typically, cramps affect the hind legs.

A blood test of sick pets gives the following picture:

• The number of lymphocytes is reduced. Cells are destroyed under the influence of steroid hormones.
• Thrombocytosis.
• Increase in the number of neutrophils.
• Alkaline phosphatase is increased.

Veterinarians are rarely able to make an accurate diagnosis based on symptoms alone. Therefore, sick animals are subjected to additional research methods.

Diagnostics

To clarify a preliminary diagnosis, veterinarians resort to various diagnostic methods. The most commonly used are ultrasound and x-ray.

The latter is needed to detect salt deposits on the mucous membranes of the trachea and bronchi. In addition, X-ray examination can reveal an enlarged liver and a distended abdominal wall. These are characteristic symptoms of Cushing's syndrome.

Ultrasounds are typically used to examine the adrenal glands. Using ultrasound, doctors can evaluate the condition of the glands and determine the presence or absence of tumors.

Various tomographs are used to use the pituitary gland and hypothalamus.

An ACT test is required. First, the dog's blood cortisol level is determined, and then an injection with ACTH is given. After 60 minutes, the cortisol level is re-determined. The disease is confirmed if the hormone level after injection exceeds 600 nmol/l.

Treatment

If the disease was caused by a tumor of any gland, then it is completely impossible to cure the dog. However, treatment makes it possible to prolong the pet’s life and relieve it of some pathological symptoms.

The choice of one or another treatment strategy is determined by the results of the study and the reasons that caused the pathology. Thus, therapeutic assistance is provided only to animals with clearly visible symptoms.

If the dog was diagnosed based on laboratory test data, but there are no symptoms of pathology, then therapy is not carried out, since it can significantly accelerate the development of the disease and worsen the animal’s well-being.

As an emergency measure, veterinarians may perform surgery. We are talking about removing the tumor. Most often it is removed along with the gland.

It is worth noting that when the pituitary gland is damaged, operations are not performed in our country. Veterinarians have too little experience in this area. In addition, surgery on the pituitary gland has the following negative aspects:

• It costs a lot.
• There are very few qualified specialists, so the result of the intervention is unpredictable.
• Lifelong hormonal therapy after surgery.
• There is a high risk of diabetes in the animal.

Veterinarians operate on the adrenal glands much more readily, since the operation is less complicated. Despite this, many animals die after surgery, and survivors experience various hormonal disorders and complications.

Due to the high risks of surgery, drug therapy remains the best treatment option.

Most often, the drug Mitotan is used to stabilize the condition of a four-legged patient. It destroys tumor cells in the adrenal cortex.

This drug should be used according to the following regimen:

• The medicine is added exclusively to the feed.
• At the beginning of the course, the dosage does not exceed 12 mg of the drug per kg of weight.
• Treatment continues until the symptoms of the pathology disappear.
• After the symptoms disappear, the medicine is continued to be given to the animal along with food at a dose of 2 mg/kg once every few days.

Mitotane prolongs the life of an animal by several years. However, this medication should be taken for life.

Sometimes Mitotane is replaced with Trilostane. The latter drug acts differently: it suppresses the production of hormones in the adrenal glands.

Trilostane is given to dogs at 6 mg per kg of body weight once a day. After two weeks of therapy, the level of cortisol in the blood is assessed, and the dosage is adjusted upward or downward.

Other drugs can be used for therapeutic purposes, however, their effectiveness is low, so today there are simply no alternatives to Trilostane and Mitotane.

In recent years, veterinarians have begun to use radiation therapy to treat hyperadrenocorticism in dogs. This technique shows good results, but is not yet widely available, since the mechanism of such therapy has not yet been sufficiently developed.

Prevention

In most cases, this pathology is detected in older dogs. Given the insufficient knowledge of the etiology of tumors of the pituitary gland and adrenal glands, the development of effective preventive methods seems impossible.

To prevent Cushing's disease, veterinarians advise dog owners to regularly examine their pets. In this case, it will be possible to promptly identify the pathology and begin its treatment, which will prolong the life of the pet.

Treatment for Cushing's syndrome is very expensive and does not provide guaranteed results. Therefore, if the dog is elderly, veterinarians suggest that the owners euthanize the pet. And here each person himself decides the fate of his four-legged friend.

Attention, TODAY only!

