VetCpd Thyroid diseases Notes

Sophie Keyte BVMS (Hons) MVetMed (Dist) FHEA DipACVIM MRCVS

Sophie.keyte@bristol.ac.uk

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 Canine Hypothyroidism

Summary
• Primary hypothyroidism is a common canine endocrinopathy
• Compatible clinical signs (especially metabolic/dermatological) and biochemical changes
(hypercholesterolaemia) should be present before performing specific testing
• Low T4 (or fT4) with high cTSH is consistent with hypothyroidism.
• Beware non-thyroidal illness and effects of drugs – low T4 does not always = hypothyroidism!
• TSH stimulation test is gold standard for diagnosis but usually requires referral.
• Treat with levothyroxine
• Good prognosis

Hypothyroidism is one of the most common canine endocrine disorders, reportedly affecting 0.2-0.6% of the
population. However, there may be a tendency for it to be over-diagnosed and understanding of the clinical signs
and diagnostic tests available is essential.

Anatomy and physiology of the thyroid gland

• Vascular, bi-lobed structure located lateral to the proximal tracheal rings
• Responsible for the production of the active thyroid hormones thyroxine (T4) and triiodothyronine (T3),
under the control of TRH from the hypothalamus and TSH from the pituitary gland.
• Thyroid hormones affect many metabolic processes, enzyme systems, and tissues. In effect, no tissue or
organ system escapes the adverse effects of thyroid hormone excess or insufficiency.
• Most thyroid hormone secreted from the thyroid gland is in the form of T4, with small amounts of T3 and
rT3 (reverse T3). More than 99% of T4 is bound to plasma proteins in the circulation. The unbound, or free,
T4 (fT4) is biologically active and exerts negative feedback on TSH production. Within the cell, fT4 is
deiodinated to form either T3 or rT3. T3 is formed during normal metabolic states and is biologically active,
binding to receptors within the cell. rT3 is biologically inactive and appears to be produced during periods of
illness or starvation.

Control of thyroid function

TRH Hypothalamus
Stimulation

Negative feedback

TSH Anterior pituitary gland

Thyroid gland

T4 Circulation

Tissues
T3

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Pathophysiology
Primary hypothyroidism
• problem at level of thyroid gland
• most common form of hypothyroidism
• lymphocytic thyroiditis – most common cause. An immune-mediated disorder with breed predispositions
(Kennedy and others 2006). Thyroglobulin autoantibodies may be a useful marker for dogs at risk (see later).
• idiopathic atrophy of thyroid gland – less common. Cause unknown, may be end-stage of autoimmune
thyroiditis
• other causes – rare, include neoplastic destruction, anti-thyroid drugs, radiation therapy and congenital
defects

Secondary hypothyroidism
• rare
• pituitary hypoplasia (congenital – disproportionate dwarfism) or dysfunction within pituitary gland (e.g.
neoplasia) leads to reduced production of TSH
• most common cause is suppression of TSH secretion by exogenous glucocorticoid administration or
hyperadrenocorticism
• central hypothyroidism described in Minature Schnauzers (Voorbij and others 2016)

Clinical features of primary hypothyroidism

• Middle-aged (2-6yo)
• Earlier in breeds at increased risk of disease e.g. Pointers, Boxer, Golden Retriever, Old English Sheepdog,
Dalmatian, Dobermann, Cocker Spaniel
• Clinical signs vary between dogs – many are non-specific
• Metabolic (~ 70% of cases)
o lethargy, mental dullness, inactivity, weight gain, cold intolerance
• Dermatologic (~ 80% of cases)
o Endocrine alopecia (symmetric or asymmetric, “rat tail”)
o Dry brittle hair coat, hyperpigmentation
o Seborrhoea, pyoderma, otitis externa
o Myxoedema +/- “tragic” facial expression
• Reproductive
o Persistent anoestrus, weak or silent oestrus, prolonged oestral bleeding
o Inappropriate galactorrhoea
• Neuromuscular
o Weakness
o Knuckling, ataxia, circling, vestibular signs, facial nerve paralysis, seizures (rare)
o Myxoedema coma (rare)
o There is little evidence that megaoesophagus and laryngeal paralysis are caused by hypothyroidism
• Miscellaneous
o Ocular – corneal lipid deposits, ulceration, uveitis
o Cardiovascular – bradycardia, decreased contractility, arrhythmias (and note similar breed
predispositions to DCM)
o Gastrointestinal – diarrhoea, constipation
o Haematological – anaemia, hyperlipidaemia, coagulopathy

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Diagnosis
• Appropriate history and clinical signs must be present before hypothyroidism is considered
• Vague clinical signs and lack of specific abnormalities on routine blood-work mean that diagnosis is based on
thyroid function testing
• None of the existing tests is 100% accurate
• Beware of the effects of drugs and non-thyroidal illness (NTI) on thyroid function

Laboratory abnormalities (Dixon and others 1999)

Haematology
• mild normocytic, normochromic, non-regenerative anaemia common
• white blood cells and platelets usually normal

Biochemistry
• hypercholesterolaemia in 60% of dogs
• +/- elevated liver enzymes

Differential diagnoses for hyperlipidaemia (*most common)

• Physiologic – *post prandial
• Secondary – *DM, *hypothyroidism, *hyperadrenocorticism, cholestatic liver disease, glomerulonephritis, nephrotic renal
disease, drug-induced (glucocorticoid therapy; megestrol acetate (cat)
• Inherited – inherited hyperchylomicronaemia in the cat, idiopathic hyperlipidaemia in the Miniature Schnauzer,
hypercholesterolaemia in the Briard
• Idiopathic

Tests of thyroid gland function

• Thyroid function testing should only be performed when consistent clinical signs and supportive
haematological/biochemical changes are present, and when non-thyroidal illness is considered unlikely. In
addition, consideration should be given to withdrawing any medications which may influence thyroid
function.
• T4, fT4 and cTSH are the most important tests. Because T3 and rT3 are formed primarily from deiodination of T4 in extrathyroidal
sites, measurement is not recommended for assessment of thyroid function.

Recommended tests for primary hypothyroidism:

Total T4 (TT4)
• useful as an initial screening test
• must be interpreted in context of history, physical examination, and haematology/biochemistry findings
• often low in dogs with non-thyroidal illness (NTI -“euthyroid sick syndrome”) or dogs on medication (e.g.
phenobarbitone, corticosteroids, NSAIDS, sulfonamides, furosemide)
• lower in sight hounds e.g. Greyhounds, Whippets (van Geffen and others 2006) than other breeds of dog,
also Sloughi and Basenjis
• requirement for breed-specific intervals (Hegstad-Davies and others 2015)
• lower in older dogs (approx. 50% cases >6 years old)
• higher in pregnant bitches or in dioestrus (due to progesterone)
• daily fluctuations in euthyroid dogs occur (Kooistra and others 2000)

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cTSH (Dixon and others 1996; Dixon and Mooney 1999b)
• increased in most hypothyroid dogs due to loss of negative feedback
• 20% of hypothyroid dogs have normal TSH (false negative)
o concurrent NTI can decrease TSH
o some drugs (corticosteroids) can decrease TSH
o daily fluctuation
o secondary (central) hypothyroidism?
• Can be elevated in some euthyroid dogs (false positive) - uncommon
o Early thyroid disease
o Drugs e.g. potentiated sulphonamides
o Recovery from NTI
• must always be interpreted in conjunction with TT4 or fT4

