Canine and feline adrenal gland diseases (Proceedings)


Canine and feline adrenal gland diseases (Proceedings)


Canine Hyperadrenocorticism (Canine Cushing's syndrome) is one of the more common endocrinopathies encountered in small animal practice; ranking behind only hypothyroidism and diabetes mellitus. The resultant hypercotisolemia has many far-reaching pathophysiologic effects on many organ systems; including the kidney, (polyuria, hyposthenuria and compensatory polydipsia, hypercalciuria), liver (gluconeogenesis, glycogenolysis, histologically-hepatic lipidosis and glycogen deposition), pancreas (insulin antagonism-approximately 10% of affected canines develop overt diabetes mellitus), skeletal muscle (increased protein catabolism-resulting in muscle weakness and myasthenia), skeleton (osteopenia-due to increased protein catabolism and negative calcium balance), adipose tissue (redistribution of fat deposits, increased lipolysis-resulting in hepatic lipidosis), immune system (blunted inflammatory and immune response-increased susceptibility to infection) and blood cells (neutrophilia, lymphopenia, eosinopenia and erythrocytosis).

Approximately 85% of affected canines suffer from PDH (pituitary-dependent hyperadrenocorticism->90% of these patients have pituitary tumors; either microadenomas {80%}or macroadenomas {10%}. The remaining (15%) cushingoid patients have functional adrenal tumors (FAT). By utilizing various diagnostic modalities (urine cotisol/creatinine ratio-as a screening test, low-dose dexamethasone suppression test {LDDST}, endogenous ACTH assay, high dose dexamethasone suppression test {HDDST} and imaging techniques {abdominal ultrasonography, abdominal/pituitary CT/MRI}, the diagnosis and type of hyperadrenocorticism can be determined on a vast majority of suspected canine patients.

Due to financial constraints and the fear of increased morbidity/mortality by the pet owners, hypophysectomies are rarely performed. This surgical procedure carries with it the added burden of having to supplement the patient (on a life-long basis) with replacement hormones due to the loss of TSH, ACTH, STH and possibly vasopressin. Even adrenalectomies are not commonly performed (even in specialty practices), because these patients are poor surgical risks (obesity, poor healing tendencies, hypertension, poor immune response to potential infections, etc.).


To review the various medical treatment options available to small animal practioner in the management of Canine Hyperadrenocorticism and to discuss their various advantages and disadvantages.

Review of medications

Mitotane (O,P'DDD) {Lysodren}

Since 1973 when a rational protocol for the medical treatment of Canine Hyperadrenocorticism was firsrt published, mitotane has been the mainstay for the medical management of PDH and selected cases of FAT and has been used by this author for >33 years in over 650 cases. The drug, a dervitive of DDT is a potent adrenolytic agent, producing marked, progressive necrosis of the zona fasiculata and zona reticularis of the adrenal cortex. Later studies demonstrated that in prolonged high doses, mitotane causes necrosis of the zona glomerulosa with subsequent mineralocoid depletion. The key approach to successful use of this agent is be conservative and slowly convert the patient from hypercortisolemia to eu or mild hypocortisolemia. The clincian should realize that the disease took many months to develop and lowering the plasma cortisol levels is not a STAT clinical situation.

Mitotane is administered in two distinct phases: 1) a loading dose phase (usually 10-14 days; sometimes 21 days are required) and 2) a maintainence phase usually administered 1-3x/week for the rest of the dog's life. The most accepted loading dosage is: 50mg/kg in divided dosages (with food) although this author cosiders the dog's age, renal and hepatic function, body composition, attitude and appetite before arriving at a starting dosage. Often it is best to begin at 35-40 mg/kg divided and take one's time. Parameters to be carefully checked 1) appetite (usually a reduction of the often ravenous appetite is detected in 8-10 days) 2) cessation of polyuria/polydipsia (<60ml/kg/day). When the above phenomena occur daily mitotane administration is stopped and the dog undergoes an ACTH stimulatoin test. If the post ACTH level of plasma cortisol is 1-5 micrograms/dl, the patient is begun on maintence therapy (25-50 mg/kg/wk) and the patient is rechecked on a quarterly basis (CBC biochemistry panel, electrolytes and ACTH stimulation test). Because of this author's conservative dosing protocol and respect for mitotane's side effects (nausea, vomition diarrhea, severe anorexia, ataxia, CNS signs due rapidly expanding pituitary macroadenoma, decreased Na:K ratio etc.) administration of glucocorticoids along with the drug is almost never done Utilizing mitotane in the above manner has resulted in satisfying clincal results (suvivals of of 450->900 days in this author's experience).