Endocrinopathies I - thyroid

Question 1

Most common endocrinopathies (5)

Answer 1

Canine hypothyroidism
Feline hyperthyroidism
Canine hypoadrenocorticism (Addison’s disease)
Canine hypercortisolism (Cushing’s syndrome)
Diabetes mellitus

Question 2

Less common feline endocrinopathies: (3)

Answer 2

hyperaldosteronism,
hypothyroidism,
hyperadrenocorticism

Question 3

Definition of canine hypothyroidism.

Answer 3

Acquired condition of adult dogs characterized by primary failure of the thyroid gland to produce adequate amounts of thyroxine (T4) and triiodothyronine (T3).

Can also be a congenital form.

Question 4

Thyroid hormones are involved with what all body functions. (7)

Answer 4

● Metabolic rate
● Growth

● CNS development
● Tissue turnover

● Positive inotropic and chronotropic effect
● Cholesterol synthesis and metabolism
● Erythropoiesis stimulation

Question 5

Pathogenesis of canine hypothyroidism depending on etiology. (4)

Answer 5

Immune-mediated thyroiditis
● Lymphocytic

Idiopathic thyroid atrophy
● End-stage thyroiditis

Genetic susceptibility
● English setters, doberman pinschers, rhodesian ridgebacks, golden and labrador retrievers

Congenital - rare
● Inherited genetic defects
● Abnormal thyroid gland development

Question 6

T4 relationship to T3

Answer 6

T4 a a precursor to T3

When T4 enters the circulation, it gets converted to T3 through the process of deiodination.

Question 7

Canine hypothyroidism typically presents in what type of patient?

Answer 7

Manifests in middle age
● Mean age of diagnosis is 6.8 years

No difference in sex predilection.

Subtle, slowly progress over months to years.

Question 8

Most common Clinical signs of canine hypothyroidism.

Answer 8

● Metabolic: lethargy, mental dullness, obesity/weight gain, exercise intolerance, cold intolerance/heat seeking, general
weakness, shivering

● Dermatologic: truncal nonpruritic alopecia, “rat tail”, dry coat and skin, poor coat quality, seborrhea, hyperpigmentation, recurrent pyoderma/otitis externa, myxedema

Question 9

Dermatologic Clinical signs of canine hypothyroidism. (8)

Answer 9

truncal nonpruritic alopecia,
“rat tail”,

dry coat and skin,
poor coat quality,

seborrhea,
hyperpigmentation,

recurrent pyoderma/otitis externa, myxedema

Question 10

Less common Clinical signs of canine hypothyroidism. (5)

Answer 10

● Cardiovascular: asymptomatic bradycardia (15%)

● Neuromuscular: facial nerve paralysis, vestibular and CNS disease, polyneuropathy

● Ophthalmic: arcus lipoides

● Reproductive

● Other: constipation, vomiting, diarrhea, gallbladder mucocele

Question 11

identify the pathology in the lower picture

Answer 11

arcus lipoides = is a deposition of lipid in the peripheral corneal stroma aka the limbus.

It is the most common peripheral corneal opacity.

is a less common sign of canine hypothyroidism due to hyperlipidemia.

(upper image depicts left sided facial nerve paralysis, also a less common sign of the above disease)

Question 12

Answer 12

gallbladder mucocele secondary to canine hypothyroidism

characteristic kiwi fruit-look on ultrasound

Question 13

Signs of congenital hypothyroidism. (10)

Answer 13

● Any signs noted in hypothyroid adults
● Disproportionate dwarfism
(vs proportionate of pituitary dwarfism)

● Wide skull
● Macroglossia

● Delayed dental eruption
● Square trunk and short limbs

● Constipation
● Mental impairment

● Goiter → dysphagia/dyspnea
● Delayed skeletal maturation, epiphyseal dysgenesis (end of long bones).

Question 14

Diagnostic testing using routine blood tests for diagnosis of canine hypothyroidism.

Answer 14

Nonspecific hematologic and biochemical changes lend supportive evidence to ap resumptive diagnosis of canine hypothyroidism.

Including/excluding non-thyroidal illnesses

Hematology:
● Mild normochromic normocytic nonregenerative anemia

Biochemistry:
● Fasted hyperlipidemia (hypercholestrolemia +/- hypertriglyceridemia)
● Increased creatine kinase activity

● Increased fructosamine
● Mild increases in liver enzyme activities (ALP, GGT)

Question 15

Possible Hematological changes in canine hypothyroidism.

