thyroid anatomy, physiology and disease

Question 1

what is the nerve innervation of the thyroid gland?

Answer 1

autonomic nerve supply (Parasympathetic from vagus nerves, and sympathetic fibres from superior, middle, and inferior ganglia of the sympathetic trunk (with blood vessels)

Question 2

what is the blood supply of the thyroid gland?

Answer 2

Superior and inferior thyroid arteries (branch of external carotid) +/- thyroidea ima

Question 3

what is the venous drainage of the thyroid gland?

Answer 3

Three pairs of veins drain- superior/ middle thyroid vein > internal jugular, inferior thyroid vein> brachiocephalic veins

Question 4

what completes the negative feedback loop in the thyroid by suppressing production of TSH and TRH?

Answer 4

T3

Question 5

what are the 6 steps of thyroid hormone synthesis?

Answer 5

1. thyroglobulin synthesis
2. uptake and concentration of iodide (I-)
3. oxidation of iodide (I-) to iodine (I)
4. iodination of thyroglobulin
5. formation of monoiodotyrosine (MIT) and di-iodotyrosine (DIT)
6. secretion

Question 6

what happens when you combine MIT and DIT?

Answer 6

MIT + DIT = T3 (triiodothyronine)
DIT + DIT = T4 (thyroxine)

Question 7

is T3 or T4 more potent?

Answer 7

T3 (4 times more potent than T4), it is the major biologically active thyroid hormone

Question 8

what type of T3 and T4 can enter cells?

Answer 8

unbound

Question 9

what effects does thyroid hormone have on metabolic rate and thermogenesis?

Answer 9

Thyroid hormones increase basal metabolic rate
-Increase number & size of mitochondria
-Increase oxygen use and rates of ATP hydrolysis
-Increase synthesis of respiratory chain enzymes

Thyroid hormones increase thermogenesis
~ 30% temperature regulation due to thyroid hormone thermogenesis

Question 10

what metabolic effects does thyroid hormone have?

Answer 10

Carbohydrate metabolism
-inc. blood glucose – due to stimulation of glycogenolysis and gluconeogenesis
-inc. insulin-dependent glucose uptake into cells

Lipid metabolism
-Mobilise fats from adipose tissue
-inc. fatty acid oxidation in tissues

Protein metabolism
-inc. protein synthesis

Question 11

what effects does thyroid hormone have on growth and development?

Answer 11

Growth
Growth hormone releasing hormone (GHRH) production & secretion requires thyroid hormones
Glucocorticoid-induced GHRH release also dependent on thyroid hormones (permissive action)
GH/somatomedins require presence of thyroid hormone for activity (permissive action).

Development of foetal & neonatal brain
Myelinogenesis & axonal growth require thyroid hormones

Normal central nervous system activity
Hypothyroidism - slow intellectual functions
Hyperthyroidism – nervousness, hyperkinesis & emotional ability

Question 12

what effects do thyroid hormones have on sympathomimetic action?

Answer 12

Permissive Sympathomimetic action
Thyroid hormones increase responsiveness to adrenaline & sympathetic NS neurotransmitter, noradrenaline, by increasing numbers of receptors

cardiovascular responsiveness also increased due to this effect – increased force and rate of contraction of heart

Question 13

what are the 3 types of de-iodinase and where are they found?

Answer 13

Type I (D1)
is commonly found in the liver and kidney

Type II (D2) is found in the heart and skeletal muscle, CNS, fat , thyroid, and pituitary

Type III (D3) found in fetal tissue and placenta and brain (except pituitary)

Question 14

describe hypothyroidism

Answer 14

Deficiency of thyroid hormones
Primary (gland) failure – may be associated
with enlarged thyroid (goitre)
Secondary to TRH or TSH (no goitre)
Lack of iodine in diet (may be associated with goitre)

Question 15

what are the symptoms of hypothyroidism?

Answer 15

Reduced BMR
Slow pulse rate
Fatigue, lethargy, slow response times and mental sluggishness
depression
deep hoarse voice
Cold-intolerance
Tendency to put on weight easily

In adults – Myxoedema – puffy face, hands & feet
Babies - Cretinism – dwarfism & limited mental functioning due to deficiency of thyroid hormones present at birth

Question 16

describe hyperthyroidism?

Answer 16

Hyperthyroidism - Grave’s disease
Autoimmune disease – TSH receptor antibodies (TRAB) acts like TSH but unchecked by T3 & T4
Exophthalmos – bulging eyes; Autoimmune inflammation of the extra-ocular muscles
Goitre –enlarged thyroid gland

Question 17

what are the symptoms of hyperthyroidism?

Answer 17

Increased BMR
Very fast pulse rate
Increased nervousness and excessively emotional
insomnia
Sweating & heat intolerance
Tendency to lose weight easily

Question 18

what is secondary thyroid disease?

Answer 18

hypothalamic or pituitary disease with no thyroid gland pathology

Question 19

what thyroid hormones do you measure to test for disease?

Answer 19

TSH, free T4 and free T3

Question 20

what are the hormone levels in primary hypothyroidism?

Answer 20

low free T3 & T4
high TSH

Question 21

what are the hormone levels in primary hyperthyroidism?

Answer 21

high free T3 & T4
low TSH

Question 22

what are the hormone levels in secondary hypothyroidism

Answer 22

low free T3 & T4
low (or normal) TSH

Question 23

what are the hormone levels in secondary hyperthyroidism?

