Screening Tests For Cushing Disease/syndrome
- Blood tests: We can measure the levels of ACTH and cortisol in your blood. We take a blood sample in the morning;because hormone levels change throughout the day.
- Urine tests: We can measure cortisol in your urine. We may ask for multiple samples. Ask your doctor if any of your current medications could affect results.
- Late-night saliva test: We look at cortisol in your saliva. Youll collect several samples just before midnight, when cortisol usually drops to its lowest level. A high level can indicate Cushing disease/syndrome.
Circadian Rhythm And Cortisol
Your sleep-wake cycle follows a circadian rhythm. Every 24 hours, roughly synchronized with nighttime and daytime, your body enters a period of sleep followed by a waking period. The production of cortisol in your body follows a similar circadian rhythm.
Cortisol production drops to its lowest point around midnight. It peaks about an hour after you wake up. For many people, the peak is around 9 a.m.
In addition to the circadian cycle, around 15 to 18 smaller pulses of cortisol are released throughout the day and night. Some of those smaller bursts of cortisol correspond to shifts in your sleep cycles.
Are You Sure The Patient Has Cushing’s Syndrome
Cushings syndrome results from chronic exposure to excess endogenous or exogenous glucocorticoids. It has significant long-term sequelae, so timely diagnosis and treatment are needed. Cardiovascular, infectious, and thrombotic disorders are the main causes of death if hypercortisolemia is left untreated.
Signs and Symptoms
The clinical phenotype caused by endogenous or exogenous cortisol excess includes a constellation of signs and symptoms, the majority of which, such as obesity, are nonspecific and commonly seen in the more prevalent pseudo-Cushing states. Prolonged exposure to excess cortisol negatively affects nearly all organ systems. Key features are weight gain, central adipose tissue deposition, and dorsocervical, supraclavicular, and temporal fat pads.
In children, growth retardation in the context of weight gain is the most sensitive marker of the disease.
Exposure to exogenous glucocorticoids must be excluded before the diagnosis of endogenous Cushings syndrome can be entertained. Such exposure may include prescription medications given orally, via inhaler, per rectum, or via parenteral routes. Occasionally, nonprescription glucocorticoid-containing topical agents may by absorbed sufficiently to cause Cushings syndrome, especially if the skin is broken over a large area and if a higher-potency glucocorticoid is used.
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Clinical And Biochemical Data: Patients With Cushings Disease Versus Controls
Table 2 shows the current characteristics of the patients with Cushings disease and the matched healthy individuals upon entry in our casecontrol study. In the group with Cushings disease, height was significantly lower than in the controls. Weight, BMI, waist, blood pressure and heart rate at rest were not significantly different between the two groups.
Patients with Cushings disease had significantly higher plasma creatinine and plasma urea levels, and significantly lower 24-h calciuria , hematocrit , total red blood cells and glucose levels than the controls. Blood lipid levels, hormonal levels , hemoglobin A1c and serum electrolytes were not significantly different between the two groups.
Micro-albuminuria was present in one patient with Cushings disease, and in one patient from the control group .
When the group of patients with Cushings disease was stratified according to corticosteroid substitution therapy, the eight patients taking hydrocortisone were older , had lower plasma cortisol and higher plasma urea levels .
The Possible Problems With Medication
Some medications approved to treat Cushing’s disease in dogs aren’t recommended for pups with kidney disease. The U.S. Food and Drug Administration has approved two medications to treat Cushing’s disease in dogs, although some human drugs also are used with pups “off label.” Trilostane is used mainly to control pituitary- and adrenal-dependent Cushing’s disease in our canine companions, but shouldn’t be administered to dogs with kidney disease, warns the FDA. Selegiline only treats pituitary-dependent Cushing’s disease and doesn’t normally affect your pup’s kidneys. Consult with your vet regarding any medications used to treat his Cushing’s disease, especially if Fido suffers from kidney issues, to avoid inducing kidney failure.
