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1. Department of Veterinary Medicine
College of Veterinary & Animal science, Bikaner
Rajasthan University of Veterinary & Animal Science , Bikaner
Submtited By
Kavita Jaidiya
PHD Scholar

2. Introduction
 Hypothyroidism (HpoT) is a multisystemic disease that results from
deficiency of thyroid hormones (TH), thyroxine (T4) and
triiodothyronine (T3)( Cooper and Ladenson 2013) .
 Hypothyroidism is of primary origin in about 95% of cases,
affecting mainly middle-aged dogs ( Feldman and Nelson 2015) .
 It is a single endocrinological disease suspected most commonly in
canine suffering from alopecia (Doering and Jensen, 1973).

3. Anatomy of Thyroid Gland
 Located lateral to the trachea, in the region of the proximal
tracheal rings (evans et al , 2013).
 Functional unit is the thyroid follicle, which comprises the
follicular cells (thyrocytes) and colloid, each gland containing
both large (resting) follicles and small (active) follicles.
1: Resting follicles (larger and with numerous
vacuoles)
2: Active follicles (smaller in size).

4. Thyroid Hormone
 It is a Iodine-containing amino acids.
 100 % of T4, but only 20% of T3 is derived from the thyroid gland. Rest of
T3 is derived from extrathyroidal enzymatic deiodination of T4 (Catharine,
2010).
 In the dog T4 is bound to: TBG (thyroid hormone-binding globulin) 60 %,
TBPA (transthyretin)17%, Albumin 12% and HDL2 (apolipoprotiens)11%
(Victor, 2011).
 Only 0.1% is free T4 fraction (FT4), which is the bioavailable hormone
(Wang et al., 2000) and determines the thyroid condition of the individual.
 In contrast to the protein-bound T4 fraction, FT4 concentration remains
constant regardless of fluctuations in plasma transporter proteins (Morreale
et al.,2002).

5. Function of thyroid
hormone
 Thyroid hormones increase the metabolic rate and oxygen
consumption of most tissues, (with the exception of the adult brain,
testes, uterus, lymph nodes, spleen, and anterior pituitary).
 Thyroid hormones have positive inotropic and chronotropic effects
on the heart. They increase the number and affinity of beta-
adrenergic receptors and enhance the response to catecholamines.
 Thyroid hormones have catabolic effects on muscle and adipose
tissue, stimulate erythropoiesis, and regulate both cholesterol
synthesis and degradation.
 Thyroid hormones are also essential for the normal growth and
development of the neurologic and skeletal systems.

6. Classification based on etiology
 Primary hypothyroidism accounts for more than 95 percent of the
cases and is usually caused by lymphocytic thyroiditis or idiopathic
thyroid atrophy (Carmel, 2003).
 Secondary Hypothyroidism (thyroid stimulating hormone, TSH)
deficiency due to congenital malformation, pituitary destruction
(tumors, trauma, autoimmune hypophysitis) or even its
suppression, normally caused by hormones or drugs such as
glucocorticoids ( Feldman and Nelson 2015)
 Tertiary hypothyroidism, caused by a thyrotropin releasing
hormone (TRH) deficiency due to pituitary adenoma. (Robert et al.,
2007)
 Not reported in dogs.

7. Primary hypothyroidism
A- Lymphocytic thyroiditis
Lymphocytic thyroiditis is a common canine condition that
can lead to functional hypothyroidism. It is associated with
more than 50% of cases of canine hypothyroidism.(Peter A.
Graham et al., 2001)
heritable in beagles and borzois(Patty, 2012)
Characterized by infiltration of the thyroid gland by
lymphocytes, plasma cells, and macrophages.
Lastly fibrous connective tissue replaces parenchyma.
Clinical hypothyroidism develops only when greater than
75% of the functioning thyroid tissue has been destroyed by
the infiltrative process.

8. B. Idiopathic atrophy
 45 -50 % of cases
 Degenerative disorder ,no inflammatory infiltrate
 although initially the disease is characterized by goiter (slight
to significant increase in gland volume) (Feldman and
Nelson, 1996), in last parenchyma replaced by adipose
tissue.
 Fibrosis and inflammation are minimal.
 Idiopathic thyroid atrophy may be the result of thyroiditis.
 As with thyroiditis, hypothyroidism develops slowly over
time .

