Today we will be discussing a relatively common disease of the endocrine system called Cushing’s disease. Mostly seen in dogs, Cushing’s disease is where the adrenal glands overproduce certain hormones leading to problems body-wide. We will discuss the types of Cushing’s disease, its symptoms, and how we diagnose and treat it.
How Does it Work in a Normal Dog?
Before all that, you may be asking, “What is the endocrine system? What do the adrenal glands do? Which hormones?” In brief, the endocrine system is made up of various organs within mammalian bodies that produce hormones. Hormones are chemical messengers that travel to other parts of our bodies and tell them what to do. This could involve making more or less of something, working faster or slower, diverting resources elsewhere, and many other effects. The adrenal glands are little organs, found on top of each kidney. These are responsible for producing hormones like cortisol, aldosterone and adrenaline. The most relevant of these today is cortisol.
Cortisol is the ‘fight-or-flight’ hormone; when we, or our dogs, are stressed, we produce cortisol. Cortisol tells various parts of our bodies to create glucose for energy, stops insulin removing glucose from our blood, and boosts our short-term immune system. In a fight-or-flight situation, these are crucial. The extra energy means we are more easily able to run or fight a potential attacker, and the immune system is prepared to fight infection if we are injured. Think of cortisol like an energy drink that is automatically injected every time we need to make a quick getaway! However, cortisol also has long-term effects, including: causing hunger and thirst; reducing calcium in our bones; increasing the rate that our kidneys create urine; and (counterintuitively) reducing the strength of our immune system.
The way cortisol is released during times of stress is complex, but it is important to know how when we talk about Cushing’s disease. Cortisol release is controlled by a chain of command, starting with the hypothalamus (the boss of the endocrine system, located in the brain); when the hypothalamus registers that we are stressed, it tells the pituitary gland (the supervisor of the endocrine system, found just below the brain) to release a hormone called adrenocorticotropic-hormone (ACTH for short). ACTH travels in the blood to the adrenal glands (lowly employees of the endocrine system) and tells them to release cortisol. Once the boss/hypothalamus has seen cortisol is getting higher, it tells the supervisor/pituitary to stop releasing ACTH, which stops the adrenals/employees releasing cortisol. This clever system is important, because if there is a break in the chain of command, we can produce too much or too little cortisol.
So What is Canine Cushing’s Disease?
Cushing’s disease, or hyperadrenocorticism, is where a dog’s adrenal glands produce too much cortisol (they can also overproduce other hormones, but cortisol is the main one). There are three types of Cushing’s disease.
The first, and most common is pituitary-dependent Cushing’s where a benign tumour in the pituitary gland causes it to overproduce ACTH. This means that both adrenals overproduce cortisol, even though the hypothalamus is releasing messages telling it to stop producing ACTH. Think of it like the supervisor going rogue and shouting at all his employees to work harder! It is most common in middle-aged dogs, especially poodles, dachshunds and terriers.
The second and much rarer form is adrenal-dependent Cushing’s. This is where one adrenal gland overproduces cortisol, usually due to a benign tumour, despite the hypothalamus and the pituitary telling it to stop. Because cortisol is so high and the chain of command to the other adrenal gland is still functional, this form of Cushing’s tends to have one completely inactive adrenal gland, and one highly active adrenal. Here, we have our employee ignoring his superior, while stopping his colleague doing any work. Adrenal-dependent Cushing’s is more common in older dogs, especially large-breed dogs.
Finally, sometimes dogs that are on long-term drugs like prednisolone and dexamethasone (both similar to cortisol) can sometimes show Cushing’s-like symptoms if the dose is too high (iatrogenic Cushing’s disease). We are aware of these side effects, but sometimes being on steroids is more important to treat certain diseases, so the side effects have to be managed instead. Luckily, this effect is temporary and removing the steroids slowly will stop symptoms of iatrogenic Cushing’s.
What Happens to a Dog With Cushing’s?
Cortisol in a Cushing’s dog is doing exactly what it is meant to; the trouble is, it’s just doing too much. This means that most of the symptoms are extremes of cortisol’s normal effects. Symptoms can develop slowly and intermittently, or can develop rapidly.
One of the most common symptoms is excess drinking and urination. Cortisol causes the kidneys to produce more urine, so excess cortisol causes excess urine production, resulting in dehydration. To compensate, a Cushing’s dog will drink more. Cortisol will also cause increased hunger. These signs are probably the most obvious for you as an owner to spot. However, there are many other causes of excess urination, hunger and thirst, not just Cushing’s. If you think your dog may be doing this, let your vet know so they can investigate further.
