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New Zealand Veterinary Journal
ISSN: 0048-0169 (Print) 1176-0710 (Online) Journal homepage: http://www.tandfonline.com/loi/tnzv20
Congenital hypothyroidism of dogs and cats: A
review
K Bojanić , E Acke & BR Jones
To cite this article: K Bojanić , E Acke & BR Jones (2011) Congenital hypothyroidism
of dogs and cats: A review, New Zealand Veterinary Journal, 59:3, 115-122, DOI:
10.1080/00480169.2011.567964
To link to this article: http://dx.doi.org/10.1080/00480169.2011.567964
Published online: 03 May 2011.
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Date: 22 October 2015, At: 21:55
New Zealand Veterinary Journal 59(3), 115–122, 2011
115
Review Article
Congenital hypothyroidism of dogs and cats: A review
K Bojanić*x, E Acke{ and BR Jones{
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Abstract
Congenital hypothyroidism is a rare and underdiagnosed
congenital endocrine disorder in dogs and cats and the true
incidence is unknown. The disorder may cause a range of
clinical signs depending on the primary defect, which affect
production of thyroid hormones; some cases present when
adult. Hallmark clinical signs of congenital hypothyroidism are
mental impairment and skeletal developmental abnormalities,
resulting in disproportionate dwarfism; goitre may or may not
be present. Documented causes of congenital hypothyroidism
in dogs include deficiency of, or unresponsiveness to,
thyrotropin-releasing hormone (TRH) or thyroid-stimulating
hormone (TSH), thyroid dysgenesis, dyshormonogenesis and
iodine deficiency. In cats, TSH unresponsiveness, thyroid
dysgenesis, dyshormonogenesis and iodine deficiency have been
confirmed. Adequate replacement therapy results in a successful
outcome in the majority of cases, especially when started early
in life, as permanent developmental abnormalities can be
prevented. This review describes reported cases in dogs and
cats, diagnostic investigation, and recommendations for
treatment.
KEY WORDS: Thyroid, congenital, dog, cat, dyshormonogenesis,
hypothyroidism, dwarfism, goitre, thyroxine, TRH, TSH
Introduction
Congenital hypothyroidism is rare in dogs and cats, with only a
small number of published papers describing different aetiologies
of hypothyroidism, whereas in humans it is common affecting
approximately 1 in 4,000 infants (LaFranchi 2007). Milne and
Hayes (1981) reported only 3.6% of cases of hypothyroidism
occurred in dogs 51 year of age, presumably resulting from a
congenital disorder of thyroid function. In the cat, the congenital
form is more common than the acquired form although both are
extremely rare (Feldman and Nelson 2004). However, the true
incidence of congenital hypothyroidism is unknown as a
proportion of cases are not diagnosed or die at birth or when
juvenile, without the cause of death being established.
Congenital hypothyroidism may be sporadic or inherited in some
breeds; in recent reports the use of molecular genetic analysis has
established the exact cause of congenital hypothyroidism, which
* Veterinary Clinic Fiziovet, Zvonimirova 72, 10000 Zagreb, Croatia.
{
Institute of Veterinary, Animal and Biomedical Sciences, Massey University,
Private Bag 11222, Palmerston North 4442, New Zealand.
x
Author for correspondence. Email: [email protected].
has led to the development of molecular diagnostic tests to screen
for carriers in certain breeds. Development of the Thyroidstimulating hormone (TSH) immunoassay has also helped in
localising the defect along the hypothalamic-pituitary-thyroid
(HPT) axis. Cases of central congenital hypothyroidism reported
before the availability of a species-specific TSH assay and without
histopathology of the hypothalamus and adenohypophysis must
be considered putative. In many reported cases of congenital
hypothyroidism the authors were unsuccessful in documenting
the exact nature of the defect.
This review aims to synthesise information from reported cases of
congenital hypothyroidism and provides new information from
cases published since the TSH assay has been available. In the
present paper we describe the use of measurement of concentrations of TSH, and discuss the absence of such assays on the
diagnosis of congenital hypothyroidism in earlier case reports.
Aetiology
Hypothyroidism is the result of decreased production of
thyroxine (T4) and triiodothyronine (T3) by the thyroid gland
(Scott-Moncrieff and Guptill-Yoran 2005). Decreased production may be due to a defect anywhere along the HPT axis, or
from a defect in the thyroid hormone receptors (LaFranchi
2007). Although many of the causes of congenital hypothyroidism described in humans have not been indentified in dogs and
cats, the aetiological classification used in humans can be applied
to veterinary medicine (Table 1). According to the site of the
defect along the HPT axis, hypothyroidism can be classified as
primary (thyroid), secondary (pituitary) or tertiary (hypothalamus). Central hypothyroidism denotes a defect that is not fully
differentiated, but occurs either at the level of the hypothalamus
or the pituitary gland.
Primary congenital hypothyroidism
In humans, primary congenital hypothyroidism is caused by
thyroid dysgenesis, dyshormonogenesis, defects in the transport
of thyroid hormones, TSH receptor-blocking antibodies, maternal medications, or a deficiency (endemic goitre) or excess of
iodine (LaFranchi 2007).
ACTH
HPT
IGF-1
T3
T4
TRH
TSH
Adrenocorticotropic hormone
Hypothalamic-pituitary-thyroid
Insulin-like growth factor-1
Triiodothyronine
Thyroxine
Thyrotropin-releasing hormone
Thyroid-stimulating hormone
116
New Zealand Veterinary Journal 59(3), 2011
Bojanić et al.
Table 1. Aetiological classification of congenital hypothyroidism in humans (LaFranchi 2007), and reported cases in dogs and cats.
