Primary Hypothyroidism in a Dog

WHAT IS YOUR DIAGNOSIS? A six year old, female neutered Dandie Dinmont was presented to the R(D)SVS Internal Medicine Service for investigation of progressive stertor and exercise intolerance. Trial therapy with carprofen had not improved the clinical signs. On physical examination, the dog was bright, alert and responsive with a body weight of 13.4kg (figure 1). Stertor was audible throughout the consultation. A left side grade II/VI systolic heart murmur was audible which had been previously detected by the referring veterinarian. The heart rate was 90 beats per minute with a sinus arrhythmia. There was no abnormal respiratory noises audible on thoracic auscultation. The oral mucous membranes were pink and moist, capillary refill time was 2 seconds and there were no pulse deficits. Abdominal palpation was generally unremarkable and all peripheral lymph nodes were within normal limits. The coat was dull and thin with generalized epidermal hyperpigementation. Her rectal temperature was 38.1°C. The dog was admitted for further evaluation. A haematology profile was unremarkable and results from a serum biochemistry analysis is shown overleaf (* above reference range) page 1 of 6 Parameter Result Reference Range Total protein (g/l) 65.2 58-73 Albumin (g/l) 33.6 26-35 Globulin (g/l) 31.6 18-37 Bile acids (μmol/l) 1.3 0-7 Total bilirubin (μmol/l) 0.1 0-6.8 Urea (mmol/l) 6.0 1.7-7.4 Creatinine (μmol/l) 94 40-132 Glucose (mmol/l) 4.7 3-5 ALKP (iu/l) 43 20-60 ALT (iu/l) 39 21-102 Sodium (mmol/l) 147 139-154 Chloride (mmol/l) 109 99-115 Potassium (mmol/l) 5.2 3.6-5.6 Inorganic phosphate (mmol/l) 1.39 0.9-2.0 Total calcium (mmol/l) 2.52 2.3-3.0 Cholesterol (mmol/l) 8.0 * 3.8-7 Triglyceride (mmol/l) 2.65 * 0.57-1.14 1) What are the differential diagnoses for hypercholesterolemia and hypertriglyceridemia? 2) How would you evaluate this case further? page 2 of 6 1. Differential diagnosis for hypercholesterolemia and hypertriglyceridemia Causes of hyperlipidemia include (1) : o o o o o o o o o Postprandial hyperlipidemia Hypothyroidism Diabetes mellitus Hyperadrenocorticism Pancreatitis Obesity Protein losing nephropathy Cholestasis Miscellaneous eg high fat diets, lymphoma, infection with Leishmania infantum, congestive heart failure due to dilated cardiomyopathy, and administration of certain drugs (e.g. glucocorticoids) o Primary lipid abnormalities 2. Further evaluation of the case In light of the hyperlipidemia findings and the history of lethargy and dermatological signs, thyroid function was assessed by measurement of serum concentrations of total thyroxine and thyroid stimulating hormone. To further examine the dog for potential causes of stertor, the structure and function of the dog’s upper airway was assessed during the induction of general anaesthesia. In addition, a computed tomography (CT) examination of the head was performed. Rhinoscopy and nasopharyngeal endoscopy was then undertaken. Since nasal biopsies may be harvested depending on CT findings, a pre-anaesthesia coagulation profile and buccal mucosal bleeding time test was performed. Serum total thyroxine concentration was <5.0nmol/l (ref. range 15-48) and thyroid stimulating hormone was 2.15ng/ml (ref. range 0-0.5). Evaluation of the upper airway on anaesthesia induction revealed that the soft palate was elongated and the laryngeal saccules were everted. Head CT scan revealed that the soft palate was elongated (figure 2). Rhinoscopy and nasopharyngeal endoscopy was unremarkable apart from confirming the presence of an elongated soft palate. No intranasal biopsies were taken due to the relatively unremarkable CT scan of the nasal turbinates and normal rhinoscopy findings and the finding of a prolonged activated thromboplastin time. In light of the findings of low total thyroxine and high thyroid stimulating hormone concentrations, hyperlipidemia and clinical signs including lethargy and coat thinning, a