Skin changes are very common with Cushing’s dogs, because cortisol affects hair growth and skin thickness, as well as the immune system. These dogs often have significant hair loss, dry skin, comedones (blackheads) and often pyoderma (whiteheads). Their skin can be thin, inelastic, easily damaged and slow to heal. Cushing’s dogs will have weak muscles as they start to waste away, particularly on the legs and back; because the stomach muscles become weaker, these dogs can look very pot-bellied, despite having less body fat. Dogs with Cushing’s will generally be slower, more reluctant to exercise, pant a lot, and get skin infections more frequently. Cushing’s itself does not kill dogs, but complications related to Cushing’s can lead to kidney failure, serious infection and can even be fatal. Thus, treatment is important.
How Do We Diagnose Cushing’s?
There are a number of ways we can identify Cushing’s disease. Many dogs with Cushing’s have a particular look, due to the hair loss, skin changes and muscle wasting. Combined with the other symptoms, we can often make an educated guess that a dog may have Cushing’s. Blood biochemistry can show elevated liver enzymes, cholesterol and glucose, and reduced urea levels, while urine analysis can give a clue that the kidneys are working too hard. Blood cell analysis can reveal reduced immune cells. Imaging via x-ray, ultrasound, CT or MRI can show changes to various organs. However, none of these changes are exclusively caused by Cushing’s disease, so they will not definitively confirm Cushing’s alone.
We can rule out Cushing’s with a test that measures the urine cortisol-creatinine ratio. If the ratio is low (low cortisol) it makes Cushing’s very unlikely. We can also rule Cushing’s out via a test called the low dose dexamethasone suppression (LDDS) test. The cortisol-like drug dexamethasone is injected, which in a healthy dog should cause reduced production of cortisol, thus ruling out Cushing’s.
To generally confirm Cushing’s, we can inject ACTH, which will cause a slight increase in cortisol in a healthy dog, and a huge increase in cortisol in Cushing’s dogs, as Cushing’s dogs’ adrenals are especially sensitive to ACTH. However, this test may not work well if the Cushing’s is adrenal-dependent.
It can also be important to identify which type of Cushing’s the dog has. ACTH will be very low in adrenal-dependent Cushing’s, but normal or high in pituitary-dependent. Sometimes we can also identify that one adrenal is very large and one is very small via imaging, which will show the Cushing’s as adrenal-dependent.
How We Treat Cushing’s
There are two drugs we can give to treat Cushing’s disease, either Trilostane or Mitotane, which inhibit production of cortisol. In overdose, these drugs can lead to not enough cortisol production and a condition known as hypoadrenocorticism, or Addison’s disease, so getting the dose just right is really important. However, dogs well managed on either of these drugs can live a normal life for several years. Trilostane is the safer of the two, and is the only form licensed for use in the UK.
The other option to treat Cushing’s is surgery. Adrenal-dependent Cushing’s can be treated by surgically removing the affected adrenal gland. Alternatively, we can chemically damage the part of the adrenal gland that produces cortisol. After this surgery, a dog will need to be given regular cortisol for life to prevent Addison’s disease. Pituitary-dependent Cushing’s is much harder to treat surgically, as it requires a surgeon to operate very close to the brain to remove the tumour. Both surgeries are very complex, expensive and will probably require referral to a specialist surgeon. They also have high rates of complications.
However Cushing’s is treated, it will require regular monitoring with your vet to check the treatment is effective. Secondary treatment may also be necessary to prevent skin disease, kidney damage, diabetes and other complications.
Cushing’s in Horses
As a little bonus, did you know that horses also get a similar disease called pituitary pars intermedia disease (PPID), or equine Cushing’s? Horse anatomy is complex, so in short, horses with Cushing’s usually have a malfunction of a region of the pituitary gland called the pars intermedia. The pars intermedia produces ACTH as well as other hormones, most importantly melanocyte stimulating hormone (MSH) that controls appetite, sexual behaviour and melanin production. PPID is strongly linked to ageing, obesity and insulin-resistance.
Horses with PPID overproduce hormones from the pars intermedia, resulting in weight loss and muscle wastage, increased thirst and urination, increased infection risk, reduced insulin activity, and lethargy, similar to dogs with Cushing’s. However, it also causes increased hair growth, rather than hair loss (due to MSH), laminitis (severely damaged hooves), infertility and sometimes neurological signs.
Diagnosis of PPID involves similar hormone tests to Cushing’s disease in dogs, while treatment involves drugs that suppress the production of hormones from the pars intermedia.