Both adrenal glands, located next to each kidney, are involved in regulating the metabolism necessary to maintain life and in the process of creating the body's "fight or flight" response. Adrenal hormones take part in the following processes in the body: metabolism of proteins, fats and carbohydrates; water exchange; regulation of blood pressure; regulation of sodium and potassium levels.

The adrenal glands produce epinephrine and norepinephrine, which increase the heart rate and blood flow to the muscles. They also produce the male sex hormone androgen. In addition, they produce two types of corticosteroid hormones: glucocorticoids (cortisol) and mineralocorticoids. These hormones are involved in the regulation of metabolic processes and inflammatory reactions. An excess of either or both of these hormones can suppress the activity of the immune system.

The "cortisone" that veterinarians use for dogs is a synthetic corticosteroid such as prednisone, prednisolone, methylprednisolone. These drugs are hormones and mimic the effects of natural hormones. Corticosteroids are effective medications; in some situations they are vital: firstly, to suppress the immune system in autoimmune diseases; secondly, with clinical shock. It may appear that corticosteroids save more animal lives than antibiotics.

Cushing's disease, also known as hyperadrenocorticism, occurs due to increased activity of the cortisol-producing region of the adrenal glands. The most common cause of this disease is an increase in the production of adrenocorticotropic hormone (ACTH) by the pituitary gland. Some dog breeds have a genetic predisposition to developing Cushing's disease.

Half of all dogs affected by pituitary-related Cushing's disease have pituitary tumors. Cushing's disease can also develop from a tumor in the adrenal gland itself, or it can develop from long-term medical use of corticosteroids (in which case the disease is called iatrogenic Cushing's disease). The main clinical signs of the disease are: increased thirst, urination and appetite, an increase in the size of the abdomen, hair loss from the body (but not from the head or limbs), lethargy, pyoderma (skin infection).

Diagnostics
Blood tests detect changes in the number of white blood cells, increased activity of liver enzymes, and increased blood sugar levels. X-ray and ultrasound examinations reveal an enlarged liver in most dogs affected by this disease. A decrease in the size of the testes is often noted in male dogs.

The final diagnosis is made by examining the level of cortisol in the blood using special tests. These tests also help determine the source of the disease: the pituitary gland or the adrenal glands.

Treatment
Cushing's disease, which is associated with the pituitary gland, is treated with medications that suppress the overactivity of the pituitary gland.

For Cushing's disease that develops as a result of an adrenal tumor, surgical removal of the tumor is performed. If this is not possible, then medications such as mitotane or ketoconazole are used to suppress excessive adrenal activity.

Iatrogenic Cushing's disease resolves on its own when the corticosteroid dose is discontinued or reduced.

Addison's disease, also known as hypoadrenocorticism, occurs as a result of underactive adrenal glands. This disease is more difficult to diagnose than Cushing's disease. Addison's disease usually affects female dogs between the ages of two and seven years. The disease is believed to be immune-mediated.

Breeds predisposed to Addison's disease include: Portuguese Water Spaniel, Leonberger, Nova Scotia Duck Tolling Retriever, and Standard Poodle. The main symptoms of Addison's disease are: loss of appetite and weight, apathy, depression.

In severe cases, a condition known as Addison's crisis can develop, which is life-threatening for the dog. Main symptoms: trembling, fever, vomiting, dehydration, collapse. In such a situation, intensive treatment is necessary: ​​intravenous administration of glucose solution and corticosteroids.

The most common cause of Addisonian crisis is abrupt withdrawal of corticosteroids after a long course of treatment.

Diagnostics
With this disease, changes in serum electrolyte levels are often found - low sodium, low chloride and high potassium. The diagnosis is made on the basis of a test for stimulation of the adrenal glands with adrenocorticotropic hormone (with hypoadrenocorticism, a weak response of the adrenal glands to the administration of ACTT is noted).

Treatment
Treatment consists of prednisolone, which has low mineralocorticoid activity, and fludrocortisone, which has high mineralocorticoid activity.

The central part of the adrenal gland is the part where adrenaline and norepinephrine are produced. Rarely, a tumor called a pheochromocytoma develops in this part of the adrenal gland. The main clinical signs of the disease are nonspecific: weakness, apathy, loss of appetite and vomiting.

Diagnosis and treatment
The diagnosis is made based on the results of a tumor biopsy. Treatment is carried out through surgery.

