thyroid Flashcards
how are the thyroid hormones made? brief summary
- dietary iodine pumped into thyroid cell via Na-I symporter, then colloid
- thyroid peroxidase uses I + thyroglobulin > MIT and DIT»_space; combos T4 and T3
- TSH > endocytosis of thyroglobulin into follicle cell > release T4 and T3
T4 vs T3
T4:
more - 4:1 T4:T3
- 7 day half life
- more protein bound, 0.02% free
T3
- 20% from thyroid, 80% converted
- short half life, 1 day
- less protein bound - 0.5% free
- x10 more metabolically active
what proteins does T4/T3 bind to?
- TBG 95%
- TTR
- albumin last
HPA axis for thyroid hormone
Hypothal TRH > ant pit for TSH > thyroid for T3/T4 > neg FB to hypothal/pit
TSH also neg FB to hypothal
factors affecting TRH vs TSH secretion
TRH: inc with cold, decr with stress
TSH: inhib by - somatostatin, DA, glucocorticoids
what happens to thyroid hormone in fetal life vs birth
- <20/40 its maternal
- > 20/40 inc foetal production
- at birth: serum TSH surges at 30 MINS from cold/cord clamping
pitfalls of the NST for thyroid dysfunction
- only detects high TSH i.e. 1’ hypothyroidism
- TSH surges in first 24-36h, so testing before 48h high false positive
- 33% neonatal T4 from mum, so hypothyroidism may be missed
- false neg in premmie/VLBW, bc they cant increase levels as much, and excess iodine
thyroid ab most likely positive in:
- graves
- AI thyroiditis
- T1DM
- graves: TSHR > Tg/TPO
- AI thyroiditis: TPO > Tg > TSHR
- T1DM: Tg and TPO only
defects of TBG: when to treat
Abnormalities of TBG are not associated with clinical disease and do NOT require treatment (T4 will be low/high, but free T4 will be normal)
most congenital hypothyroidism - sporadic or hereditary?
sporadic 85% - most by thyroid dysgenesis
hereditary only 15% - most by inborn errors of thyroid hormone synthesis
levothyroxine - what can’t you mix it with?
soy formulas and iron - they’ll bind the T4
goal T4 for thyroxine treatment?
T4 in upper half of reference range
thyroid dysgenesis - key features
- most common cause of permanent congenital hypothyroidism worldwide
- 2/3 have ectopic remnants
- most unknown cause, some monogenic causes (**congenital heart defects)
dyshormogenesis of thyroid hormone- key features
- AR mutations
- 15% of congenital hypothyroidism
- always have GOITRE
causes inc:
1) defect of iodine transport
2) TPO defect **most common
3) TBG defect
4) deoidination defect
important example of a TPO defect
Pendred syndrome:
AR mutation in Cl-I transporter
triad of:
1) hypothyroid
2) SNHL
3) goitre
types of TSH hormone resistance
- fully compensated: via hypersecretion of TSH
- partially compensated: high TSH can’t fully compensate > mild hypoT: initial euthyroid, hypoT over time
- uncompensated: severe hypoT
WON’T have goitre
sick euthyroid =
normal TSH, low T3/T4
not from a thyroid problem e.g. prem, stress, sepsis
NO treatment required
Resistance to Thyroid Hormone (RTH) - key features
- AD mutations, HIGHLY heterogenous
- all: thyroid dysfunction despite high T4/T3
- not suppressed HIGH TSH
Thyrotropin Receptor (= TSH Receptor) Blocking Antibody - key points
- b/g maternal AI thyroid disease > placental t/f of Abs > TSH does not bind to receptor in neonates
- half life of Ab 21 days, remission of disease in 6 months, so don’t need tx for so long!
most common cause of acquired hypothyroidism
Hashimoto’s
examples of aetiologies for accquired hypothyroidism
- AI
- hypothal/pituitary disease
- drugs e.g. amiodarone
- haemangiomas
- infiltrative e.g. LCH
- syndromes e.g. DiGeorge
how often to monitor thyroxine treatment in hypothyroidism?
