thyroid anatomy, physiology and disease Flashcards
what is the nerve innervation of the thyroid gland?
autonomic nerve supply (Parasympathetic from vagus nerves, and sympathetic fibres from superior, middle, and inferior ganglia of the sympathetic trunk (with blood vessels)
what is the blood supply of the thyroid gland?
Superior and inferior thyroid arteries (branch of external carotid) +/- thyroidea ima
what is the venous drainage of the thyroid gland?
Three pairs of veins drain- superior/ middle thyroid vein > internal jugular, inferior thyroid vein> brachiocephalic veins
what completes the negative feedback loop in the thyroid by suppressing production of TSH and TRH?
T3
what are the 6 steps of thyroid hormone synthesis?
- thyroglobulin synthesis
- uptake and concentration of iodide (I-)
- oxidation of iodide (I-) to iodine (I)
- iodination of thyroglobulin
- formation of monoiodotyrosine (MIT) and di-iodotyrosine (DIT)
- secretion
what happens when you combine MIT and DIT?
MIT + DIT = T3 (triiodothyronine)
DIT + DIT = T4 (thyroxine)
is T3 or T4 more potent?
T3 (4 times more potent than T4), it is the major biologically active thyroid hormone
what type of T3 and T4 can enter cells?
unbound
what effects does thyroid hormone have on metabolic rate and thermogenesis?
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
what metabolic effects does thyroid hormone have?
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
what effects does thyroid hormone have on growth and development?
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
what effects do thyroid hormones have on sympathomimetic action?
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
what are the 3 types of de-iodinase and where are they found?
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)
describe hypothyroidism
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)
what are the symptoms of hypothyroidism?
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
describe hyperthyroidism?
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
what are the symptoms of hyperthyroidism?
Increased BMR
Very fast pulse rate
Increased nervousness and excessively emotional
insomnia
Sweating & heat intolerance
Tendency to lose weight easily
what is secondary thyroid disease?
hypothalamic or pituitary disease with no thyroid gland pathology
what thyroid hormones do you measure to test for disease?
TSH, free T4 and free T3
what are the hormone levels in primary hypothyroidism?
low free T3 & T4
high TSH
what are the hormone levels in primary hyperthyroidism?
high free T3 & T4
low TSH
what are the hormone levels in secondary hypothyroidism
low free T3 & T4
low (or normal) TSH
what are the hormone levels in secondary hyperthyroidism?
high free T3 & T4
high (or normal) TSH
what is myxoedema?
severe hypothyroidism and is a medical emergency
what is pretibial myxodema?
is a rare clinical sign of Graves’ disease - infiltrative buildup on lower 3rd of legs
what are the 3 causes of primary hypothyroidism?
goitrous (e.g. hashimoto’s, iodine deficiency)
non-goitrous (e.g. atrophic thyroiditis)
self-limiting (e.g. following withdrawal of antithyroid drugs)
what are the causes of secondary hypothyroidism?
Diseases of the hypothalamus and pituitary gland:
Infiltrative
Infectious
Malignant
Traumatic
Congenital
Cranial radiotherapy
Drug-induced
what are the causes of secondary hypothyroidism?
Diseases of the hypothalamus and pituitary gland:
Infiltrative
Infectious
Malignant
Traumatic
Congenital
Cranial radiotherapy
Drug-induced
what are the skin & hair clinical features of hypothyroidism?
Coarse, sparse hair
Dull, expressionless face
Periorbital puffiness
Pale cool skin that feels doughy to touch
Vitiligo may be present
Hypercarotenaemia
pitting oedema
what is the treatment of hypothyroidism?
gradual restoration of normal metabolic rate to avoid cardiac arrythymias
levothyroxine
who does myxoedema coma commonly affect?
Typically affects elderly women with long standing but frequently unrecognized or untreated hypothyroidism
what are the typical findings of myxoedema coma?
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
how do you treat myxoedema coma?
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)
what is the difference between thyrotoxicosis and hyperthyroidism?
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
what causes of thyrotoxicosis are not associated with hyperthyroidism?
- 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)
what are the hormone abnormalities in grave’s disease?
low TSH and high T3 & T4 (hyperthyroidism)
describe thyroid bruits
rare clinical sign specific to grave’s disease
associated only with large goitres
hypervascularity of the thyroid
auscultate over thyroid
describe thyroid storm
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
what is the 1st line treatment of hyperthyroidism?
carbimazole (TPO inhibitor which blocks thyroid hormone synthesis)
what drug is used as 1st line treatment of hyperthyroidism in the 1st trimester of pregnancy?
propylthiouracil (PTU)
what are the side effects of anti-thyroid drugs?
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
what other types of drugs can be used to treat hyperthyroidism?
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
what are some causes of thyroiditis?
Hashimoto’s
De Quervain’s/subacute (viral)
Post-partum
Drug-induced (amiodarone, lithium)
Radiation
Acute suppurative thyroiditis (bacterial)
what are the hormone levels in subclinical thyroid disease
abnormal TSH (high=hypo, low=hyper) with normal T3 & T4