diagnosis of primary hypothyroidism was made. The dog was treated with levothyroxine 0.3mg SID. At the two week recheck, the owner reported that the dog was much brighter and her stertor was significantly improved. A 5 hour post pill serum total thyroxine concentration was slightly increased (56.9nmol/l) so the thyroxine dose was lowered to 0.2mg SID. Further coagulation profiles were within normal limits. At the four page 3 of 6 week recheck her stertor was further improved, albeit still present. Serum thyroxine concentration was within the reference range. Discussion This case had many typical features of primary hypothyroidism; the clinical findings of lethargy and a thinning, dull coat are typical of dogs with primary hypothyroidism as are the biochemical findings of hyperlipidemia (2). The most widely used screening test for primary hypothyroidism remains the measurement of serum concentrations of total thyroxine in conjunction with thyroid stimulating hormone (2). In many cases of primary hypothyroidism, the total thyroxine concentration is low and the thyroid stimulating hormone is high. Although these typical changes were observed in this case, it is important to acknowledge many cases of primary hypothyroidism do not have these typical changes, not least because the presence of thyroxine autoantibodies can interfere with some total thyroxine assays (3, 4). A notably feature of this case was the presence of stertor at initial evaluation and its subsequent improvement following treatment with thyroxine. It is difficult to make firm cause and effect conclusions between the development of hypothyroidism and the onset of stertor in this case; however, it is possible that the progressive upper airway noise reported during initial examination was due to myxoedema of the soft palate. Myxoedema most commonly occurs in the skin and is a well recognised complication of hypothyroidism in dogs. Myxoedema is caused by deposition of dermal acid mucopolysaccharides, notably hyaluronic acid. In dogs with hypothyroidism it can lead to a thickened appearance of the skin which does not pit with pressure. Myxoedema of the upper airway has been occasional reported in human patients with hypothyroidism (5,6). As with this case, treatment with thyroxine can lead to improvement in clinical signs of upper airway obstruction in humans with hypothyroidism (5,6). The residual stertor observed in this dog may have been caused by everted laryngeal saccules or possibly due to incomplete resolvement of the myxoedema of the soft palate. Due to the much improved stertor and good exercise tolerance following thyroxine treatment, further assessment was not deemed necessary at the moment. page 4 of 6 Figure 1 Figure 2 : Sagittal computed tomography image of the head. Note the elongated soft palate. page 5 of 6 References 1. Xenoulis PG, Steiner JM. Lipid metabolism and hyperlipidemia in dogs. Vet J. 2010;183(1):12-21. 2. Mooney CT. Canine hypothyroidism: a review of aetiology and diagnosis. New Zealand veterinary journal. 2011;59(3):105-14. 3. Nachreiner RF, Refsal KR, Graham PA, Bowman MM. Prevalence of serum thyroid hormone autoantibodies in dogs with clinical signs of hypothyroidism. Journal of the American Veterinary Medical Association. 2002;220(4):466-71. 4. Randolph JF, Lamb SV, Cheraskin JL, Schanbacher BJ, Salerno VJ, Mack KM, et al. Free thyroxine concentrations by equilibrium dialysis and chemiluminescent immunoassays in 13 hypothyroid dogs positive for thyroglobulin antibody. Journal of veterinary internal medicine / American College of Veterinary Internal Medicine. 2015;29(3):877-81. 5. Uzunpinar A. (2006) Upper Airway Obstruction in a patient with severe hypothyroidism presenting as postextubation stridor. Chest, 130.4 6. Bidkar V, Naik A, Anita R. (2013) Myxedema of Upper Airway: a rare cause of stridor. Journal of Case Reports. 3(2): 249-253 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