01 Canine Thyroid Disease

• Brief overview of endocrinology • Brief overview of physiology and anatomy • Acquired hypothyroidism • Disease definition , presentation, clinical signs, differential diagnoses, aetiology/pathophysiology, disease testing, disease treatment • Congenital hypothyroidism • Canine thyroid neoplasia

Excess production (hyper…): is usually 2

• tumour of the gland

• hyperstimulation of the gland.

Decreased production (hypo…) is usually 3

• autoimmune destruction

• injury to the gland

• hypostimulation of the gland.

Hormone resistance is caused by

defect in the target tissue—> not responding normally

Other causes of endocrine disease

not hyper, hypo or hormone resistance

• defecting synthesis

• changes in hormone transport

• cysts

• tumour ± hormone effects

hormone produced in largest amount by thyroid gland (95-99% of production)

• what comes second

Thyroxine (T4)

then T3 (and rT3)

T4 controlled by

TSH

T4 production is controlled by TSH.

• this is regulated by

TRH

Thyroid hormones is formed by

iodines

4- T3

3- T3

major active Thyroid hormone

T3

T4—>T3 in vitro

T4 in the blood 1

• difference between dog and cat 2

99% is protein bound

• albumin in cats

• albumin and Thyroboundinn in dogs

Protein bound T4 acts as

reservoir

• maintain steady state concentration of free T4

Unbound Thyroid hormones are biologically

• can they enter cells?

active, capable of entering cells

Only 20% of T3 is produced by

majority of T3 is derived from

thyroid gland.

extrathyroidal enzymatic deiodination of T4.

Hypothyroidism in dogs can be

• difference between them is

Acquired (common) or congenital (rare)

time of onset

• aquired old, congenital young dog

Site of pathology: hypothyroidism can be

primary, secondary, tertiary

Site of pathology: primary, secondary and tertiary hypothyroidism 3

• most common is 1

Primary – thyroid pathology (common) Secondary – pituitary pathology (very rare) Tertiary – hypothalamus pathology

most common forms of hypothyroidism:

• time of onset

• site of pathology

Acquired (common)

Primary – thyroid pathology (common

Aetiology/pathophysiology of Primary acquired hypothyroidism 3

• which one most common

1. Lymphocytic thyroiditis (autoimmune) (common)

2. Idiopathic follicular atrophy (possible end-stage of above)

3. Neoplasia (very rare)

Congenital hypothyroidism can be 2

primary or secondary

Primary Acquired Hypothyroidism:

• signalment— age

Age: middle age to older dogs (6 – 10 y)

Primary Acquired Hypothyroidism:

• signalment—breed

Increased risk in

• Boxers,

• Dobermann pinscher,

• Border terrier

Decreased risk:

• Frenchies

• Yorkies

• pugs

Primary Acquired Hypothyroidism:

• signalment— Sex/neuter status

Neutered dogs reported increased odds

aq pri hypothyroisdiusm History and Clinical signs Two main categories

Metabolic: Dermatological:

main categories of clinical presenation: canine hypothyroidism 2

metabolic and dermatological

Metabolic clinical presentation of canine hypothyroidism 3

• name one thing that WILL NOT be seen in normal caine hypothyroid

• Lethargy

• Weight gain

• Exercise intolerance

NOT PU/PD

Dermatological cliincal presentatino: canine aquired hypothyroidism 5

• describe alopecia pattern 4

1. Alopecia/Poor hair regrowth

   • bilateral, symmetrical, flank, non-puritic

2. Pyoderma

3. Seborrhoea

4. Dry/poor quality coat

5. Hyperpigmentation

Other (uncommon) clinical signs of canine aquired primary hypothyroidism 6

• Diarrhoea

• Irregular oestrus

• Facial nerve paralysis

• Megaoesophagus

• Vestibular disease

• Laryngeal paralysis

• Lipid corneal dystrophy

pattern of alopecia in hypothyroidism

Classically bilateral, symmetric, non pruritic flank alopecia

Haematology 1, Biochemistry 4 and Urinalysis 1 reuslts : primary hypothydoisim

• what is the MOST IMPORTANT?

Non‐specific changes on haematology:

• Mild non‐regenerative anaemia

Serum biochemistry

• Increased lipids – triglycerides and cholesterol

• Mild increases in ALP, ALT, CK

Urinalysis unremarkable

Ddx hyperlipidaemia 4

• Postprandial hyperlipidaemia (post feed)

  • starve minimum 14 hr (?)

