case 9 - thyroid gland and thyroid hormone

Question 1

where is TRH released from

Answer 1

the hypothalamus and acts on the anterior pituitary

Question 2

what does the anterior pituitary then release

Answer 2

TSH from the anterior pituitary

Question 3

what does this TSH do

Answer 3

it activates the thyroid - T3 and T4 secretion

Question 4

what is thyroid hormone formed from

Answer 4

sequential iodination of tyrosine

Question 5

what is thyroid hormone stored as in the thyroid gland

Answer 5

colloid

Question 6

what is T4 produced by

Answer 6

entirely by the thyroid

Question 7

what is T3 produced by

Answer 7

partially by the thyroid, however peripheral T4 mono-deiodination in the liver and kidney make it metabolically active??

Question 8

what is the half life of T3 and T4

Answer 8

half life of T3 is 1-3 days and half life of T4 is 5-7 days

T3 has to be given three times daily, T4 once daily

Question 9

what does TR do

Answer 9

acts in the nucleus on gene expression, therefore thyroid hormone effects are slow

Question 9

what does TR do

Answer 9

acts in the nucleus on gene expression, therefore thyroid hormone effects are slow

Question 10

what is the HPT axis regulated according to

Answer 10

the principles of negative feedback; for primary thyroid disorders, TSH indicates thyroid status - a biomarker

Question 11

what is a goitre

Answer 11

an enlarged thyroid gland

Question 12

what is the active form of thyroid hormone

Answer 12

T3

Question 13

where does T4 get converted

Answer 13

in the peripheral tossues

Question 14

what does T3 do

Answer 14

regulates gene expression - for it to have effect it has to get into the cell and turn genes on - it is a slow process

Question 15

what is the aetiology of primary hypothyroidism

Answer 15

autoimmune thyroiditis (Hashimoto disease)
4.1/1000 females; o.6/1000 males per year over 20 years, increasing
5% of over 60s
Classic Hashimoto (goitrous)
Atrophic (non-goitrous)
In reality, a mix of antibody mediated/ T cell mediated
TPO, TSHR, Tg auto-antibodies - most important one is TSH

Question 16

what drugs can cause hypothyroidism

Answer 16

drugs (amiodarone, iodides, lithium) - these can cause hypothyroidism

Question 17

what is the aiteology of secondary hypothyroidsm

Answer 17

pituitary adenoma, congenital deficiency, irradiation
Sarcoid, infection

Question 18

what are the symptoms and signs of hypothyroidism

Answer 18

insidious
Weight gain
Cold intolerance, particularly at extremities
Fatigue, leathery
Depression
Mentally slowed, dull, expressionless
Coarse skin, puffy, (possible carpal tunnel syndrome) - aminoglycans
Dry, brittle, thinning hair
Hoarse voice
Constipation, faecal loading
Menstrual disturbance
Muscle stiffness, cramps, slow-relaxing reflexes
Generalised weakness and paraethesias
Cerebellar ataxia
Bradycardia
Macroglossia

family history
History of other autoimmune disorders

Question 19

what are some examples of organ-specific autoimmune diseases that increase the risk

Answer 19

graves disease
Autoimmune hypothyroidism
Pernicious anaemia

Addison disease
Autoimmune atrophic gastritis
Type 1 diabetes mellitus

Question 20

what does pernicious anaemia arise from

Answer 20

arises from autoimmune destruction of the parietal cells, loss of intrinsic factor secretion and consequently vitamin B12 deficiency

Question 21

what are the investigations done

Answer 21

blood tests
(TFTs)
Normochromic normocytic anaemia
Macrocytosis (also to do with B12 deficiency), mixed dyslipidaemia
Consider other autoimmune endocrinopathies
Adrenal, ovary, T1DM, pernicious anaemia, vitiligo
no need for an ultrasound scan

Question 22

what is the treatment for hypothyroidism

Answer 22

once daily thyroxine, lifelong, usually 100 mcg; young, rapid start; elderly, gentle increment
Goal; normalise TSH, repeat blood tests after 4-6 weeks