Classification
Occurrence
Reference(s)
Central hypothyroidism
Mutations of genes encoding PIT-1a and PROP-1a
Not reported in dogs and cats
Thyrotropin-releasing hormone (TRH) deficiency
Not reported in cats, possible in a dog
TRH unresponsiveness (mutation of TRH receptor)
Mooney and Anderson (1993)
Not reported in dogs and cats
Thyroid-stimulating hormone (TSH) deficiency/defect
Reported in dogs
Medleau et al. (1985); Greco et al. (1991);
Mooney and Anderson (1993)
Multiple pituitary deficiencies
Pituitary dwarfism in German Shepherd dogs
Kooistra et al. (2000)
Possible defect in a dog and a cat
Robinson et al. (1988); Tanase et al. (1991)
Reported in dogs and cats
Greco et al. (1985); Robinson et al. (1988);
TSH unresponsiveness (mutation of TSH receptor)
Primary hypothyroidism
Defects of development of the thyroid gland (dysgenesis)
Tanase et al. (1991); Traas et al. (2008)
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Defects of thyroid hormone synthesis (transport of iodide,
Reported in dogs and cats
Chastain et al. (1983); Arnold et al. (1984);
thyroglobulin synthesis, thyroid peroxidase/oxidase
Sjollema et al. (1991); Jones et al. (1992);
activity, de-iodination process)
Fyfe et al. (2003); Pettigrew et al. (2007);
Quante et al. (2010)
Defects of receptors and protein transporters of thyroid
Not reported in dogs and cats
hormones
Iodine deficiency or excess
Reported in dogs and cats
Maternal antibodies
Not reported in dogs and cats
Maternal medications
Not reported in dogs and cats
a
PIT-1, PROP-1 (prophet of PIT-1)¼pituitary transcription factors
Thyroid dysgenesis
Thyroid dysgenesis accounts for 85% of cases of congenital
hypothyroidism in children, the most common form of
congenital hypothyroidism (LaFranchi 2007). Mutations of
different genes (TTF-1 (thyroid transcription factor 1), TTF-2
(thyroid transcription factor 2), NKX2.1 (NK2 homeobox 1),
FOXE1 (foxhead box E1), Hhex (hematapoietically-expressed
homeobox) and PAX-8 (Paired box gene 8)) are associated
with aplasia, hypoplasia and ectopia of the thyroid gland. These
genes encode thyroid transcription factors involved in morphogenesis of the thyroid, i.e. differentiation and migration of the
thyroid gland. The transcription factors also influence production of thyroid hormones by binding to the promoters of
thyroglobulin and thyroid peroxidase genes (Djemli et al. 2006;
LaFranchi 2007). Thyroid dysgenesis has been described in a
German Shepherd crossbred dog (Greco et al. 1985), a Boxer
dog (Schawalder 1978) and in one report of familial congenital
hypothyroidism in two related Scottish Deerhound puppies
(Robinson et al. 1988). In cats, thyroid hypoplasia in two
littermate kittens was described by Traas et al. (2008), and
primary congenital hypothyroidism in cats in Japan by Tanase
et al. (1991), presumably due to a defect in the TSH receptor
or its subsequent signalling system. Thyroid agenesis was
suspected in a domestic longhaired cat in New Zealand, based
on an impalpable thyroid gland and absent uptake of radioactive
iodine by the thyroid gland, but central hypothyroidism was
not eliminated (WG Guilford1, pers. comm.). Unfortunately,
the molecular genetic defects in those reported cases of
1
Feldman and Nelson (2004)
WG Guilford, Massey University, Palmerston North, New Zealand
congenital hypothyroidism in dogs and cats have not been
established.
Dyshormogenesis
Dyshormogenesis accounts for 10% of congenital hypothyroidism cases in humans and comprises a variety of inborn errors in
the biosynthesis of thyroid hormones, the majority of which are
transmitted in an autosomal recessive manner (LaFranchi 2007).
The severity of clinical signs varies, and their onset may be
delayed as the defects of biosynthesis of hormones can be
incomplete. For goitre to develop, increased concentrations of
TSH with a functional transduction of signal via the TSH
receptor and a block in the synthesis of thyroid hormones within
the thyroid gland itself must be present. Furthermore, goitre may
be present at birth or develop postnatally, depending on the
severity of the block in the synthesis of thyroid hormones, the
degree of the deficiency of maternal iodine or transfer of
hormones and postnatal concentrations of dietary iodine. Uptake
of iodide by the thyroid gland is mediated through the sodium–
iodide symporter, and defects can cause an inability of the thyroid
(and salivary) gland to concentrate iodide. The next step in the
synthesis of thyroid hormones, organification and coupling of
iodine, is mediated by thyroid peroxidase and thyroid oxidase-2
enzymes, and a transport protein, pendrin. Defects can involve
each of these components, with considerable clinical and
biochemical heterogeneity. (LaFranchi 2007).
A defect in organification of iodide was reported in a 10-monthold male pup (Chastain et al. 1983). More recently, Fyfe et al.
(2003) identified a nonsense mutation of the thyroid peroxidase
gene in Toy Fox Terriers, completely preventing the synthesis of
functional thyroid peroxidase enzyme. This disorder is transmitted as an autosomal recessive inheritance, and a DNA-based
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Bojanić et al.
New Zealand Veterinary Journal 59(3), 2011
test was developed to help breeders identify the heterozygote
carriers. Recently, the same mutation was found in Rat Terrier
dogs (Pettigrew et al. 2007), and those authors suspected that this
mutation had been introduced from Toy Fox Terriers when they
were used in Rat Terrier breeding programmes in order to obtain
a smaller stature in the breed. Congenital hypothyroidism due to
defective organification of iodine was diagnosed in two puppies of
a litter of four Miniature Fox Terriers in New Zealand in 1996
(BR Jones, unpubl. obs.). The genetic defect was presumed the
same as in the dogs reported by Fyfe et al. (2003). There was
another cluster of three Papillon puppies in New Zealand in
2010. The dogs showed disproportionate dwarfism and depression; a small goitre was palpated. Concentrations of total and free
T4 in serum were reduced, and concentrations of TSH increased.
Unfortunately the owners declined further investigation, but the
response to oral thyroid hormone supplementation was excellent
(E Acke, unpubl. obs.). There are reports of defects in
organification of iodine in cats (Sjollema et al. 1991; Mazrier
et al. 2003). Jones et al. (1992) identified an organification defect
in a family of Abyssinian cats that presented with goitre, by
determining the uptake of radioactive iodine and discharge of
perchlorate; the disorder had an autosomal recessive mode of
inheritance.
Maternal TSH receptor-blocking antibodies and thyroid peroxidase
antibodies
Maternal TSH receptor-blocking antibodies and thyroid peroxidase antibodies as a cause of transitory congenital hypothyroidism
in humans (LaFranchi 2007) have not been described in small
animals. In dogs, Patzl and Möstl (2003) reported a prevalence of
T3 autoantibodies, without any other thyroid-specific autoantibodies present in 2.5% of healthy, and 3–6.5% of hypothyroid,
dogs. Interestingly, T3 autoantibodies have been detected in the
sera of pregnant bitches even though they delivered healthy
puppies (Schäfer-Somi et al. 2006). Autoantibodies to thyroglobulin, thyroid peroxidase and T4 in sera were also tested, but were
not present. Elsewhere, a case of spontaneous Hashimoto-like
thyroiditis has been described in kittens of 6–9 weeks of age
(Schumm-Draeger et al. 1996). It was interesting that early
therapy with thyroid hormone significantly decreased the severity
of autoimmune thyroiditis, while untreated kittens and kittens
treated with excess iodine showed aggravation of inflammation.
Central congenital hypothyroidism
Central congenital hypothyroidism can be a deficiency of a single
hormone (thyrotropin-releasing hormone (TRH) or TSH), a
component of multiple hormone deficiencies, or due to TRH
and TSH resistance (LaFranchi 2007).