Free T4
• useful initial screening test if:
o NTI suspected - less affected than TT4
o Unable to withdraw drug therapy e.g. phenobarbitone, corticosteroids – less affected than TT4
o T4 autoantibodies suspected (see below) – fT4 is not affected
• equilibrium dialysis is the only reliable assay technique

Additional tests:
Tests for lymphocytic thyroiditis (T4AA, T3AA, TgAb) (Dixon and Mooney 1999a)
• The presence of antibodies to T4 (T4AA) or T3 (T3AA), or to thyroglobulin (TgAb), is thought to correlate with
the presence of lymphocytic thyroiditis.
• TgAb is a better screening test than T4AA or T3AA – present in approximately 50% hypothyroid dogs.
• The presence of TgAb implies thyroid gland pathology but gives no information regarding severity or clinical
significance. Presence caused by leakage of thyroglobulin into circulation secondary to thyroiditis.
• TgAb should not be used alone in the diagnosis of hypothyroidism. Dogs with confirmed hypothyroidism can
be negative, and euthyroid dogs can be positive. It may be used as a pre-breeding screen in breeds at
increased risk of hypothyroidism.
• T4AA are present in <1% of dogs and interfere with assay of T4, causing falsely elevated T4 values. FT4 is not
affected. Measurement of T4AA may be appropriate in dogs with unexpected T4 concentrations.

TSH and TRH stimulation tests

• TSH stimulation test has previously been the gold standard for differentiating hypothyroid from euthyroid
sick dogs; however pharmaceutical grade TSH is no longer available, and recombinant human TSH (rhTSH)
(which has been validated in dogs) is prohibitively expensive (Daminet and others 2007). TRH stimulation
test is recommended by some authors but is less reliable.

Thyroid scintigraphy
• This has undergone initial evaluation and may be useful in equivocal cases (Pinilla and others 2009)

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Tests summary

Test Advantages Disadvantages

TT4 Readily available, not expensive
Normal values usually allow
“exclusion” of hypothyroidism
TSH Readily available, not expensive
fT4 Less influenced by systemic disease or
drug administration
Anti-thyroglobulin Ab Tests for thyroid autoimmunity
Pre-breeding screen for at risk breeds
Scintigraphy Reliable, considered gold-standard
TSH stimulation test Reliable, considered gold-standard
(rhTSH); dose 50-100µg (150 µg if
concurrent disease/drugs).
Decreases with systemic disease
(euthyroid sick syndrome)
Decreases after administration of
certain drugs
Can’t be used alone to diagnose
hypothyroidism (low specificity)
25% hypothyroid dogs have normal
values (low sensitivity)
Always use in combination with TT4
Must be measured by equilibrium
dialysis – not readily available
Not routinely available
Does not reflect thyroid function
Limited availability, short period of
isolation post-procedure
Need for sedation
rhTSh is expensive, takes 6 hours to
complete
If use bovine TSH – anaphylaxis
possible

Drugs affecting thyroid function testing (Daminet and Ferguson 2003)

Drugs TT4 fT4 TSH TSH stim test

Glucocorticoids ↓ = or ↓ = Blunted at high dose
(immunosuppressive) and long tx duration
Potassium bromide = = = =

Phenobarbital ↓ = or ↓ = or ↓

Imepitoin(Bossens and = = =
others 2016)
Sulfonamides ↓ ↓ ↑ ↓

Carprofen = or ↓ = or ↓ = or ↓ ?

Aspirin(Daminet and ↓ = = ?
others 2003)
Clomipramine ↓ ↓ = ?

Anaesthesia (and ↓ ↑ ? ?
surgery)

Summary of diagnosis of hypothyroidism

Appropriate historical, physical examination, and haematological/biochemical abnormalities should be present
before thyroid function tests are performed. In the presence of supportive clinical findings, low T4 or fT4 in
conjunction with high TSH is highly suggestive of hypothyroidism. Positive TgAb suggests lymphocytic thyroiditis as
the underlying aetiology.

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Unfortunately, discordant test results are common. In these situations, thyroid function should be retested in 3-
6months, dynamic function testing considered (TSH stimulation test), or, only if clinical signs and history are highly
suggestive, trial therapy may be initiated. A positive response to treatment indicates that the dog either has
hypothyroidism or a “thyroid-responsive disease”; for example, many dogs with hair changes will show improvement
on thyroxine even if euthyroid. If a positive response is noted, treatment should be gradually discontinued and, if
signs recur, hypothyroidism is likely. If a dog has received thyroid supplementation, tests of thyroid function should
not be performed until 6-8 weeks after cessation of therapy.

Treatment
• Sodium levothyroxine (Soloxine, Thyroxyl, Forthyron© – tablets; Leventa© – liquid (Dijl and others 2014; Le
Traon and others 2009))
o Starting dose: 0.02mg/kg SID or 0.01mg/kg BID
o Maximum dose 0.8mg/dog BID
o SID dosing may be adequate in many dogs as the duration of biological activity of thyroid hormones
exceeds the plasma half-life. Cheaper and better owner compliance
o Many dogs can be managed on lower doses
o Lifelong therapy required
o Give 2-3 hours before a meal if possible (food decreases absorption)
• Absorption and metabolism vary between dogs
• In dogs with cardiac disease, hypoadrenocorticism, or diabetes mellitus, start with 25% of dose and titrate
up
• Continue for 4-8 weeks before evaluating effect
• Therapeutic monitoring (Dixon and others 2002)
o 4-8 weeks after starting treatment, or 2-4 weeks after altering dose
o Evaluation of clinical response
§ Lethargy often improves within 1-2 weeks
§ Dermatological/neurological changes take several months to resolve
o Measurement of T4 and TSH
§ Can be done just before and/or 3-6h post medication
§ TT4 just before medication (pre-pill) = assessment of duration of action
§ Post-pill TT4 = assessment of dose (peak action)
§ Aim for T4 in upper half of or above reference range 3-6h post pill
§ Aim for normal TSH; measurement does not always add significantly to the treatment plan
§ Follow normal daily routine for patient i.e. time of feeding, dosing so this means the patient
may not be fasted
§ Once euthyroid re-assess every 6months
• If there is failure to respond to therapy, consider:
o Incorrect diagnosis
o Inappropriate dose
o Poor intestinal absorption
• Thyrotoxicosis
o Rare
o Panting, anxiety, aggression, PUPD, polyphagia, weight loss
o Reduce dose/discontinue for few days depending on severity
• Myxoedema coma
o Rare – may occur in dogs with undiagnosed hypothyroidism overwhelmed by concurrent disease
such as heart disease or sepsis
o Stupor, coma, hypothermia, respiratory and cardiovascular suppression
o Supportive care – warming, I/V fluids, glucose, respiratory support, antibiotics as appropriate
o Thyroid supplementation – 5ug/kg levothyroxine intravenously BID initially, followed by oral
administration once stabilised

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Prognosis
• Good in adult dogs with primary hypothyroidism
• Guarded in puppies or dogs with secondary hypothyroidism

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 Congenital hypothyroidism (cretinism)

Pathophysiology
• Defects in thyroid gland (thyroid gland dysgenesis)
• Defects in pituitary gland (pituitary malformation – pituitary dwarfism)
• Defects in thyroid hormone production (dyshormonogenesis)

Clinical features
• Dwarfism – short broad skull, shortened mandible, enlarged cranium, shortened limbs, kyphosis – disproportionate
stunting
• Dull, lethargic
• Persistence of puppy hair coat, alopecia, dry hair, thick skin
• Inappetance, constipation
• Gait abnormalities, delayed dental eruption
• Radiography – delayed epiphyseal ossification, epiphyseal dysgenesis

Diagnosis
• Interpret T4 levels with care – puppies <3 months of age typically have circulating T4 levels 2-5 times greater than adult
dogs
• TSH – increased with primary disease; normal/low in hypothalamic or pituitary disease; consider TRH stimulation with
measurement of TSH and T4.
• DDX – other diseases cause proportionate stunting
o Endocrine – pituitary dwarfism
o Non-endocrine – malnutrition, GI disease (maldigestion, EPI, malabsorption, parasitism), Hepatic disease
(portosystemic shunt, microvascular dysplasia), renal disease, cardiovascular disease
Treatment
• Thyroid hormone supplementation

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 Canine thyroid neoplasia

Thyroid tumours represent 1-4% of canine tumours and 10-15% of those occurring in the neck.

