Hypothyroidism and Hyperthyroidism in dogs

By:-Rajeev MishraL-2015-V-38-MGADVASU, Ludhiana

Credit Seminar

Introduction• Thyroid gland is a vascular bilobed structure.

Hypothalamic-pituitary-thyroid axis

Hypothyroidism-Introduction• In hypothyroidism,impaired production and secretion

of the thyroid hormones result in a decreased metabolic rate.

• Most common in dogs but rarely in other species including cats,horses.

• One of the most common yet challenging endocrine diseases recognized in small animal practice.

Etiology• Structural and functional abnormalities of the thyroid

gland.

• Dysfunction anywhere in the hypothalamic- pituitary-thyroid axis may result in thyroid hormone deficiency.

• More than 95% of clinical cases result from destruction of the thyroid gland itself.

•Result from thyroid dysgenesis or from dyshormonogenesis.

Causes of Primary HypothyroidismCauses of Primary Hypothyroidism

• Lympocytic thyroiditis

• Idiopathic atrophy

• Neoplastic destruction

• Iatrogenic

Surgical removal

Antithyroid medications

Radioactive iodine treatment

Drugs

Most common causes

Lymphocytic thyroiditis

Half of all cases of adult-onset hypothyroidism result from lymphocytic thyroiditis. (Gosselin et al,1981)

Immune mediated disorder characterized by a diffuse infiltration of lymphocytes,plasma cells and macrophages into the thyroid gland.

Destruction of thyroid gland is progressive,require 1-3 years to develop.

Clinical signs of hypothyroidism only develop when approx. 75% of gland is destroyed.

Half of all cases of adult-onset hypothyroidism result from lymphocytic thyroiditis. (Gosselin et al,1981)

Immune mediated disorder characterized by a diffuse infiltration of lymphocytes,plasma cells and macrophages into the thyroid gland.

Destruction of thyroid gland is progressive,require 1-3 years to develop.

Clinical signs of hypothyroidism only develop when approx. 75% of gland is destroyed.

fgggghhResults in progressive destruction of follicles and secondary fibrosis.More prevalent in certain breeds of dogs. (Boxers,Great danes)

Results in progressive destruction of follicles and secondary fibrosis.More prevalent in certain breeds of dogs. (Boxers,Great danes)

Idiopathic thyroidal atrophy

Loss of thyroid parenchyma and replacement by adipose connective tissue.

No inflammatory infiltrate.

May be primary degenerative disorder or represent an end stage of autoimmune lymphocytic thyroiditis.

Cause of Secondary HypothyroidismCause of Secondary Hypothyroidism Pituitary malformation

-Pituitary cyst

-Pituitary hypoplasia

Pituitary destruction

-Neoplasia

Iatrogenic causes

-Drug therapy(glucocorticoids)

-Radiation therapy

Pituitary thyrotropic cell suppression.

Congenital hypothyroidism

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.

Clinical signsClinical signsDisease is most common in middle aged dogs(2-6

years).No sex related predilection.Affects middle to large size breeds.Golden Retrievers,Cocker Spaniel,Dobermann

Pinschers,Dachshunds,Boxers,setters and terrier breeds are more prone to hypothyroidism.

Neutered males and females have higher risk than intact ones.

Affects function of all organ systems.

Mainly metabolic signs+dermatological problems.

NMS,CVS,Reproductive,Gastrointestinal systems are less involved.

-Metabolic signs

•Lethargy•Mental dullness

•Weight gain•Exercise intolerance

•Heat seeking

-Dermatological signs

•Alopecia(usually bilateral symmetric)“Rat tail”

•Hyperpigmentation•Seborrhea sicca or oleosa or dermatitis

•Pyoderma•Myxedema

•Dry,brittle hair coat•Otitis externa

Hair loss and Hyperpigmentation at trunk region

Rat tail conditionRat tail condition

Alopecia at caudal thighs and lateral trunk

Tragic facial expression

• Neuromuscular signs Weakness

Peripheral neuropathy(rare)

Ataxia,Vestibular signs,circling

Facial nerve paralysis

• Cardiovascular signs Bradycardia

Cardiac arrythmias

Decreased contractility

• Reproductive signs Persistent anestrus Weak or silent estrus

• Others Corneal lipidosis,Uveitis Diarrhea Anemia Hyperlipidemia Bleeding disorders

Common clinical signs•Lethargy/mental dullness

•Alopecia/Hair loss

•Weight gain/obesity

•Dry hair coat/excessive shedding

•Anestrus

•Hyperpigmentation

•Cold intolerance/ hypothermia

•Bradycardia

% affected7o%

65%

60%

60%

40%

25%

15%

10%

• Cretinism Hypothyroidism in puppies is termed cretinism.