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How Do Doctors Treat Cushings Syndrome
Treatment depends on the cause and may include surgery, radiation, chemotherapy, or cortisol-reducing medicines. If the cause is long-term use of glucocorticoids to treat another disorder, your doctor will gradually reduce your dosage to the lowest dose that will control that disorder. Sometimes disorders that doctors treat with glucocorticoids can be treated with a non-glucocorticoid medicine instead.
What Causes Cushings Syndrome
The most common cause of Cushings syndrome is the long-term, high-dose use of the cortisol-like glucocorticoids. These medicines are used to treat other medical conditions, such as asthma, rheumatoid arthritis, and lupus. Glucocorticoids are often injected into a joint to treat pain. Use of glucocorticoids also suppresses the immune system after an organ transplant to keep the body from rejecting the new organ.
Other people develop endogenous Cushings syndrome because their bodies make too much cortisol. Several types of tumors can cause the body to make excess cortisol.
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Medical Therapy For Cushing’s Disease
There is no effective drug that lowers ACTH production and shrinks the pituitary tumor. There are medications that inhibit the adrenal gland’s production of cortisol. In some patients, these medications can effectively reduce the symptoms related to excessive cortisol when:
- Surgery fails to completely remove the tumor.
- Medication is necessary before surgery, in a patient who is very ill.
What Are The Final Stages Of Cushings Disease In Dogs
Obvious, intense, and multiple symptoms appear when a dog enters into the advanced or later stages of this condition. Following are these clinical symptoms:
- Cold ears, abdomen, and back
- Extremely thinned urine
- Extreme weight loss and unobvious thinness
Although pituitary tumors can be brought under control in most cases, they can transform into macroadenomas in some cases. These tumors are larger than 1cm due to which they are likely to put much pressure on the adjacent tissues. This can result in other neurological symptoms.
These are the most extreme cases. In such a situation, you will definitely work with your vet to retain your pets comfort as long as possible. This is also when you may want to know when to put the dog down. Fortunately, these are highly uncommon circumstances.
This is because the benign macroadenomas are removable via surgery. Even the malignant tumors are removable but a lot of complications are involved in it. Thus, most vets do not take this risk.
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Who Gets Cushing Disease/syndrome
- Incidence: Cushing disease/syndrome is rare. About 10 to 15 new cases per million people are diagnosed in the U.S. each year. These numbers may not reflect the true number of people with this illness, though, because its not uncommon for people to go undiagnosed.
- Age: It is typically found in people ages 20 to 50.
- Sex: It affects roughly three times as many women as men.
What Are The Symptoms Of Cushings Disease In Dogs
The most common symptoms of Cushings disease seen in dogs include:
- Increased appetite
If your dog has Cushings disease you will see at least one of these symptoms, however it is uncommon for all of these symptoms to be present.;
It is essential to contact your vet immediately if your dog is displaying any of the symptoms above. Dogs with Cushings disease have an increased risk of diabetes, kidney damage, blood clots, and high blood pressure.
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What Is Cushings Disease In Dogs
Cushings disease is an endocrine disorder of middle-aged and older dogs. Its the result of the overproduction of cortisol by the adrenal glands located on each kidney.
Normally, your dog responds to stress by producing something called ACTH . ACTH is a hormone produced by the pituitary gland, which is a pea-sized gland at the base of the brain. This release of ACTH stimulates his adrenals to produce more cortisol , which is the bodys main stress hormone.
In Cushings disease, the adrenals produce really high levels of cortisol hormone continually. Cushings disease can be the result of 3 possible situations:
#1 Your dog has a microscopic benign tumor of the pituitary gland.
This tumor overproduces ACTH. That stimulates the adrenal glands to produce too much cortisol. About 85% of Cushings cases in dogs are due to a pituitary tumor.
#2 Your dog has an adrenal gland tumor.
Tumors on the adrenal gland can produce excess cortisol levels. This is the case in about 15% of dogs.
#3 A veterinarian prescribes excessive steroids as a medication.
