Virtual Congress speaker Ian Ramsey – Endocrinology Stream notes

Case Based Investigation of an Endocrine Alopecia

Ian Ramsey BVSc PhD DSAM DipECVIM-CA FHEA MRCVS
University of Glasgow Veterinary School, Bearsden Road, Bearsden, Glasgow G61 1QH  Ian.Ramsey@glasgow.ac.uk

Case Details: Ami, a 6 year old FN Toy Poodle Wt = 8.5 kg

History and clinical examination: Originally presented 2 months ago with back pain that was responsive to steroids. Increased liver enzymes were noted and (as the dog was getting better) it was weaned off steroids. Two weeks later at a recheck hyperglycaemia and glucosuria were noted. There had been no history of PU/PD, polyphagia, nevertheless it was clear that the dog had developed diabetes mellitus and so it was started on 2 units lente insulin q12h.  A bile acid stimulation test ACTH stimulation and urine culture were all normal at this time. Over the next 2 months increasing insulin resistance was noted – there was persistent hyperglycaemia and increasing fructosamine concentration such by the time of our examination these have increased to 700 mmoll/ and the dog is getting 7 units lent insulin  q12h. In addition the owner has noted Weight gain and that the dog is ‘quieter than normal’. On clinical examination there is alopecia but no skin thinning. The dog is obese, (BCS = 7/9). It is currently off steroids but on cephalexin for pyoderma.

Routine clinical pathology results:  

Biochemistry Haematology
TP 67 g/l (60-80) RBC 9.55 x 1012/l (5.5-8.5)
   Albumin 40 (30 – 40) Haemoglobin 18.1 g/dl (12-18)
   Globulin 27 (30 – 45) PCV 0.55 l/l (0.37-0.55)
Urea 5.5 mmol (3.3-8.0) MCV 58.1 fl (60-77)
Creatinine 106 mmol/l (45-150) MCHC 32.7 g/dl (32-37)
ALT 67 iu/l (21-59) MCH 19 pg (19.5-24.5)
AP 835 iu/l (3-142) WBC 6.8 x 109/l (6-17)
GGT 6 iu/l (0-10)   Neuts  (band) 0 x 109/l (0-0.3)
Bilirubin 0 mmol/l (0-10)   Neuts  (seg’d) 6.2 x 109/l (3-11.5)
Cholesterol 12.8 mmol/l (2-6)   Eosinophils 0 (0.1-1.3)
Glucose 6.1 mmol/l (3.4-5.3)   Basophils 0 (0)
Sodium 150 mmol/l (135-155)   Lymphocytes 0.3 x 109/l (1-4.8)
Potassium 4.2 mmol/l (3.5-5.8)   Monocytes 0.3 x 109/l (0.2-1.5)
Chloride 115 mmol/l (105-120) Platelets 202 x 109/l (175-500)
Calcium 3.0 mmol/l (2.2-2.7) Urinalysis
Phosphate 1.12 mmol/l (0.6-1.3) Dipstick All negative, pH = 6.5
Bile salts (pre) 241 mmol (0-5) S.G 1.002
              (post) 167 mmol (0-10) Deposit exam NSAD

Endocrine results:

ACTH stimulation test
pre ACTH    54 nmol/l    (20-250)
post ACTH    283 nmol/l    (<550)

Thyroid panel
T4            < 3.2 nmol/l        (15-55)
fT4ed            <2 pmol/l        (8-30)
cTSH            0.13 nmol/l        (<0.6)
AntiTG Ab        89%            (<200)

Notes on approach
Diagnosis of hypothyroidism is initially based on historical and clinical findings consistent with the condition. If the history or clinical examination are inconsistent with the diagnosis, then other differential diagnoses should be thoroughly investigated before any investigations are conducted on the thyroid gland. Unfortunately, many dogs present with a history that is at least suggestive of hypothyroidism (for example, lethargy and poor coat condition), but clinical examination proves unrewarding. In these cases further tests are indicated.

Clinical Signs and Routine clinicopathological features
Many clinical signs have been associated with hypothyroidism. In one study of 50 hypothyroid dogs, the most common clinical characteristics associated with hypothyroidism were lethargy (76%), obesity or weight gain (44%), and exercise intolerance (24%); and dermatological abnormalities (80%), including alopecia (56%), poor coat quality (30%) and hyperpigmentation (20%).
A routine haematology and biochemistry screen should be obtained prior to specific thyroid function tests. In the same study of 50 hypothyroid dogs, the most common biochemical and haematological abnormalities were increased concentrations of triglycerides (88%), cholesterol (78%), glucose (49%), fructosamine (43%), creatine kinase (35%) and decreased concentrations of inorganic phosphate (63%), and red blood cells (40%).

Specific thyroid tests
Total thyroxine
The diagnostic value of a single low basal tT4 is limited because basal tT4 concentrations can be reduced in a number of non-thyroidal disease states and by several commonly used drugs such as prednisolone and potentiated sulphonamides. Nevertheless the vast majority of hypothyroid dogs have low levels of tT4.
Free thyroxine
In human medicine, fT4 concentrations are less frequently reduced in non-thyroidal disease states compared to tT4 concentrations. In one study of 30 hypothyroid dogs and 77 euthyroid dogs in which cTSH, tT4 and fT4 by equilibrium dialysis (fT4ed) were measured the cut offs of  less than 14.9 nmol/litre (tT4), less than 5.42 pmol/litre (fT4ed), greater than 0.68 ng/ml (cTSH) were suggested as being optimal for the diagnosis of hypothyroidism(Dixon and Mooney 1999). These had a sensitivity and specificity of 100 and 75.3 per cent, 80 and 93.5 per cent, 86.7 and 81.8 per cent, respectively, for diagnosing hypothyroidism. The authors concluded that estimation of fT4d adds only limited additional information over total T4 measurement in dogs (Dixon and Mooney 1999).
Thyroid stimulating hormone
Many hypothyroid dogs having increased concentrations of cTSH. However, about 25% of naturally occurring cases of canine hypothyroidism have cTSH concentrations that are within the reference range.
It has also been shown that sick euthyroid dogs may have occasionally have high levels of cTSH. In man, increased hTSH concentrations are noted in patients recovering from serious illness and those receiving certain drugs (eg, potentiated sulphonamides).
Stimulation tests
Stimulation tests using either recombinant human TSH (rhTSH), bovine TSH (bTSH) or TRH have been advocated by many authors. Most workers consider some form of TSH stimulation to be the more reliable method; however, false positive diagnoses of hypothyroidism do still occur (Nelson and Feldman 1996). Unfortunately, pharmaceutical grade bTSH and TRH are no longer available and recombinant human TSH is in short supply and currently is only available for human use.
Antithyroglobulin antibodies
Antithyroglobulin antibodies have been demonstrated in about 50% of dogs suffering from lymphocytic thyroiditis, but they have also been identified in a few normal dogs

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