Deficiency of TSH
In dogs, there are two reports of an apparent deficiency of TSH
causing central congenital hypothyroidism, one in a family of
Giant Schnauzers with an apparent autosomal recessive mode of
inheritance (Greco et al. 1991), and the other in a Boxer dog
(Mooney and Anderson 1993). Unfortunately, in the Boxer dog,
a TRH-stimulation test, to try to differentiate secondary from
tertiary hypothyroidism, was not carried out, whereas in the
Giant Schnauzers a T4 response to TRH stimulation was virtually
non-existent, supporting a deficiency of TSH. Pituitary dwarfs
with combined deficiencies of pituitary hormones (deficiency of
TSH, growth hormone and prolactin, with secretion of
adrenocorticotropic hormone (ACTH) unaffected) have been
reported in German Shepherd dogs (Hamann et al. 1999;
Kooistra et al. 2000).
117
Resistance to TSH
Thyroid-stimulating hormone unresponsiveness is caused by a
mutation in the TSH receptor or gene, causing either an
ineffective transduction of signal or a defective TSH molecule
respectively. Defects in the binding of TSH to its receptor result
in increased concentrations of TSH, without goitre, which has
not been reported in dogs. On the other hand, inherited
autosomal recessive primary congenital hypothyroidism with
resistance to TSH has been reported in cats (Tanase et al. 1991).
Whether the signs were due to a defect in TSH or its receptor
remains unknown, and the validity of the non-feline-specific
TSH assay used in that study is of concern. In another report,
there was a similar possibility of a defect in TSH or its receptor in
thyroid hypoplasia in two littermate kittens (Traas et al. 2008).
Since further testing, e.g. for TSH resistance or genetic analysis,
was not performed, the true defect present remains unconfirmed.
Clinical signs
Clinical signs of congenital hypothyroidism are not usually present
at birth, but develop postnatally. In general, puppies and kittens
with congenital hypothyroidism are of normal birthweight, and
sometimes they are the largest in the litter at birth (Scott-Moncrieff
and Guptill-Yoran 2005). However, between 3 and 8 weeks of age
the first signs of failure to thrive appear, signs which usually become
obvious to owners by 8–12 weeks of age when they compare the
animal’s size with that of their littermates. Signs of disproportionate dwarfism develop over the following months (Feldman and
Nelson 2004). Since thyroid hormones are crucial for normal
physical and nervous system development, the hallmarks of
congenital hypothyroidism are retarded growth and impaired
mental status. The clinical signs of developmental abnormalities
are not features of acquired hypothyroidism, whereas other clinical
signs may be present in both acquired and congenital hypothyroidism. As thyroid hormones affect virtually every system of the
body, the spectrum of possible clinical signs is huge but not all will
be present in every animal with congenital hypothyroidism.
Disproportionate dwarfism is characterised by a large and broad
skull, shortened mandible and ears, a thick protruding tongue,
delayed eruption of deciduous teeth and their replacement by
permanent teeth, wide/squared trunks with short limbs usually
with a valgus malpositioning, a short neck, and sometimes
kyphosis. Growth retardation is due to epiphyseal dysgenesis and
delayed skeletal maturation, resulting in disproportionate dwarfism, which is in contrast with the proportionate dwarfism in
isolated growth hormone deficiency, but similar to the disproportionate dwarfism in a combined growth hormone and TSH
deficiency (Feldman and Nelson 2004). Delayed epiphyseal
maturation is observed in vertebral bodies and long bones, where
the most common sites affected are the humeral and femoral
condyles and proximal tibia (Saunders and Jezyk 1991). Skeletal
abnormalities may, as the animal grows older, lead to development
of orthopaedic problems such as joint luxations and degenerative
joint disease (Medleau et al. 1985; Mooney and Anderson 1993).
Likewise, tetraparesis, exaggerated spinal reflexes, decreased
conscious proprioception and diffuse hyperesthesia have also
been reported associated with multiple disc protrusions in
juvenile-onset congenital hypothyroidism in a mixed-breed dog
(Greco et al. 1985), and vertebral physeal fracture in an adult
Affenpinscher dog with congenital hypothyroidism (Lieb et al.
1997). Those findings were considered to be due to skeletal
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New Zealand Veterinary Journal 59(3), 2011
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developmental abnormalities resulting in joint laxity and
consequent vertebral instability. Impaired mental status is
manifested as mental dullness and lethargy, somnolence or lack
of playfulness compared with their healthy littermates (Feldman
and Nelson 2004) and, as animals with congenital hypothyroidism grow older, impaired learning (Mooney and Anderson 1993).
Neuromuscular signs may include: weakness, hyporeflexia,
spasticity, proprioception deficits, muscle tremors and ataxia.
Some of these clinical signs are probably caused by abnormal
cerebellar development, most of which occurs postnatally.
Hypomyelination and reduction of axons in various parts of the
central nervous system have been described in Rat Terrier dogs
with a defective thyroid peroxidase enzyme (Pettigrew et al. 2007).
Dermatological signs include retention of the juvenile haircoat,
dry and thickened skin, and thinning of the haircoat that
progresses to alopecia with a lack of guard hairs. With time,
chronic dermatological problems such as recurrent episodes of
otitis externa, excessive skin folds over the body and face,
seborrhoea (Mooney and Anderson 1993) and alopecia with
hyperpigmentation (Medleau et al. 1985) develop, as is seen in
adult-onset hypothyroidism.
Other abnormalities which are often reported include constipation with or without megacolon, abdominal distension,
hypothermia, sealed eyelids and stenotic ear canals (ScottMoncrieff and Guptill-Yoran 2005). Macroglossia and abdominal
distension result from accumulation of myxoedematous fluid
(Greco 2006). Exophthalmia, lateral strabismus and syncope may
also occur (Chastain et al. 1983). In a recent report of congenital
hypothyroidism in a kitten, bilateral cryptorchidism was
reported, though its association with congenital hypothyroidism
is unknown (Quante et al. 2010). Chastain et al. (1983) reported
finding small testicles that enlarged following treatment in a dog
with congenital hypothyroidism, but signs of puberty did not
occur.
The presence of goitre is inconsistent as enlargement of the
thyroid gland depends on the aetiology of congenital hypothyroidism. Defects of organification and, less commonly, iodine
deficiency, usually result in goitre (Feldman and Nelson 2004).
Animals that develop goitre may present with signs of dysphagia
and dyspnoea, resulting from mechanical obstruction of the
oesophagus (Chastain et al. 1983).
Although cardiovascular signs and electrocardiographic abnormalities can be encountered in acquired hypothyroidism, consistent
cardiac abnormalities have not been reported in congenital
hypothyroidism in dogs and cats. One report of congenital
hypothyroidism in a dog described QRS complexes with a
decreased R-wave amplitude in lead II with both primary and
secondary atrio-ventricular blocks. Electrocardiographic abnormalities resolved with treatment (Mooney and Anderson 1993).
