Endocrine One

Question 1

Where is all circulating T4 produced?

Answer 1

Produced by the thyroid glands

Question 2

What are the two sources of T3 production?

Answer 2

1. Thyroid glands 2. Rest is generated from T4 around the body

Question 3

What is is the precursor of thyroid hormones?

Answer 3

Thyroglobulin

Question 4

Does T3 and T4 normally travel around the body by itself?

Answer 4

No the majority is bound to protein

Question 5

T4 and T3 are both bound to proteins within the blood of dogs and cats. What are the proteins in dogs and what are they in cats?

Answer 5

Dogs; T4 is bound to thyroid hormone-binding globulin (TBG), transthyretin, albumin + apolipoproteins Cats: only prealbumin

Question 6

What are the three main actions of thyroid hormone?

Answer 6

1. Development 2. Growth 3. Metabolism

Question 7

What are the effects of thyroid hormone on metabolism?

Answer 7

1. Increased basal metabolic rate - increased HR, cardiac contractility, promote vasodilation
2. Effects on lipid metabolism - stimulate fat mobilisation, enhance oxidation of fatty acids
3. Effects on carbohydrate metabolism - insulin dependant entry into cells, increased gluconeogenesis + glycogenolysis

Question 8

Fill in the following:

i) Name location 1 and 3
ii) Pre-hormone 12
iii) The rest are hormones

Answer 8

Question 9

T3 and T4 can only exert their negative feedback and metabolic actions when they are in free/protein bound form:

Select the appropriate answer

Answer 9

Must be in free form

Question 10

Comment on the frequency of primary hyperthyroidism and provide three examples of conditions that could cause this:

Answer 10

Primary hypothyrodism = caused by thyroid gland disease (++++ common)

ACQUIRED:

• Iodine deficiency = goitre (can be congenital or acquired)
• Lymphocytic throiditis
• Idiopathic follicular atrophy

Question 11

For secondary and tertiary hypothyrodism:

i) Comment on the frequency of these conditions
ii) State the location where the defect occurs
iii) Provide a specific example of a condition that could lead to these defects

Answer 11

i) Both of these conditions are very rare
ii) Secondary hypothyroidism = caused by pituaritary disease whereas tertiary hypothyrodism = caused by hypothalamus
iii) Examples of secondary = pituitary neoplasia and surgical hypophysectomy, tertiary hypothyrodism = tumour entering into the hypothalamus

Question 12

What are goitrogens?

Answer 12

Goitrogens = compounds that cause hyperplastic goitre (access to cauliflower or brocoli)

Question 13

Breifly explain the pathogenesis of lymphocytic immune mediated thyroiditis:

Answer 13

Developement of canine hypothyroidism is associated with a loss of self tolerance in lymphocytes

Question 14

What are the four main clinicopathological changes that are seen with hypothyroidism in dogs?

Answer 14

1. Mild normochromic, normocytic, non-regenerative anamia - reduced metabolic rate = decreased need for O2 in peripheral tissue - decreased O2 leads to decreased EPO production
2. Hyperlipaemia - accumulation of lipids in the hepatocytes
3. Increased hepatobiliary enzymes due to hepatic lipidosis
4. Increased fructoasamine - albumin binding to glucose - occurs due to decreased protein turnover
5. Increased CK - hypothyroidism induced myopathy

Question 15

What is euthyroid sick syndrome?

Answer 15

The condition wherby a systemic conditon outside of thyroid gland creates hypothyroxaemia

Common disorders associated with ESS: Inflammatory, Neoplastic, Metabolic (e.g. renal failure), Endocrine (hyperadrenocorticism +++ common)

Question 16

What are the mechanisms of euthyroid sick syndrome?

Answer 16

• Decreased protein bound T4 decreased concentration/affinity for binding proteins
• Inhibition of TSH secretion
• Inhibition of T4 production

Question 17

Why does measurement of serum T3 have limited value is assesing whether or not an animal has hypothyroidism?

Answer 17

Significant overlap in serum T3 concentration between healthy, hypothyroid and euthyroid dogs –> limited diagnostic value

Question 18

Why might serum tT3 concentrations be used?

Answer 18

These tests can be used to assess owner compliance

Question 19

Explain what the implication of high sensitivity and low specificity is when measuring total T4:

Answer 19

If T4 is high hypothyrodism is unlikely. Low specificity - if T4 is low hypothyroidism in not confirmed

Question 20

What breed is total T4 generally low in?

Answer 20

Greyhounds

Question 21

State three conditions that can result in reduced total t4 in euthyroid dogs:

Answer 21

• Age
• Breed
• Durgs administration (particularly NSAID’s + corticosteroids)

Question 23

Evaluate the sensitivity and specificity of free T4:

Answer 23

High specificity - less affected by extra-thyroidal factors/T4AA

Medium- high sensitivity - concentration of fT4 remains on low end of RI in up to 20% of cases

Free T4 test: More expensive test, Could be useful when tT4 cocentration could be low due to extra-thyroidal factors

Question 24

Name the likely condition in each of the following circumstances:

i) Increases TSH and decreased tT4
ii) Increased TSH and increased tT4
iii) Decreased TSH

Answer 24

i) Hypothyrodism
ii) Hyperthyrodism
iii) Not primary hypothyroidism, Secondary hypothyroidism, ESS

Question 25

Complete the diagram below:

Answer 25

Question 26

What is the cause of primary hyperthyroidism in cats?

Answer 26

Caused by thyroid hyperplastic nodules or follicular adenomas

Question 27

What is the main cause of secondary hyperthyroidism in cats?

Answer 27

Excessive TSH production due to pituitary adenoma

Question 28

What factors predispose to hyperthyrodism in cats?

Answer 28

Middle ages to the elderly cats (12-13 yo)

Question 29

What are the clinicopathologic changes seen in cats hyperthyrodism?

Answer 29

1. Mild to moderate erthyrocytosis -increased metabolic rate means greater oxygen use by the tissues and hence increased production of EPO 2. Stress leucogram - mature neutrophilia, lymphopenia and eosinopenia 3. Hyperazotaemia - increased protein catabolism 4. Decreased fructosamine - increased prtoein turnover 5. Increased liver enzymes (ALT, ALP, LDH, AST) - mildly to markedly increased -due to malnutrition, liver hypoxia, direct toxic effects of thyroid hormones 6. Decrease creatinine - due to loss of muscle mass

Question 30

The measurement of free T4 has high sensitivity and lower specificity for the diagnosis of hyperthyrodism?

Answer 30

High sensitivity (98%) - if free tT4 is high hyperthyrodism is likely - useful for detecting early stages of hyperthyrodism Lower specificity (about 90%) - false negative due to ESS

Question 31

How useful is total T4 in the diagnosis of hyperthyrodism - given high sensitivity (91%) and high specificity (almost 100%)

Answer 31

High sensitivity (91%): If tT4 is also low, hyperthyrodism could be ruled out High specificity (almost 100%): tT4 is high, hyperthyroidism is likely

Question 32

How usefull is total T3 in the diagnosis of hyperthyoridism given the low sensitivity (67%)?

Answer 32

This means that we are likely to get numerous false positive results