| Location: | Pituitary gland, underneath the brain |
| Behaviour: | Mostly benign |
| Diagnostics: | Endocrine testing and diagnostic imaging: CT or MRI |
| Treatment: | Surgery, drugs that inhibit adrenal hormone production, or radiotherapy |
| Prognosis: | Depends on the tumour size |
This tumour type is located in the pituitary gland. The pituitary gland lies just below the centre of the brain.
The pituitary gland consists of two parts: an adenohypophysis and a neurohypophysis. Pituitary tumours in dogs usually arise from the adenohypophysis.
Most pituitary tumours are benign (pituitary adenomas). They vary in size from small microtumours which hardly grow to large tumours which can compress or invade neighbouring tissues. In addition, pituitary tumours can excessively secrete hormones.
In the adenohypophysis, several different hormones are produced and secreted. Pituitary tumours can be either functional (actively secreting hormones) or non-functional (no hormone secretion). In dogs, the most commonly diagnosed pituitary tumour type is an adrenocorticotropic hormone (ACTH)-secreting tumour. This excessively secreted ACTH will signal to the adrenal glands that they have to produce more cortisol. This uncontrolled and excessive cortisol production is known as hypercortisolism or Cushing’s syndrome. In most cases (~75%) hypercortisolism is caused by pituitary tumours, which is referred to as pituitary-dependent hypercortisolism (PDH. In 25% of cases hypercortisolism is caused by adrenal tumours or adrenal dysfunction, which is referred to as adrenal-dependent hypercortisolism (ADH) – more about this via adrenal cortex tumour.
Another type of functional pituitary tumours are growth-hormone secreting tumours, but these are far less common.
The prevalence of PDH is approximately 1 in every 500 dogs, and mostly occurs in middle-aged and older dogs. The prevalence of (small) non-functional pituitary tumours can be underestimated, because they do not cause clinical symptoms.
A higher risk to develop Cushing’s syndrome has been reported for the following breeds: basset hound, bichon frisé, border terrier, dachshund, German shepherd, Irish setter, miniature schnauzer, miniature poodle, and Yorkshire terrier.
The onset of hypercortisolism is often slow, and the signs can progress slowly. The most common clinical signs in dogs with PDH include excessive eating and drinking, increased urination, muscle weakness, accumulation of fat in the abdomen, panting, progressive bilateral alopecia, thinning of the skin, and poor wound healing. When the pituitary tumour is large, it can cause pressure on neighbouring brain tissue and induce neurological signs such as anorexia, lethargy, and altered behaviour.
The veterinarian can suspect Cushing’s syndrome based on the dog’s medical history, clinical signs, and laboratory analyses such as blood and urine tests. To confirm the diagnosis, the veterinarian should perform endocrine tests.
Recommended endocrine tests include the low-dose dexamethasone suppression test (LDDST), or the urinary corticoid:creatinine ratio (UCCR) in combination with the oral high-dose dexamethasone suppression test (HDDST). In the LDDST, three blood samples are necessary: one before injection of dexamethasone and one 4 and 8 hours thereafter. Several patterns of cortisol response are described and are used to make a diagnosis and determine the origin of hypercortisolism (pituitary vs adrenal). The UCCR is measured via the first morning urine (shows the cumulation of cortisol secretion overnight). Urinary samples are to be collected on two consecutive days at home in the dog’s own environment a few days after a stressful event, such as a visit to the veterinarian. On the second day, tablets of dexamethasone are administered (HDDST) and on the third day a urinary sample is collected again. E.g. on Monday the dog visits the veterinarian, on Friday the owner collects morning urine and administers the dexamethasone tablets, on Saturday the owner collects morning urine once more. Both urine samples are then sent to a suited medical laboratory. Both tests, the LDDST, and the UCCR combined with HDDST, can serve as a screening and differentiation test.
Additionally, diagnostic imaging with CT or MRI should be performed to evaluate the size of the pituitary tumour and hence adapt the treatment approach.
Dogs with PDH can be treated with surgery, radiotherapy, and/or pharmacotherapy.
Pituitary surgery (hypophysectomy) in dogs is performed using a transsphenoidal (going through the nose and sphenoid bone) approach, in which the entire pituitary gland is removed. After hypophysectomy, life-long replacement therapy with hormones is necessary. Hypophysectomy is a therapy with a high success percentage but can only be performed in large veterinary specialized centres with an established team of experienced surgeons, anaesthetists, critical care specialists and endocrinologists. Hypophysectomy is performed on a routine basis at
(non-exhaustive list)
Radiotherapy can be useful to decrease tumour size and reduce neurological signs in large pituitary tumours but has limited success in controlling the hypercortisolism. Consequently, additional therapy with the drug trilostane may be required temporarily or permanently. As with hypophysectomy, radiotherapy can only be performed in a limited number of specialized veterinary clinics.
Dogs with PDH are often treated with drugs, for which trilostane is the drug of choice. Trilostane inhibits an adrenal enzyme that is required for cortisol production. As such, trilostane is effective in controlling the clinical signs associated with hypercortisolism but does not inhibit the pituitary tumour growth. Trilostane is absorbed rapidly from the gastrointestinal tract and should always be given with food. The optimal trilostane dose varies markedly between patients. The current recommendations are to start with a low dose and to evaluate its effect with the ACTH stimulation test. Two to three hours after administration of trilostane with food to the dog, the veterinarian injects the dogs with synthetic ACTH. Then, within the hour, a blood sample is taken and analysed for cortisol response to the ACTH (ACTH stimulation test). The veterinarian will always take the dog’s clinical symptoms into account when interpreting the results of the ACTH stimulation test. The ACTH stimulation test should be performed 2 to 3 weeks after start of the treatment and should be repeated after every adaptation of the dose. When the dosage is stable, testing every 6 months is sufficient.
Another medical treatment option is mitotane, however, it is only applied in dogs in which medical treatment with trilostane is not successful.
The prognosis of PDH depends greatly on the pituitary tumour size. In dogs with large pituitary tumours, treatment addressing the tumour (surgery or radiation) has the best prognosis. In dogs with pituitary microtumours the prognosis is usually good, when hypercortisolism is treated properly with trilostane.
In a retrospective study including 85 dogs with PDH treated with trilostane, the median survival time was 852 days (range 2-3210 days); 60/85 (70 %) and 25/85 (29 %) dogs survived more than one and three years, respectively. Another retrospective study with 91 dogs with PDH treated with trilostane reported a median survival of 998 days (range 26-1832 days). The size of the pituitary tumour in these studies is unknown.
For hypophysectomy, a recurrence rate of 27% was reported with hypercortisolism recurrence most commonly observed at 555 days after surgery. The median survival time in a study of 300 dogs after hypophysectomy was 781 days (range 0-3808 days) with an estimated one and two-year survival of 84% and 80%, respectively. The disease-free interval in 257 dogs was 951 days (range 31-3808 days). Most dogs in this study had an enlarged pituitary tumour.