9. C- Thyroid neoplasia
Does not develop until at least 75% of the thyroid has been destroyed
(Patty, 2012).
Most are euthyroid , 7 % hyperthyroid , 40 % hypothyroid
D- Other congenital or acquired forms of primary hypothyroidism
(thyroid gland dysgenesis, dyshormonogenesis, iodine deficiency) are rare.
-Many affected puppies die early in life and are categorized as ‘fading puppy’
syndrome.
-Also due to deficient dietary iodine intake.
- Causes disproportionate dwarfism.
-Ruled out in dogs being evaluated for pituitary dwarfism.

10. Central Hypothyroidism (secondary and tertiary)
 Naturally-occurring secondary hypothyroidism is rare and is
usually congenital but if acquired is most likely the result of a
pituitary tumour.
 Central hypothyroidism is most commonly associated with
congenital disorders affecting the pituitary gland (Kooistra et
al., 2000) in association with neoplasia (Mooney and
Anderson , 1993).

11. Congenital hypothyroidism
Congenital hypothyroidism (CH) is one of the most common
neonatal endocrine disorders, presenting with abnormal growth
and intellectual impairment.(shiguo liu et al,2018)
 Congenital hypothyroidism is caused by thyroid dysgenesis,
dyshormonogenesi, defects in the transport of thyroid hormones,
TSH receptor-blocking antibodies, maternal medications, or a
deficiency (endemic goitre) or excess of iodine (LaFranchi 2007).
 Congenital hypothyroidism causes impaired development of the
central nervous system (CNS) and skeleton (Beaver and Haug ,
2003 ).
 Congenital hypothyroidism is an inherited autosomal recessive
trait in rat terriers, toy fox terriers, and giant schnauzers
(Patty,2012).

12. Sings of Congenital hypothyroidism
 Congenital hypothyroidism results in mental retardation and
stunted disproportionate growth due to epiphyseal dysgenesis and
delayed skeletal maturation (Cathrine, 2010).
 Affected dogs are mentally dull and have large, broad heads, short
thick necks, short limbs, macroglossia, hypothermia, delayed
dental eruption, ataxia, and abdominal distention.
 Dermatologic findings are similar to those seen in the adult
hypothyroid dog.
 Other clinical signs may include gait abnormalities, stenotic ear
canals, sealed eyelids, and constipation.
 Affected puppies are often the largest in the litter at birth but start
to lag behind their littermates within three to eight weeks of age.

13. Subclinical hypothyroidism
 Subclinical hypothyroidism is the first phase of the disease, representing
approximately 25% of all cases (Snyder,2000).
 Subclinical hypothyroidism is defined as an elevated serum TSH level associated
with normal total or free T4 and T3 values(Michael et al .,2001)
 Subclinical hypothyroidism is associated with an increased risk of CHD events and
CHD mortality in those with higher TSH levels, particularly in those with a TSH
concentration of 10 mIU/L or greater.(rodondi et al.,2010)
 The system responds with increased thyrotropic cell sensitivity to TRH
stimulation (Castillo et al., 2001).
 The first changes are seen in lipid metabolism (increase in the LDL-cholesterol
fraction), the reproductive and immune systems, and the skin (with recurrent
infections) (Victor, 2011) .

14. Clinical hypothyroidism
 At this stage the daily secretion of T4 is severely affected.
 Clinical signs vary greatly because thyroid hormone impacts
myriad of systems .
 Clinical are not always the typical obesity, lethargy and poor hair
cover as described in many textbooks (Victor, 2011) .
1- Dermatological sign
 Dermatologic abnormalities are the most common presenting
complaints (Beale, 1993). But they appear in later stages of the
disease.
 Dermatologic changes occur in 60-80 percent of hypothyroid
dogs (Catharine, 2010).