Answer 23

high free T3 & T4
high (or normal) TSH

Question 24

what is myxoedema?

Answer 24

severe hypothyroidism and is a medical emergency

Question 25

what is pretibial myxodema?

Answer 25

is a rare clinical sign of Graves’ disease - infiltrative buildup on lower 3rd of legs

Question 26

what are the 3 causes of primary hypothyroidism?

Answer 26

goitrous (e.g. hashimoto’s, iodine deficiency)
non-goitrous (e.g. atrophic thyroiditis)
self-limiting (e.g. following withdrawal of antithyroid drugs)

Question 27

what are the causes of secondary hypothyroidism?

Answer 27

Diseases of the hypothalamus and pituitary gland:
Infiltrative
Infectious
Malignant
Traumatic
Congenital
Cranial radiotherapy
Drug-induced

Question 28

what are the causes of secondary hypothyroidism?

Answer 28

Diseases of the hypothalamus and pituitary gland:
Infiltrative
Infectious
Malignant
Traumatic
Congenital
Cranial radiotherapy
Drug-induced

Question 29

what are the skin & hair clinical features of hypothyroidism?

Answer 29

Coarse, sparse hair
Dull, expressionless face
Periorbital puffiness
Pale cool skin that feels doughy to touch
Vitiligo may be present
Hypercarotenaemia
pitting oedema

Question 30

what is the treatment of hypothyroidism?

Answer 30

gradual restoration of normal metabolic rate to avoid cardiac arrythymias
levothyroxine

Question 31

who does myxoedema coma commonly affect?

Answer 31

Typically affects elderly women with long standing but frequently unrecognized or untreated hypothyroidism

Question 32

what are the typical findings of myxoedema coma?

Answer 32

ECG: bradycardia, low voltage complexes, varying degrees of heart block, T wave inversion, prolongation of the QT interval
Type 2 respiratory failure: hypoxia, hypercarbia, respiratory acidosis
Co-existing adrenal failure is present in 10% of patients

Question 33

how do you treat myxoedema coma?

Answer 33

Intensive care, remember – A, B, C!
Passively rewarm: aim for a slow rise in body temperature
Cardiac monitoring for arrhythmias
Close monitoring of urine output, fluid balance, central venous pressure, blood sugars, oxygenation
Broad spectrum antibiotics
Thyroxine cautiously (hydrocortisone)

Question 34

what is the difference between thyrotoxicosis and hyperthyroidism?

Answer 34

thyrotoxicosis is the clinical, physiological and biochemical state arising when the tissues are exposed to excess thyroid hormone

Hyperthyroidism refers specifically to conditions in which overactivity of the thyroid gland leads to thyrotoxicosis

Question 35

what causes of thyrotoxicosis are not associated with hyperthyroidism?

Answer 35

• Thyroid inflammation (thyroiditis)
  Subacute (de Quervain’s) thyroiditis
  Post-partum thyroiditis
  Drug-induced thyroiditis (e.g. amiodarone)
• Exogenous thyroid hormones
  Over-treatment with levothyroxine
  Thyrotoxicosis factitia
• Ectopic thyroid tissue
  Metastatic thyroid carcinoma
  Struma ovarii (teratoma containing thyroid tissue)

Question 36

what are the hormone abnormalities in grave’s disease?

Answer 36

low TSH and high T3 & T4 (hyperthyroidism)

Question 37

describe thyroid bruits

Answer 37

rare clinical sign specific to grave’s disease
associated only with large goitres
hypervascularity of the thyroid
auscultate over thyroid

Question 38

describe thyroid storm

Answer 38

Medical emergency, so… A,B,C!
Severe hyperthyroidism
Respiratory and cardiac collapse
Hyperthermia
Exaggerated reflexes
May require mechanical ventilation
Typically seen in hyperthyroid patients with an acute infection/illness or recent thyroid surgery
Treatment: Lugol’s Iodine, glucocorticoids, PTU, β-blockers, fluids, monitoring

Question 39

what is the 1st line treatment of hyperthyroidism?

Answer 39

carbimazole (TPO inhibitor which blocks thyroid hormone synthesis)

Question 40

what drug is used as 1st line treatment of hyperthyroidism in the 1st trimester of pregnancy?

Answer 40

propylthiouracil (PTU)

Question 41

what are the side effects of anti-thyroid drugs?

Answer 41

Generally well tolerated drugs
1-5% will develop allergic type reactions – rash, urticaria, arthralgia
Cholestatic jaundice, ↑liver enzymes, fulminant hepatic failure (PTU)
agranulocytosis - stop all ATDs

Question 42

what other types of drugs can be used to treat hyperthyroidism?

Answer 42

beta blockers (propanolol drug of choice) - immediate symptomatic relief of thyrotoxic symptoms

radioiodine- 1st line for grave’s disease relapse (cant be used in pregnancy), risk of hypothyroidism

Question 43

what are some causes of thyroiditis?

Answer 43

Hashimoto’s
De Quervain’s/subacute (viral)
Post-partum
Drug-induced (amiodarone, lithium)
Radiation
Acute suppurative thyroiditis (bacterial)

Question 44

what are the hormone levels in subclinical thyroid disease

Answer 44

abnormal TSH (high=hypo, low=hyper) with normal T3 & T4