Addisons disease: Whats new with the great pretender?
Natalie Stilwell, DVM, MS, PhD
Dr. Natalie Stilwell provides freelance medical writing and aquatic veterinary consulting services through her business, Seastar Communications and Consulting. In addition to her DVM obtained from Auburn University, she holds a MS in fisheries and aquatic sciences and a PhD in veterinary medical sciences from the University of Florida.
According to internal medicine specialist Dr. Daniel Langlois, long-term maintenance of hypoadrenocorticism can be a controversial topic.
Daniel Langlois, DVM, DACVIM, a professor at Michigan State University College of Veterinary Medicine, freely admits that his favorite endocrine disease is Addison's. But he also acknowledges that this uncommon yet potentially fatal endocrine disorder, often called “the great pretender,” can be a moving target for veterinarians in terms of diagnosis and treatment. In a session at Fetch dvm360 in Kansas City, Dr. Langlois focused on current issues surrounding the disease.
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Addison's disease, or hypoadrenocorticism, is characterized by inadequate adrenal production of glucocorticoid (i.e. cortisol). Many patients with hypoadrenocorticism are also deficient in the mineralocorticoid aldosterone. Although the etiology of Addison's disease is not fully understood, immune-mediated destruction of the adrenal cortices leads to adrenal failure. Many dog breeds are considered to be at increased risk for developing Addison's, including the bearded collie, Great Dane, Nova Scotia duck tolling retriever, Portuguese water dog, standard poodle and West Highland white terrier. As prevalence in certain dog populations approaches 10%, the disease likely has a hereditary component.
Clinical and laboratory features
Dogs with Addison's disease typically experience nonspecific signs; therefore, a diagnostic workup is typically necessary to rule out non-adrenal causes. Gastrointestinal (GI) abnormalities, such as vomiting and diarrhea, are common in dogs with Addison's disease, as are lethargy and weakness. Signs may wax and wane or worsen steadily over time, particularly if the disease is not recognized or the patient is managed at home without medical workup. Critical patients experiencing an “Addisonian crisis” usually present with acute hypovolemic shock and cardiac arrhythmia, although owners frequently report a history of GI signs, lethargy and weakness lasting several days.
Generally speaking, routine lab work will not provide a diagnosis of Addison's disease. According to Dr. Langlois, complete blood count (CBC) and biochemistry abnormalities are common yet variable and inconsistent-the disease can mimic acute kidney injury, postrenal obstruction, cavity effusions (pleural and peritoneal) and intestinal disease. Addisonian patients usually lack a stress leukogram, and 5% to 20% of cases have mild to moderate lymphocytosis, eosinophilia, or both. Less than 60% of glucocorticoid-insufficient dogs are also hypoglycemic and hypocholesterolemic.
Although electrolyte abnormalities are considered “classic” signs of aldosterone deficiency, Dr. Langlois cautions that about 20% of cases have normal electrolyte levels-but these “abnormal hypoadrenocorticism” patients are more likely to have biochemical signs of glucocorticoid deficiency more likely than dogs with typical Addison's.
Diagnostic testing: Current options and future possibilities
The ACTH stimulation test continues to be the gold standard diagnostic test for Addison's disease. ACTH stim is an accurate indicator of adrenal reserve and yields easily interpretable results. The test involves serum (or plasma) cortisol measurement immediately before 5 µg/kg of a synthetic ACTH (Cosyntropin) is administered intravenously. Cortisol measurement is repeated one hour later.
But ACTH stim does have some limitations, Dr. Langlois explained. Cosyntropin is expensive and not readily available, and diagnosis relies on an external laboratory's turnaround time. A few alternative and accurate tests, such as aldosterone-to-renin and cortisol-to-ACTH ratios, are gaining popularity but are not yet readily available.
A single basal cortisol concentration measurement exceeding 55 nmol/L (2 µg/dl) can also be used to rule out Addison's disease. However, the positive predictive value for basal cortisol measurement is poor, so this option should not be used to confirm diagnosis. Although very low measurements (< 5.5 nmol/L [< 0.1 µg/dl]) are indeed consistent with hypoadrenocorticism, Dr. Langlois added that such levels typically lie beneath the lower limit of detection for most laboratory tests.
So what warrants testing for this confusing disease? Here's Dr. Langlois' list: Unexplained abnormal sodium-potassium ratios, undiagnosed GI (or esophageal) disease, biochemical signs of glucocorticoid deficiency and nonspecific lethargy. If you have a high index of suspicion for Addison's or the dog is very sick, go straight to ACTH testing, he says. With a low index of suspicion or if the dog seems clinically stable, start with baseline cortisol, then follow with ACTH stim if you get a low result.
According to ongoing research conducted at Michigan State University, urine cortisol-to-creatinine ratio may serve as both a sensitive and specific screening tool for Addison's disease. Also, measurement of urine electrolyte concentrations (particularly urine sodium, urine potassium and sodium-to-potassium ratio) may offer some diagnostic value, although further research is needed in this area.
Critical patients require intensive treatment to address hypovolemia and correct electrolyte and acid-base abnormalities. Aggressive IV fluid therapy with 0.9% saline, lactated Ringer's solution or Norm-R is usually sufficient to stabilize the patient, although calcium gluconate, dextrose and/or insulin may also be indicated for hyperkalemic patients with electrocardiographic abnormalities. Dr. Langlois added that dexamethasone (0.2 mg/kg IV every 24 hours) can be used as a short-term treatment of suspected cortisol deficiency and won't interfere with post-ACTH cortisol measurement. While acute use of other glucocorticoids has also been studied, Dr. Langlois considers these unnecessary for in-hospital management of Addison's disease.
With fluid therapy and supportive care, most patients can be discharged within 48 to 72 hours of hospitalization. Aldosterone therapy is initiated before discharge, and corticosteroids are gradually tapered to a physiologic dose (approximately 0.1 to 0.3 mg/kg/day prednisone) after discharge. Dr. Langlois warns that large breeds can be more sensitive to glucocorticoids than smaller dogs, with greater risk of side effects such as polyuria and polydypsia, and their doses may need to be even lower-for example, 0.05 mg/kg. The goal is to find the lowest effective dose, he says, but never to discontinue glucocorticoids completely. “They may not need 0.1 to 0.3 mg of prednisone, but they do need some,” he says.
Dr. Langlois considers long-term management of aldosterone deficiency to be one of the most controversial aspects of Addison's disease. Specifically, professional opinions differ on the comparative use of monthly injection of desoxycorticosterone pivalate (DOCP-Zycortal or Percorten) versus daily oral fludrocortisone (Florinef). Dr. Langlois has a definite opinion here-he's found that the fludrocortisone dose required to alleviate the aldosterone deficiency often results in dogs showing signs of glucocorticoid excess (plus the dose often has to be increased over time). So his choice is DOCP and prednisone for the management of aldosterone and cortisol deficiencies, respectively.
Dr. Langlois adds that he and his fellow internists at Michigan State have been able to lower treatment costs for hypoadrenocorticism by more than 50% in many cases. How do they do this? By using a lower-than-labeled dosage of DOCP, which can range in cost from $475 a year for a Westie to $2,851 for a Great Dane at the labeled dose. They've cut the dosage in half with excellent results in their patients and are currently studying this low-dose DOCP protocol for publication.
Dr. Natalie Stilwell provides freelance medical writing services through her business, Seastar Communications and Consulting. In addition to her DVM obtained from Auburn University, she holds an MS in fisheries and aquatic sciences and a PhD in veterinary medicine from the University of Florida.