15.  Dry scaly or greasy skin (Seborrhea sicca or oleosa), change in
coloration, strong smelling of skin , hyperkeratosis, hyperpigmentation.
Poor hair coat quality, fading of hair color, failure of hair re-growth.
 The hair is often brittle and easily epilated, and loss of undercoat or
primary guard hairs may result in a coarse appearance or a puppy hair
coat (short, softer under coat).
 Most dogs with hypothyroidism do not show generalized hair loss but
“rat tail” is common (Victor, 2011), which spares head and extremities.
 Hypothyroid dogs are predisposed to recurrent bacterial infections of the
skin like Malassezia spp. infections and demodicosis.
 Myxedema (cutaneous mucinosis) is a rare dermatologic manifestation
of hypothyroidism characterized by puffy but nonpitting thickening of
the skin, especially of the eyelids, cheeks, and forehead and is
classically referred to as ‘tragic face’ (Doering and Jensen, 1973).
Dermatological sign---
----

16.  Appearance is due to drooping of the eyelids and thickening of the lips and
of the skin over the forehead, leading to more skin folds .
 It is caused by deposition of hyaluronic acid and glycosaminoglycan in the
dermis.
 Satish et al. (2007) found skin abnormality – 94%, Generalized hair loss -
88%, Typical rat tail - 83%, Skin lesions, pigmentation and pruritus - 27%,
Brittle, dry and lusterless coat - 83% . Puppy – like coat - 22% , Myxedema -
16%.
 Other changes include ceruminous otitis, poor wound healing and increased
bruising.
 A variety of other ‘atypical’ and secondary dermatological abnormalities are
also possible. The alopecia may be patchy and asymmetric or may only affect
one area (e.g., the bridge of the nose) (Carmel, 2003).
 Retarded turnover of hair (carpet coat) or hypertrichosis can occur
particularly in Irish setters and boxers (Carmel,2003).
Dermatological sign---
----

17. Tragic facial expression

18. BMR related Signs
 Common clinical signs attributable to decreased metabolic rate
include lethargy, mental dullness, weight gain, unwillingness to
exercise, and cold intolerance.
 Obesity occurs in approximately 40% of hypothyroid dogs, but most
obese dogs suffer from over-nutrition rather than hypothyroidism
(Catharine, 2010). Many dogs may present with normal body
weight or even weight loss. This is due to poor digestion and
nutrient assimilation, as a result of altered motility of the small
bowel and less bile secretion (Gebhard et al., 1992).
 The decrease in glucose consumption leads to lethargy and
increased sleepiness, though some dogs may become aggressive
(Beaver and Haug , 2003).
 Satish et al. (2007) recorded obesity - 88%, generalized weakness,
lethargic, dull and listless, exercise intolerance, dyspnoea, gasping,
bradycardia, cyanotic tongue - 55%

19. Myxedema/tragic face

20. Obesity

21. Rat tail appearance

22. Corneal lipidosis

23. Head tilt

24. Short, soft under coat – Puppy
Coat

25. Excess callus formation.

26. Alopecia with Hyperpigmentation

27. 3- Neurologic dysfunction
A-Peripheral neuropathy
 About 2-4% dogs exhibit some behavioral changes and neurological signs such
as, head tilt, seizures, ataxia, circling and facial nerve paralysis (Nesbit et al.,1980
and Baker, 1997).
 Peripheral neuropathy caused by hypothyroidism affects primarily middle-aged
and older individuals (Jaggy et al., 1994), especially of middle- to large-sized
breeds.
 Neurological symptoms of hypothyroidism can originate from the central and
peripheral nervous systems (Rudas et al.,2005 and Nunez et al., 2008) as well as
from the muscles.
 Specific presentations and their incidence that would be included under behavioral
signs include aggression, cold intolerance (15%), decreased libido, exercise
intolerance, lethargy or mental dullness (20% to 70%), prolonged anestrus (4% to
40%), and weight gain or obesity (41% to 60%).(Bonnie V. Beaver et al,2013)

