Newer tests shed light on causes, treatment of adrenal disorders


Newer tests shed light on causes, treatment of adrenal disorders

Jan 01, 2008

Q: Could you update the diagnosis and management of atypical hyperadrenocorticism?

A: Dr. Jack W. Oliver gave an excellent lecture on "Steroid Profiles in the Diagnosis of Canine Adrenal Disorders" at the 2007 American College of Veterinary Internal Medicine Forum in Seattle. Here are some relevant points:

Diagnosis of adrenal disease in dogs, cats and ferrets usually is dependent on the manipulation of the hypothalamo-pituitary-adrenal axis (HPA) and the measurement of cortisol (i.e., ACTH stimulation test; low-dose dexamethasone suppression (LDDS) test; urine cortisol-to-creatinine ratio test; or the combined dexamethasone suppression/ACTH stimulation test).

More recently, other steroid measurements have been used to evaluate the HPA, including steroid hormone profiles and 17-hydroxyprogesterone, which have revealed that suspected adrenal-disease conditions may be caused by steroids other than cortisol (or in addition to cortisol).

Determination of pituitary-dependent hyperadrenocorticism (PDH) or adrenal-dependent hyperadrenocorticism (ADH) usually is made now by evaluation of the four-hour time-point of the LDDS test, by endogenous ACTH measurement or by ultrasound visualization of the adrenal glands.

Hyperadrenocorticism (HAC) is defined as an overproduction of steroid hormones by the adrenal cortex. Cushing's syndrome refers to all causes of hyperadrenocorticism with excess production of cortisol, while atypical Cushing's disease refers to hyperadrenocorticism caused by increased levels of intermediate adrenal steroids that frequently are referred to as "sex steroids."

General steroid hormone profiles

Steroid hormone profiling in veterinary medicine started at the University of Tennessee Clinical Endocrinology Service, on the premise that multiple steroid hormone analyses would increase the diagnostic accuracy of adrenal-function tests.

Measurement of multiple steroids in Pomeranians led to the recognition of a syndrome dermatologists called "Alopecia-X."

Others have reported on adrenal syndromes in dogs called "atypical Cushing's disease" or "adrenal hyperplasia-like syndrome" that used steroid profiling. Cortisol is known to have negative control effect on the HPA axis, but it's now understood that other steroids can have this effect as well.

Steroid profiling in dogs and cats led to the realization that HAC can be due to primary adrenal tumors that secrete other steroids besides cortisol. Steroid profiling in ferrets led to the realization that HAC in this species is primarily due to increased levels of estradiol, 17-hydroxyprogesterone and/or androstenedione in blood, and measurement of these steroids has helped define medical control of ferret adrenal disease.

Steroid profiles have helped us understand the condition of SARDS in dogs, where steroids other than cortisol frequently are involved. Steroid profiling also is aiding the understanding of drug effects on adrenal secretory activity (mitotane, trilostane and melatonin).

Specific steroid hormone profiles

Steroid hormone profiles are indicated when other routine tests of adrenal function are negative (normal findings from ACTH stimulation test; LDDS test; or combined dexamethasone suppression/ACTH stimulation test) and the dog still exhibits signs of Cushing's syndrome, indicating the likely presence of atypical Cushing's disease.

The issue of non-adrenal illness has been raised as a possible consideration in atypical Cushing's disease cases. Results of studies in dogs with chronic illness, but without clinical evidence of HAC, have shown that 17-hydroxyprogesterone (17OHP) concentration may be increased. However, results of other studies of adrenal function testing in dogs with non-adrenal illness have demonstrated only minor effects on test results.

Also, in studies that have measured only 17OHP as a means of detecting HAC, the sensitivity and specificity of using post-ACTH 17OHP concentration as a diagnostic test for HAC were low, and post-ACTH 17OHP analysis was not recommended as a screening test for HAC.

These studies provide evidence that measurement of a singular adrenal intermediate steroid (such as 17OHP) may give equivocal results, but when profiles of steroid intermediates are used, the sensitivity and specificity of the test procedure is much improved. It has been emphasized that adrenal function testing should be performed in dogs with clinical and/or serum chemistry profile evidence of HAC, and not in dogs with non-adrenal-related disease.