Answer 15

● Mild normochromic normocytic nonregenerative anemia

Question 16

Possible biochemical changes in canine hypothyroidism.

Answer 16

● Fasted hyperlipidemia (hypercholestrolemia +/- hypertriglyceridemia)

● Increased creatine kinase activity

● Increased fructosamine (due to be protein bound and thyroid hormones affect blood proteins)

● Mild increases in liver enzyme activities (ALP, GGT) (secondary increase)

Question 17

Diagnostic testing using thyroid testing. What tests may be used? (4)

Answer 17

● Total thyroxine - TT4
● Free T4 - fT4

● Thyroid-stimulating hormone - TSH

Question 18

When suspecting immune mediated thyroiditis, what specific blood test should you order?

Answer 18

Thyroglobulin autoantibody - TgAA

Question 19

Isolated low TT4 should not be the only criteria used to diagnose canine hypothyroidism so how can it be definitively diagnosed?

Answer 19

High clinical suspicion + TT4 below/lower end of the reference range → evaluation
of fT4 and TSH next.

● Definitive diagnosis requires: TT4 ↓ + fT4 ↓ + TSH ↑

NB! 20-40% of dogs with overt hypothyroidism have TSH within ref. values.

NB! Two of the three hormone concentrations indicative of hypothyroidism is enough to support the diagnosis in a patient with compatible clinical/biochemical abnormalities.

Question 20

Why should Thyroid testing be done after clinical stabilization/disease recovery?

Answer 20

Other illness may cause reduced TT4 - euthyroid sick syndrome. Gives the illusion of hypothyroidism.

● Severe illness can also suppress fT4
● during euthyroid sick syndrome, TSH will be subnormal/WRI

Drugs can cause the illusion as well:
decreased TT4 and/or fT4, TSH increased/WRI
● e.g. Phenobarbital, clomipramine, toceranib phosphate, glucocorticoids, sulfonamides.

Question 21

Why Consider patient’s breed and purpose when presented with low thyroid hormone?

Answer 21

Some animals may have naturally low T4 levels due to breed or work.

● Certain breeds: greyhounds, salukis, Alaskan sled dogs, shar peis, deerhounds
● Active working dogs

Question 22

Thyroglobulin autoantibody - TgAA can cause falsely elevated TT4 result. Why?

When is it warranted to test for TgAA? (3)

Answer 22

It cross reacts.

Test for it when you have a strong suspicion of Lymphocytic thyroiditis
and when a Normal dog has elevated TT4.

As well as when TT4 WRI in a dog with clinical/biochemical abnormalities suggesting hypothyroidism.

Question 23

Describe the TSH response test.

Answer 23

Use when:
● You have TT4/fT4 low-normal + no antithyroid antibodies
● When Diagnosis cannot be confirmed using clinical signs and basal tests due to the above.
● When Differentiating hypothyroidism and euthyroidism (non-thyroidal illness)

Human recombinant TSH IV 50-75 mcg/dog, 100 mcg for dogs >20 kg, samples before and 6 h after administration.
Not done commonly because its so expensive.

Euthyroidism: post-TSH TT4 >1.5 times the basal level with an absolute value
>30 nmol/L.

Hypothyroidism: minimal stimulation, post-TSH TT4 <20 mmol/L

Question 24

Review.

Question 25

Summary of categorical approach to diagnosing suspect. canine hypothyroidism.

Answer 25

fT4ed = free T4 equilibrium analysis (more accurate than normal version)

Question 26

Therapy for treatment of canine hypothyroidism.

Answer 26

Oral hormone replacement for life using levothyroxine sodium.

Synthetic T4 in tabl form, ideally Given on an empty stomach to increase bioavailability which is already low with thyroxine in dogs.

Starting dosage 0.02 mg/kg q12h
● Based on lean body weight! (lipophilic drugs)

Needs to be twice daily!
● q12h lower peak concentrations, less fluctuation in circulating TT4 than q24h and less side effects.

Veterinary approved medications on the market.

Question 27

Monitoring of canine hypothyroidism includes what. (2)

Answer 27

● Clinical improvement should be rapid.
No clinical signs = adequately treated.

