Testing Adrenal Glands Gone Rogue: Hyperadrenocorticism in Dogs
In this VETgirl online veterinary continuing education blog sponsored by Zomedica, Dr. Cynthia Ward, DACVIM, PhD reviews what you need to know about hyperadrenocorticism testing in dogs. Please note the opinions in this blog are the expressed opinion of the author and not directly endorsed by VETgirl.
Although a common endocrinopathy in dogs, hyperadrenocorticism (HAC) can be a diagnostic and treatment challenge. Most practitioners easily recognize the common clinical signs including the 7 Ps: Polyuria, Polydipsia, Polyphagia, Pot-bellied appearance, Pyoderma, Panting, aloPecia. Further suspicion is usually raised by baseline laboratory abnormalities of an elevated alkaline phosphatase, thrombocytosis, and isosthenuria. At this point, the practitioner needs to prove the presence of HAC before starting treatment. Adrenal function testing can be confusing. This guide is intended to help guide the diagnostics.
Step 1: Choose the right time to test.
When performing adrenal function testing, the animal should be as stable as possible. Eliminate or control any concurrent disease as they may interfere with proper interpretation of test results. For instance, if the dog has an ear infection or hot spot, treat this problem until resolved before attempting testing. If the dog is diabetic, provide some insulin control before testing.
Step 2: Which test to choose.
Three adrenal function screening tests are available:
1. The urine cortisol:creatinine ratio (UC:CR). This is a very sensitive (100%) although not specific test. Therefore, if the UC:CR is positive, results from another screening test will be necessary to diagnose the disease. The UC:CR is not recommended to test for adrenal activity in diabetics since it will likely be positive and performing another screening test will be necessary. The UC:CR should be performed to RULE-OUT HAC. The rationale of this test is to measure excess cortisol that is excreted in the urine since the last time the animal urinated. Thus, this test provides (somewhat) a cortisol measurement over time. An animal with HAC should have an elevated UC:CR. To perform this test the owner should collect first morning urine from the dog at home and refrigerate it until delivery to the veterinarian.
2. The low dose dexamethasone suppression test (LDDST). This should be the “go to” test unless there is significant concurrent disease such as diabetes mellitus. It is sensitive (89-92%) but with a decrease in specificity (75%). It is least specific in animals with concurrent disease. The practitioner measures cortisol before and 4 and 8 hours after IV administration of 0.01 mg/kg dexamethasone. In a normal animal, the hypothalamic-pituitary-adrenal (HPA) axis should be suppressed below the normal range for 8 hours by dexamethasone. The dog with HAC will show a lack of suppression at the 8-hour time point. Another advantage of the LDDST is that it can serve as a differentiating test and indicate whether HAC is pituitary (PDH) or adrenal dependent (ADH). If the 4-hour cortisol is suppressed below the normal cortisol range, or by 50% of the baseline, and the 8-hour cortisol is not suppressed, it is indicative of PDH.
3. The ACTH Stimulation Test: This test is less sensitive (75-83%) than the LDDST but it is more specific (85%) and is recommended for use in animals with significant concurrent disease (e.g., concurrent diabetes mellitus). This test looks for excess cortisol secretion from hypertrophied adrenal glands (PDH) and adrenal tumors (ADH) in response to ACTH administration. The practitioner measures serum cortisol before and 60 min after IV injection of 5 ug/kg synthetic ACTH (Cortrosyn®). ACTH gel is available from compounding pharmacies and may be less expensive. In this case, the practitioner would take serum cortisol samples before and 2 hours after ACTH gel is given IM. The practitioner should be cautioned that use of compounded ACTH gel may cause unreliable results as there can be differing activity in gel preparations. Using the ACTH-stimulation test, aldosterone can also be measured in cases of potential aldosterone secretion abnormalities.
Step 3: Differentiating between PDH and ADH.
Even if the owner would never consider adrenal surgery, it is worth determining where the disease is located. This information will direct therapy choice as well as help predict cost of treatment, explain potential neurologic disease, predict time of resolution of signs, and mitigate owner frustration with therapy (hopefully). Differentiating tests include:
1. The LDDST 4-hour time point as discussed above.
2. Endogenous plasma ACTH concentration. This is the most sensitive differentiating test. Dogs with ADH have low endogenous ACTH levels (<10 pg/ml); dogs with PDH may have very high levels of ACTH. ACTH levels are labile, so sample handling is crucial to the accuracy of the test. Blood must be collected on ice, centrifuged with refrigeration, frozen, and sent on dry ice to the laboratory. Mishandling of the plasma sample will result in artificially low ACTH levels, leading the practitioner to erroneously conclude the presence of ADH. A point of care (POC) endogenous ACTH is coming to market soon, which may be a solution to the difficulty of sample handling.
3. Abdominal ultrasound or CT. Imaging can be very helpful in identification of an adrenal tumor (indicating ADH) or bilateral adrenal hyperplasia (indicating PDH). The practitioner should be cautious in interpreting results of an abdominal ultrasound in that adrenal masses may be nonfunctional, may be a pheochromocytoma, or the animal may have pituitary-dependent disease as well as an adrenal tumor. Bilateral adrenal hyperplasia may also occur in animals with concurrent non-adrenal disease. However, there are benefits of abdominal imaging in that it may identify other abdominal diseases and potential adrenal tumor invasion of the liver or vascular structures.
Step 4. Don’t get frustrated.
Often this happens to practitioners when the animal has clinical signs and lab work findings all indicating HAC, BUT testing does not prove the disease. It can be tempting to just treat these animals without a diagnosis, and monitor response to drug therapy. This approach should only be taken as a last resort as adrenolytic drugs given to a normal animal can result in fatal hypoadrenocorticism. If the adrenal function tests are borderline or negative in an animal in which HAC is strongly suspected, the practitioner should wait 1 month and repeat the testing. Unfortunately, there is not a 100% accurate test to prove HAC and repeat testing is certainly performed even by endocrine specialists.