Retarded growth and impaired mental development are the hallmarks of cretinism.

Disproportionate body size,large broad heads, short limbs and delayed skeletal maturation due to epiphyseal dysgenesis.

Clinical signsLaboratory testsTests of thyroid gland functionUltrasonographic findingsThyroid gland biopsyTherapeutic trial as diagnostic test

Diagnosis

Laboratory tests CBC:-A mild normocytic,normochromic,non-

regenerative anemia may be present.

Increase in the number of leptocytes(target cells).

Biochemical tests:-Hypercholesterolemia and hypertriglyceridemia are the biochemical hallmark of hypothyroidism.

Hypercholesterolemia is commonly reported in 80% of affected dogs.

Cholesterol concentration can exceed 1000 mg/dl.

Increase in ALKP,ALT and creatine kinase is less common.

Tests of thyroid gland function

Serum Thyroxine(T4)Serum Free Thyroxine(FT4)Serum Thyrotropin(TSH)Serum 3,5,3’-Triiodothyronine(T3)Serum Thyroglobulin(Tg) autoantibody test,

T3 and T4 autoantibody tests.

Pre-testing recommendations

Review the dog’s current and recent drug Therapy.

Investigate and exclude non-thyroidal causes of clinical signs.

Serum Thyroxine:- Most commonly used initial screening test for

hypothyroidism.

Normal serum T4 rules out hypothyroidism.

Low serum T4 does not,by itself,confirm hypothyroidism.

Serum Free Thyroxine:- Usually measured in dogs with non-diagnostic serum

T4 test results.

Normal fT4 rules out hypothyroidism.

Decreased values are more specific for hypothyroidism than total T4.

More expensive than total T4.

T4 concentration

>2ug/dl

1.5 to 2 ug/dl

0.8 to1.5 ug/dl

0.5 to 0.8ug/dl

<0.5 ug/dl

fT4 concentration

>2 ng/dl

1.5 to 2 ng/dl

0.8 to1.5ng/dl

0.5 to 0.8ng/dl

<0.5 ng/dl

Probability of

Hypothyroidism

Very unlikely

Unlikely

Unknown

Possible

Very likely

Canine TSH:- Helps differentiate low T4 of hypothyroidism from

other causes. Should not be interpreted alone. Provides additional evidence for or against the

diagnosis of hypothyroidism.

Thyroglobulin autoantibody test:- Test of thyroid gland pathology,not thyroid gland

function. Used to identify lymphocytic thyroditis.

Total T4 decreased Total T4 normal

cTSH normal

•Non thyroidal illness

•Drug therapy

(Recommend wait and retest )

•Euthyroid

(End thyroid investigation)

cTSH increased

•Hypothyroid

(Treat with T4 therapy)

•Sulphonamide therapy

•Recovery from non thyroidal illness

(Withdraw sulphonamide therapy and retest)

Combination of elevated serum TSH and decreased T4 or fT4 has a specificity of 98% for diagnosis of hypothyroidism.

Serum TSH concentration greater than 0.6 ng/ml is consistent with hypothyroidism.

T3 is a poor gauge of thyroid gland function and should not be used to diagnose hypothyroidism.

TSH stimulation test:-• This test is currently the best means of confirming

hypothyroidism in dogs.• Low serum T4 concentration that fails to increase

adequately following administration of exogenous, bovine TSH(0.1 u/kg) confirms a diagnosis of hypothyroidism in dog.

• Obtain blood sample before and 6 hour after I/V adm. of TSH.

• Post TSH adm. ,T4 conc. <19 nmol/l is diagnostic for hypothyroidism while T4 >30 nmol/l is consistent with normal thyroid function.

Variables that may affect thyroid hormone function test results in the dog

Factor Effect•Age

Neonate(<3 month)

Aged(>6 yr)

•Body size

Small(<10 kg)

Large(>30 kg)

•Breed

(Greyhounds,Basenji,Huskies,Scottish deerhounds)

Increased T4

Decreased T4

Increased T4

Decreased T4

T4,fT4 lower than normal

No difference for TSH

Factor Effect•Gender

•Time of day

•Weight gain/obesity

•Weight loss/fasting

•Estrus

•Pregnancy

•Concurrent illness

•Surgery/anesthesia

•Drugs

No effect

No effect

Increased T4

Decreased T4,no effect on fT4

No effect

Increased T4

Decreased T4 and fT4

Decreased T4

Decreased T4

Non thyroidal illness and some specific diseases such as Hyperadrenocorticism induces a low T4 concentration.

Drugs including Sulphonamides,Glucocorticoids, Phenobarbital and aspirin can decrese T4.

