Disease Investigation Index
Disease Investigation 1
INVESTIGATION OF THYROID FUNCTION IN DOGS
Hypothyroidism is the commonest endocrine disorder in dogs. Approximately 90% of cases are due to acquired, primary disease (lymphocytic thyroiditis or idiopathic necrosis and atrophy). Males and females are equally affected with the age of onset most commonly between six and ten years (Thoday, 1990). The most frequent clinical findings are skin changes (alopecia, seborrhoea, pyoderma, puppy coat, hyperpigmentation, hyperkeratosis, myxoedema and slow hair growth), lethargy, obesity, intolerance to cold and reproductive abnormalities (Bush, 1991). Laboratory tests are commonly requested to confirm a clinical suspicion of hypothyroidism.
NON SPECIFIC LABORATORY TESTS
Non specific laboratory findings include hypercholesterolaemia (73% of cases), non-regenerative anaemia (32%), high serum alkaline phosphatase activity (30%) and high serum creatinine kinase activity (18%) (Panciera,1994). None of these changes are pathognomonic for hypothyroidism. Skin biopsy may reveal non-specific histological findings (eg. orthokeratotic hyperkeratosis, epidermal atrophy and epidermal melanosis) or histological findings suggestive of hypothyroidism (vacuolated and/or hypertrophied erector pilae muscles, thickened dermis and increased dermal mucin) (Thoday, 1990).
SPECIFIC LABORATORY TESTS
1. THYROID HORMONE CONCENTRATIONS
Low circulating total thyroxine (T4) or free thyroxine (FT4) concentrations may support but not confirm a diagnosis of hypothyroidism. The measurement of the triodothyronine (T3) concentration does not offer any additional diagnostic information (Thoday, 1990; Bush, 1991).

T4 levels may be low in euthyroid animals suffering from non-thyroidal illnesses including chronic hepatic and renal disease, auto-immune disorders, diabetes mellitus and hyperadrenocorticism. Whilst it might be considered that the metabolically active FT4 levels would be normal in these "euthyroid-sick syndrome" dogs (Bush, 1991), there is evidence that FT4 levels are depressed in some non-thyroidal illnesses (Feldman and Nelson, 1987). Drug therapy, prolonged fasting and hourly fluctuations can also cause low basal T4 and FT4 levels in euthyroid dogs.

2. FT4 AND CHOLESTEROL
Larsson (1988) evaluated the use of FT4 and cholesterol as a screening test for hypothyroidism in dogs. Using the discriminate function k = 0.7 x FT4 (pmol/L) - cholesterol (mmol/L), it was shown that dogs with a k value < -4 were hypothyroid and that dogs with a k value of > +1 were normal or non responsive to thyroid hormone replacement therapy.

FT4 and cholesterol should only be performed on fasted serum or plasma samples. A stimulation test should be considered in dogs giving a k value between -4 and +1.

This function has not been validated for this laboratory’s reference ranges and should be used as a guide to diagnosis only.

3. TSH STIMULATION TEST
The measurement of T4 concentrations before and after thyroid stimulating hormone (TSH) administration has been the most widely applied test for the diagnosis of primary hypothyroidism in dogs. TSH is not available in the UK and is reported to be no longer commercially available in the USA, the major potential source for importation (Anon, 1994).

4. TRH STIMULATION TEST (Test Protocol 6)
The measurement of T4 concentrations before and after thyrotropin releasing hormone (TRH) administration has been recommended both as an alternative to the TSH stimulation test and to detect cases of secondary hypothyroidism (due to pituitary defects). However, the results of TRH stimulation testing in dogs have been inconsistent and the effects of non-thyroidal illness and drugs on TRH stimulation have not been documented (Jeffers, 1990; Thoday, 1990).

A number of diagnostic protocols appear in the literature. The following protocol and interpretation is offered to clients wishing to undertake thyroid stimulation testing in the absence of an identifiable source of TSH.
Protocol
1. Take 2ml of clotted/heparinised blood.
2. Inject 0.2mg of TRH per dog slowly i/v over 1 minute.
3. Take a second 2ml of clotted/heparinised blood 4 hours after TRH injection.
4. Separate the serum or plasma before despatch to the laboratory.
Interpretation
A normal dog will show an increase over basal levels of >1.2 x rising to a value of >30 nmol/l.
TRH is currently available as ProtirelinR (Roche). This is licensed for use in humans but does not have a veterinary product licence and is available from your veterinary wholesaler or pharmacy at a concentration of 0.2 mg/vial (200 m g/vial).
 

Test Code Test Name Sample
T4 Thyroxine T4 Serum or Heparin plasma
FT4 Free T4 (Canine) Serum or Heparin plasma
FT4C Free T4 and Cholesterol (Canine) Serum or Heparin plasma (fasted)
TRHS TRHS Stimulation Test (Canine) Serum or Hep plasma x 2
REFERENCES
ANON, (1994) In: Small Animal Clinical Endocrinology. Daniels Pharmaceuticals Inc. 4 (3);p 9.

Beale K.M, (1990) Current diagnostic techniques for evaluating thyroid function in the dog. Veterinary Clinics of North America: Small Animal Practice. 20 (6); p 1429 - 1441

Bush B.M, (1991). The Endocrine System. In: Canine Medicine and Therapeutics 3rd Edition. Eds. Chandler E.A, Thompson D.J, Sutton J.B, and Price C.J. Blackwell Scientific Publications. Oxford p 323 - 332.

Feldman E.C, and Nelson R.W, (1987).In Canine and Feline Endocrinology and Reproduction. W.B Saunders, Philadelphia p 55.

Jeffers J.G, (1990). Recognising and managing the effects of canine hypothyroidism. Veterinary Medicine. 85 (12) p 1294 - 1308

Larsson M.G (1988). Determination of free thyroxine and cholesterol as a new screening test for canine hypothyroidism. Journal of the American Animal Hospital Association. 24 (2) p 209 -217.

Panciera D.L, (1994). Hypothyroidism in dogs: 66 cases (1987-1992) Journal of American Veterinary Medical Association. 204 (5) p 761 - 767.

Thoday K.L, (1990). The Thyroid gland In: Manual of Small Animal Endocrinology. Ed. Hutchison M. BSAVA. Cheltenham p 25 - 57.
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