Endocrinology Flashcards
1
Q
regulation of thyroid axis
A
TRH
- released from hypothalamus
- increases TSH production and secretion
TSH
- released from anterior pituitary
- stimulates thyroid hormone synthesis
- > via TSH-receptor
- > G protein coupled
- > increases cAMP
thyroid hormones
- high levels
- > inhibit TRH and TSH
- low levels
- > increase basal TSH and responsiveness to TRH
other
- cold
- > increased TRH secretion
- emotions
- > excitement/anxiety = increase in TRH
- smoking
- > decreases action of thyroid hormones
- estrogen
- > increases thyroxine binding protein
- > increases total thyroid hormone
- androgen
- > do the opposite
- drugs (eg. phenytoin)
- > interfere with thyroid hormone protein binding
2
Q
thyroid hormone synthesis
A
iodine
- source
- > fish, seaweed and seafood
- > diary products
- > iodised salt
- blood transport
- > bound to albumin
- basolateral transport
- > Na Iodide Symporter (NIS)
- > increased expression in deficiency
- > decreased expression in excess
- apical transport
- > pendrin
in lumen (colloid)
- organification
- > oxidation by thyroid peroxidase
- > iodide -> iodine
- bind to tyrosine residues of thyroglobulin
- > monoiodotyrosine
- > diiodotyrosine
- ester bonds join iodotyrosines
- > catalysed by thyroid peroxidase
- > MIT + DIT = T3
- > DIT + DIT = T4
- thyroglobulin transported by into follicular cell
inside follicular cell
- T3/T4 released from thyroglobulin within lysosomes
- > MIT and DIT recycled
transported into blood
- serum binding proteins
- > thyroxine binding protein
- > albumin
- 99% protein bound
- > higher proportion of T3 free
- T4 produced 20x more than T3
- > T3 binds to receptor with higher affinity
- T3 is more potent hormone
- > T4 converted to T3 by deiodinases
- > types I, II, III
3
Q
thyroid hormone action
A
predominately gene transcription
- T3/4 binds to nuclear thyroid hormone receptors
- > alpha and beta
- bind to thyroid response elements
- > promoter region of target genes
- > increase or decrease gene expression
metabolism
- greatly increased by thyroid hormones
- > food utilisation
- > protein synthesis and catabolism
- mitochondria
- > increase in number and size of
- > increase in ATP formation
- ion transport
- > increases activity of Na/K ATPase ->generates heat
- > leaky membranes to Na drives Na/K ATPase further
- carbohydrates
- > increased insulin secretion and glucose uptake
- > increase glycolysis/gluconeogenesis
- lipids
- > increased lipolysis
- > increased fatty acid oxidation
- > increased free fatty acids, but decreased cholesterol, triglycerides and phospholipids
- > increases LDL receptor on liver
- > hypo results in fatty liver and atherosclerosis
- weight
- > increase and decrease with hormone level
cardiac
- production of metabolic waste and consumption of O2
- > vasodilation and peripheral blood flow
- > increases CO
- heart rate
- > increases excitability of the heart -> increase HR
- contractility
- > initially increased
- > in chronicity leads to decompensation and failure
- blood pressure
- > mean pressure remains normal
- > pulse pressure widened
resp
- increased O2 consumption with metabolism
- > tachypnea
- > increased tidal volume
GI
- increased appetite
- increased motility and gastric secretions
- > diarrhoea
Muscles
- hyper = initially increased reflexes
- > weakened with chronicity due to catabolism
- hypo = weak and sluggish reflexes
Neuro
- racing thoughts
- anxiety, paranoia, worry
- tremor
- > due to excitability
sleep
- increased metabolism = tiredness
- increased excitability = insomnia
sexual function
- men
- > hypo = loss of libido
- > hyper = impotence
- women
- > hypo = menorrhagia/amenorrhea, irregularity
- > hypo = loss of libido
growth
- skeletal growth in children
- brain development in neonate and fetus
4
Q
high/low TSH causes
A
High TSH
- hypothyroidism
- TSH secreting pituitary tumour
- thyroid hormone resistance
Low TSH
- thyrotoxicosis
- first trimester pregnancy
- > suppression by hCG
- after treatment for hyperthyroid
- medications
- > glucocorticoids
5
Q
causes of hyperthyroidism
A
IGNITE
- Inflammation (thyroiditis)
- > infection
- > radiation
- > amiodarone
- > occasionally early silent or subacute thyroiditis
-Graves
- Neoplasia
- > hydatiform mole
- > chorciocarcinoma
- Iodine induced
- > jod basedow phenomenon in autonomous nodules
- > contrast
- > amiodarone
- Toxic nodules and adenoma
- > gain of function mutations giving autonomy
- > TSH receptor
- > alpha subunit of stimulating G protein
- Exogenous
- > thyroxine replacement
6
Q
causes hypothyroidism
A
II CHRIST
- Iodine
- > deficiency most common
- > excess (wolff chaikoff effect)
- Infiltration