• Secondary hyperlipidaemia

• Primary hyperlipidaemia: breed related

breed with congenital 1ry hyperlipidaemia 3

1. Mini Schnauzer

2. Beagle,

3. Shetland sheepdog

Secondary hyperlipidaemia ddx 7

• Hypothyroidism

• Hyperadrenocorticism

• Diabetes mellitus

• Pancreatitis

• Cholestasis

• Hepatic insufficiency

• Protein ‐losing enteropathy

Range of specific endocrine tests available to assess the thyroid axis 5

1. Total T4 (TT4)

2. Thyroid stimulating hormone (TSH)

3. free T4 (fT4)

4. Total T3 (TT3)

5. Thyroglobulin autoantibodies (TgAA): indicate IM-thyroditis

most important first line test to assess the thyroid axis 2

Total T4 (TT4)

Thyroid stimulating hormone (TSH)

Specific Disease Testing – TT4 Very good for

initial screen for hypothyroidism in patients with compatible clinical signs

Specific Disease Testing – TT4

• If normal

• name 2 consideration/ situation when interperating normal T4 odd situations! (2)

normal—> hypothyroidism is effectively ruled out

consider when interperate:

• false negative: elevated in dogs with anti‐T4 antibodies (—> test free‐T4)

• Sighthounds have lower TT4 ‐-> consider breed specific ranges

Specific Disease Testing – TT4

• If low, then indicates 1

• false positive can be caused by

may be hypothyroidism or

(false +ve) sick‐euthyroid or drugs

• TMPs, glucocorticoid, phenobarbital

Drug effects on Thyroid testing: Trimethoprim‐sulfonamides 2

• when show? will this improve?2

Trimethoprim‐sulfonamides disturb thyroid function

• T4 below and TSH above reference ranges after 4 weeks

  • normal after 14 days

Drug effects on Thyroid testing: Phenobarbitone

alter T4 and TSH concentrations

• T4 significantly decreased

• TSH significantly increased

Drug effects on Thyroid testing: glucocorticoid

decrease T4 with normal TSH

What is sick euthyroid? 3

• what is the test result for sick euthyroid

• In response to almost any systemic illness, surgery or trauma, stress

• decreases TSH —> decrease release of TT4

• Physiologic adaptation: decreases cellular metabolism T4, increase TT4—>T3

—> Low TT4 and normal TSH

T4 value in sick euthyroid: severity of decrease depends on

more severe diseas, lower the T4 value

TSH value in sick euthyroid

decreased in most but some can be the same

So not 100% definitive

Avoid testing for thyroid when

patients are sick—sick euthyroid syndrome

Specific Disease Testing – TSH

• expected value 1

• what do you interperate this with? 1

• interperate alone?

• expect to be high but sometimes normal in dog hypothyroidism

• Elevated in little euthyroid dogs

—> Useful when interpreted with TT4 or FT4

Low TT4 with increased TSH is highly supportive of

hypothyroidism in a dog with appropriate clinical signs

Specific Disease Testing – TgAA

• is TgA common?

• what disease is it linked to

is it commonly used?

50% of hypothyroid dogs TgAA +ve

• found in dogs with lymphocytic thyroiditis

• 20% dogs with TgAA +, normal free T4 and TSH developed low free T4 and/or elevated TSH after 12 months

not generallly used

hypothyroidism: Treatment approach

Replace the missing hormone

hypothyroidism: Treatment of choice

• how to assese response 2

• when and what to measure: blood and clinical sign 4

Levothyroxine PO q12/24

• Assess response by clinical signs and TT4 concentrations

  • Measure TT4: 4 – 8 weeks after starting medication

  • Lethargy improve 4 – 6 hours after giving medication in the morning

hypothyroidism: Treatment of clinical sign: when do they imporve?

• Lethargy usually improves quickly

• Cholesterol and triglycerides can take weeks

• Dermatological changes can take months

• Anaemia slowly resolves as well

types of congenital canine hypothyroidism

primary and secondary congenital

Congenital hypothyroidism

• common clinical presentation 3

• Puppies: normal at birth and then fail to thrive or gain weight. ± dull or lethargic

• Develop disproportionation dwarfism

  • large and broad heads, protruding tongues, square trunks and short limbs

• Persistence of puppy haircoat or alopecia

Thyroid neoplasia in dogs are 3

• uncommon in dogs

• usually non‐functional

• Most are carcinomas.

Thyroid neoplasia Typically present due to 1

it may be 1

mass in the thyroid region

may be compressing local tissues

Thyroid neoplasia: best option for localised lesions

Surgery

Thyroid neoplasia: helpful palliative options in some cases with metastatic disease

chemotherapy +/‐radiotherapy