Bradycardia has also been reported in congenital hypothyroidism
of dogs and cats (Chastain et al. 1983; Stephan and Schütt-Mast
1995). Finally, other clinical signs may be present if there are
concurrent illnesses, and when congenital hypothyroidism is
present with panhypopituitarism (Feldman and Nelson 2004).
Diagnosis
There are many recognised laboratory abnormalities associated
with acquired hypothyroidism (Panciera 1994; Dixon et al.
Bojanić et al.
1999). To confirm a diagnosis of congenital hypothyroidism an
animal must have an appropriate history, clinical signs of
congenital hypothyroidism and supportive evidence for the
diagnosis, especially demonstration of reduced concentrations of
total or free T4 on further diagnostic evaluation.
Clinical pathology findings
Complete blood count revealed a mild non-regenerative anaemia
in approximately 30% of adult hypothyroid dogs (Panciera
1994). In the case reports described previously, a similar
proportion of cases of congenital hypothyroidism had nonregenerative anaemia confirmed.
Serum biochemistry typically reveals fasting hypercholesterolaemia and hypertriglyceridaemia in the majority of cases of acquired
hypothyroidism (Dixon et al. 1999). Thyroid hormones are
intimately involved in the metabolism of lipid. Diminished
degradation of lipid is pronounced in hypothyroidism, which
leads to accumulation of lipids in plasma (Scott-Moncrieff and
Guptill-Yoran 2005). Those changes are not specific to
hypothyroidism, but they provide supportive evidence for
congenital hypothyroidism when appropriate clinical signs are
present. However, in some cases of congenital hypothyroidism in
both dogs and cats, concentrations of cholesterol in serum were
below the reference range (Chastain et al. 1983; Jones et al.
1992).
Other abnormalities reported less commonly include increased
activities of alkaline phosphatase, alanine transaminase and
creatine kinase in serum, and increased concentrations of blood
urea nitrogen. Those changes are extremely inconsistent, and the
relationship to hypothyroidism is unexplained. The activity of
alkaline phosphatase in serum was increased in young healthy
animals (Stockham and Scott 2008), and increased activities have
been reported in congenital hypothyroidism, but decreased
concentrations of glucose and decreased activity of alkaline
phosphatase have also been reported (Chastain et al. 1983;
Tanase et al. 1991). Hypercalcaemia has occasionally been
documented in dogs (Greco et al. 1985, 1991), and in cats with
congenital hypothyroidism (Greco 2006). In humans, hypercalcaemia secondary to congenital hypothyroidism is due to
increased gastrointestinal absorption and decreased renal clearance of calcium (Tau et al. 1986), but this has not been
confirmed in dogs and cats.
Results of bile acid stimulation tests and measurements of
insulin-like growth factor-1 (IGF-1) were reported to be
abnormal in one kitten (Quante et al. 2010), the significance
of which is unknown, and results returned to the reference ranges
with treatment.
Endocrine testing
Hypothyroidism is the result of decreased production of T4 and
T3 by the thyroid gland (Scott-Moncrieff and Guptill-Yoran
2005). Thyroid function testing can confirm the diagnosis, but a
significant proportion of cases can have discordant results as
concentrations of thyroid hormones and of TSH are affected by
many different factors (Feldman and Nelson 2004). It is
important to remember that any given hormone tests currently
available may give false-positive or false-negative results, although
diagnostic accuracy varies significantly for the different tests.
Nevertheless, measurements of hormones must be performed,
and one should follow the same principles of interpretation of
measurements of hormone in puppies and kittens as applies to
adults. A recent review of the use of hormone tests in diagnosing
Bojanić et al.
New Zealand Veterinary Journal 59(3), 2011
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acquired hypothyroidism is found elsewhere (Mooney 2011).
Notwithstanding the usefulness of these tests, due to the very low
incidence of congenital hypothyroidism in dogs and cats there are
no specific studies determining diagnostic performance of
hormone assays in confirming congenital hypothyroidism, hence
most of the data regarding hormone tests are derived from
acquired hypothyroidism.
Factors affecting function tests of the thyroid gland
Age influences concentrations of thyroid hormones, and is
important for interpretation of concentrations of hormones in
puppies and kittens. Healthy puppies 56-weeks-old have much
higher concentrations than adults and, as they grow older,
concentrations of T4 decline to the reference range of adult dogs.
In particular, the mean concentration of T4 in serum in euthyroid
puppies 56-weeks-old was significantly increased compared with
dogs between 6 weeks and 1 year of age, and even more so when
compared with middle-aged and older dogs (Reimers et al. 1990).
In that report, dogs between 6 weeks and 1 year of age were
divided into three groups (6–12 weeks, 3–6 months and 6–12
months), between which no significant difference was found.
Puppies 56-weeks-old had a mean concentration of T4 in serum
of 39.1 nM/L, while those between 6- and 12-weeks-old had
24.9 nM/L. In the vast majority of cases of canine congenital
hypothyroidism described above, the concentrations of T4 in
serum were below the reference ranges for the respective age
groups.
In contrast with puppies, healthy kittens 512-weeks-old had
concentrations of total and free T4 in serum at the low end of the
reference range for adults, whereas concentrations of T3 and free
T3 were lower in kittens than adult cats until 5 weeks of age
(Zerbe et al. 1998). Conversely, some authors reported healthy
kittens of 5–6-weeks-old had a concentration of total T4 two to
five times higher than that in adult dogs and two to three times
higher than that in normal adult cats (Greco 2006). There is a
report of feline congenital hypothyroidism where the concentration of T4 in serum was in the low end of the reference range for
adult cats (Jones et al. 1992). Therefore, a kitten with congenital
hypothyroidism might have a concentration of T4 in serum
within the reference range for normal adult cats, and one should
not rule out hypothyroidism in such a case.
Unfortunately, there are no reports on the effect of age on
concentrations of free T3, free T4 and TSH in serum in dogs, but
higher concentrations of these hormones in puppies than in
healthy adult animals would be expected. Also, there are no
studies on the concentrations of TSH in kittens. To conclude, in
our opinion, when measuring T3, T4, free T3, free T4 and TSH
in puppies and kittens, in order to avoid age as a confounding
factor, it is recommended concentrations of hormones be
measured in age-matched controls, preferably littermates.
Non-thyroidal illness is another complicating factor and,
although its influence on thyroid hormone function and the
concentrations of thyroid hormones has not been specifically
studied in puppies or kittens, the concurrent disease would be
expected to affect measurements of thyroid hormones in
congenital hypothyroidism in a similar way as non-thyroidal
illness does in acquired hypothyroidism. The concentration of
total T4 in serum may be lowered below the reference range by
non-thyroidal illness. Measurement of free T4 in serum may be
helpful as it is less affected by non-thyroidal illness (Kantrowitz
et al. 2001), but is a less sensitive diagnostic test than that for
119
total T4 (Dixon and Mooney 1999). The concentration of TSH
is affected by non-thyroidal illness as well, potentially being
normal or increased with severe concurrent illness (Dixon and
Mooney 1999; Kantrowitz et al. 2001).
