Inappetence and weight loss in a dog

SIGNALMENT AND HISTORY

An 8 years old, female neutered, Collie cross dog presented to the veterinary practice with anorexia lasting for three days. The owner reported that she had lost 2 kg of body weight. The dog was urinating normally. Vomiting and diarrhoea were not observed. She was not receiving any medications. The owner had an impression that she “was not well in herself” already for the last couple of months.

 

PHYSICAL EXAMINATION

Clinical examination was unremarkable, except for evidence of mild dehydration and a low body condition score (3/9).

 

INVESTIGATION

Biochemistry

A complete serum biochemistry profile was performed (Table 1). Given the suspicion of gastrointestinal disease, TLI, folate and vitamin B12 measurements were also requested (Table 2). Serum for analyses was separated shortly after collection. There was no evidence of haemolysis or lipaemia in the sample submitted.

Haematology

Haematology was performed and revealed mild leucocytosis (15.27x10^9/L, reference interval, RI: 6-12x10^9/L) due to mild lymphocytosis (5.75x10^9/L, RI: 1-3.6x10^9/L). Peripheral blood smear was unremarkable – lymphocytes were predominantly small with scant light blue cytoplasm and small round nuclei.

Imaging

Brief abdominal ultrasound was performed and no free fluid was detected in the peritoneal cavity.

What is your interpretation of the clinicopathological findings? 

What is the most likely diagnosis and what further tests would you perform in order to confirm it?

INTERPRETATION OF RESULTS

Biochemistry

Biochemistry showed moderate hyperkaliaemia and moderate hyponatraemia which resulted in a decrease of sodium:potassium ratio (21.0, RI: 27-40). This electrolyte pattern could reflect the presence of hypoadrenocorticism – ACTH stimulation was recommended to confirm / exclude adrenocortical dysfunction. A decrease in sodium:potassium ratio can be also caused by whipworm infestation (so called pseudo-Addison disease) – faecal examination should be a consideration in patients suspicious of hypoadrenocorticism. Acid-base disorder was unlikely given lack of respiratory signs or vomiting/diarrhoea. Other possible explanations of low sodium:potassium ratio were excluded given no evidence of anuric or oliguric renal failure, urinary tract obstruction, severe gastrointestinal disease, diabetes mellitus, oedematous disease or body cavity effusion. Artifactual decrease of the ratio was very unlikely given that the serum was separated immediately after clotting and there was no evidence of haemolysis or lipaemia upon visual inspection of the sample.

Mild azotaemia was also revealed. Given that urea was increased proportionally more than creatinine, the azotaemia was likely prerenal (e.g. due to dehydration / hypoadrenocorticism). Rechecking after correction of the hydration status or checking urine specific gravity would be required to rule out renal azotaemia.

Mild hyperphosphataemia was likely secondary to decreased renal excretion of phosphorus.

Marked hypocholesterolaemia and mild hypoproteinaemia secondary to mild hypoalbuminaemia with borderline low globulin were present. Hypocholesterolaemia could be associated with hypoadrenocorticism. Decreased intake / loss of nutrients (e.g. due to anorexia, alimentary disease) or liver insufficiency  / portosystemic shunting were also a consideration. Checking urine protein:creatinine ratio would be required to rule out renal protein loss.

There was a marked elevation of CK. AST was moderately elevated and ALT was mildly increased. These could reflect myocyte injury (e.g. secondary to hypoxia and/or intramuscular injection). Mild hepatocellular injury was also a consideration.

TLI was likely elevated secondary to decreased renal clearance given the presence of azotaemia. Exocrine pancreatic insufficiency was excluded. Although lipase and amylase were normal, inflammatory pancreatic disease could not have been ruled out.

Increased folate and cobalamin might not have been clinically significant in this case – increased folate concentrations can be suggestive of intestinal bacterial overgrowth but do not provide definitive evidence of the disease.

Haematology

Mild mature lymphocytosis may be secondary to hypoadrenocorticism (so called “reverse stress leukogram) or immune stimulation / chronic inflammation / infection. Other differentials were unlikely – physiologic lymphocytosis (fight or flight response) is more common in young animals, whereas lymphoproliferative neoplasia is usually associated with a higher lymphocyte count, atypical morphology of the cells and the presence of other haematological abnormalities.

Summary

Hypoadrenocorticism was felt to be the most likely explanation of the above findings. Parasitic, intestinal or liver disease were other less likely considerations.

FURTHER TESTS

ACTH stimulation test

Pre-ACTH (basal) and post-ACTH cortisol were below 27.6 nmol/L.

Low basal cortisol values are expected in dogs with hypoadrenocorticism, but ACTH stimulation test is required for a definitive diagnosis of hypoadrenocorticism. The disease is unlikely when the basal cortisol value exceeds 55 nmol/L.

Post-ACTH cortisol was also below <27.6 nmol/L indicating inadequate response to ACTH, confirming the presence of hypoadrenocorticism.

Other

Faecal examination was negative for parasites.

Fasted bile acids (0.7 µmol/l, RI: <10 µmol/L) were within the reference interval. Although this result was not supportive of liver dysfunction or portosystemic shunting bile acid stimulation test would be a more sensitive way of investigating liver function, indicated if clinically relevant.

Urinalysis was not performed.

DIAGNOSIS: HYPOADRENOCORTICISM

TREATMENT AND FOLLOW-UP

After correction of the hydration status, the dog was started on prednisolone and desoxycortone pivalate (aldosterone analogue). Her general condition improved and the biochemistry results normalized after initiation of the therapy. The dog returned to normal weight and is doing very well.

SUMMARY

Hypoadrenocorticism is a potentially life-threatening endocrine disorder. The disease usually develops due to idiopathic destruction or atrophy of both adrenal glands (primary hypoadrenocorticism). Secondary hypoadrenocorticism is much less common and is associated with a decreased production of ACTH by the pituitary gland.

As in this case, the clinical and laboratory signs of the disease are non-specific. Depression, lethargy, weight loss, anorexia, as well as, vomiting and diarrhoea are most frequently reported. Common clinicopathologic changes include decreased sodium:potassium ratio, hyperkaliaemia, hyponatraemia, hypocholesterolaemia, azotaemia, hypercalcaemia, hypocholesterolaemia, hypoglycaemia and the co-called reverse stress leukogram. The disease can be exacerbated by stress – in the case described it was suspected that the worsening of the clinical condition was caused by a firework display.

ACTH stimulation test is the gold standard for diagnosis of hypoadrenocorticism. The test should be performed prior to initiation of glucocorticoid treatment – in acute cases which require immediate treatment, dexamethasone should be administered (no cross-reaction in cortisol assays). A recent study has shown that a lower dose of cosyntropin (1 μg/kg) provides results of the ACTH stimulation test which are equivalent to the results obtained using standard recommendations (5 μg/kg), thereby allowing cost reduction.

After stabilization (acute cases) patients with hypoadrenocorticism require lifelong supplementation of mineralocorticoids and glucocorticoids. Patients treated with desoxycorticosterone pivalate and glucocorticosteroids should be monitored by evaluation of the clinical response and changes in the sodium:potassium ratio. The prognosis is good with appropriate therapy.