Despite being the most common endocrinopathy, hypothyroidism can be a challenging disease to diagnose. Although there are many diagnostic tests, they all have their limitations, as thyroid function can be influenced by many different intrinsic and extrinsic factors. Hypothyroidism can cause a wide variety of symptoms involving almost any organ system; however, dermatological signs are the most common. This report describes a case where the cutaneous signs were prominent.
The condition most commonly affects mainly middle-aged to older dogs and certain breeds are predisposed (see ‘Epidemiology’ section). Cutaneous signs are gradual in onset and generally non-pruritic, unless there is a concurrent secondary infection. Most clients are unaware of systemic signs such as lethargy, exercise intolerance, heat seeking and weight gain. Close questioning on changes in demeanour and general health is therefore essential during the history taking.
Physical and skin examinations may reveal a great variety of systemic and cutaneous symptoms that vary from case to case (Tables 22.1 and 22.2). The relevant findings in this case were:
|Common signs||Uncommon or rare signs|
|Common||Uncommon or rare|
|Thin, easily epilated hair coat||Pyoderma|
|Symmetrical alopecia||Ceruminous otitis externa|
|Failure of hair growth after clipping||Demodicosis|
|Hyperpigmentation||Lightening of the hair coat colour|
At this stage, given the short duration of the disease, cyclical flank alopecia could not be ruled out, but in such cases thyroid function is unaffected. Because there was no history of polyuria, polydipsia or polyphagia, hyperadrenocorticism was unlikely.
Making a definitive diagnosis of hypothyroidism can prove challenging in some cases. The diagnosis is based on history, clinical signs and the demonstration of suppressed thyroid function. Because there are so many factors affecting thyroid hormone concentrations including age, breed, concurrent disease and drug therapy (see ‘Anatomy and Physiology Refresher’), the diagnosis is not always easy to confirm. At the time of writing, there are no completely reliable tests that can distinguish euthyroid from hypothyroid dogs. A single thyroid assay is almost invariably misleading and multiple tests are recommended to try and confirm the diagnosis.
Haematology and biochemistry: If the history or clinical examination suggests hypothyroidism, routine haematological and biochemical examinations should be performed. This helps to exclude intercurrent disease leading to the euthyroid sick syndrome (see below). A mild, normochromic normocytic anaemia may be present in up to half of all cases of hypothyroidism. Hypercholesterolaemia is another frequent, but non-specific, finding in up to 70% of cases.
Thyroid function tests: Thyroid function tests should be performed where there are clinical signs suggestive of hypothyroidism. The clinician should rule out or treat concurrent diseases before evaluating thyroid function and, wherever possible, stop any drug treatment at least 4 weeks prior to testing. Where this is not possible, any results should be interpreted in the knowledge that drugs which could affect thyroid function have been administered. The following is a summary of the thyroid function tests currently available and their application in the diagnosis of hypothyroidism. Always use a combination of thyroid function tests to support the diagnosis.
TT4: Basal serum total thyroxine (TT4) measures protein- and non-protein-bound ‘free’ serum thyroxine. The concentration decreases in hypothyroidism, but also decreases with euthyroid sick syndrome and drug administration. There is a large overlap between euthyroid and hypothyroid dogs, and up to 25% of euthyroid dogs will have suppressed TT4 values; however, as a general rule, 99% of dogs with TT4 > 15 nmol/l will be euthyroid and >95% of dogs with TT4 < 5 nmol/l will be hypothyroid. Concentrations will be artificially (markedly) elevated in the presence of anti-T4 autoantibodies (AT4A), although this is an uncommon situation.
fT4ED: Basal free T4 by equilibrium dialysis (fT4ED) measures non-protein-bound circulating T4. Concentrations of fT4 will decrease in hypothyroidism, but may be maintained in early hypothyroidism, reducing the sensitivity of this test. It is expensive in comparison to TT4, but fT4 should be less affected by non-thyroidal illness than TT4 and is unaffected by the presence of AT4A. Note: some laboratories may measure free T4 using ‘analogue’ assay techniques, which is no more use than measuring TT4 alone.
cTSH: Canine thyroid-stimulating hormone (cTSH) measures circulating TSH. It is often used in conjunction with TT4 or fT4 as a screening test for hypothyroidism. Concentrations of cTSH increase in hypothyroidism, due to the decreased negative feedback effect of T4 and T3 on the anterior pituitary gland. This test may be affected by drug administration and by non-thyroidal illness. Between 13% and 38% of hypothyroid dogs have cTSH in the normal range (usually 0.02–0.68 ng/ml) and 7–18% of euthyroid dogs have cTSH in the hypothyroid range.
TT3 and fT3: Total and free triiodothyronine (TT3 and fT3) measurements are of little value in the diagno-sis of most cases of hypothyroidism. TT3 concentrations tend to be preferentially maintained during early hypothyroidism.
TSH stim: Thyroid-stimulating hormone stimulation test (TSH stim) is considered the gold standard test in the diagnosis of canine hypothyroidism. Serum TT4 is measured before and 6 hours after intravenous injection of 0.1 IU/kg of thyrotropin (TSH). Thyroxine response to TSH is small to non-existent in hypothyroid dogs; however, a normal response may be seen in very early cases of hypothyroidism. Some drug treatments and severe non-thyroidal illness can also interfere with this test. As bovine TSH is no longer available, the use of recombinant human TSH (rhTSH) has been validated for this test.
TRH stim: In the thyrotropin-releasing hormone stimulation test (TRH stim), TT4 is measured before and 4 hours after intravenous injection of TRH. At least one study has concluded that this is not a useful test in the diagnosis of hypothyroidism, although the debate continues. Up to 25% of euthyroid dogs will fail to stimulate at all.
Thyroglobulin autoantibodies (TGAA): Thyroglobulin is a protein involved in the production and storage of thyroid hormones within the thyroid gland. The presence of TGAA is an indicator of lymphocytic thyroiditis, but does not diagnose clinical hypothyroidism.
Anti-thyroid hormone antibodies AT3A/AT4A: These antibodies are occasionally found in canine sera and can interfere with the assays for TT4, fT4, TT3 and fT3, producing spuriously increased concentrations. They are not used as a diagnostic test for hypothyroidism.