Specific endocrine testing
Thyroid hormones commonly measured in dogs and cats include
total T4, total T3, free T4 and TSH. TRH- and TSH-stimulation
tests have been employed, particularly in determining the
position of the defect along the HPT axis. These assays test the
functional capacity and reserve of the HPT axis.
The concentration of total T4 is used as the screening test for
hypothyroidism, although there is no clear cut-off separating
euthyroidism from hypothyroidism. The concentration of T4 in
serum is considered more as a measure of euthyroidism because
factors such as non-thyroidal illness can suppress baseline
concentrations of T4. Therefore, it is considered a sensitive test
but lacking specificity (Feldman and Nelson 2004), thus
measurement of free T4 is recommended in cases where nonthyroidal illness is suspected (Scott-Moncrieff and Guptill-Yoran
2005).
In central hypothyroidism, the concentration of TSH is
decreased, due to a defect at the level of either the hypophysis
or the hypothalamus, while the concentration of T4 is invariably
reduced or undetectable. In primary hypothyroidism, TSH
should be elevated due to the negative feedback effect of T4 on
the pituitary gland. Unfortunately, canine TSH assays currently
available are not accurate enough to distinguish low concentrations below and at the lower end of the normal reference range,
and there is no assay available to measure TRH in dogs and cats.
Hence, diagnosis of secondary hypothyroidism relies on
hormone-stimulation tests and other supporting data. Conversely, in reported cases of primary congenital hypothyroidism,
concentrations of TSH were commonly elevated. However,
regarding the diagnostic efficacy, in acquired hypothyroidism
current TSH assays have poor sensitivity as up to 38% of
hypothyroid dogs may have a concentration of TSH within the
reference range (Scott-Moncrieff and Guptill-Yoran 2005). It is
presumed that long-standing primary hypothyroidism in time
leads to pituitary exhaustion, which lowers initially high
concentrations of TSH into the reference range. Therefore,
measurement of TSH holds similar limitations in the diagnosis of
congenital hypothyroidism as it does in acquired hypothyroidism.
Should concentrations of TSH be normal or increased, secondary
hypothyroidism is still possible as the hormone might be
defective, rendering it non-functional, while its production is
not adversely affected. In such a situation, the clinician should
perform a T3-suppression test, after which stimulation of the
thyroid gland with repeated administration of exogenous TSH, as
described above, should be made. Thereafter, the finding of a
normal thyroid response would prove central congenital
hypothyroidism due to a defective TSH molecule, whereas if
subnormal resistance to TSH is confirmed, causes of primary
congenital hypothyroidism should be investigated.
A commercial immunoradiometric assay for canine TSH has
been validated for use in monitoring the treatment of
hyperthyroid cats, and could assist in diagnosing spontaneous
hypothyroidism (Graham et al. 2000). In a report of presumed
primary congenital hypothyroidism in two littermate kittens due
to thyroid hypoplasia, concentrations of TSH, measured using a
canine assay, were elevated (Traas et al. 2008).
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120
New Zealand Veterinary Journal 59(3), 2011
Dynamic thyroid function testing
These tests were generally considered better confirmatory tests for
primary hypothyroidism compared with measurement of baseline
thyroid hormones. However, recent data dispute the use of the
TSH-stimulation test as a ‘gold standard’ in the diagnosis of
acquired primary hypothyroidism, in favour of quantitative
measurement of the uptake of pertechnetate by the thyroid gland
(Diaz Espineira et al. 2007). Additionally, the TRH-stimulation
test, with measurement of either total T4 (Frank 1996) or TSH
(Scott-Moncrieff and Nelson 1998), may yield false-positive
results in dogs. As is the case in dogs, the TRH-stimulation test in
cats has limitations in differentiating euthyroidism from nonthyroidal illness (Tomsa et al. 2001). It is worth noting that
despite lacking data on the accuracy of hormone stimulation tests
in diagnosing congenital hypothyroidism, in reported cases the
results of hormone stimulation tests agreed with proposed cut-off
values taken from studies in normal animals or animals with
acquired hypothyroidism. Although bovine TSH is no longer
commercially available, recombinant human TSH has been
validated for use in dogs, and could be used as a substitute (Sauvé
and Paradis 2000). Its use has also been reported in cats
(Stegeman et al. 2003).
Another potential use of the TRH- and TSH-stimulation tests
lies in differentiation of secondary from tertiary hypothyroidism.
In reported cases of congenital hypothyroidism in dogs, there was
no possibility, at the time, to differentiate secondary from tertiary
hypothyroidism, hence the defects were classified as central
hypothyroidism (Medleau et al. 1985; Greco et al. 1991; Mooney
and Anderson 1993). Measurement of TSH is now available, and
if results of a TSH-stimulation test are normal while subsequent
stimulation with TRH is abnormal, pituitary dysfunction is
implied. Conversely, the post-TRH increase in concentrations of
total T4 greater than 1.5 fold or 46 nM/L increase over the basal
concentration makes both primary and secondary hypothyroidism unlikely (Panciera 1998).
In animals with suspected central congenital hypothyroidism,
measurement of other hormones may be important. In central
congenital hypothyroidism, persistently low concentrations of
cortisol in the serum, but a normal response to ACTH
stimulation, have been described (Mooney and Anderson 1993).
Pre-treatment results of measurements of growth hormone may
be elevated or reduced, and a suppressed growth hormone
response in plasma to xylazine stimulation has been reported in
dogs with congenital hypothyroidism (Medleau et al. 1985;
Greco et al. 1991; Mooney and Anderson 1993).
Diagnostic imaging
Radiography
Radiographic studies in animals with congenital hypothyroidism
show variable abnormalities. Radiographs of limbs most
commonly show epiphyseal dysgenesis of humeral, femoral
and proximal tibial condyles (irregularly formed, fragmented or
stippled epiphyseal centres), with delayed maturation and
ossification. Thus, the overall length of long bones is reduced,
which results in disproportionate dwarfism. Valgus deformities
are common, and result from retarded ossification of carpal and
tarsal bones. Thickening of radial and ulnar cortices, with
increased medullary opacity and bowing of these bones, may be
present (Saunders and Jezyk 1991). Degenerative joint disease
and arthritis may develop in affected joints over time. These
radiological findings are not pathognomonic for congenital
hypothyroidism, as similar changes have been reported in
Bojanić et al.