This article is just a review of hyperadrenocorticism and does not pretend to be a guide to diagnosis and treatment. To obtain more complete information, you should refer to specialized sources.

Definitions

Hyperadrenocorticism is a clinical syndrome that develops when there is an excess of corticosteroids in the body.

Synonym: Cushing's syndrome

Regulation of corticosteroid synthesis

The adrenal glands are paired endocrine glands located craniomedial to the kidney. Each consists of two functionally different endocrine glands of different embryonic origin. The medulla is responsible for the secretion of adrenaline and norepinephrine, the cortex secretes glucocorticoids, mineralocorticoids and androgens.

The synthesis and release of glucocorticoids and androgens is under the absolute control of the concentration of adrenocorticotropic hormone (ACTH), which is secreted in the anterior pituitary gland under the influence of corticotropin releasing hormone (CRH) of the hypothalamus. The production of CVH increases with low levels of plasma hydrocortisone and under the influence of stress factors, and decreases with high levels of plasma corticosteroids.

Etiology

There are two main reasons for the development of hyperadrencorticism - excess production of corticosteroids with an increase in ACTH levels (pituitary hyperadrenocorticism), excess production of corticosteroids by the adrenal glands in the absence of an increase in ACTH levels (adrenal hyperadrenocorticism). Separately, iatrogenic hyperadrenocorticism is highlighted - an increase in the level of corticosteroids when they are introduced into the body in the form of various drugs.

Table. Causes of pituitary and adrenal hyperadrencorticism and frequency of occurrence.

Pituitary hyperadrenocorticism (≈85%)
Pituitary microadenoma (≈70%)
Pituitary macroadenoma (≈30%)
Adrenal hyperadrenocorticism (≈15%)
Adrenal neoplasms (adenoma and adenocarcinoma ≈50/50)

Pathogenesis

Cortisol has various effects on the body. It mainly affects the metabolism of carbohydrates, proteins and fats, supporting gluconeogenesis. Below are the main changes in the body due to excess corticosteroids.

Carbohydrate metabolism
Stimulates gluconeogenesis (increased glycogen deposition in the liver).
Causes the development of secondary hyperinsulinism in an attempt to limit cortisol activity.
Predisposes to the development of insulin resistance.
Protein metabolism
Stimulates protein catabolism with a subsequent decrease in muscle tissue volume.
Stimulates the conversion of amino acids into glucose.
Stimulates protein synthesis in the liver.
Fat metabolism
Stimulates lipolysis with subsequent release of free fatty acids and glycerol.
Stimulates the redistribution of adipose tissue.
Inflammatory and immune response
Decreased inflammatory response.
Suppression of immune system function and weakening of the immune response.
Bone
Osteoporosis due to increased protein catabolism and negative calcium balance.
Leather
Thinning and impaired healing due to increased protein catabolism.
Calcium deposits.
Blood
Erythrocytosis.
Neutrophilia, lymphopenia, eosinopenia.
Kidneys.
Increased diuresis due to impaired ADH release.
Increased calcium excretion.
Hypothalamus, pituitary gland
Suppression of the production of CVH and ACTH

Clinical signs

Morbidity

In dogs, the disease most often manifests itself in middle and old age (7-12 years), but it is also likely to develop in young animals. A breed predisposition to pituitary adrenocrticism has been identified in such breeds as the miniature poodle, dachshund, boxer, Boston terrier, and beagle. Adrenal neoplasms develop more often in large breed dogs, with a higher incidence in females (3:1)

Medical history

The disease develops gradually over several months and the owner usually does not attach importance to the first symptoms. Initially, exercise intolerance is noted; the dog quickly gets tired and refuses to climb stairs due to muscle weakness. Then polyuria/polydipsia, polyphagia, sagging abdomen, visible muscle atrophy, and areas of alopecia on the skin develop.

Physical examination findings

Skin changes are characterized by bilateral symmetrical alopecia, hyperpigmentation, comedones, thinning and hypotonia. Possible development of cutaneous calcinosis (calcinosis cutis), skin infection and demodicosis.

Muscle wasting is determined by a decrease in the volume of muscle mass of the extremities and sagging of the abdomen, upon palpation of which hepatomegaly is likely to be identified. Changes in the reproductive system are likely in the form of atrophy of the testes, hypertrophy of the clitoris, prostatomegaly in castrated males. The formation of perianal adenoma in females and castrated males is also likely.