Corticosteroid drugs including cortisone, hydrocortisone and prednisone can cause Cushings disease in dogs. With NSAIDs , the incidence of this is waning.
Testing For Cushings Disease In Dogs
Because of its sensitivity, many vets consider the Low Dose Dexamethasone Suppression Test the best option. But the problem with this test is it gives too many false positive results.
As I said before, the stress your dog goes through can influence the test results. Being locked in a cage and having blood drawn is definitely enough stress to create a false positive.
Another test called the ACTH Stimulation Test is also a popular screening test. But I couldnt tell you why!
In general, this kind of test would be used for hypofunction not hyperfunction of the adrenal glands. This test misses many animals that have the disorder typically 20% to 30% of dogs with pituitary abnormality and 50% with an adrenal tumor.
Your vet should only use these tests when your dog has clinical signs of the disease. In other words, all the signs I mentioned above that Spot didnt have.
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How Cushings Disease Is Diagnosed
Diagnosing any form of this disease is not that easy. This is because the symptoms differ, are vague, and can be along with the symptoms of other disorders. However, an expert vet knows how to diagnose dogs effectively. So, there is no need to worry.
Dog owners are likely to take their dogs for two or more tests, including the blood tests. An ultrasound test is done in some cases to know whether a tumor exists on just one or both adrenal glands.
Above all, the urine and blood of the dog are tested for identifying the markers such as liver-produced enzymes and cortisol levels. One of the indicators is alkaline phosphatase, an enzyme that the liver produces and is studied to be more in dogs with Cushings disease.
Furthermore, it is common for these dogs to suffer from one or more urinary tract infections. These are the markers or abnormalities.
If these tests are positive, your vet would then suggest some more specific tests namely, ACTH test and Low Dose Dexamethasone Suppression test. The former is helps in discriminating between the pituitary- and adrenal-based conditions.
Herein, blood is taken for observation and then the dog is given an ACTH shot. This allows the vet to observe the response of the body to ACTH.
This test has come up due to the sensitivity involved in conducting several screening tests. These tests are reliable only if there are symptoms and abnormalities. They are likely to give false-positive results for dogs that are not showing these symptoms.
Cushing’s Disease: Understanding Normal Cortisol Physiology
Cortisol affects the body in many ways, including:
- Maintaining normal blood pressure; inadequate cortisol production is usually associated with low blood pressure.
- Response to stress situations. Cortisol is one of the “fight or flight” hormones.
- An increased blood level of cortisol is essential for you to be able to cope with acutely stressful situations, including surgery.
- Inadequate cortisol release can be fatal.
The adrenal glands produce cortisol in varying amounts throughout the day:
- Blood and saliva cortisol levels are very low at midnight.
- Blood cortisol levels are usually highest in the early morning.
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What Are The Cushings Signs And Symptoms
The biggest impact of the chronic overproduction of stress hormones is on the immune system of your dog, which weakens. This can make the pet more vulnerable to other ailments and infections. It can even harm a few vital organs, compromising the pets overall health.
Before you let this happen, it is wise to know the common symptoms of Cushings disease. This will help you to take quick remedial actions. Following are the common clinical symptoms to check out in a dog with Cushings:
- Polyuria or increased urination
- Neurologic changes in case of pituitary-dependent Cushings disease
- Testicular atrophy or reproductive cycle mismatches in females
It is worth noticing that not all of these symptoms tend to develop or surface in the affected dog. Dogs with Cushings can even show just two of these symptoms, which you are more likely to attribute to other diseases such as hypothyroidism, canine diabetes, or a nervous disorder.
Many times, the tangible symptoms are often linked with the healthy aging of the dog. Thus, the presence of Cushings disease can go unnoticed in the early stage. As a result, it becomes tough to detect this ailment early.
However, early detection is indispensable for healthy recovery. Yes, it is possible to recover if this is done. Nevertheless, this is rare because the symptoms typically surface slowly and some years can pass for them to become visible as a whole. This makes it tough for you to find out what is happening.