Beagles and a Miniature Poodle with multiple epiphyseal
dysplasia, and in dogs with panhypopituitarism (Feldman and
Nelson 2004). Radiographs of the axial skeleton reveal short,
broad skulls, open vertebral epiphyses, and a lack of longitudinal growth of vertebral bodies, resulting in scalloped ventral
vertebral borders.
Ultrasonography
Ultrasound examination is a useful technique for anatomical
assessment of the thyroid gland, but it provides no information
on its function. In humans, it is used to identify the form of the
dysgenesis (aplasia/hypoplasia, hemi-agenesis and ectopia), and it
is possible to find an eutopic gland when scintigraphy fails to
show functional tissue (Kreisner et al. 2003). Additionally,
ultrasound examination can reveal morphological changes in the
gland with changes in echogenicity, and can aid fine-needle
aspiration or biopsy of the thyroid gland. Ultrasound examination of the thyroid gland was not performed in the majority of
reported cases of congenital hypothyroidism in dogs and cats, and
data for comparison with animals with acquired hypothyroidism
are lacking.
Nuclear medicine
Scintigraphy studies using radioactive iodine or pertechnetate are
useful in determining the size, shape and location of the thyroid
gland, and its uptake of iodine and discharge of pertechnetate
(Feldman and Nelson 2004). However, scintigraphy studies do
not test functional hormone secretion of the thyroid gland.
Nuclear imaging studies are used to help in differentiation of
dysgenesis from dyshormogenesis in primary congenital hypothyroidism, and in distinguishing central congenital hypothyroidism from thyroid dysgenesis. In animals with aplasia or
hypoplasia, radionuclide scans fail to detect remnant thyroid
tissue but a low or absent uptake of technetium or iodine may
also be obtained in animals with central hypothyroidism as a
result of atrophy of the thyroid gland. A characteristic finding in
all organification defects is a normal to increased uptake of
radioactive iodine, with a marked decrease in radioactivity of the
thyroid gland when perchlorate is given I/V after administration
of radioactive iodine, in contrast to dysgenesis, where low or
undetectable accumulation of isotope is found (Feldman and
Nelson 2004).
In central congenital hypothyroidism, low or undetectable
accumulation of radioactive iodine may be found. Therefore, in
order to differentiate central congenital hypothyroidism from
thyroid dysgenesis, re-testing after repeated stimulation with
TSH (5 IU/day S/C over 3 days) is advised, as a normal thyroid
image may be obtained after TSH stimulation, in central
congenital hypothyroidism. In central hypothyroidism, this
finding is indicative of hypoplasia or atrophy of the thyroid
gland due to a long-standing lack of TSH stimulation (Greco
et al. 1991; Fyfe et al. 2003).
Computed tomography and magnetic resonance imaging
Thyroid glands have been evaluated using computed tomography
in healthy dogs and cats, and by magnetic resonance imaging in
healthy dogs, but both imaging modalities have not been
evaluated in animals with congenital hypothyroidism. Nevertheless, if computed tomography and scintigraphy studies are
both to be performed, scintigraphy needs to be performed first
because the I/V injection of iodinated contrast medium alters the
uptake of radioactive iodine for 6–8 weeks (Taeymans et al.
2008).
Bojanić et al.
New Zealand Veterinary Journal 59(3), 2011
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Histopathology
Biopsy of the thyroid gland is generally accepted as a definitive
diagnostic procedure for documenting pathology of the gland,
although it does not provide information on its functional
capacity. The thyroid gland is comprised of follicles surrounded
by a basement membrane. The wall of the follicle is a single
layer of epithelial cells which are cuboidal when quiescent and
columnar when active. In the lumen of the follicle is colloid, a
viscous gel that contains thyroglobulin secreted by the thyroid
follicular cells. However, variants of normal histology can be
difficult to differentiate from the histopathological appearance of
secondary hypothyroidism, primary atrophy, follicular cell
hyperplasia and changes occurring due to concurrent illness
(Feldman and Nelson 2004). This is of importance in
congenital hypothyroidism when differentiating central hypothyroidism due to a deficiency of TSH/TRH from primary
thyroid dysgenesis. Histopathology of the hypophysis would
help in assessing the thyrotropic reserve of the adenohypophysis
and hypothalamus, however this is not possible ante mortem. In
reported cases of goitrous primary congenital hypothyroidism in
both dogs and cats, histopathological findings included a
diffusely hyperplastic parenchyma, with small follicular acini
lined by cuboidal epithelial cells, with little accumulation of
colloid (Chastain et al. 1983; Jones et al. 1992; Fyfe et al. 2003;
Pettigrew et al. 2007). A characteristic finding of TSH
stimulation is irregularly shaped nuclei. Colloid is pale to
weakly eosinophilic, and may be scalloped (Arnold et al. 1984).
Normal-appearing follicles with large columnar epithelial cells
and deeply eosinophilic colloid may be few in number
(Chastain et al. 1983). The proportion of normal follicles is
probably related to the degree of the block in the synthesis of
thyroid hormones. Non-goitrous primary congenital hypothyroidism may have variable histopathological findings. For
instance, hypoplasia of the thyroid gland is characterised by a
loss of glandular tissue, replaced by adipose tissue, and very few
small follicles with little eosinophilic colloid, suggesting an
inactive thyroid gland (Greco et al. 1985; Robinson et al. 1988;
Traas et al. 2008). In contrast, in central congenital
hypothyroidism in Giant Schnauzers, most likely due to TSH
deficiency, follicular inactivity was evidenced by a distended
colloid that had decreased numbers of resorption vacuoles lined
by flattened epithelial cells (Greco et al. 1991). Unfortunately,
those authors provided no histological description of the
hypophysis. In congenital hypothyroidism in Scottish Deerhound puppies, follicles were small, with cuboidal cells and no
colloid, but active thyrotropic cells in the adenohypophysis were
characterised by increased numbers of large vacuolated
basophilic cells containing few cytoplasmic granules (Robinson
et al. 1988). This finding suggests thyrotrophs are secreting
large amounts of TSH, but the cause of inactivity of the thyroid
gland might be due to a defect of the TSH molecule or TSH
receptor.
Treatment and prognosis
The treatment of choice for hypothyroidism is sodium
levothyroxine, at an initial dose of 0.02 mg/kg bodyweight twice
daily for puppies, and 0.05 or 0.1 mg once daily for kittens
(Feldman and Nelson 2004). Adequate therapy is monitored by
measurement of T4 and TSH, and by a favourable clinical
response. Therapeutic monitoring is essentially the same as that
121
in acquired hypothyroidism. Critical assessment of the response
to therapy should be made after at least 6 weeks of treatment.
Although the response to therapy may be excellent and quick,
many clinical and laboratory abnormalities resolve gradually,
usually within 1–3 months, while skin changes and skeletal
abnormalities may take longer, up to 6 months or more. On the
other hand, clinical signs such as constipation may persist and
require ongoing treatment, with a variable response.