Metabolic improvement within days,
10% loss of weight within the first few months

Dermatologic improvement within a month, can take 2-3 months to normalize, phase of increased hair loss
preceding hair regrowth.

Neurologic improvement can take as long as 6 months.

● Serial TT4 testing (measure PEAK concentrations, 4-6 hours after morning pill)

Question 28

When to check T4 after initiation of therapy?
What level do you aim for?

Answer 28

4 weeks after starting supplementation

● Unless signs persist or signs of iatrogenic hyperthyroidism develop.

Peak serum TT4 concentration assessment
● Blood sample 4-6 hours post-pill

Dose adjustments monthly until post-pill T4 is in the upper half/slightly above the reference range.

● Doubling the T4 dose increases peak circulating TT4 concentrations by about 50-60%

Question 29

When to check TSH after initiation of therapy?

Answer 29

TSH
● Normalizes with treatment
● Not required to confirm
● Identification of poor owner compliance

Question 30

Once control of hypothyroidsim is achieved, how often to you ask the client back for a recheck?

Answer 30

continue therapy q12h,
and monitor TT4 q 6-12m

Alternative option:
after several months assess pre-pill level TT4:

If T4 is higher than >1.5 mcg/dL: q12h → q24h (you can attempt 1x/day.

If T4 is lower, <1.5 mcg/dL: continue q12h/increase the q24h dose by at least 50% and assess a month later both
pre- and 4-6 h post-pill T4.

Question 31

Describe Myxedema coma.

Answer 31

● Rare, life-threatening complication (controversial in vet med)

● Significant reduction in metabolic rate

In addition to typical clinical signs:
● Impaired mental status ranging from obtundation to coma
● Hypothermia without shivering
● Bradycardia
● Cold extremities
● Poor pulse quality
● Systemic arterial hypotension
● Myxedema
● Hypovolemia, dehydration possible

Initially PO/SC/IM not adequate - T4 5 microg/kg IV q12h, PO once stabilized.

Resolution of abnormal mentation, ambulation and systolic hypotension within 30 h.

Question 32

Overview of Feline hyperthyroidism.
Typical patient?

Answer 32

● Extremely common
● Benign adenomatous hyperplasia of one or both thyroid glands, (thyroid
carcinoma)

● Cause not known
● Genetic and environmental influences

● Excessive circulating levels of T4 and T3
● Hypermetabolic state

Typically cats Older than 10 years (but test from 5 years up if indicated)

Question 33

Clinical signs Feline hyperthyroidism.

Answer 33

Classic presentation:
weight loss,
polyphagia,
hyperactivity

May be minimally symptomatic/asymptomatic.

Apathetic hyperthyroidism is also possible - opposite of the typical hyperactive type. This one has lethargy and poor appetite.

Question 34

Physical examination findings in Feline hyperthyroidism. (5+)

Answer 34

● Weight loss, muscle loss (Decreased skin elasticity)
● Unkempt appearance

● Palpably enlarged thyroid glands
● Heart murmur, arrhythmia, gallop

● Hypertension (causes hypertensive retinopathy) (and measuring BP isn’t reliable due to stress intolerance in FHT so more reliable is a fundic exam)

● Comorbidities

(panting due to stress intolerance)

Question 35

Common comorbidities in Feline hyperthyroidism. (6)

Answer 35

● Thyrotoxic heart disease
● Hypertension
● Retinopathy (caused by hypertension)

● CKD (FHT might mask CKD so when FHT is managed, CKD comes to light)

● Gastrointestinal disease, malabsorption, cobalamin deficiency

● Insulin resistance (elevated thyroid hormones cause this)

Question 36

Common conditions with similar signs. (5)

(PU/PD, weight loss + good/excessive appetite)

Answer 36

● Diabetes mellitus (PU/PD & weight loss is similar to FHT)

● Gastrointestinal malabsorption/maldigestion (weight loss with polyphagia similar to FHT)

● Gastrointestinal neoplasia (lymphosarcoma)

● Parasitism

● Chronic kidney disease (PU similar)

Question 37

minimum diagnostics to diagnose FHT and identify comorbidities

Answer 37

CBC
● Mild erythrocytosis, macrocytosis
● Eosinopenia, lymphopenia

Chemistry
● ALT/ALP increase
● Azotemia - dehydration/concurrent renal disease

Urinalysis
● USG <1.030

(Chest radiographs, echocardiography, abdominal imaging)

Question 38

Hematological changes that can be seen in FHT.