Chronic adm. of Sulphonamides (>2-4 weeks) can induce clinical hypothyroidism.

Appropriate clinical signs

Clinical exclusion of NTI

Routine biochemistry and haematology test

NTI confirmed

NTI excluded

First line endocrine tests

Low total T4,

high cTSH

Normal T4, normal cTSH

Low T4 but normal cTSH

Hypothyroid

Normal thyroid function

2nd line endocrine test

fT4 and TgAA Results still unclear Start therapeutic trial test

Thyroid Ultrasonography:-Helpful in differentiating dogs with hypothyroidism

from euthyroid dogs with nonthyroidal illness causing low thyroid hormone test results.

Thyroid gland size and echogenicity decreased in hypothyroid dogs,the parenchyma may be heterogenous and the margins of thyroid gland are irregular compared with euthyroid dogs.

Lymphocytic thyroiditis and idiopathic atrophy cause a decrease in size and echogenicity of thyroid lobe.

Thyroid gland biopsy:-Reliable means of diagnosing primary

hypothyroidism. Best means to confirm lymphocytic thyroiditis.

The major disadvantage of this diagnostic test is the anesthetic and surgical risk involved.

Differential diagnosis

• Alopecia must be differentiated from:- -other endocrine disorders (hyperadrenocorticism). -Follicular dysplasia -Poor hair coat and seborrhea as a result of numerous

other disorders.• Obesity results:- -most commonly from overfeeding. -also occur in hyperadrenocorticism.

• Lethargy and exercise intolerance:-

-can also occur in metabolic,neurologic and cardiovascular disorders.

• Hypercholesterolemia can also caused by:-

-Hyperadrenocorticism

-Diabetes mellitus

-Cholestasis

-Pancreatitis

-Primary hyperlipidemia disorders.

TreatmentSynthetic levothyroxine is the treatment of

choice for hypothyroidism.Liquid and tablet formulations are effective.The initial dosage is 0.02 mg/kg,with a

maximum initial dose of 0.8 mg.The initial frequency of administration is

every 12 hours unless the levothyroxine product has been specifically formulated for once daily administration.

Initial MonitoringResponse to treatment should be critically

evaluated 4 to 8 weeks after initiating treatment.

Serum T4 and TSH concentrations should be measured 4 to 6 hours after adm. of levothyroxine.

T4 and TSH conc. should be in the reference range.

Improvement in mental alertness and activity usually occurs within the first week of treatment.

Some hair regrowth usually occurs with in the first month in dogs with endocrine alopecia.

May take several months for complete regrowth and marked reduction in hyperpigmentation of skin.

Good clinical response

Post pill

T4: <2.5ug/dl

TSH: >0.6ng/ml

2.5-6ug/dl

<0.6ng/ml

2.5-6ug/dl

>0.6ng/ml

>6 ug/dl

Increase dose

Recheck in 4 weeks

No change Measure pre-pill T4

Pre pill T4

>1 ug/dl

No change

Pre pill T4

<1 ug/dl

Increase dose

Decrease dose or once-a-day therapy

Recheck in 4 weeks

If poor clinical response then measure post-pill T4 and TSH.

If T4 value less than normal and TSH value more than normal,then increase the dose and recheck with in 4 weeks.

If T4 value normal or more than normal then re-evaluate diagnosis.

Potential Reasons for Poor Clinical Response to Treatment

Use of inactivated or outdated product.Inappropriate levothyroxine dose.

Inappropriate frequency of administration.Low tablet strength.Poor bioavailability.

Inadequate time for clinical response to occur.Incorrect diagnosis of hypothyroidism.

PrognosisFor adult dogs with primary hypothyroidism that

are receiving appropriate therapy is excellent.

Prognosis for puppies is guarded and depends on the severity of skeletal and joint abnormalities.

For dogs with acquired secondary hypothyroidism caused by suppression of pituitary function by medications is excellent.

Hyperthyroidism in dogs • Very rare condition in dogs.

• Excessive thyroid hormone secretion.

• Caused by a functional thyroid tumor(malignant thyroid carcinoma).

• Sometimes overdosing of levothyroxine for hypothyroidism.

• Older dogs,particularly (Boxers,Beagles,Golden retrievers).

Clinical signs:-• Weight loss

• Polyphagia,Polydipsia

• Polyuria

• Panting,Dyspnea

• Muscle wasting

• Tachycardia

• Mass in ventral cervical area is the most common finding.

Diagnosis

Clinical signsElevated serum T4 conc.Biopsy of cervical massCervical radiographs

Ultrasound examination

Treatment

Surgical excision of tumor.

External beam radiation therapy.

Chemotherapy.