28.  In neurological manifestations of hypothyroidism, the dog may not show
any of the classical symptoms such as lethargy and dermatological
changes (Srivastava et al., 2013 and Budsberg et al.,1993).
 However, (Indrieri et al., 1987) reported dermatological changes, weight
gain and hypercholesterolaemia (Cuddon, 2002) in dogs with peripheral
neuropathies.
 Symptoms from the peripheral nervous system are exercise intolerance,
general weakness, ataxia, paraparesis, tetraparesis, deficits of conscious
proprioception, and decreased spinal reflexes (Catharine, 2010) and
symptoms of the cranial nerves such as facial paralysis (McKeown, 2002)
vestibular syndrome, trigeminal nerve (Fors, 2006), reduced spinal
reflexes and muscle atrophy (Bischel et al.,1988).
 Proprioceptive positioning deficits and decreased spinal reflexes are
generally more evident in the hind limbs, however(jaggy et al., 1994).
 The clinical signs of generalised peripheral neuropathy reduced spinal
reflexes in all four limbs can occur caused by hypothyroidism are usually
reversible after two to three months treatment using thyroid hormone
supplements (Cizinauskas et al.,2000). Intermittent, as well as constant,
forelimb lameness is described in dogs with hypothyroidism (Budsberg et
al.,1993).

29. Cardiovascular system:
 Sinus bradycardia, weak apex beat, low QRS voltages, and
inverted T waves occur in hypothyroid dogs.
 Reduced left ventricular pump function but rarely myocardial
failure in dogs.
 Dilated cardiomyopathy and hypothyroidism may occur
concurrently with dramatic long-term improvement in cardiac
function after treatment with l-thyroxine.
 Canine hypothyroidism may occur in association with other
immune-mediated endocrine disorders such as
hypoadrenocorticism and diabetes mellitus.
 Hypothyroidism causes insulin resistance and may mask the
classic electrolyte changes of hypoadrenocorticism.
Polyendocrinopathies

30. Ocular changes:
 Corneal lipidosis, corneal ulceration, uveitis, lipid effusion
into the aqueous humor, secondary glaucoma, lipemia retinalis,
retinal detachment, and keratoconjunctivitis sicca may occurs
in hypothyroidism.
Hemostasis
• Decreased plasma von Willebrand factor concentration has
been reported in hypothyroid dogs but canine hypothyroidism
is rarely associated with clinical bleeding, and platelet
function.

31. Epidemiology:
 Hypothyroidism is the most common hormone imbalance of
dogs with the incidence rate at about 1: 150 to 1: 500 (Chastain
and Panaciera, 1995).
 Dogs beyond 8 yrs are more susceptible (Panaciera, 1994).
 Most cases are seen in dogs over one year of age middle-aged
dogs and is rarely diagnosed in dogs less than two years of age
(Carmel, 2003) although perhaps 10% may be in younger
animals.
 A small number (approx. 3%) of cases are congenital, while the
rest relate to pathology acquired during growth (Victor, 2011).
 Hypothyroidism can affect any age or breed of dog (Dixon et
al., 1999).

32.  Hypothyroidism secondary to lymphocytic thyroiditis appears to
develop at a younger age than idiopathic thyroid atrophy (Patty,
2012).
 Labrador, Doberman, Golden Retriever, German shepherd,
Spaniels, Great Dane, Dachshund have great risk (Patty, 2012
and Nesbitt et al., 1980).
 More common in mid to large pure-bred dogs (Carmel, 2003).

33.  In india Spitz was showing high incidence (56%) followed
by Labrador (28%) and German shepherd (17%) (Satish et
al., 2007).
 This variation could probably be due to the habitation of
different breeds in different regions.
Spayed females and castrated males are at greater risk
(Panaciera, 1994).
Males and females, either neutered or entire, appear to be
affected equally (Carmel, 2003).

34. Diagnosis
and
Treatment

35. Total triiodothyronine (T3)
 T3 is three to five times more potent than T4 (pro-hormone).
 Measurement of T3 therefore reflects metabolic status more
accurately, but it plays no role in the diagnosis of hypothyroidism
(Carmel, 2003), as circulating concentrations are often maintained
in the reference range in hypothyroid dogs (Peterson et al., 1997).
 This is because of compensatory mechanisms both within the
thyroid gland (increasing secretion of T3), and possibly in extra-
thyroidal tissue (up-regulating peripheral T4 conversion).
 TT3 concentrations fluctuate out of reference ranges even more
than TT4 concentrations in euthyroid dogs (Catharine,2010).