Aetiology/clinical features (Wucherer and Wilke 2010)

• Boxers, beagles, golden retrievers and Siberian huskies predisposed
• Adenomas usually an incidental ultrasound or PM finding
• Carcinomas more common; usually large, solid, palpable and noticed by owners. Locally invasive and can
metastasize
o 2 types: 2/3rd are follicular cell thyroid carcinomas (FTC) and 1/3rd medullary thyroid carcinomas
(MTCS) which arise from parafollicular cells (C-cells). Immunohistochemistry differentiates.
• Most dogs with thyroid tumours are euthyroid or hypothyroid. Only 10% have functional tumours and
present with signs of hyperthyroidism
• Clinical signs – average age 10 years. Usually owner has noticed mass in ventral region of neck +/-
dyspnoea/cough (compression of airway) +/- signs of hyperthyroidism similar to cats (but rare in dogs).
• T4 usually normal/low.

Diagnosis
• Usually very vascular – biopsies can be difficult. FNA recommended initially - often contaminated with blood
but may confirm thyroid origin.
• Staging is important: Group I-IV based on tumour size, regional lymph node involvement and metastasis

WHO staging system for thyroid carcinoma

Primary tumour
T0 No evidence of tumour
T1 <2 cm
T2 2-5 cm
T3 >5 cm
Regional lymph nodes
N0 No evidence
N1 Ipsilateral regional involvement
N2 Contralateral regional involvement
Distant metastasis
M0 No evidence
M1 Distant metastasis detected
a: not fixed, b: fixed

T N M
I T1 a, b N0 M0
II T0 N1 M0
T1 a, b N1
T2 a, b N0, N1
III T3 Any N M0
IV Any T Any N M1

Treatment
• Depends on size, local invasion, functional status, and histological diagnosis of adenoma vs carcinoma.
Assume malignant until proven otherwise
• Surgical removal is treatment of choice if freely movable, ideally followed by chemotherapy or external beam
radiation therapy – seek specialist advice. MST > 3 years if no metastasis (Klein and others 1995)

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 • External beam radiation therapy associated with a 3-year progression free survival of 72% (Théon and others
2000)
• Little published information on radioactive iodine treatment in dogs. MST 28-30 months reported if no
metastasis. No current availability in the UK. (Turrel and others 2006)
• High levels (76-100%) of positive IHC staining for vascular epidermal growth factor (VEGF), moderate levels of
COX-2 (13% FTCs; 50% MTCs) and P-glycoprotein (7% FTCs; 70% MTCs) may mean these are a potential future
treatment target with tyrosine kinase and COX-2 inhibitors.(Campos and others 2014; London and others
2012)
• Discussion regarding role of levothyroxine therapy and TSH suppression (TSH <0.1 ng/ml) to prevent residual
neoplastic cell proliferation. Studies currently show no benefit, but randomised clinical studies are needed.

Prognosis
• Most dogs have large, invasive masses at time of diagnosis and even with aggressive treatment prognosis is
guarded to poor (6-24 months with aggressive treatment)
• 38% cases present with pulmonary metastases at the time of diagnosis
• Approximately 50% cases undergoing thyroidectomy have recurrence or metastatic disease within 2 years
• MTCs significantly less likely to be locally invasive
• Tumour features (e.g. size, local invasiveness, localisation) correlated with metastatic disease at diagnosis
• Vascular invasion is a negative prognostic indicator
• Prognosis excellent following surgical removal of adenomas, and overall considered good following removal of
small, well-circumscribed carcinomas.

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 Feline Hyperthyroidism

Summary
• Hyperthyroidism is the most common endocrine disease of cats
• It is frequently diagnosed in middle-aged and older cats
• Common clinical signs are polyphagia, weight loss, and a palpable goitre. Diagnosis is usually confirmed
with a high T4 level.
• Treatment can be undertaken with medical management (methimazole or carbimazole), surgery, diet or
radioactive iodine therapy.
• The prognosis for uncomplicated cases is excellent with good management.
• Care must be taken in patients with concurrent disorders (particularly chronic kidney disease or cardiac
disease).

Feline hyperthyroidism is the clinical syndrome which results from excessive circulating levels of the thyroid
hormones triiodothyronine (T3) and thyroxine (T4).

Aetiology
• 98-99% of cases are caused by benign adenomatous hyperplasia/adenoma of thyroid tissues. ≥ 70% of cases
are bilateral (involve both thyroid lobes)
• 1-2% of cases are caused by malignant thyroid adenocarcinoma

Epidemiology
• First diagnosed in the USA in 1979; now most common feline endocrine disease, with world-wide occurrence (with
geographical variation)
• Recognised with increasing frequency: Increased awareness of this disease, cats are living longer, and possibly the
disease is becoming more common.
• Cause unknown
o Resembles toxic nodular goitre seen in man
o Potential risk factors identified
§ Nutritional factors (iodine levels in the diet, presence of goitrogens)
§ Environmental factors (indoor cats higher risk, ? flea sprays, exposure to garden pesticides)
§ Genetic factors (Siamese and Himalayan cats 10 times less likely to be hyperthyroid, mutations
in TSH receptor identified)
§ Circulating factors (thyroid growth stimulating immunoglobulins)
§ Age
o Risk factors described (Crossley and others 2017; Kass and others 1999; Scarlett 1994; Scarlett and
others 1988)
§ Breed
§ Hair length - longhaired, non-purebred
§ Regular use of flea sprays or powders (3-4 fold increase in risk)
§ Indoor cats (4 fold increase in risk)
§ Reported exposure to lawn herbicides, fertilisers and pesticides (3-4 fold increase in risk)
§ Cats fed mainly canned food (3-4 fold increase in risk)(Wakeling and others 2009)

Clinical findings
The disease is seen in:
• Middle aged and elderly cats (4-22 years reported, mean 10-13 years)
• No sex predilection
• Signs vary from mild to severe depending on
o duration of hyperthyroidism (slowly progressive disease)

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 o presence of concurrent disease e.g. chronic kidney disease, cardiac disease

In general, thyroid hormones result in an increase the metabolic rate and, when given in physiological amounts, the
hormones are anabolic. When present in excess (hyperthyroidism), the effects are catabolic with the following
resulting in increased metabolic rate, cardiac output, heart rate, blood pressure, GI motility and CNS activity, and
reduced body weight and sleep.

