By Dr. Kirsten Prosser, BVMS, Dip ACVIM
Darby, a four-year old, female spayed, Standard Poodle, presented to the Internal Medicine service at the Mississauga-Oakville Veterinary Hospital (MOVEH) for further investigation of anorexia and weight loss of approximately two weeks duration. Referral blood work demonstrated mild hypoalbuminemia, mildly elevated alanine transaminase enzyme activity, mild hypocholesterolemia, marginal hyponatremia, and marginally elevated serum spec cPL concentration. Referral abdominal radiographs and barium series were within normal limits.
On presentation, Darby was bright and the physical examination demonstrated moderate peripheral lymphadenopathy. Peripheral lymph node cytology was consistent with reactive hyperplasia. Abdominal ultrasound demonstrated bilaterally small adrenal glands and abdominal lymphadenopathy. Serum creatinine concentration, urea concentration, electrolyte assessment, packed cell volume, total solid assessment, and ACTH Stimulation Test results are below:
42% / 6.0g/dL
iSTAT (Chem 8)
Na 146 mmol/L (142-150)
K 3.7 mmol/L (3.4-4.9)
Cl 118 mmol/L (106-127)
iCa 1.42 mmol/L (1.12-1.40)
TCO2 18 mmol/L (17-25)
Glu 4.4 mmol/L (3.0-5.75)
BUN 16 mg/dL (10-25)
Crea 1.3 mg/dL (0.5-1.3)
Hct 39% (35-50)
Hb 13.3 g/dL (12-17)
AnGap 15 mmol/L (8-25)
ACTH Stimulation Test (Idexx)
Cortisol (0 hour) < 10 nmol/L (15-120)
Cortisol (1 hour) < 10 nmol/L (220-550)
Cortisol (2 hour) < 10 nmol/L (220-550)
What is your diagnosis?
The diagnostic evaluation is consistent with atypical or secondary hypoadrenocorticism. Spontaneous canine hypoadrenocorticism is a well-recognized endocrine disorder. Hypoadrenocorticism is characterized by a deficiency of glucocorticoid (cortisol) and/or mineralocorticoid (aldosterone) production by the adrenal cortices. Although mild destruction or atrophy of adrenocortical tissue can impair adrenocortical reserve, typically at least 90% of the adrenal cortex needs to be non-functional before clinical signs are observed under non-stressful conditions. Primary hypoadrenocorticism results from destruction or atrophy involving all three layers of the adrenal cortex (i.e. zona glomerulosa [ZG], zona fasiculata [ZF], zona reticularis [ZR]). Clinical signs develop because of decreased secretion of glucocorticoid from the ZF and ZR as well as mineralocorticoids from the ZG. Causes include idiopathic spontaneous (likely immune-mediated) primary hypoadrenocorticism (Addison’s Disease), iatrogenic disease resulting from mitotane or trilostane therapy, and very rarely granulomatous disease, metastatic neoplasia, or hemorrhage.
A subset of dogs with primary hypoadrenocorticism do not have classic electrolyte abnormalities and develop a selective glucocorticoid deficiency, commonly referred to as ‘atypical’ hypoadrenocorticism. It has recently been reported that most dogs with atypical hypoadrenocorticism actually do not have measurable aldosterone levels. These dogs appear to maintain normal serum electrolyte concentrations by an alternative, aldosterone-independent, yet-to-be defined mechanism. In most of these dogs electrolyte alterations requiring intervention eventually develops; however, occasionally a few dogs do not develop serum electrolyte changes when followed for months to years. More rarely, Addison’s disease may be due to pituitary dysfunction or cranial trauma resulting in a failure of ACTH secretion, atrophy of the ZF and ZR, and subsequent decrease in cortisol production and secretion. This condition is referred to as secondary hypoadrenocorticism and can result from overly rapid discontinuation of long-term or high-dose glucocorticoid therapy, pituitary or hypothalamic lesions, or idiopathic isolated ACTH deficiency. In secondary hypoadrenocorticism mineralocorticoid secretion is expected to be normal. Measuring endogenous ACTH levels and serum aldosterone concentration can help to confirm whether the hypoadrenocortisicm is due to primary adrenocortical failure (atypical hypoadrenocorticism) or secondary to pituitary disease (secondary hypoadrenocorticism).
Dogs with naturally occurring primary hypoadrenocorticism typically require both glucocorticoid and mineralocorticoid replacement therapy for life. Glucocorticoid supplementation is achieved with prednisone, administered at physiological doses. Mineralocorticoid supplementation can be achieved by either DOCP or fludrocortisone. The few dogs with atypical primary hypoadrenocorticism can be started on glucocorticoid replacement therapy alone, but must have serum electrolyte concentrations monitored frequently since most of these dogs will develop the typical electrolyte abnormalities after weeks to months and require mineralocorticoid supplementation as well. Patients with secondary hypoadrenocorticism can be successfully managed with glucocorticoid therapy alone.
Dr. Kirsten Prosser completed a Bachelor of Science degree at the University of Guelph, Ontario, in 2003. She subsequently pursued her veterinary degree in Perth, Australia, graduating with honours from Murdoch University with a Bachelor of Veterinary Medicine & Surgery (BVMS) in 2007. Upon returning to Ontario, Dr. Prosser completed a one-year rotating internship in small animal medicine and surgery at Mississauga-Oakville Veterinary Emergency Hospital (MOVEH). After completing the internship, Dr. Prosser worked in Mississauga in both general practice and with the emergency service at MOVEH.
Dr. Prosser returned to MOVEH in June 2011 to commence an ACVIM approved three-year clinical Internal Medicine Residency. As part of her residency program, she researched the benefits of routine blood and urine testing in healthy cats and dogs with the goal of making recommendations on the best timing to perform testing based on a pet’s age and breed.
Dr. Prosser obtained board certification with the American College of Veterinary Internal Medicine in 2014.