36. Total Thyroxin (T4)
 Circulating total T4 concentration is invariably low in hypothyroid
dogs (Peterson et al., 1997; Dixon and Mooney, 1999).
 Extremely valuable screening test to rule out hypothyroidism unless
anti-T4 antibodies cause a spurious increase, which are produced in
2% of dogs with hypothyroidism (Graham et al., 2001).
 Basal T4 has a 95% positive predictive value, the 5% lacking are
due to the presence of T4 antibodies (Cauzinille, 2005), but it is
poorly specific due to numerous nonthyroidal factors like non-
specific hormone fluctuation in healthy dogs, breed, any non-
thyroidal illness and numerous drug therapies including
glucocorticoids, potentiated sulphonamides and anticonvulsants
(Muller et al., 2000; Kantrowitz et al., 2001).
 Thus, a low total T4 concentration alone does not confirm
hypothyroidism. Total T4 concentrations do not differ significantly
between males and females but are higher in small dogs than in
medium and large-breed dogs

37. Differential diagnosis for Thyroid hormone

38. Free thyroxin (FT4)
 Free T4 is the active fraction of total T4 and is more closely reflect
metabolic status at the tissue level than total T4.
 It is less affected by the myriad factors (drug therapies, non-
thyroidal illness, breed) and T4 autoantibodies etc. capable of
lowering total T4 and is thus a more specific diagnostic test for
hypothyroidism.
 Overall, it is considered to be the best single diagnostic test for
hypothyroidism but it is not without problems (Peterson et al.,
1997; Dixon and Mooney, 1999), as free T4 is only accurately
measured by equilibrium dialysis or ultrafiltration techniques and
these are not widely available and are relatively expensive.

39.  Certain drugs, particularly anticonvulsants and glucocorticoids,
are capable of lowering both total and free T4 concentrations
(Muller et al., 2000) and severe nonthyroidal illness has also been
associated with decreased free T4 concentration in a few cases
(Kantrowitz et al., 2001).
 With regard to THs, FT4 is the fraction that best reflects the
peripheral thyroid condition and is the first to become affected
(Wang et al., 2000).
 A decrease in FT4 is indicative of hypothyroidism in all dogs
diagnosed for clinical hypothyroidism, 30% presented with
protein-bound T4 levels close to the lower limit, with diminished
FT4 and increased TSH levels, together with morphological
alterations of the gland and clinical signs (Victor, 2011).

40. Endogenous thyroid-stimulating hormone
(TSH)
 Decreased circulating thyroid hormone concentrations reduce the
negative feedback effect on the pituitary gland and consequently, in
primary hypothyroidism, TSH concentrations rise.
 Approximately 20 to 30% (Kooistra et al., 2000), 13% to 38%
(Catharine,2010) of hypothyroid dogs have a TSH concentration
within the reference range, which might be due to suppressive
effects of concurrent non-thyroidal illnesses or from drug
therapies, non-specific fluctuation, existence of secondary
hypothyroidism or production of unrecognizable TSH isomers

41.  TSH concentrations increase above the reference range in 7% to
18% of euthyroid dogs, however, limiting the specificity of
measuring TSH alone for diagnosis of hypothyroidism
(Catharine,2010).
 TSH is the best estimator of the thyroid gland axis, and is the most
sensitive marker for evaluating thyroid function. TSH elevation is
diagnostic of hypothyroidism, independently of the T4 values
(Snyder, 2000).
 Despite the low specificity of TSH alone for diagnosis of
hypothyroidism, in dogs with concurrent low TT4 or fT4
concentration, specificity of an increased TSH concentration for
diagnosis of hypothyroidism approaches 100%.

42. Effect of Drugs on Thyroid Hormone Concentrations
 Glucocorticoids influence
peripheral metabolism of thyroid
hormones and inhibit TSH
secretion. The effect of
glucocorticoids is dependent on
the dose and specific preparation.
 In most studies oral
administration of
glucocorticoids at
immunosuppressive doses (1 to 2
mg/kg q12h) resulted in rapid
decreases in TT4, fT4, and T3,
but little change in serum TSH.