Characteristics Of Patients With Cushings Disease
We enrolled 18 patients previously diagnosed with Cushings disease: 3 patients with active Cushings disease and 15 patients cured of Cushings disease .
The initial diagnosis of Cushings disease was based on three diagnostic tests in eight patients , and on two tests in ten patients . The clinical features of the patients at initial diagnosis are shown in Table 1.
All 18 patients had undergone transsphenoidal pituitary adenomectomy one or more times. In 12 patients this was unsuccessful, and additional therapy was needed. Additional therapy included pituitary irradiation and chemical or surgical adrenalectomy.
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Treatment For Cushings Disease Overview
Before we discuss treatment we need to keep things in perspective. This is a chronic disease, and most dogs do not die from this disease. We tend to treat when the symptoms described previously are affecting a dogs quality of life or are a major nuisance to a pet owner. We do not routinely treat just because the tests say your dog has Cushings- the symptoms of the disease need to be present also.
It might be years before this dog shows signs, if any, of Cushings. At the same time, we want to start treatment at the optimal time just as the symptoms of Cushings starts. Any dog diagnosed with Cushings should have follow up tests performed periodically to look for changes to help in this decision.
Dogs that have significant symptoms of Cushings that have been confirmed by screening tests need to be treated to prevent potentially serious diseases secondary to Cushings that include Diabetes Mellitus, Urinary Tract Infection , pancreatitis and High Blood Pressure .
This Staph bacteria was cultured from a urine and numerous antibiotics were tested to find the most effective one. The S means this Staph infection is sensitive to everyone of these antibiotics in this in vitro test. This is a rare occurrence, and shows no antibiotic resistance.;
Key Screening Laboratory Tests
Because the symptoms and signs of Cushings syndrome are rarely pathognomonic, an appropriate biochemical evaluation is key to establishing the diagnosis.
The diagnosis of Cushings syndrome rests on the demonstration of elevated cortisol levels in body fluids and on the demonstration of impaired negative feedback inhibition of the corticotropes by glucocorticoid. Three tests are recommended, and the choice of tests should be individualized for each patient, taking into account the caveats for each test.
The 24-hour UFC represents the daily integrated production of cortisol. The limitations to this test are that it requires an ability to collect a complete 24-hour specimen and to avoid overcollection or undercollection. Generally, the patient discards the first morning urine void and collects all subsequent voids until and including the next mornings first void, hopefully at about the same time of day. Falsely elevated results may occur in association with high fluid intake or with overcollection. Falsely low results may occur in association with renal failure or with undercollection. The completeness of the collection may be evaluated by measuring the total volume of the collection as well as the creatinine excretion, which should remain within 10%-15% among multiple collections.
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Canine Cushings And Dog Bladder Problems
My 11 year old terrier has recently been diagnosed with Cushings. She’s been on treatment for 2 weeks now. Shes suddenly lost her bladder control. I’m not sure if this is the treatment that is causing this. She doesn’t seem to know shes doing it.
Canine Cushings Dog Bladder Problems Editor Comment
Characteristics Of Study Participants
The demographic, clinical and biological characteristics of the study population are summarized in Table 1. All 118 men and 60 women were diagnosed with essential hypertension. The antihypertensive medications included angiotensin-converting enzyme inhibitors , angiotensin receptor blockers , calcium channel blockers , -Blockers, diuretic and others , and the number of participants who used ACEI, ARB, CCB, -Blockers, diuretic and others were 19, 35, 113, 13, 34, 40, respectively. Serum cortisol concentration was 372.6±98.5 nmol/L. The median eGFRcr-cys was 85 ml/min/1.73 m2. Serum cortisol level was significantly higher in subjects whose eGFRcr-cys<90 ml/min/1.73 m2 than subjects whose eGFRcr-cys>90 ml/min/1.73 m2 . Serum cortisol levels according to CKD stage 1-3 were 343.2±98.4 nmol/L, 390.7±95.3 nmol/L, 403.0±66.7 nmol/L, respectively.
Demographic and clinical characteristics in patients with essential hypertension
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