Hypoadrenocorticism in a Dog

WHAT IS YOUR DIAGNOSIS? A 4 year old, male neutered Lurcher was presented to the R(D)SVS Internal Medicine Service for investigation of lethargy, reduced appetite and regurgitation which had progressively worsened over the previous two weeks. The dog had been completely inappetant during the two days prior to referral. The dog had been less keen to run on his walks for the last two months. He tired quickly on walks and was also seen to shiver more frequently. He had lost weight over the last month. On clinical examination, the dog was quiet but alert with a body condition score of 3/9. Mucous membranes were pink and a moist (the dog had been on fluid therapy prior to referral) and the heart rate was 90 bpm with no arrhythmia or pulse deficits. The respiratory rate was 24 breaths/minute, with no adventitious lung sounds. Abdominal palpation was unremarkable but borborygmi was heard. Rectal temperature was reduced at 37.3°C. 1) What are your first steps in the investigation of this case? 1. The most specific clinical sign is regurgitation. All cases of regurgitation should have thoracic radiographs taken to assess for oesophageal disease such as megaoesophagus and oesophageal foreign bodies or masses. Thoracic radiographs are also important to check for the presence of concurrent aspiration pneumonia. Also, given the lethargy, poor appetite/anorexia and weight loss, it would be prudent to perform routine haematology and serum biochemistry. page 1 of 6 Haematology Parameter Result Reference Range RBC (x 1012/l) 5.64 5.5-8.5 PCV (%) 39 39-55 Hb (g/dl) 13.5 12-18 MCV (fl) 69 60-77 MCHC (%) 33.3 32-36 TWBC (x 109/l) 9.0 6-15 Neutrophils (x 109/l) 7.29 3.6-12 Lymphocytes (x 109/l) 1.26 0.7-4.8 Monocytes (x 109/l) 0.36 0-1.5 Eosinophils (x 109/l) 2.2* 0-1 Basophils (x 109/l) 0 0-0.2 Platelets (x 109/l) 471 200-500 Serum biochemistry Parameter Result Reference Range Total protein (g/l) 66.7 58-73 Albumin (g/l) 24.5* 26-35 Globulin (g/l) 22 18-37 Bile acids (μmol/l) 1.5 0-7 Total bilirubin (μmol/l) 2.5 0-6.8 Urea (mmol/l) 6.9 1.7-7.4 Creatinine (μmol/l) 133* 40-132 Glucose (mmol/l) 6.0* 3-5 AP (iu/l) 59 20-60 ALT (iu/l) 29 21-102 Sodium (mmol/l) 139 139-154 Chloride (mmol/l) 100 99-115 Potassium (mmol/l) 5.8* 3.6-5.6 Inorganic phosphate (mmol/l) 1.62 0.9-2.0 Total calcium (mmol/l) 2.0 2.0-3.0 page 2 of 6 Figure 1: Lateral radiograph of thorax and cranial abdomen demonstrating megaoesophagus. 2) What are your differential diagnoses for megaoesophagus and what testing would you perform to investigate these possibilities further? page 3 of 6 2) Causes of generalized megaoesophagus Testing Congenital idiopathic Diagnosis of exclusion – unlikely in this patient due to age and short duration of clinical signs Glycogen storage disease DNA tests, wbc enzyme assays, urine metabolic screening, muscle/liver biopsyunlikely in this case due to lack of other compatible clinical signs and age Hiatal hernia Radiography- no evidence in this case Aquired idiopathic Diagnosis of exclusion Myaesthenia gravis Edrophonium response test, acetycholine receptor antibody titres Polymyositis Serum creatine kinase levels, EMG, muscle biopsy Polyneuritis Nerve conduction velocities, nerve biopsy Hypothyroidism T4/TSH, dynamic thyroid function tests Hypoadrenocorticism Serum electrolytes, ACTH stimulation test Lead toxicity Whole blood lead concentration Organophosphate toxicity Blood cholinesterase activity Oesophagitis Endoscopy GDV Abdominal radiography Systemic lupus erythematosus Clinical syndrome plus ANA Dermatomyositis Skin and muscle biopsy – unusual breed as normally Shelties/Rough collies and no skin signs Dysautonomia Clinical diagnosis- clinical signs did not support diagnosis in this case Neoplasia Thoracic radiography, endoscopy, biopsy Causes of localised megaoesophagus included oesophageal diverticulae, vascular ring anomalies, strictures, neoplasia and foreign bodies. In this case, eosinophilia was present on haematology. Eosinophilia can be due to allergy, parasites, inflammatory disease, Addison’s disease and neoplasia. In this case, the presence of eosinophilia in a systemically ill dog, together with azotaemia and page 4 of 6 hyperkalaemia, increased the clinical suspicion of hypoadrenocorticism. An ACTH stimulation test (pre-stimulation cortisol <13.6 nmol/l post <13.6 nmol/l) confirmed the diagnosis. Management and Outcome The dog was started on prednisolone 0.2 mg/kg PO q24hrs and fludrocortisone 0.015mg/kg PO q24hrs. Within one week, the dog had returned to his normal demeanour, regained his appetite and regurgitation had resolved. There was weight gain and the dog was keen to exercise. Haematology and serum biochemistry values returned to normal and repeat radiography showed the megaoesophagus was no longer present (Figure 2). Figure 2: Lateral thoracic radiograph taken five days after starting treatment showing resolution of megaoesophagus. Discussion This case highlights the differential diagnoses for megaoesophagus and what tests are needed to reach a definitive diagnosis for the underlying cause. It also demonstrates how the use of historical and clinical findings, together with routine blood tests, helped to narrow down the likely causes and quickly reach a final diagnosis. Megaoesophagus associated with hypoadrenocorticism typically resolves with treatment, as seen in this case. Resolution of megaoesophagus may also be seen with treatment of GDV (acute and chronic), myaesthenia, toxicites and immune-mediated diseases (e.g. polymyositis/polyneuritis/SLE) so highlights the importance of searching for an underlying cause. Other causes of megaoesophagus have a variable response to treatment and many are managed by feeding in an upright position and treating episodes of aspiration pneumonia. Overall median survival times for all causes of megaoesophagus is only 90 days but is likely to be higher in those cases were resolution can be achieved. page 5 of 6 References Johnson BM, DeNovo RC, Mears, EA. In: Kirk’s Current Veterinary Therapy XIV. Eds. Bonagura JD, Twedt DC. Saunders, Elsevier, Missouri. 2009 pp486-492 McBrearty AR, Ramsey IK, Courcier EA, Mellor DJ, Bell R. Clinical factors associated with death before discharge and overall survival time in dogs with generalized megaesophagus. Journal of the American Veterinary Medical Association 2011; 238(12):1622-1628 The University of Edinburgh is a charitable body, registered in Scotland, with registration number SC005336. www.ed.ac.uk/vet/hfsa-int-med page 6 of 6