43. Evaluation of the lipid
profile
 30-40% of all dogs with hypothyroidism present with total
cholesterol elevation (Xenoulis and Steiner ,2010).
 It is important to measure LDL-cholesterol, since an
increase in relation to HDL-cholesterol can indicate thyroid
deficiency (Xenoulis and Steiner , 2010).

44. Diagnostic Tests for
Hypothyroidism in Dogs

45. Therapeutic response
 Therapeutic response has also been suggested as a method of
confirming hypothyroidism in dogs with inconclusive total T4 and
cTSH concentrations. However, caution is advised. Thyroid
hormone supplementation suppresses TSH production and
endogenous thyroid function. Hypofunction invariably occurs once
supplementation is withdrawn and can lead to confusing clinical
signs for up to eight weeks later (Panciera et al., 1989).
 Thyroid hormone supplementation is known to have several
physiological effects that can easily be misinterpreted as a
successful response to therapy in euthyroid dogs.

46. Thyroid Ultrasound
thyroid gland in many hypothyroid dogs has a smaller volume and
s-sectional area and tends to be less echogenic (Catharine, 2010).
 Ultrasound is a useful imaging tool for assessment of thyroid glands
and measurement of thyroid size.(Lyshchik et al,2004)
 Three-dimensional ultrasound is a useful and precise image method in
the measurement of thyroid volume as compared with 2D
ultrasonography, and this method enables to exactly detect the alteration
of the thyroid lobe volume in a relatively short time.(Alireza Vajhi et
al,2010)

47. How are hypothyroid dogs
treated?
 Synthetic T4 products have greater standardization and potency
and a longer shelf life compared with crude preparations. T4 itself
is considered to be a physiological pro-hormone, serves to
normalize both circulating T4 and T3 concentrations and pituitary
cTSH production, and can effectively be administered once daily.
 The recommended dose in clinical hypothyroidism is 11-22 μg/kg,
starting with the lower dose and gradually increasing the dosage
until the desired concentration has been reached. (Dixon et al.,
2002).

48.  In adequately treated dogs, there is usually a dramatic improvement
in metabolic signs within days. Dermatological abnormalities can
take several months to improve and, frequently, there is worsening
of alopecia before new hair re-growth commences.
 There is wide inter-individual variation in gastrointestinal
absorption and response to T4 replacement therapy. As a
consequence, it is important to monitor dogs after commencing
therapy.

49.  Administration of lower doses (3-10 μg/kg) in subclinical
hypothyroidism.
 Administration of lower doses in elderly animals.
 Presence of heart failure or kidney disease: administration of
lower doses in order not to overburden the affected organs.
 Gestation or proximity to mating: administration of higher doses
(between 25-50%) in order to secure good ovulation or
spermatogenesis and avoid embryonic and fetal
deaths/reabsorptions.
 Dogs with oncological diseases or chronic infections, where
metabolic rest is indicated: administration of lower doses.
Recommendation for treatment
(Victor, 2011)

50.  Dixon and Mooney (1999) advise initially administering
levothyroxine every 12h, progressing to once daily dosing).
 Reassessment can then be performed every 6-12 months (Dixon
et al.,2002).
 In the case of congenital hypothyroidism, treatment should start as
soon as possible in order to avoid irreparable damage to the
central nervous system. The dosage in puppies with congenital
hypothyroidism or juvenile hypothyroidism is 5-20 μg/kg.
 Adequately treated animals have a normal life expectancy and
quality of life.
 Regular monitoring is required and consideration needs to be
given to the development of other immune mediated
endocrinopathies (polyglandular syndromes). In such cases,
hypothyroidism most commonly occurs in association with
hypoadrenocorticism or diabetes mellitus.

53.  Improvement in activity - first 1 to 2 weeks of treatment.
 Weight loss - within 8 weeks.
 Normal hair coat- several months and the coat may initially appear
worse as telogen hairs are shed.
 Improvement in myocardial function - 8 weeks but may be delayed
for as long as 12 months.
 Neurologic deficits - 8 to 12 weeks.
 Vestibular symptoms - two to four months (Jaggy et al., 1994 and
Bischel et al., 1988 ).
Time of Clinical Improvement