The long-term prognosis is generally guarded in congenital
hypothyroidism as the response to treatment depends on the
aetiology and time treatment first commenced. The most
important problems are musculoskeletal abnormalities and
mental impairment, and if therapy is delayed, although most
other clinical signs resolve, abnormal development of bones and
joints inevitably leads to problems such as degenerative
osteoarthritis, osteochondrosis-type lesions, radial bowing, widening of the humeroradial joint and subluxation of the humeroulnar
joint, as seen in dogs (Saunders and Jezyk 1991). Similarly,
mental impairment may be irreversible if therapy is commenced
after 6 months of age (Greco and Chastain 2001).
Conclusion
Congenital hypothyroidism is uncommon in dogs and cats.
This paper has reviewed the literature to date of all cases that
have been reported. Identification of subtle differences in the
growth of puppies and kittens in a litter, and being suspicious
of hypothyroidism, increases the likelihood of a diagnosis being
made of congenital hypothyroidism, the animal investigated and
treated, and advice being given to the breeder to prevent
recurrence. Congenital hypothyroidism in dogs and cats needs
more research to increase our knowledge of its pathogenesis,
inheritance and importantly its molecular basis in different
breeds. Considering that most reports of congenital hypothyroidism were published before the use of sophisticated hormone
assays, such as for TSH, or molecular genetic analysis, the exact
pathogenesis has not been identified in most breeds. However,
some recent studies were successful in establishing the exact
cause of congenital hypothyroidism, which has resulted in a
better understanding and has provided potential areas for
beneficial research.
References
Arnold U, Bader R, Grossier I, Eigenmann JE, Opitz M. Goitrous
hypothyroidism and dwarfism in a kitten. Journal of the American Animal
Hospital Assocciation 20, 753–8, 1984
Chastain CB, McNeel SV, Graham CL, Pezzanite SC. Congenital hypothyroidism in a dog due to an iodide organification defect. American Journal of
Veterinary Research 44, 1257–65, 1983
Diaz Espineira MM, Mol JA, Peeters ME, Pollak YWEA, Iversen L, van Dijk
JE, Rijnberk A, Kooistra HS. Assessment of thyroid function in dogs with
low plasma thyroxine concentration. Journal of Veterinary Internal Medicine
21, 25–32, 2007
Dixon RM, Mooney CT. Evaluation of serum free thyroxine and thyrotropin
concentrations in the diagnosis of canine hypothyroidism. Journal of Small
Animal Practice 40, 72–8, 1999
Dixon RM, Reid SW, Mooney CT. Epidemiological, clinical, haematological
and biochemical characteristics of canine hypothyroidism. Veterinary Record
145, 481–7, 1999
Djemli A, van Vliet G, Delvin EE. Congenital hypothyroidism: from paracelsus
to molecular diagnosis. Clinical Biochemistry 39, 511–8, 2006
Downloaded by [Texas A&M University Libraries] at 21:55 22 October 2015
122
New Zealand Veterinary Journal 59(3), 2011
*Feldman EC, Nelson RW. Hypothyroidism. In: Canine and Feline Endocrinology and Reproduction. 3rd Edtn. Pp 86–151. Saunders, St Louis, USA, 2004
Frank LA. Comparison of thyrotropin-releasing hormone (TRH) to thyrotropin
(TSH) stimulation for evaluating thyroid function in dogs. Journal of the
American Animal Hospital Association 32, 481–7, 1996
Fyfe JC, Kampschmidt K, Dang V, Poteet BA, He Q, Lowrie C, Graham PA,
Fetro VM. Congenital hypothyroidism with goiter in toy fox terriers. Journal
of Veterinary Internal Medicine 17, 50–7, 2003
*Graham PA, Refsal KR, Nachreiner RF, Provencher-Bolliger AL, The
measurement of feline thyrotropin (TSH) using a commercial canine
immunoradio-metric assay. Journal of Veterinary Internal Medicine (Abstract)
14, 342, 2000
Greco DS. Diagnosis of congenital and adult-onset hypothyroidism in cats.
Clinical Techniques in Small Animal Practice 21, 40–4, 2006
*Greco SD, Chastain CB. Endocrine and metabolic systems. In: Hoskins JD
(ed). Veterinary Pediatrics. 3rd Edtn. Pp 344–70. WB Saunders, Philadelphia,
USA, 2001
Greco DS, Peterson ME, Cho DY, Markovits JE. Juvenile-onset hypothyroidism in a dog. Journal of the American Veterinary Medical Association 187, 948–
50, 1985
Greco DS, Feldman EC, Peterson ME, Turner JL, Hodges CM, Shipman LW.
Congenital hypothyroid dwarfism in a family of Giant Schnauzers. Journal of
Veterinary Internal Medicine 5, 57–65, 1991
Hamann F, Kooistra HS, Mol JA, Gottschalk S, Bartels T, Rijnberk A.
Pituitary function and morphology in two German shepherd dogs with
congenital dwarfism. Veterinary Record 144, 644–6, 1999
Jones BR, Gruffydd-Jones TJ, Sparkes AH, Lucke VM. Preliminary studies on
congenital hypothyroidism in a family of Abyssinian cats. Veterinary Record
131, 145–8, 1992
Kantrowitz LB, Peterson ME, Melian C, Nichols R. Serum total thyroxine,
total triiodothyronine, free thyroxine, and thyrotropin concentrations in dogs
with nonthyroidal disease. Journal of the American Veterinary Medical
Association 219, 765–9, 2001
Kooistra HS, Voorhout G, Mol JA, Rijnberk A. Combined pituitary hormone
deficiency in german shepherd dogs with dwarfism. Domestic Animal
Endocrinology 19, 177–90, 2000
Kreisner E, Camargo-Neto E, Maia CR, Gross JL. Accuracy of ultrasonography
to establish the diagnosis and aetiology of permanent primary congenital
hypothyroidism. Clinical Endocrinology (Oxford) 59, 361–5, 2003
*LaFranchi S. Disorders of the thyroid gland. In: Kliegman RM, Jenson HB,
Stanton BF, Behrman RE (eds). Nelson Textbook of Pediatrics. 17th Edtn. Pp
2316–25. WB Saunders, Philadelphia, USA, 2007
Lieb AS, Grooters AM, Tyler JW, Partington BP, Pechman RD. Tetraparesis
due to vertebral physeal fracture in an adult dog with congenital
hypothyroidism. Journal of Small Animal Practice 38, 364–7, 1997
*Mazrier H, French A, Ellinwood NM, van Hoeven M, Zwiegle J, O’Donnell P,
Jezyk PF, Haskins ME, Giger U. Goiterous congenital hypothyroidism caused
by thyroid peroxidase deficiency in a family of domestic shorthair cats. Journal
of Veterinary Internal Medicine (Abstract) 17, 395–6, 2003
Medleau L, Eigenmann JE, Saunders HM, Goldschmidt MH. Congenital
hypothyroidism in a dog. Journal of the American Animal Hospital Association
21, 341–4, 1985
Milne KL, Hayes HM Jr. Epidemiologic features of canine hypothyroidism.