These changes lead to the common clinical signs of feline hyperthyroidism:

Sign Approximate frequency (%)

Palpable thyroid nodule 90-100
• Bilateral 70%
Weight loss 90-100
Polyphagia 70-80
Hyperactivity 70-80
PUPD 70-80
Tachycardia 60-70
Heart murmur 50
Cardiomegaly 50
Diarrhoea 30-50
Vomiting 30-50
Skin/coat lesions 30-50

Approximately 20% of hyperthyroid cats have ectopic thyroid tissue, in these cases a goitre may not be palpable.
Likelihood of hyperthyroidism increases with increasing size of the thyroid gland (Boretti and others 2009).

As many cats are diagnosed with milder hyperthyroidism than previously they tend to present with fewer and less
severe clinical signs and physical examination findings. Therefore, many are detected through geriatric cat screening
schemes.

Cardiac abnormalities (murmur, gallop rhythm) are common on auscultation since secondary ventricular hypertrophy
is common. Evidence of hypertensive retinopathy may be evidence on retinal examination. Less frequently seen
clinical signs include lethargy, intermittent anorexia, voice changes, muscle weakness/tremors, congestive heart
failure, heat intolerance, mild pyrexia, and dyspnoea/tachypnoea.

Apathetic or masked hyperthyroidism occurs in a small number of cases with cats showing clinical signs including
depression, lethargy, weakness and inappetence. Frequently, these cats have cardiac abnormalities including
arrhythmias and congestive heart failure, or another significant co-morbidity.

Differential diagnoses
• Causes of weight loss: chronic kidney disease (also PUPD), diabetes mellitus (also PUPD, PP), GI disease (may
be polyphagic), neoplasia, FIV/FeLV

Screening tests
• As most hyperthyroid cats are older patients, the screening tests help identify concurrent disease and should
be performed in every case.
• Haematology – often mild erythrocytosis (increased RBC, PCV and Hb), microcytosis anecdotally common
• Biochemistry – mild-moderate increases in liver enzymes VERY common (ALT, ALP, AST); 90% have at least
one enzyme activity increased (usually ALT); may be evidence of concurrent disease (e.g. elevated urea,
creatinine and phosphate consistent with kidney disease)
• Urinalysis – may suggest concurrent disease e.g. sub-maximally concentrated urine with chronic kidney
disease; glycosuria with diabetes mellitus.

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 • Blood pressure measurement
• Approximately 18% of cases have a concurrent disease
o The two most common concurrent diseases in one study was alimentary lymphoma and chronic
enteropathy (Puig and others 2015)

Diagnosis

• Diagnosis of hyperthyroidism is suspected in cats with compatible history, clinical and physical findings
(especially if a palpable thyroid nodule is present).
• No test of thyroid function is perfect and clinical status impacts on interpretation of result.

• Confirmation of the diagnosis is important (not all thyroid nodules are “active”) and can be done in the majority
of cases by measuring resting total serum T4 concentration (TT4) (increased in 90-95% cases).
o If get a high result in an asymptomatic cat (i.e. measured on a general profile), although falsely high
values are rare, especially if no thyroid nodule is palpated re-testing is a sensible option
o Occasionally normal results are obtained in hyperthyroid cats (usually in upper 1/3 of reference
interval)
§ Levels may fluctuate (into the normal range) in early/mild disease (40%)
§ Severe non-thyroidal disease can depress T4 levels so that these are in the normal range
§ Drug effect e.g. clomipramine, phenobarbital
o If this occurs, repeat T4 after 1-2 weeks. If still normal at this point but you are concerned about
hyperthyroidism, consider:
§ Wait and retest in 2-3 months
§ Free T4 (fT4) - more sensitive but less specific (so more false positives and more expensive!)
§ TSH with T4 – very sensitive, not specific. 98% hyperthyroid cats have suppressed TSH; 69.9%
euthyroid cats have detectable TSH therefore if in reference interval hyperthyroidism is
unlikely. Never measure TSH alone. (Peterson and others 2015). 96% homology to cTSH
§ Thyroid scintigraphy (limited availability) is particularly useful in locating non-palpable thyroid
tissue and identifying metastases in adenocarcinoma cases. 99mTc (pertechnate) is given i/v.
A gamma camera is then used to compare quantity and ratio of uptake in thyroid: salivary
glands (equal in normal cats; increased in hyperthyroidism), thyroid to background ratio,
thyroid to heart ratio, percentage update of 99m-TC-pertechnetate and calculate tumour
volume. Considered the gold standard for diagnosis. Can be used to direct radioiodine
dosing.(Peterson and Broome 2015)
§ (T3 suppression test; TRH stimulation test – rarely done; refer to textbooks)
o Serum total T3 concentration is rarely useful as a sole screening test. Studies suggest that 1/3
hyperthyroid cats and up to 80% cats with mild disease have normal reference values. Falsely
increased levels can occur, although rare.
o Note that in-house T4 analysers are less reliable than those available at commercial laboratories

Approach to diagnosis of hyperthyroidism based on clinical signs

Overt hyperthyroidism (obvious compatible clinical signs)

• Serum total T4 concentration = screening test of choice
• Should not need to measure fT4; especially if increased TT4 and clinical signs.
• TSH concentration: decreased in hyperthyroid cats and helps support diagnosis but not usually needed
if high TT4.

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Common thyroid function test summary characteristics in overtly hyperthyroid cats

Test Sensitivity Specificity

Total T4 concentration 90-95% 90-95%
Total T3 concentration 60-65% 95-99%
Free T4 concentration 95-98% 75-85%
Serum TSH concentration 97-98% 60-70%

Mild/ Occult hyperthyroidism

• Definition = serum TT4 concentration in high-normal to slightly high range (>35- <75nmol/l; reference
interval 10-50) in a cat with only mild clinical signs of thyroid disease
• Overall lower test sensitivity compared to overtly hyperthyroid cats
• Measure total T4 first
o Lower sensitivity in mild cases (80 c.f. 90-95% in overt hyperthyroid cats)
o 20-40% cases of mild hyperthyroidism will have results within the reference interval
o Single normal value does not exclude hyperthyroidism
o In cases with mild clinical signs do not diagnose hyperthyroidism based on high-normal or
borderline high TT4 concentrations alone (false positives are possible)
• If normal total T4 and suspicious of hyperthyroidism measure free T4 concentration
o fT4 increased in >98% hyperthyroid cats (more sensitive)
o BEWARE: up to 20% sick (and some clinically normal) euthyroid cats may have false positives
o Do not definitively diagnose hyperthyroidism based on slightly high fT4 +/- borderline high
TT4; approx. 20-25% of these cats are actually euthyroid.
• If normal total T4 and slightly increased free T4 concentration measure TSH concentration
o Never use TSH concentrations alone
o TT4 in upper third reference interval (or borderline high) with high fT4 and suppressed TSH
concentration is consistent with a diagnosis of hyperthyroidism
o Measurable TSH concentration makes hyperthyroidism less likely. In this case monitor for
development of clinical signs, thyroid nodule tec.
• Consider thyroid scintigraphy (gold standard)
o High sensitivity >95% helps confirm hyperthyroidism
o 99-100% specificity

Common thyroid function test summary characteristics in mildly hyperthyroid cats

Test Sensitivity Specificity

Total T4 concentration 60-85% 90-95%
Total T3 concentration 15-25% 95-99%
Free T4 concentration 85-90% 75-85%
Serum TSH concentration 90-95% 60-70%

Other challenging cases

o “SHIM-RAD”
§ Severe Hyperthyroid (T4 >300nmol/l)
§ Intrathoracic tumour nodule
§ Multifocal disease (multiple nodules)
§ Refractory to Antithyroid Drugs on presentation (may have worked earlier)
§ Above characteristics mean they are often suspected to be thyroid carcinomas. But they are
a specific subgroup that overlap with large chronic adenomas.
§ Affected cats are more likely to be chronically hyperthyroid.