Question 23

what is *fT4↓; fT3↓; TSH↑ treated with

Answer 23

thyroxine

Question 24

what is *fT4 →; fT3 →; TSH treated with

Answer 24

nothing - this is normal - never treat with thyroxine

Question 25

what does *fT4 →; fT3 →; TSH↑ mean

Answer 25

compensated response - if there are symptoms - treat with thyroxine if there are no symptoms - wait and repeat test

Question 26

what does *fT4↓; fT3↓; TSH ↓  or → mean

Answer 26

consider potential pituitary disease / sick euthyroid syndrome

Question 27

what is a major cause of goitre and hypothyroidism

Answer 27

iodine deficiency

Question 28

what is thyrotoxicosis

Answer 28

excess circulation thyroid hormone - this is not hyperthyroidism

Question 29

what is hyperthyroidism

Answer 29

an over active thyroid gland

Question 30

what are symptoms of hyperthyroidism

Answer 30

(From most common to less usual) *Irritability, nervousness *Hyperactivity *Heat intolerance, sweating *Palpitations *Weight loss *Dyspnoea *Fatigue, weakness *Increased appetite *Increased bowel frequency *Altered mood *Insomnia *Oligo/amenorrhoea *Hair loss * *Sore throat *Family history *History of other autoimmune disorders (Graves disease)

Question 31

what would inspection show if got hyperthyroidism

Answer 31

Inspection: (clothing, weight, hair loss, eye disease, obvious goitre, ask patient to swallow)

Question 32

what would hands show if got hyperthyroidism

Answer 32

Hands:  (warm moist palms, fine tremor, palmar erythema, onycholysis, pulse rate and rhythm)

Question 33

what does percussion have

Answer 33

retrosternal goitre

Question 34

what are the extra findings

Answer 34

Extra findings:  (hyperreflexia, muscle weakness, congestive cardiac failure)

Question 35

what are the Graves specific findings

Answer 35

Graves-specific:  (thyroid orbitopathy, pretibial myxoedema, vitiligo)

Question 36

what is the integrate clinical thyroid statuses

Answer 36

Hyperthyroid Euthyroid Hypothyroidism

Question 37

what is the differential diagnosis for primary hyperthyroidism

Answer 37

(transient thyroiditis) Graves disease Toxic nodule (part of multinodular goitre) Pituitary adenoma Thyroid hormone resistance symtoms

Question 38

what would thyroid function test show

Answer 38

fT4 increases, fT3 increases, TSH decreased fT4 —>; fT3—> TSH decreased: subclinical hyperthyroidism thyroid auto-antibodies (stimulatory, mimic TSH) - helps distinguish

Question 39

what would an ultrasound of primary hyperthyroidism show

Answer 39

Increased echogenicity: homogenous (Graves) or heterogenous (MNG)

Question 40

what is the treatment for hyperthyroidism

Answer 40

block thyroid hormonogenesis - Thionamide: Carbimazole or propylthiouracil (use PTU if trying for pregnancy) - Goal: restore normal thyroid hormone levels; in time TSH should normalise Definitive treatment options (radioiodine or surgery; radioiodine is very useful for toxic nodule)

Question 41

what is Graves diseae

Answer 41

autoimmune characteristics Associated with T1DM, Addison’s disease, vitiligo, pernicious anaemia, alopecia areata, myasthenia gravis, coeliac disease

Question 42

what is the major autoantigen involved in graves disease

Answer 42

TSHR

Question 43

what are the symptoms of graves disease

Answer 43

Thyroid eye disease / Graves orbitopathy pretibial myxoedema

Question 44

what is the treatment for Graves disease

Answer 44

–Carbimazole (immunosuppressive; N.B. agranulocytosis) –Carbimazole + thyroxine –Beta blockers for symptomatic relief –Monitor thyroid function test –Trial off treatment –1/3 ‘cure’; 1/3 relapse sometime; 1/3 relapse soon

Question 45

what is graves orbitopathy

Answer 45

inflammation of the extra ocular eye muscles, causing increases retro-orbital pressure - proptosis or optic nerve damage

Question 46

what are the aggravates in graves orbitopathy

Answer 46

radioiodine aggravates

Question 47

what is it treated with

Answer 47

Treated with artificial tears, immunosuppression, debatable effects of radiotherapy