Other, less common signs include torn anterior cruciate ligament in small dogs, non-healing corneal ulcers, and blindness.

Laboratory data

A complete blood count often reveals an increase in hematocrit and a stress leukogram. The biochemical profile is characterized by a significant increase in alkaline phosphatase, an increase in ALT, hypercholesterolemia, hyperglycemia, and a decrease in urea levels. Urinalysis often reveals bacteriuria without pyuria, hyposthenuria or urine with minimal concentration, glycosuria and proteinuria are likely.

Radiography data

Plain radiography is characterized by an increase in the liver and the volume of the abdominal cavity; it is likely to detect bronchial calcification, skin calcification, and osteoporosis.

Diagnostics

Preliminary diagnosis of hyperadrenoorticism - based on clinical manifestations, to make a final diagnosis, various methods are used to determine the level of hormones and then imaging methods of the pituitary gland and adrenal glands are used.

Screening and differentiating tests.

Determination of basal resting cortisol levels alone has limited diagnostic value because levels are likely to be similar in sick and healthy animals. Most often, the following tests are used to make a diagnosis: stimulation test with ACTH; low-dose dexamethasone suppression test; measuring the ratio of corticosteroids and creatinine in urine, a test for determining ACTH levels and some others. None of these tests are perfect, and all of them can produce both false positive and false negative results. Descriptions of research protocols and other tests should be found in specialized manuals; only a brief description of them is given here.

Low-dose dexamethasone suppression test to confirm the presence of hyperadrenocorticism per se. The animal is given a low dose of dexamethasone and blood is collected 8 hours later to determine basal hydrocortisone levels. In a healthy animal, a decrease in cortisol levels is observed; in a sick animal, the level of hydrocortisone remains at a high level (plasma cortisol ≥ 40 nmol/l). The reliability of this test is about 90-95%.

The urinary cortisol to creatinine ratio test provides an integrated assessment of cortisol production over a period of time. It also aims to confirm the presence of hyperadrenocorticism as the previous test. A positive result is assessed at 0.88, negative at 0.98.

An ACTH stimulation test is performed in an attempt to distinguish between pituitary and adrenal hyperadrenocorticism. After measuring the basal cortisol level, synthetic ACTH is injected and after 30-60 minutes the cortisol level is measured again. In dogs with adrenal hyperadrenocorticism, there is a significant increase in cortisol levels; in dogs with pituitary hyperadrenocorticism, cortisol levels do not undergo significant changes.

A test measuring basal ACTH levels is also performed in an attempt to distinguish between pituitary and adrenal hyperadrenocorticism. Endogenous ACTH concentrations in normal dogs range from 20 to 80 pg/ml. In dogs with adrenal neoplasms, ACTH levels are significantly reduced (< 10 пг/кг), тогда как при гипофизарном гиперадренокортицизме отмечается высокий уровень АКТГ (>45 pg/kg).

Diagnostic Imaging

The optimal imaging methods for hypoadrenocorticism are CT and MRI; they make it possible to clearly distinguish the volume and structure of formations of the pituitary gland and adrenal glands. Ultrasound can also evaluate adrenal tumors, but CT and MRI data are preferred for accurate diagnosis. Plain radiography may identify mineralization in the projection area of ​​the adrenal glands.

Treatment

Mitotane

Mitotane (o,p'-DDD) – causes severe and progressive necrosis of the zona reticularis and zona fasciculata of the adrenal glands, but usually does not affect the zona glomerulosa. For a long time, this drug served as the drug of choice in the treatment of hyperadrenocorticism, but with the introduction of trilostane into practice, it is used almost exclusively for inoperable adrenal tumors.

Trilostane (trilostane, vetoril, vetoryl)

Trilostane ( trilostane, vetoryl, vetoryl) is an inhibitor of the synthesis of corticosteroids and aldosterone in the adrenal glands. The effect of the drug is dose-dependent and reversible. With its introduction into practice, it practically replaced mitotane due to the reversibility of the action and the small number of side effects.

Adrenalectomy and hypophysectomy.

Single or bilateral adrenalectomy is the method of choice for adrenal tumors. Hypophysectomy performed in specialized clinics shows encouraging results in pituitary adrenocorticism.

Radiotherapy of the pituitary gland

Gives good long-term results for pituitary tumors. The method requires a lot of time and money.

Valery Shubin, veterinarian, Balakovo.