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 o Thyroid cysts
§ Often a palpable large neck mass in cats with chronic hyperthyroidism.
§ Clinical signs (CS) vary from none to those of a space occupying lesion including dysphagia,
dyspnea and cough.
§ Percutaneous cyst drainage relieves some of the CS for a short time as refilling is common.
The fluid is typically serosanguineous in nature (due to possible small bleeds) and fluid TT4
concentration is increased but is not associated with serum concentrations.
§ Histology is essential as equal chance of being an adenoma or carcinoma.
§ Management: thyroid cysts needed higher doses of radioactive iodine (RAI), with a reported
lower response with refilling occurring. Cystectomy is recommended after RAI.

Treatment options
1. Treatment of hyperthyroidism
o Treatment of choice varies for each individual case since all treatments carry some disadvantages.
An owner information sheet is an invaluable resource.
o Four main choices
§ Medical management – Anti-thyroid drugs
§ Diet – Low iodine (Hills y/d)
§ Surgical management - Thyroidectomy
§ Radioactive iodine
o Wherever possible, patients should be managed with medical management initially in order to
§ Assess renal function when the patient is euthyroid, before undertaking irreversible
treatment.
§ Stabilise the patient prior to anaesthesia is surgery is planned

2. Treatment of complications of hyperthyroidism

o Cardiovascular complications
§ Congestive heart failure e.g. furosemide 2 mg/kg twice daily
§ Tachycardia – e.g. propranolol at 2.5-5.0 mg/cat every 8 hours can be considered
§ Hypertension – range of therapies available. e.g. amlodipine at 0.625mg once or twice daily,
benazepril at 0.25mg/kg once daily
o Age, proteinuria and hypertension decrease overall survival

Anti-thyroid drugs
Suggested reading: 2016 AAFP Guidelines for management (Carney and others 2016)and JSAP 2014 Consensus on
Pharmacologic therapy (Daminet and others 2014)

§ Methimazole (Felimazole©, Dechra – 1.25, 2.5 & 5 mg tablets; Thiafeline©, Animalcare – 2.5 and 5mg
tablets; Thyronorm© – liquid formulation 5mg/ml, Norbrook) and slow-release carbimazole (Vidalta©,
Intervet – 10 & 15 mg tablets). Methimazole also available as unlicensed transdermal formulation.
o Carbimazole is rapidly metabolised to methimazole after administration
o Methimazole blocks synthesis of T4 and T3 within the thyroid (inhibits thyroid peroxidase enzyme)
o Dose
§ Methimazole 2.5 mg every 12 initially
§ Carbimazole 10-15 mg sid initially
§ For both, the T4 should be reassessed 10 – 14 days after starting treatment and the dose
adjusted accordingly
o Normally euthyroid in less than 2 weeks
o Important to monitor T4 (dose to effect) and haematology and biochemistry in the first 3 months of
treatment (see side effects below)

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 o Determination of the T4 concentration not more than 4–6 hours after the last dose of methimazole
has been recommended
o Goal = total T4 in low-normal range (but >20nmol/l)
o Long-term or short-term treatment (stabilisation) possible. Long-term treatment more appropriate
for older cats or those with concurrent disease and for owners that decline surgery or radioactive
iodine.
§ Advantages of methimazole and carbimazole therapy
o Readily available
o Rapidly effective
o Inexpensive
o Practical – no skill (apart from cat-pilling!) or special licences required
o No anaesthetic/hospitalisation required
§ Disadvantages of methimazole and carbimazole therapy
o Needed for the rest of the cat’s life (not a curative treatment)
o Some cats need increasingly high doses/become refractory to treatment
o Poorer long-term control compared to radioactive iodine
o Risk of continued tumour growth and/or conversion of benign adenoma to malignancy(Peterson and
others 2016)
o Does not treat underlying cause
o Poor long-term owner compliance
o Side effects (usually seen within first 3-6 weeks)
§ Minor, common (10-20%), transient side effects include vomiting, anorexia, and lethargy,
minor haematological abnormalities-often do not require drug withdrawal.
§ Major, rare (1-5%) side effects include persistent gastrointestinal signs, thrombocytopenia
and bleeding, leucopenia, granulocytopenia, dermatitis causing self-induced excoriation
(especially face) and hepatopathy. Very rare – myasthenia gravis; lymphoid hyperplasia. If
seen, these require cessation of treatment.
o Prognosis
§ Methimazole MST = 2 years (Milner and others 2006)
Diet
• Hill’s y/d is a very low iodine diet (<0.3ppm) which may be a useful choice for cats that are difficult to
medicate and for whom surgery/RAI is not an option
• Iodine is essential for thyroid hormone synthesis; therefore, restriction leads to reduced thyroid hormone
production by the thyroid gland
• It should be fed as an only diet source and it may be necessary to ensure that iodine levels in drinking water
are low.
• Implications of long term restriction not yet clear.
• Used most where cat is not a candidate for definitive treatment, significant non-thyroidal illness is present,
unable to administer medication, financial constraints. (Hui and others 2015)
• Re-check TT4 after 4-8 weeks
o If not euthyroid: investigate other iodine sources (e.g. water, human food, supplements)

• Advantages:
o No need to medicate
o Can be used in cats with significant concurrent disease for which curative treatments are not an
option
o Use in cats that have suffered side effects from methimazole/carbimazole
• Disadvantages:
o Does not cure disease
o Should be fed as sole food with no treats to be most effective
o Lifelong treatment required
o Long-term consequences unknown – especially normal healthy cats in same environment

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 o High CHO/low protein diet – not great choice if significant muscle wasting

Surgical management (Naan and others 2006)

§ A number of techniques described
o Modified extra-capsular best in terms of risk of post-operative hypoparathyroidism (see later) and
risk of recurrence of hyperthyroidism
§ Pre-operative stabilisation with carbimazole or methimazole recommended
§ Unilateral or bilateral thyroidectomy? – decision taken at time of surgery
§ Advantages
o Curative (removes abnormal tissue)
o Simple
o Rapidly effective
o Short hospitalisation period (3-5 days)
§ Disadvantages
o Requires general anaesthesia which may be a problem in some cases (presence of cardiac or renal
disease)
o Technically more difficult than medical treatment
o Only possible if thyroid nodule is accessible to surgical removal (most cases); the presence of any
undetected ectopic tissue will lead to failure to achieve a cure.
o Can be expensive
o Complications associated with surgery
§ Damage to or removal of parathyroid tissue
(post-operative hypoparathyroidism – see below)
§ Damage to the recurrent laryngeal nerve – uncommon; often detected as voice change
(laryngeal paralysis)
§ Damage to the sympathetic trunk – uncommon
(Horner’s syndrome)
§ Hypothyroidism – often transient in unilateral thyroidectomy (lasting 2-3 months);
permanent following bilateral thyroidectomy and life-long supplementation is
recommended
§ Possible recurrence of disease (especially if unilateral surgery performed)