- > reidells thyroiditis (fibrous)
- > sarcoid/amyloid/haemochromatosis
- Central (rare)
- > secondary = anterior pituitary
- > tertiary = hypothalamus
- Hashimotos
- Resistance (rare)
- > mutation in nuclear receptor for T3
- Iatrogenic
- > radiation
- > surgery
-Subacute/silent thyroiditis
- Transient
- > ->withdrawal of exogenous
7
Q
symptoms of hyperthyroidism
A
SWEATTIIINGG
- skin
- > sweaty
- > warm
- > onycholysis
- > alopecia
- > thyroid acropatchy in graves
- weight loss
- eyes
- > staring
- > lid lag
- > exophthalmos in graves
- appetite increased
- tachycardia
- tremor
- insomnia
- intolerance of heat
- irregular menstruation
- neuro
- > nervous
- > emotional lability
- GI
- > diarrhoea and malabsorption
- goitre
8
Q
symptoms hypothyroidism
A
MOM’S SO TIRED
- memory loss
- obesity
- menstrual irregularity
- slowness (speech/mental and physical)
- skin
- > dry, coarse (including hair)
- > cool
- > dry
- > myxedema
- output (cardiac) decreased
- > reduced exercise tolerance
- > SOB
- tiredness
- intolerance of cold
- reflexes sluggish
- eyes
- > periorbital oedema
- depression
9
Q
thyroid storm aetiology, manifestations, management
A
cause
- usually in patients with longstanding hyperthyroidism
- > graves
- > toxic nodules or adenoma
- thyroid surgery
- trauma
- infection
- acute iodine load
- parturition
clinical manifestations
- exaggerated presentation of thyrotoxicosis
- cardiovascular
- > tachycardia
- > arrhythmias
- > cardioresp failure
- fever
- altered mental status
- > anxiety
- > delirium/psychosis
- > coma
lab manifestations
- TSH and thyroid hormone levels are not greatly altered
- free T3 and T4 greatly increased
management
- in ICU
- same as usual thyrotoxicosis treatment but larger doses
- > beta blockers
- > glucocorticoids
- > iodine solution
10
Q
what is sick euthyroid syndrome
A
any acute illness can cause abnormalities in circulating TSH or thyroid hormones in the absence of thyroid disease
-thought to be due to release of cytokines such as IL-6
low T3 syndrome
- most common
- features
- > normal TSH and T4
- > decrease in total and unbound T3
- cause
- > impaired deiodination of T4 in the periphery
- > decreased clearance of reverse T3
low T4 syndrome
- very sick patients
- type 3 deiodinase
- > increased expression in muscle and liver with decreased tissue perfusion
- accelerates T3 and 4 metabolism
11
Q
Graves aetiology and autoimmunity
A
Aetiology
- genetic
- > eg. HLA-DR polymorphism
- environmental
- > smoking
- > stress
- > post partum
- > iodine (amiodarone, contrast)
Autoimmunity
- anti bodies to TSH receptor
- > thyroid stimulating Ig (TSI)
- > activate receptor
- also antibodies to
- > thyroid peroxidase
- > thyroglobulin
- spectrum
- > graves, hashimotos, silent thyroiditis
12
Q
Graves pathophys and path
A
Pathophys
- insult or infection to thyroid epithelial cell
- infiltrating T cells
- > produce interferon gamma
- expression of HLA class II molecule
- > initiates autoimmune cascade
- TSI
- > hormone over production
- > follicular cell hypertrophy and hyperplasia
pathology
- thyroid diffusely englarged
- > follicular hyperplasia
- > intracellular colloid
- > reduced follicular colloid
- lymphocytic infiltration
- > predominately T cells
- > some B cells
13
Q
pathophys of pretibial myxoedema and orbitopathy
A
fibroblasts
- express TSH receptor
- > stimulation by TSI
- also activated by local cytokines from lymphocytes
- produces GAGs
- > in mucinous oedema
- > dermis = myxedema
- > retro-orbital = proptosis
also in orbitopathy
- invasion of muscles
- > lymphocytes
- > mast cell
- > macrophages
- causing
- > impaired venous return
- > pressure on optic nerve
- > ulceration
also in myxedema
- non pitting oedema
- > fragmentation of dermal collagen
- > compression of lymphatics
14
Q
aetiology, pathophys and path of hashimotos
A
aetiology
- genetic
- > HLADR polymorphisms
- > CTLA-4 polymorphisms
- environmental
- > pregnancy
- > smoking
- > excessive iodine intake
pathophys
- antibodies
- > TPO/Tg = secondary role fix complement/membrane attack complex
- > TSH-R = blocking antibody
- lymphocytes
- > CD8 cytotoxic t cells destruction
- > cytokines, interferon gamma = apoptosis
path
- profuse lymphocytic infiltration
- > both T and B cell
- > within follicle = peripolesis
- lymphoid germinal centers
- destruction of thyroid follicles
- > absence of colloid
- > varying degrees of fibrosis
- progression to atrophic in chronicity
- > more extensive fibrosis
15
Q
autoimmune associations thyroid disease
A
CRASHPADS
- coeliac
- rheumatoid
- alopecia areata
- srojens
- hepatitis (chronic)
- pernicious anaemia
- addisons
- diabetes (type I)
- SLE
+vitiligo
