loader image

Cushing’s Disease (Hyperadrenocorticism or HyperA)

What is Cushing’s disease?
Cushing’s disease, also known as hyperadrenocorticism, is one the most commonly diagnosed hormonal (or endocrine) disease in senior dogs.

Hormones are the chemical messengers of the body, relating signals to different organs to make sure they’re functioning normally (e.g. downregulating or upregulating the production of certain chemicals). Small changes in hormone levels can trigger massive overall changes to the body so when these signals are inappropriately sent, hormonal (or endocrine) diseases occur and can have many negative effects on the body.

Cushing’s disease occurs when there is an excessive production of the hormone, cortisol, by the adrenal glands, which are located on top of both kidneys. Cortisol, also known as the ‘stress steroid hormone’, is crucial for normal function of the body. In fact almost every organ system in the body has a receptor for cortisol! Hence Cushing’s disease can have a wide array of systemic effects on the body.

What causes Cushing’s disease?
There are 3 main causes of Cushing’s disease, which are named after where the inappropriate hormonal signs are coming from.

Pituitary-dependent (arising from the pituitary gland). This is the most common cause with 85-90% of cases occurring due to a tumour of the pituitary gland (which is located at the base of the brain), which is usually microscopic and benign, however can be large or cancerous in a small number of cases. This tumour causes the pituitary gland to overproduce a hormone (ACTH) that then over-stimulates the adrenal glands to overproduce cortisol.

Adrenal-dependent (arising for the adrenal glands). This is a less common cause and occurs due to a tumour at the adrenal gland itself.

Latrogenic (prolonged steroid use). Since cortisol is a type of glucocorticoid (a class of steroid hormones), iatrogenic Cushing’s disease occurs secondary to excessive or prolonged use of glucocorticoid medications (e.g. steroids), which are often prescribed to manage skin allergies, immune-mediated diseases and autoimmune disease.

What are the clinical signs of Cushing’s disease?
Most importantly, Cushing’s disease is a disease of clinical signs! It is important to look at BOTH the diagnostic test results as well as the patient (and the presence/absence of clinical signs), as this will influence the treatment plan.

The clinical signs of Cushing’s disease can initially be quite subtle, however there are numerous symptoms that you may be able to notice at home. These include:

  • Excessive thirst (polydipsia)
  • Excessive urination (polyuria)
  • Increased appetite
  • Thinning of the skin and coat cover with potential hair loss
  • Muscle wastage
  • A ‘pot bellied’ appearance
  • Lethargy
  • Restlessness

These symptoms are not exclusive to Cushing’s disease and can also be indicators of other disease processes.

How is Cushing’s disease diagnosed?

  • Clinical signs & physical examination. As previously mentioned, Cushing’s disease is a disease of clinical signs! If there are no clinical signs, then there is no strong indication for further diagnostic testing or to commence treatment.
  • Blood tests: In addition to a routine screening blood test (Total Annual Health Profile blood test) to help assess for other other concurrent diseases that may present with similar clinical signs (e.g. diabetes mellitus), there are two different types of blood tests specifically to diagnose Cushing’s disease. The type of blood test chosen is often dependent on certain patient factors, and in some trickier cases, both may be required.
    • Low dose dexamethasone suppression test (LDDST). This involves collecting a baseline cortisol blood sample at 0-hours, then administering a low dose of dexamethasone intravenously, and then collecting a second and third blood sample at 4-hours and 8-hours post-dexamethasone administration. Dexamethasone is a steroid, so when administered, the body should respond by suppressing the production of its own steroid hormone, cortisol, through a negative feedback system over time (telling the adrenal glands to stop producing cortisol). If the cortisol levels do not suppress after dexamethasone, then your pet most likely has hyperadrenocorticism.
    • ACTH stimulation test. This involves collecting a baseline cortisol blood sample at 0-hours, then administering an intravenous dose of synthetic ACTH (the hormone produced by the pituitary gland that targets the adrenal glands to upregulate cortisol production). A blood sample is then taken again at 1-hour post-synthetic ACTH administration. Similar to the LDDST, the body should respond to the excess synthetic ACTH acting on the adrenal glands by suppressing its own production of cortisol, through a negative feedback system. If the cortisol levels remain persistently high, then your pet most likely has hyperadrenocorticism.
  • Abdominal ultrasound: An abdominal ultrasound is also usually recommended to help visualise and screen the adrenal glands themselves for any structural abnormalities, such as adrenal gland tumours which may be responsible for adrenal-dependent Cushing’s disease.
  • Other (e.g. urine test – urine cortisol:creatinine ratio (UCCR). In some cases, where Cushing’s disease is less likely but needs to be ruled out, a special urine test called a urine cortisol:creatinine ratio may be recommended. This is a great rule-out test as if the ratio returns low (normal), then Cushing’s disease is highly unlikely.

How is Cushing’s disease managed or treated?
Generally speaking, there are two ways to manage Cushing’s disease – medical therapy and surgical intervention, and treatment is dependent on the type of Cushing’s disease, whether it be pituitary-dependent or adrenal-dependent.

With pituitary-dependent Cushing’s disease, medical therapy is more commonly used, and often the more practical management option as brain surgery to remove a pituitary gland tumour may not be feasible. Medical management is often through a medication called trilostane. This medication works by reducing cortisol production at the adrenal glands, and is given daily long-term and life-long.

For adrenal-dependent Cushing’s disease, surgical removal of tumours at the adrenal gland(s) may be required, with success dependent on the size and behaviour (benign or malignant) of the mass. If surgical treatment is not feasible, especially in the face of potential life-long complications, then medical management may be used instead.

What monitoring is required with Cushing’s treatment?
One key thing to understand is that the success of Cushing’s treatment with trilostane medication is assessed by the reduction of clinical signs which will need to be assessed closely by owners from home (e.g. reduction in excessive thirst, reduction in excessive hunger). Finding the exact dosing of trilostane medication is extremely important, as inappropriately high doses can lead to oversuppression of cortisol production, which can lead to life-threatening Addisonian crisis or HYPOadrenocorticism (when the cortisol level is too low!).

To achieve this fine balance, multiple blood tests (ideally a repeat ACTH stimulation test or pre-pill cortisol) are required each time the dose is adjusted until it is titrated to the optimal level to achieve control of the disease. This optimal level is different for every patient and it can be a lengthy and sometimes frustrating process, however it is absolutely necessary to take it one step at a time.

Once the optimal dose is achieved, regular monitoring blood tests will be performed as Cushing’s disease is dynamic and adjustments from the optimal dose may occasionally be required.

What does this mean for my furbaby now that they have Cushing’s disease?
This is a question we get asked a lot at My Vet – and for good reason, as Cushing’s disease is unfortunately a life-long disease. Cushing’s disease is a very common old dog disease, and some studies have estimated around 2-4 years life expectancy after diagnosis, however we need to keep in mind that many older dogs have co-morbidities and often Cushing’s disease isn’t life-limiting on its own. However, Cushing’s disease can increase the progression of other diseases such as heart conditions, and the clinical signs can impact their quality of life. Many older dogs will be able to continue living several more years of their normal happy lives if their Cushing’s disease is managed well.