Introduction: Often called simply "Cushing's Syndrome", hyperadrenocorticism describes the clinical signs referable to theexcessive levels of serum glucocorticoids produced by the adrenal gland. Cushing's Diseaseis a subset of Cushing's Syndrome whereby the excessive production of glucocorticoids by the adrenal gland(s) is specifically due to excessive production of ACTH by the pituitary gland. This is known as Pituitary-Dependent Hyperadrenocorticism (PDH). Autonomous unregulated synthesis of glucocorticoids by the adrenal gland is known as Adrenal-Dependent Hyperadrenocorticism (ADH). The first appreciation for the connection of certain pituitary abnormalities and stomach ulcers (secondary to excessive circulating corticosteroids) was by a fascinating genius and neurosurgeon,Dr. Harvey Cushing(see above)
The normal regulation of adrenal gland activity by the pituitary and hypothalamic centers of the central nervous system is shown elsewhere on this website. It is suggested that the reader review that page before proceeding.
Predilections (naturally acquired disease):
· Middle aged (6yr +) to older dogs (rarely, it is seen is dogs under 2yrs (and has been seen in dogs 6-9 months old!)
· ADH more likely in oldest dogs, on average, though incidences of ADH and PDH occur over the same age range
· Slightly greater frequency in males than in females
· PDH (85% of cases) is more common than ADH (15% of cases)
· Breed Associations
Occurs in any breed
PDH: a) most common breeds affected are Dachshunds, Poodles, Terrier breeds, Beagles and German Shepherds
b) however, most cases are observed in the smaller (less than 20 kg) dogs
.ADH:: a) most often seen in Toy Poodles, Terrier breeds, German Shepherds, Dachshunds, Labrador Retrievers
b) There is little difference in size-dependent incidence of ADH...i.e. it is equally likely to occur in small (<20kg) vs large (>20kg) dogs.
Etiology of Hyperadrenocorticism:As described elsewhere on this website, the regulation of glucocorticoid production by the adrenal gland involves the coarse and fine level of control by hypothalamic and pituitary centers of the brain which respond to various neuronal stimuli for the synthesis/release, then the cessation of synthesis/release of adrenal glucocorticoid hormones.
Hence (in the case of PDH): aberrations resulting in excessive ACTH synthesis and release by the pituitary gland (or excessive CRH release by the aberrations in the hypothalamus...in theory...at this time) can result in excessive (unregulated) adrenal gland stimulation and resultant elevations in serum glucocorticoid levels. To date, the most common locally invasive pituitary gland tumors that secrete excessive quantities of ACTH are nonmalignant micro- and macro-adenomas.
Alternatively (in the case of ADH): functional tumors (or, rarely, hyperplastic nodules) of the adrenal gland occur and these manufacture and release into the blood exorbitant amounts of glucocorticoid hormones. This process occurs independently of central nervous system regulatory centers. The tumors are, therefore, autonomous glucocorticoid "factories". If the tumor occurs on only one adrenal gland (rare to see two gland with tumors), the other "atrophies" due to lack of stimulation...i.e. the excess serum glucocorticoids suppresses further release of ACTH. As will be seen later ("Diagnosis"), measurement of serum ACTH levels can be used to determine whether hyperadrenocorticism is PDH (technically, this is "Cushing's Disease") or ADH. Some of these adrenal tumors are malignant (carcinomas)!
Iatrogenic Cushings Disease: In this form of hyperadrenocorticism, animals exhibit clinical signs as a result of excessive or prolonged exposure to exogenous corticosteroids. For example, clinical hyperadrenocorticism can be seen when a steroid-containing medication such as prednisone, dexamethasone, betamethasone, methylprednisolone, triamcinolone, or similar class of corticosteroid medication has been given orally, by injection or even topically (topical corticosteroid eye, ear or skin preparations, when used in excess or for prolonged periods, are absorbed into the blood stream) at high doses and/or for prolonged periods of time. Some discussion of Iatrogenic Cushing's Disease can be found with the discussion about the use of steroids in veterinary medicine, also on this website.
The most common methods for to ascertain a definitive diagnosis involve measuring urine and serum cortisol levels, provocative testing and imaging studies . The theory, method and interpretation of each of these is discussed separately.
Again, another area with lots of options, considerations and worries. This is an interesting topic in an of itself, as medical and surgical options are described in related pages....