Monitor 4-6 monthly as well as 6 weeks after dose change
sick euthyroid neonate - what to do?
if T21, treat
if no T21:
- TSH > 10: treat if persists
compare:
Transient hypothyroxinaemia
Transient primary hypothyroidism
Transient hyperthyrotropinaemia
Transient hypothyroxinaemia:
- low T4, =/low TSH
- from prems, immature HPA axis, will self-correct over 1-2mo
Transient primary hypothyroidism:
- low T4, high TSH
- idiopathic/prems, self-corrects over 2-3 mo
Transient hyperthyrotropinaemia:
- high TSH, self-correct after 9mo, but must follow up to exclude dyshormonogenesis / ectopia
Hashimoto’s - 4 genetic syndromes to think of
i. APS-1 (10%) and APS-2 (70%)
ii. IPEX syndrome
iii. Turner syndrome and T21
iv. Klinefelter syndrome
hashimoto’s - key features
= chronic lymphocytic thyroiditis
- goitre + growth retardation most common, with mental dullness
- most children clinically asymptomatic
- NO ophathalmopathy!!
- TPO and Tg-Abs in 95%
- heterogenous echogenicity on USS
prominent nodules in Hashimoto’s - what to do?
should have FNA as thyroid carcinoma or lymphoma can occur
Subacute granulomatous thyroiditis (= Dequervain disease) - key features
- rare in kids
- acute: URTI + thyroid pain
- weeks-months: hypothyroid
- then normalisation in most
acute suppurative thyroiditis: most common cause?
alpha-haemolytic strep
acute suppurative thyroiditis: recurrent episodes suggest?
infection from piriform sinus fistula / thyroglossal duct remnant
congenital goitre =
Pendred syndrome (unless mum was on thyroxine/iodides)
most common cause of acquired goitre
Hashimotos (i.e. lymphocytic thyroiditis)
what is cretinism?
= severely stunted physical and mental growth due hypothyroidism
types of cretinism
- neurologic: ID, pyramidal signs. Euthyroid, normal growth. GOITRE
- myxedematous: ID, AND delayed growth with NO GOITRE, and low T4/high TSH
common causes of primary hypethyroidism
AI:
Grave’s
Initial Hashimoto’s (hashitoxicosis)
sub-acute thyroiditis (after virus)
Autonomous:
McCune-Albright
adenoma (Plummer) / MNG
carcinoma
Exogenous: iodine/thyroxine
grave’s disease - key features
- HLA-B8 and DR3
- Th cells produce TRSAb > bind to TSH receptor > hyperthyroid
- also anti-TPO
hyperthyroid + ophthalmopathy = what?
grave’s = due to antigens to eye muscle too, and may NOT resolve when euthyroid!
which anti-thyroid med to give in grave’s? key points.
carbimazole > PTU
- block TPO to reduce stores in 2-6 weeks
- trial cessation after 1-2y
important AE of anti-thyroid medications
carbimazole:
1. agranulocytosis
2. pancreatitis
3. reversible cholestatic jaundice
- teratogen!
4. GN
5. lupus like polyarthritis
PTU:
1. ANCA vasculitis
2. **fulimnant hepatic necrosis **
complications of thyroidectomy
- Hypothyroidism (50%)
- Recurrent thyrotoxicosis (10-20%)
- Hypoparathyroidism (1-2%)
- RLN palsy (1%), ELN palsy – husky voice (30%)
- BLEEDING
- Thyroid storm – if not prepared for surgery adequately
thyroid storm
increased TH from stress, infection surgery or radio-iodine therapy»_space; inc SNS drive
EMERGENCY - IV PTU/carbimazole beta-blocker, steroids and rehydrate.
most common cause of neonatal hyperthyroidism?
neonatal grave’s
key features of neonatal grave’s
- from maternal graves: transplacental TSHR-IgG
- hyperthyroid at birth unless mum taking Rx (~D7-10)
- test TSHR-Ab in 3rd trim, and TFTs D1, D7-10
- give carbimazole if needed, or iodide
key features of thyroid carcinoma in childhood
- F>M, adolescents
- high rate of mets, but usually indolent
- highest risk 15y post radiation
- papillary differentiated most common > follicular > medullary
medullary thyroid carcinoma = ??
MEN2! RET mutation, high calcitonin in serum/FNA