Answer 38

● Mild erythrocytosis, macrocytosis (due to T4 causing increased erythropoiesis etc., macrocytosis = younger, bigger cells)

● Eosinopenia, lymphopenia (chronic diseases cause anemia)

Question 39

Biochemical changes that can be seen in FHT.

Answer 39

● ALT/ALP increase (secondary to primary dz)

● Azotemia - dehydration or concurrent renal disease

(Urinalysis in FHT: USG <1.030 )

Question 40

Diagnosis of FHT - explain the thyroid hormone assays and results used.

Answer 40

Persistently elevated thyroid hormones + one or more clinical signs.
● T4 above reference intervals confirms the diagnosis in >91% of FHT cats.

Concurrent disease may cause the serum T4 level to be lower - fT4 helps confirm this.

● Cats with clinical hyperthyroidism and normal T4:
T4 + fT4 2-4 weeks after the first blood analysis (T4 naturally fluctuates so 2 measurements is more reliable):
T4 in the upper half of the reference + elevated fT4 supports diagnosis.

TSH if early/subclinical disease - postpone treatment if TSH is measurable to
avoid iatrogenic hypothyroidism.

Question 41

Summary of categorical approach to diagnosing suspected feline hyperthyroidism.

Answer 41

Question 42

Describe T3 suppression testing.

Answer 42

● Indication: clinical FHT but equivocal basal thyroid hormone results (uncertainty).

Administration of exogenous T3 to see what type of response.

● Normal cats should: TSH ↓ → TT4 ↓

● FHT cats: TSH is chronically suppressed - little or no effect on TT4.

● 2 days of injections with 8 hours between and 2 visits for blood collection.

Question 43

Thyroid scintigraphy refers to:

Answer 43

Thyroid gland uptake of pertechnetate or radioactive iodine.

Question 44

Treatment of FHT.

Answer 44

Fatal if left untreated.

Same treatment regardless of clinical presentation/concurrent disease.

Goal: restore euthyroidism, avoid hypothyroidism, minimize side effects.

Therapy options:
● Radioactive iodine
● Oral antithyroid medication: methimazole/thiamazole
● Iodine-deficient therapeutic diet
● Surgical removal of the adenomatous thyroid gland.

Question 45

Describe Treatment of FHT with radioactive iodine.

Answer 45

● Treatment of choice because its curative.
● Cure in >95% of cases, relapse rate 5%

● Kills abnormal cells - definitive treatment.
● One inj/oral capsule.

● T4 is WRI 4-12 weeks post-treatment, resolution of clinical signs may take several months.

● Requires special license and facility, isolation of the cat for 3 days-4 weeks.

● Minimal risk of iatrogenic hypothyroidism
● Ensure TSH is undetectable before treatment
● May not be available everywhere.

Question 46

Treatment of FHT with antithyroid medication.

Answer 46

● Methimazole/thiamazole: oral/transdermal
- 1.25-2.5 mg q24h 1 week, then 2.5-5 mg q12-24h

● Inhibits biosynthesis of thyroid hormones by blocking thyroid peroxidase.

● Does not destroy hyperplastic/adenomatous thyroid tissue.

● Long term (life long)/short term (before surgery/trial to predict the risk of renal compromise after definitive therapy).

● Response rate ⩾95%
● Euthyroid within 2-3 weeks, clinical response when T4 is WRI for 2-6 weeks.

Question 47

Periodic monitoring when treating FHT with antithyroid medication.

Answer 47

To avoid hypothyroidism, drug does not affect the growth of the adenomatous hyperplasia so doses need to be adjusted over time.

● T4-check q2-4w until T4 between 12.9-32.3 nmol/l.

● Dose adjustments in 1.25-2.5 mg/day increments.

● Blood sample may be taken at any time during the day.

Initially q2-4w.
Stable, uncomplicated hyperthyroid cats q4-6m: T4, CBC, chemistry panel,
urinalysis

Question 48

Treatment of FHT with thyroidectomy.