Cornell Veterinarian 71, 3–14, 1981
Mooney CT. Canine hypothyroidism: A review of aetiology and diagnosis. New
Zealand Veterinary Journal 59, 105–114, 2011
Mooney CT, Anderson TJ. Congenital hypothyroidism in a boxer dog. Journal of
Small Animal Practice 34, 31–5, 1993
Panciera DL. Hypothyroidism in dogs: 66 cases (1987–1992). Journal of the
American Veterinary Medical Association 204, 761–7, 1994
*Panciera DL. Canine hypothyroidism. In: Torrance AG, Mooney CT (eds).
Manual of Small Animal Endocrinology. 2nd Edtn. Pp 103–13. British Small
Animal Veterinary Association, Cheltenham, UK, 1998
Patzl M, Möstl E. Determination of autoantibodies to thyroglobulin, thyroxine
and triiodothyronine in canine serum. Journal of Veterinary Medicine A
Physiology, Pathology, Clinical Medicine 50, 72–8, 2003
Pettigrew R, Fyfe JC, Gregory BL, Lipsitz D, deLahunta A, Summers BA,
Shelton GD. CNS hypomyelination in rat terrier dogs with congenital goiter
and a mutation in the thyroid peroxidase gene. Veterinary Pathology 44, 50–6,
2007
Bojanić et al.
Quante S, Fracassi F, Gorgas D, Kircher PR, Boretti FS, Ohlerth S, Reusch
CE. Congenital hypothyroidism in a kitten resulting in decreased IGF-I
concentration and abnormal liver function tests. Journal of Feline Medicine and
Surgery 12, 487–90, 2010
Reimers TJ, Lawler DF, Sutaria PM, Correa MT, Erb HN. Effects of age, sex,
and body size on serum concentrations of thyroid and adrenocortical
hormones in dogs. American Journal of Veterinary Research 51, 454–7, 1990
Robinson WF, Shaw SE, Stanley B, Wyburn RS. Congenital hypothyroidism in
Scottish Deerhound puppies. Australian Veterinary Journal 65, 386–9, 1988
Saunders HM, Jezyk PF. The radiographic appearance of canine congenital
hypothyroidism; skeletal changes with delayed treatment. Veterinary Radiology
32, 171–7, 1991
Sauvé F, Paradis M. Use of recombinant human thyroid-stimulating hormone
for thyrotropin stimulation test in euthyroid dogs. Canadian Veterinary Journal
41, 251–9, 2000
Schäfer-Somi S, Herkner KR, Neubauer S, Egerbacher M, Patzl M, Pollak S,
Ali Aksoy O, Beceriklisoy HB, Kanca H, Findik M, Kalender H, Aslan S.
A screening for the occurrence of autoreactive antibodies in sera of pregnant
and non-pregnant bitches. Reproduction in Domestic Animals 41, 48–54, 2006
Schawalder VP. Zwergwuchs beim hund [Dwarfism in a dog]. KleintierPraxis 23,
1–48, 1978
Schumm-Draeger PM, Länger F, Caspar G, Rippegather K, Herrmann G,
Fortmeyer HP, Usadel KH, Hübner K. Spontane Hashimoto-artige
Thyreoiditis im Modell der Katze [Spontaneous Hashimoto-like thyroiditis
in cats]. Verhandlungen der Deutschen Gesellschaft für Pathologie 80, 297–301,
1996
*Scott-Moncrieff JCR, Guptill-Yoran L. Hypothyroidism. In: Ettinger SJ,
Feldman EC (eds). Textbook of Veterinary Internal Medicine. 6th Edtn. Pp
1535–43. Elsevier-Saunders, St Louis, USA, 2005
Scott-Moncrieff JCR, Nelson RW. Congenital hypothyroidismange in serum
thyroid-stimulating hormone concentration in response to administration of
thyrotropin-releasing hormone to healthy dogs, hypothyroid dogs, and
euthyroid dogs with concurrent disease. Journal of the American Veterinary
Medical Association 213, 1435–8, 1998
Sjollema BE, den Hartog MT, de Vijlder JJ, van Dijk JE, Rijnberk A.
Congenital hypothyroidism in two cats due to defective organification:
Data suggesting loosely anchored thyroperoxidase. Acta Endocrinologica
(Copenhagen) 125, 435–40, 1991
Stegeman JR, Graham PA, Hauptman JG. Use of recombinant human thyroidstimulating hormone for thyrotropin-stimulation testing of euthyroid cats.
American Journal of Veterinary Research 64, 149–52, 2003
Stephan I, Schütt-Mast I. Kongenitale hypothyreose mit disproportioniertem
Zwergwuchs bei einer Katze [Congenital hypothyroidism with disproportionate dwarfism in a cat]. KleintierPraxis 40, 701–6, 1995
*Stockham SL, Scott MA. Enzymes. In: Fundamentals of Veterinary Clinical
Pathology. 2nd Edtn. Pp 639–74. Blackwell Publishing Professional, Ames,
USA, 2008
Taeymans O, Schwarz T, Duchateau L, Barberet V, Gielen I, Haskins M, Van
Bree H, Saunders JH. Computed tomographic features of the normal canine
thyroid gland. Veterinary Radiology & Ultrasound 49, 13–9, 2008
Tanase H, Kudo K, Horikoshi H, Mizushima H, Okazaki T, Ogata E.
Inherited primary hypothyroidism with tyrotrophin resistance in Japanese cats.
Journal of Endocrinology 129, 245–51, 1991
Tau C, Garabedian M, Farriaux JP, Czernichow P, Pomarede R, Balsan S.
Hypercalcaemia in infants with congenital hypothyroidism and its relation to
vitamin D and thyroid hormones. Journal of Pediatrics 109, 808–14, 1986
Tomsa K, Glaus TM, Kacl GM, Pospischil A, Reusch CE. Thyrotropinreleasing hormone stimulation test to assess thyroid function in severely sick
cats. Journal of Veterinary Internal Medicine 15, 89–93, 2001
Traas AM, Abbott BL, French A, Giger U. Congenital thyroid hypoplasia and
seizures in 2 littermate kittens. Journal of Veterinary Internal Medicine 22,
1427–31, 2008
*Zerbe CA, Casal ML, Jezyk PF, Refsal KR, Nachreiner RF. Thyroid profiles in
healthy kittens from birth to 12 weeks of age. Journal of Veterinary Internal
Medicine (Abstract) 12, 212, 1998
Submitted 04 October 2010
Accepted for publication 15 February 2011
*Non-peer-reviewed