Post-operative hypoparathyroidism
§ Results from damage to or removal of the parathyroid glands – most commonly seen when surgery has been
bilateral (only need one functional parathyroid gland to maintain calcium concentrations)
§ Usually a transient problem with recovery of the glands or functional ectopic tissue restoring function. May
take weeks or months to recover.
§ Signs usually evident within 2 to 3 days
o Clinical signs: inappetence, weakness, tremors, ptyalism, hyperaesthesia (e.g. face rubbing, chewing
paws), progressing to tetany, seizures, coma and death.
o Monitor serum calcium once/twice daily post-op if bilateral surgery or concerned
o If calcium 1.6-1.9mmol/l treatment is often not required
§ Therapy – see table on next page for advice on when this is needed
o Intravenous 10% calcium gluconate, 1.0 – 1.5 ml/kg given slowly (10-20 mins) to effect, monitor for
bradycardia
o Followed by constant rate intravenous infusion (2.5-3.75mg/kg/h of calcium)
§ avoid bicarbonate, lactate or phosphate containing fluids à precipitate calcium
§ 10% calcium gluconate contains 9.3mg calcium per ml
§ Add the following to 1 litre 0.9% NaCl and give at 60ml/kg/day
• 40ml 10% calcium gluconate à 1mg/kg/h
• 80ml 10% calcium gluconate à 2mg/kg/h
• 120ml 10% calcium gluconate à 3mg/kg/h

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 o Subcutaneous 10% calcium gluconate diluted 1:1 in 0.9% saline may be given in mild or subclinical
cases (beware skin sloughs with repeated s/c; so, this is not recommended)
o Monitor calcium levels and adjust regime accordingly
o Institute oral regime as soon as possible (takes >24-96h to work)
§ Calcium: 50 –100 mg/kg/day elemental calcium in divided doses, wean off the intravenous
drip.
(e.g. Calcium carbonate contains 40% elemental calcium so a 4kg cat could be dosed with
one 650mg tablet per day as this provides 260mg of elemental Calcium)
• Vitamin D:
0.03 – 0.06µg/kg/day. Active calcitriol e.g. Rocaltrol, Roche (0.25µg capsules) or partially
active form e.g. One-Alpha, Leo Pharmaceuticals (suspension). The latter is easier to dose
accurately. These are rapidly effective and once the cat is eating, blood calcium levels can
usually be maintained by only supplementing with oral Vitamin D.

The dose of Vitamin D should be titrated to the lowest effective dose aiming for blood calcium levels in the low-
normal range (around 2.0 mmol/l) and the cat should be gradually weaned off therapy by reducing the daily dose or
dosage frequency. Several months of supplementation is often required.

Total Blood Calcium Interpretation Action Required

1.8-2.0 mmol/l • Mild hypocalcaemia • Monitor calcium twice daily

• Relatively common
• Usually no clinical signs
1.5-1.8 mmol/l • Moderate hypocalcaemia
• May need treatment
< 1.5 mmol/l • Severe hypocalcaemia
• Requires treatment
• Usually requires no treatment
• If no clinical signs, can either monitor closely or treat
prophylactically with subcutaneous and oral calcium
and vitamin D
• Cats showing severe clinical signs (seizures, coma)
require immediate treatment with intravenous calcium
• Subsequent oral calcium and vitamin D therapy is
required

Radioactive iodine treatment (131I)

§ Radioactive iodine given s/c (usually with the cat lightly sedated) is concentrated in the thyroid tissue where
it irradiates and destroys functioning thyroid cells
§ Goal is to administer an appropriate dose that will restore euthyroidism whilst avoiding hypothyroidism
§ Dose chosen dependent on: severity of clinical signs, size of goitre and serum total T4 concentration
§ Prognosis: MST 2-4 years
§ Advantages
o Simple procedure
o Curative
o Targets predominantly abnormal thyroid tissue – treats the cause
o No anaesthetic required
o No risk hypoparathyroidism (c.f. surgery)
o No need for daily oral administration of drugs
o Usually only one treatment required
o Variable dosing possible in some centres (individualised treatment)
o Adverse reactions extremely rare
o Recurrence of hyperthyroidism extremely rare
o Only treatment that is effective for thyroid adenocarcinomas
(but much higher dose required)
§ Disadvantages
o Limited availability (usually waiting list for treatment) – post-treatment facilities imp.

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 o Expensive – largely due to long hospitalisation period required by Radiation Safety/Environmental
Health Authorities (7-14 days)
o May take several weeks or months for cats to become euthyroid
o Very occasional permanent iatrogenic hypothyroidism (diagnosis based on clinical signs, low serum
total T4, free T4 concentrations and high canine TSH concentrations-currently a feline TSH assay is not
available).

Treatment of asymptomatic cats with no thyroid nodule and only high serum fT4 and/or low TSH concentration may
not be appropriate and regular monitoring is recommended (every 3-6 months).

Chronic medical management

• Possible contributor to more severe disease that is more challenging to then treat later in the disease
progression (e.g. larger goitres, more intra-thoracic tissue, advanced concurrent disease making curative
options higher risk, poor response to increasing medical management).

Hyperthyroidism, pre-existing azotaemia and chronic kidney disease (CKD) (Vaske and others 2016)
• Hyperthyroidism increases the renal glomerular filtration rate (GFR) via increasing cardiac output and causing
intra-renal vasodilation. This may mask pre-existing CKD by decreasing urea and creatinine concentrations
• Treatment of hyperthyroidism results in a significant fall (normalisation) in GFR which may unmask existing CKD
• CKD can be difficult to diagnose in the hyperthyroid cat
o erythrocytosis seen in hyperthyroidism may mask anaemia seen in some CKD cases
o hyperthyroid cats are often thin and therefore have less muscle mass than normal cats. This means
that their creatinine levels are often lower than expected which may make diagnosis of renal disease
difficult.
o Cats with USG >1.035 can still have underlying renal dysfunction develop post-treatment (Riensche
and others 2008)
o SDMA can be helpful (Peterson and others 2018).
o Cats with pre-existing azotaemia have a less favourable prognosis. In such cases, median survival
times reported are approximately 6 months (Syme 2007)(Peterson, 2013).
o In cases with confirmed CKD lower starting doses of medical management are advised (e.g. 1.25mg
methimazole SID)
o Failing to treat hyperthyroidism or achieve euthyroidism can contribute to progression of renal
dysfunction (Van Hoek and others 2009)

Post-treatment development of azotaemia

• All hyperthyroid cats should be carefully assessed before treatment is started and following starting medical
management
o CKD/borderline cases should be treated medically and monitored carefully for clinical and
biochemical evidence of a worsening in renal function (approx. every 2 weeks); unmasking of mild
azotaemia (IRIS 2 and 3) may not preclude irreversible treatment options
o Up to 20-25% cases with unknown CKD develop azotaemia following treatment
o Most cats are unlikely to increase by more than 1 IRIS stage following treatment
o No major predictive factors for which cats will develop azotaemia post-treatment; but some
suggestion of higher risk with isosthenuric urine pre-treatment
o If treatment and euthyroidism precipitates a significant clinical deterioration (e.g. fragile stage 3 or
stage 4 IRIS CKD case), medical treatment can be reduced to levels where the cat remains stable or
stopped if necessary.
o Therapy for concurrent cardiovascular disease (e.g. antihypertensive treatment) should also be
monitored carefully in view of the potential for adverse effects via reduction of renal blood flow
o If the renal disease remains stable, then consider more curative therapies such as radioactive iodine
or surgery