Answer 48

● May be curative
● ⩾90% cure rate
● Relapse rate 5% within 3 years

Risks:
● Anesthesia in a cat with potential cardiac compromise

● Parathyroid gland damage - hypoparathyroidism (hypocalcemia) transient/permanent.

● Horner’s syndrome, laryngeal nerve paralysis.

● Hypothyroidism risk

● Possible ectopic thyroid tissue that is not easily removed.

● Medically stabilized before surgery
● Euthyroidism within 24-48 h

Question 49

Treatment of FHT with iodine deficient diet.

Answer 49

● The only function of ingested iodine is for thyroid hormone synthesis.

● Response rate ⩾82%

● Improvement of clinical signs in 1 month, may take several months.

● No access to any other food, indoor cats.
● Palatability may be a problem

● Feeding the iodine-deficient diet to non-hyperthyroid cats in the household is not harmful.
● Safe in cats with CKD.

Question 50

What to watch out for when monitoring FHT treatment?

Answer 50

T4, TSH
- Avoid iatrogenic Hypothyroidism

Renal parameters
- BUN, creatinine, USG, P, K

CBC
- Hematological side effects (methimazole can cause side effects here)

Question 51

Explain thyroid storm.

Answer 51

Rare, life-threatening complication of FHT.
Rapid increase in serum thyroid hormone

Causes
● Damage to the thyroid gland: I therapy, vigorous thyroid gland palpation.

● Abrupt withdrawal of antithyroid medication
● Anesthesia

● Exacerbation of non-thyroid disease
● Stressful event

● Prophylactic treatment: atenolol (beta-adrenergic antagonist) 6.25 mg/cat q24h
at least 24 h prior to the event

Question 52

Overview of feline HYPOthyroidism.

Answer 52

Rare

Single low T4 - interpret in the light of the entire clinical picture just in case of euthyroid sick syndrome (seems hypo but is actually eu-).

Question 53

Clinical signs of feline hypothyroidism.

Answer 53

Lethargy,
constipation,
retained deciduous teeth,
abnormal hair coat, and
thickened gingiva are common findings.

cats with naturally occurring hypothyroidism are more likely to be azotemic compared to dogs with it.

Question 54

Congenital hypothyroidism is usually identified in

Answer 54

cats younger than 1 yr of age and most frequently in kittens younger than 8 mo.

Affected kittens are usually stocky, with shorter limbs and a broader than usual head and neck.

+ retained deciduous teeth

Question 55

Diagnosis of feline HYPO thyroidism.

Answer 55

requires demonstration of a low serum T4 (0.8 mcg/dL) and elevated TSH concentrations.

Demonstration of low serum fT4 levels may also suggest hypothyroidism.

+ azotemia

Question 56

Treatment of feline hypothyroidism.

Answer 56

similar to treatment in dogs.

Levothyroxine sodium is recommended, with an initial dose range of 0.05–0.1 mg daily.

The dosage is adjusted to target T4 levels between 1.0 and 3.0 mcg/dL.

Clinical signs may persist for 2–3 months before responding to treatment.

Question 57

Describe iatrogenic hypothyroidism in cats.

Answer 57

is caused by overdosing with antithyroid drugs such as methimazole, surgical removal of the thyroid glands, or I treatment.

Can contribute to decreased renal function.

Treatment when T4 <1 mcg/dL + elevated TSH

Question 58

A possible cause of symmetrical alopecia in male dogs.

Answer 58

Hyperestrogenism syndrome: estrogen-producing testicular Sertoli cell tumor.

Question 59

what hematological changes can hypothyroidism cause?

Answer 59

Mild normochromic normocytic nonregenerative anemia and thrombocytosis

Question 60

what biochemical changes can hypothyroidism cause?

Answer 60

increased CHOL/TRIG
increased CK
increased FRU
mild increases in liver values
rare but can also cause hyperkalemia

Question 61

plain low TT4 is not enough to diagnose thyroid disease in

Answer 61

dogs

measure TT4, fT4 & TSH

if 2 out of 3 are abnormal, hypothyroidism criteria is filled.

Question 62

starting dosage for levothyroxine in dogs?
when recheck?

Answer 62

0.02 mg/kg q12h

give on empty stomach

(recheck in 4 weeks, measure T4)

eventually rechecks can be q6-12m