Atypical hyperadrenocorticism (Proceedings)
Naturally occurring hyperadrenocorticism (HAC) is an endocrine disorder resulting from the excess production of cortisol or other adrenal hormones by the adrenal cortex. The clinical syndrome was first documented in people by Dr. Harvey Cushing in 1932 and is also known as Cushing's syndrome. Hyperadrenocorticism in dogs is one of the most common endocrinopathies in small animal practice, and it is also one of the most complicated to diagnose, treat and monitor clinically. This session will focus on what is currently referred to as the atypical form of the disease. This is a somewhat controversial area as there are still many unknowns associated with what is referred to as atypical HAC.
HAC is caused by either excess adrenocorticotropic hormone (ACTH) production due to a pituitary adenoma leading to pituitary-dependent hyperadrenocorticism (PDH) or a functional adrenocortical tumor (AT) independent of pituitary control. Historically, the clinical signs associated with the disease were attributed to the excess of cortisol secreted by the adrenal glands. It is now realized that the clinical syndrome can also be caused by excesses of other adrenal hormone(s) in the cascade. Hormones that may be involved are androstenedione, estradiol, progesterone, 17-hydroxyprogesterone (17-OHP), and aldosterone. It is suggested that these cases have a derangement of the steroid production pathway and that some of the precursors of cortisol, such as 17-OHP may be abnormally increased. In some instances cortisol may in fact be measured below the normal range, which can confuse the diagnosis.Diagnosis
Diagnosis of atypical or the classic form of this disease is based on the combination of clinical signs, typical findings on routine lab work and urinalysis, and results of specific screening and differentiating tests. It must be kept in mind that all of the potential screening tests and differentiating tests have important limitations, and therefore there is the possibility of false positive tests and false negative tests frequently. All clinical signs, routine test results, and specific test results must therefore be assessed in conjunction to obtain an accurate diagnosis. Testing may lead to a diagnosis of PDH or AT, and specifically which hormone(s) is abnormal.
Screening and Differentiating Tests
Routine testing may include performing some or all of the following: the urine cortisol to creatinine test (UCCR), the ACTH stimulation test and the low dose dexamethasone suppression test (LDDST). The UCCR has a high sensitivity (85-100%) and a low specificity (20-25%). Because of the low specificity, the UCCR may be used to rule out HAC but not rule in HAC. A positive result indicates the need to perform an additional screening test. In cases of Atypical HAC, the cortisol levels are not necessarily elevated. The ACTH stimulation test measures the adrenal gland response to injected ACTH or synthetic analog. The sensitivity is between 60-85% and the specificity is between 85-90%. Post stimulation cortisol levels above 22 ug/dL are consistent with HAC. The ACTH stimulation test function is to diagnose or rule out hyperadrenocorticism and does not differentiate PDH from AT. Some dogs with HAC can have normal measured cortisol levels and in Atypical HAC the cortisol levels may be normal or low, but other hormones are elevated. The LDDS test may differentiate PDH and AT. Cortisol secretion is sometimes suppressed at 4 hours and then escapes to above normal concentrations at 8 hours with PDH. In 40% of the cases the suppression does not occur due to dexamethasone resistance. The high dose dexamethasone suppression test (HDDS) is also used to differentiate PDH and AT. Nearly all AT cases fail to suppress cortisol in HDDS test. In PDH cases suppression does occur in approximately 80% of the cases. If cortisol suppression occurs the dog likely has PDH but if no suppression occurs, the dog is more likely to have AT. Measurement of endogenous ACTH concentration may differentiate PDH from AT. ACTH is suppressed in dogs with AT. ACTH is normal to elevated in dogs with PDH.