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 o Good control of hyperthyroidism may be beneficial in the long term in slowing progression of renal
disease (through combating glomerular hypertension, hyperfiltration and development of
glomerulosclerosis)
• Post-radioactive iodine treatment
o Renal function will stabilise within one month of 131I and therefore should be assessed at this point
o Development of mild azotaemia does not affect survival

Iatrogenic hypothyroidism and renal function

• Iatrogenic hypothyroidism appears to contribute to the development of azotaemia after treatment of
hyperthyroidism, and reduced survival time in azotaemic cats
• Iatrogenic hypothyroidism is diagnosed by measurement of low total and free T4 and increased TSH
concentration in azotaemic cats and prevents misdiagnosis as non-thyroidal illness (Peterson and others 2017)
• Hypothyroid cats that developed azotaemia within 6 months post-treatment had significantly shorter survival
times (median survival time 456 days, range 231-1589 days) than those that remained nonazotemic (median
survival time 905 days, range 316-1869 days). (Williams and others 2010)
• Cats with hypothyroidism and post-irreversible treatment azotaemia (post-thyroidectomy or 131I) require
immediate treatment with thyroxine supplementation
• Normalisation of thyroid hormones should restore GFR and improve renal function/azotaemia (Williams and
others 2014).

Choice of therapy for hyperthyroidism

The choice of therapy will be affected by the cat and owner’s individual circumstances.

Prognosis
• Largely dependent on
o Severity/duration of hyperthyroidism
o Severity of complications associated with hyperthyroidism (cardiovascular disease in particular)
o Presence and nature of concurrent disease
• Uncomplicated hyperthyroid cats have an excellent prognosis following curative treatment
• Iatrogenic hypothyroidism appears to contribute to the development of azotaemia after treatment of
hyperthyroidism, and reduced survival time in azotaemic cats. Therefore, thyroid supplementation in this group
of cats is recommended.

Early Late/chronic
Mild hyperthyroidism Severe hyperthyroidism
Lower TT4 Higher TT4
Fewer and subtle CS More obvious clinical signs
(mild weight loss/polyphagia only CS?)
Often incidental finding (24%) Older?
Younger? ↑ tumour volume (large goitre?)
Multifocal ( >3nodules), intra-thoracic
> Bilateral
Often received long-term medical management
Refractory to medical treatment
Carcinoma -malignant transformation?

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 References

BORETTI, F. S., SIEBER-RUCKSTUHL, N. S., GERBER, B., LALUHA, P., BAUMGARTNER, C., LUTZ, H.,
HOFMANN-LEHMANN, R. & REUSCH, C. E. (2009) Thyroid enlargement and its relationship to
clinicopathological parameters and T4 status in suspected hyperthyroid cats. Journal of feline medicine and
surgery 11, 286-292
BOSSENS, K., DAMINET, S., DUCHATEAU, L., RICK, M., VAN HAM, L. & BHATTI, S. (2016) The effect of
imepitoin, a recently developed antiepileptic drug, on thyroid parameters and fat metabolism in healthy
Beagle dogs. Vet J 213, 48-52
CAMPOS, M., DUCATELLE, R., RUTTEMAN, G., KOOISTRA, H. S., DUCHATEAU, L., DE ROOSTER, H.,
PEREMANS, K. & DAMINET, S. (2014) Clinical, pathologic, and immunohistochemical prognostic factors in
dogs with thyroid carcinoma. J Vet Intern Med 28, 1805-1813
CARNEY, H. C., WARD, C. R., BAILEY, S. J., BRUYETTE, D., DENNIS, S., FERGUSON, D., HINC, A. & RUCINSKY,
A. R. (2016) 2016 AAFP Guidelines for the management of feline hyperthyroidism. Journal of feline
medicine and surgery 18, 400-416
DAMINET, S., CROUBELS, S., DUCHATEAU, L., DEBUNNE, A., VAN GEFFEN, C., HOYBERGS, Y., VAN BREE, H. &
DE RICK, A. (2003) Influence of acetylsalicylic acid and ketoprofen on canine thyroid function tests. Vet J
166, 224-232
DAMINET, S. & FERGUSON, D. C. (2003) Influence of drugs on thyroid function in dogs. J Vet Intern Med
17, 463-472
DAMINET, S., FIFLE, L., PARADIS, M., DUCHATEAU, L. & MOREAU, M. (2007) Use of recombinant human
thyroid-stimulating hormone for thyrotropin stimulation test in healthy, hypothyroid and euthyroid sick
dogs. Can Vet J 48, 1273-1279
DAMINET, S., KOOISTRA, H., FRACASSI, F., GRAHAM, P., HIBBERT, A., LLORET, A., MOONEY, C., NEIGER, R.,
ROSENBERG, D. & SYME, H. (2014) Best practice for the pharmacological management of hyperthyroid
cats with antithyroid drugs. Journal of Small Animal Practice 55, 4-13
DIJL, I., LE TRAON, G., MEULENGRAAF, B., BURGAUD, S., HORSPOOL, L. & KOOISTRA, H. (2014)
Pharmacokinetics of total thyroxine after repeated oral administration of levothyroxine solution and its
clinical efficacy in hypothyroid dogs. Journal of veterinary internal medicine 28, 1229-1234
DIXON, R. M., GRAHAM, P. A. & MOONEY, C. T. (1996) Serum thyrotropin concentrations: a new diagnostic
test for canine hypothyroidism. Vet Rec 138, 594-595
DIXON, R. M. & MOONEY, C. T. (1999a) Canine serum thyroglobulin autoantibodies in health,
hypothyroidism and non-thyroidal illness. Research in Veterinary Science 66, 243-246
DIXON, R. M. & MOONEY, C. T. (1999b) Evaluation of serum free thyroxine and thyrotropin concentrations
in the diagnosis of canine hypothyroidism. J Small Anim Pract 40, 72-78
DIXON, R. M., REID, S. W. & MOONEY, C. T. (1999) Epidemiological, clinical, haematological and
biochemical characteristics of canine hypothyroidism. Vet Rec 145, 481-487
DIXON, R. M., REID, S. W. & MOONEY, C. T. (2002) Treatment and therapeutic monitoring of canine
hypothyroidism. J Small Anim Pract 43, 334-340
HEGSTAD-DAVIES, R. L., TORRES, S. M., SHARKEY, L. C., GRESCH, S. C., MUNOZ-ZANZI, C. A. & DAVIES, P. R.
(2015) Breed-specific reference intervals for assessing thyroid function in seven dog breeds. J Vet Diagn
Invest 27, 716-727
HUI, T., BRUYETTE, D., MOORE, G. & SCOTT-MONCRIEFF, J. (2015) Effect of feeding an iodine-restricted
diet in cats with spontaneous hyperthyroidism. Journal of veterinary internal medicine 29, 1063-1068
KASS, P. H., PETERSON, M. E., LEVY, J., JAMES, K., BECKER, D. V. & COWGILL, L. D. (1999) Evaluation of
environmental, nutritional, and host factors in cats with hyperthyroidism. J Vet Intern Med 13, 323-329
KENNEDY, L. J., QUARMBY, S., HAPP, G. M., BARNES, A., RAMSEY, I. K., DIXON, R. M., CATCHPOLE, B.,
RUSBRIDGE, C., GRAHAM, P. A., HILLBERTZ, N. S., ROETHEL, C., DODDS, W. J., CARMICHAEL, N. G. &

