A recent case through the laboratory highlighted the challenges when diagnosing hypoadrenocorticism and in differentiating the typical from atypical form of the disease.
Hypoadrenocorticism or Addison’s disease is an uncommon endocrinopathy that occurs when there is destruction or atrophy of layers of the adrenal cortex. The most common form is when both the zona glomerulosa (the outer layer which makes mineralocorticoids) and zona fasciculata (middle layer which makes glucocorticoids) are affected, leading to glucocorticoid and mineralocorticoid-deficient hypoadrenocorticism.
In about 30-40% of cases only the zona fasciculata is affected, leading to glucocorticoid deficient hypoadrenocorticism. The ensuing glucocorticoid and/or aldosterone deficiencies result in clinical signs that are frequently vague, episodic and nonspecific, including anorexia, vomiting, weight loss and diarrhoea, but can sometimes be dramatic with patients presenting recumbent and in acute circulatory collapse.
Laboratory findings can be similarly non-specific and attributable to a number of different underlying disease processes. Commonly seen are pre-renal azotemia, hyperkalemia, hyponatremia and lack of a stress leucogram (lymphocyte concentration in the normal range). Other abnormalities may also include hypochloremia, hypercalcaemia, hypoglycaemia, hypoalbuminemia and a mild nonregenerative anaemia.
The patient in question, a 1-year-old entire female Kelpie dog “Fern” (not her real name) had collapsed and was nonresponsive with haemorrhagic gastroenteritis. Initial in-clinic laboratory results revealed a mild azotaemia, marginal hyponatraemia, marked panhypoproteinaemia and hypocholesterolaemia with an unremarkable CBC and mid-normal range lymphocyte concentration.
Supportive treatment, including intravenous fluids, was initiated and an internal medicine specialist consulted. Atypical Addison’s disease was suspected and the veterinarian performed an ACTH stimulation test.
Further laboratory testing:
Resting and 1-hour post ACTH stimulation serum cortisol concentrations were both <4.04 nmol/L (<55 nmol/L at both times consistent with hypoadrenocorticism).
With the absence of typical electrolyte disturbances and marginal hyponatremia attributed to gastrointestinal loss, a presumptive diagnosis of atypical hypoadrenocorticism was made and Fern was started on prednisone therapy. She made an excellent recovery with resolution of the majority of clinical signs over the following two weeks, other than reports of lethargy and tiring easily.
The possibility that electrolyte disturbances not seen at initial presentation were now apparent couldn’t be discounted so repeat bloods were taken, this time revealing hyperkalemia, hyponatremia and hypochloremia, consistent with typical hypoadrenocorticism. At the time of writing, Fern had just started on mineralocorticoid replacement therapy (Florinef).
Gastrointestinal haemorrhage can be a presenting sign in dogs with hypoadrenocorticism as glucocorticoids have an important influence on epithelial integrity and vascular permeability. It is proposed that low concentrations predispose gastrointestinal mucosa to erosion, ulceration and consequent haemorrhage. More common rule outs for GI haemorrhage in a young dog like Fern, might include acute haemorrhagic gastroenteritis, acute pancreatitis, parvovirus, severe hookworm infection, rodenticide toxicity, and ulceration/perforation due a GI foreign body.
While Fern’s gastrointestinal signs had an acute onset, it was interesting to read a paper published by Hauck et al, JVIM 2020, that determined a 4% prevalence of hypoadrenocorticism in dogs with signs of chronic gastrointestinal disease compared to 0.3% in the general population. They also established there was no significant difference in history, physical examination and laboratory variables between dogs with hypoadrenocorticism and those with chronic enteropathies and recommended an ACTH stimulation test be part of the standard workup for dogs presenting with gastrointestinal signs.
Some patients initially diagnosed with atypical Addison’s disease, go on to develop electrolyte abnormalities during follow up, leading to the hypothesis that destruction of the adrenal cortex is first limited to the zona fasciculata but spreads to the zona glomerulosa over time. This may have been the explanation for the development of electrolyte abnormalities in Fern’s case.
In summary, the diagnosis of hypoadrenocorticism can be tricky to make due to the considerable overlap in clinical signs and laboratory results between this and other conditions, in Fern’s case haemorrhagic gastroenteritis. This case also demonstrated the importance of careful monitoring following a presumptive diagnosis of atypical Addison’s disease, due to the possibility of progression to typical hypoadrenocorticism and development of electrolyte abnormalities.
Thank you to Beth Campbell from Vetlife Wanaka for this interesting case and follow up information.
Hauck C, Schmitz SS, Burgener IA, et al. Prevalence and characterisation of hypoadrenocorticism in dogs with signs of chronic gastrointestinal disease; a multicenter study. J Vet Intern Med. 34:1399-1405, 2020.
Hatoya S, Kanegi R, Nabetani T, et al. Atypical hypoadrenocorticism with intact zona glomerulosa of the adrenal cortex after long-term observation: a case report of a dog. J Vet Med Sci. 85:9-13, 2023.