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OLLIER, W. E. (2006) Association of canine hypothyroidism with a common major histocompatibility
complex DLA class II allele. Tissue Antigens 68, 82-86
KLEIN, M. K., POWERS, B. E., WITHROW, S. J., CURTIS, C. R., STRAW, R. C., OGILVIE, G. K., DICKINSON, K. L.,
COOPER, M. F. & BAIER, M. (1995) Treatment of thyroid carcinoma in dogs by surgical resection alone: 20
cases (1981-1989). J Am Vet Med Assoc 206, 1007-1009
KOOISTRA, H. S., DIAZ-ESPINEIRA, M., MOL, J. A., VAN DEN BROM, W. E. & RIJNBERK, A. (2000) Secretion
pattern of thyroid-stimulating hormone in dogs during euthyroidism and hypothyroidism. Domest Anim
Endocrinol 18, 19-29
LE TRAON, G., BRENNAN, S., BURGAUD, S., DAMINET, S., GOMMEREN, K., HORSPOOL, L., ROSENBERG, D. &
MOONEY, C. (2009) Clinical evaluation of a novel liquid formulation of l-thyroxine for once daily treatment
of dogs with hypothyroidism. Journal of veterinary internal medicine 23, 43-49
LONDON, C., MATHIE, T., STINGLE, N., CLIFFORD, C., HANEY, S., KLEIN, M. K., BEAVER, L., VICKERY, K., VAIL,
D. M. & HERSHEY, B. (2012) Preliminary evidence for biologic activity of toceranib phosphate (Palladia®) in
solid tumours. Veterinary and comparative oncology 10, 194-205
MILNER, R. J., CHANNELL, C. D., LEVY, J. K. & SCHAER, M. (2006) Survival times for cats with
hyperthyroidism treated with iodine 131, methimazole, or both: 167 cases (1996–2003). Journal of the
American Veterinary Medical Association 228, 559-563
NAAN, E. C., KIRPENSTEIJN, J., KOOISTRA, H. S. & PEETERS, M. E. (2006) Results of thyroidectomy in 101
cats with hyperthyroidism. Veterinary Surgery 35, 287-293
PETERSON, M., GUTERL, J., NICHOLS, R. & RISHNIW, M. (2015) Evaluation of serum thyroid-stimulating
hormone concentration as a diagnostic test for hyperthyroidism in cats. Journal of veterinary internal
medicine 29, 1327-1334
PETERSON, M., NICHOLS, R. & RISHNIW, M. (2017) Serum thyroxine and thyroid-stimulating hormone
concentration in hyperthyroid cats that develop azotaemia after radioiodine therapy. Journal of Small
Animal Practice 58, 519-530
PETERSON, M., VARELA, F., RISHNIW, M. & POLZIN, D. (2018) Evaluation of Serum Symmetric
Dimethylarginine Concentration as a Marker for Masked Chronic Kidney Disease in Cats With
Hyperthyroidism. Journal of veterinary internal medicine 32, 295-304
PETERSON, M. E. & BROOME, M. R. (2015) Thyroid scintigraphy findings in 2096 cats with
hyperthyroidism. Veterinary Radiology & Ultrasound 56, 84-95
PETERSON, M. E., BROOME, M. R. & RISHNIW, M. (2016) Prevalence and degree of thyroid pathology in
hyperthyroid cats increases with disease duration: a cross-sectional analysis of 2096 cats referred for
radioiodine therapy. Journal of feline medicine and surgery 18, 92-103
PINILLA, M., SHIEL, R. E., BRENNAN, S. F., MCALLISTER, H. & MOONEY, C. T. (2009) Quantitative thyroid
scintigraphy in greyhounds suspected of primary hypothyroidism. Vet Radiol Ultrasound 50, 224-229
PUIG, J., CATTIN, I. & SETH, M. (2015) Concurrent diseases in hyperthyroid cats undergoing assessment
prior to radioiodine treatment. Journal of feline medicine and surgery 17, 537-542
RIENSCHE, M. R., GRAVES, T. K. & SCHAEFFER, D. J. (2008) An investigation of predictors of renal
insufficiency following treatment of hyperthyroidism in cats. Journal of feline medicine and surgery 10,
160-166
SCARLETT, J. M. (1994) Epidemiology of thyroid diseases of dogs and cats. Veterinary Clinics of North
America: Small Animal Practice 24, 477-486
SCARLETT, J. M., MOISE, N. S. & RAYL, J. (1988) Feline hyperthyroidism: A descriptive and case-control
study. Preventive Veterinary Medicine 6, 295-309
SYME, H. M. (2007) Cardiovascular and renal manifestations of hyperthyroidism. Veterinary Clinics: Small
Animal Practice 37, 723-743

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THÉON, A. P., MARKS, S. L., FELDMAN, E. S. & GRIFFEY, S. (2000) Prognostic factors and patterns of
treatment failure in dogs with unresectable differentiated thyroid carcinomas treated with megavoltage
irradiation. Journal of the American Veterinary Medical Association 216, 1775-1779
TURREL, J. M., MCENTEE, M. C., BURKE, B. P. & PAGE, R. L. (2006) Sodium iodide I 131 treatment of dogs
with nonresectable thyroid tumors: 39 cases (1990-2003). J Am Vet Med Assoc 229, 542-548
VAN GEFFEN, C., BAVEGEMS, V., DUCHATEAU, L., DE ROOVER, K. & DAMINET, S. (2006) Serum thyroid
hormone concentrations and thyroglobulin autoantibodies in trained and non-trained healthy whippets.
Vet J 172, 135-140
VAN HOEK, I., MEYER, E., DUCHATEAU, L., PEREMANS, K., SMETS, P. & DAMINET, S. (2009) Retinol-binding
protein in serum and urine of hyperthyroid cats before and after treatment with radioiodine. Journal of
veterinary internal medicine 23, 1031-1037
VASKE, H. H., SCHERMERHORN, T. & GRAUER, G. F. (2016) Effects of feline hyperthyroidism on kidney
function: a review. Journal of feline medicine and surgery 18, 55-59
VOORBIJ, A. M., LEEGWATER, P. A., BUIJTELS, J. J., DAMINET, S. & KOOISTRA, H. S. (2016) Central
Hypothyroidism in Miniature Schnauzers. J Vet Intern Med 30, 85-91
WAKELING, J., EVERARD, A., BRODBELT, D., ELLIOTT, J. & SYME, H. (2009) Risk factors for feline
hyperthyroidism in the UK. Journal of Small Animal Practice 50, 406-414
WILLIAMS, T., ELLIOTT, J. & SYME, H. (2010) Association of iatrogenic hypothyroidism with azotemia and
reduced survival time in cats treated for hyperthyroidism. Journal of veterinary internal medicine 24, 1086-
1092
WILLIAMS, T., ELLIOTT, J. & SYME, H. (2014) Effect on renal function of restoration of euthyroidism in
hyperthyroid cats with iatrogenic hypothyroidism. Journal of veterinary internal medicine 28, 1251-1255
WUCHERER, K. L. & WILKE, V. (2010) Thyroid cancer in dogs: an update based on 638 cases (1995-2005).
Journal of the American Animal Hospital Association 46, 249-254

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