Lecture 4 - Thyroid, hypothyroidism

embryology of thyroid

3rd w - thyroid premordium

7th w - final form

12th w - follicles w/ colloid, can bind iodine

th biosynthesis

1. active transport iodine

2. oxidation of I → I2

3. organification - iodine links to tyrosine residues of thyroglobulin

4. coupling of iodotyrosine residues

active transport iodine is stimulated by

tsh

pendrin

active transporter of iodine, in oxidation step

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is cataluzed by tpo

coupling of iodotyrosine residues

what makes up t3 and t4

t3 : dit + mit

t4 : dit + dit

secretion thyroid hormoens

colloid resoprtion, tG hydrolysis inside phagolysosomes, hormones released in perifollicular cap., iodine from mit + dit reused

which thyroid hormone is more active

t3

where is t3 produced

some thyroid

mostly extrathyroidal deiodination of t4

types iodothyronine deiodinase

1. at liver, kidney, thyroid, inhibited by pto

2. @ muscles, brain, pituitary, placenta

rt3

biologically inactive, peripheral conversion of t4 mediated by 5-deiodinase

thyroid hormones are bound to which proteins

tbg

tbpa

albumin

trh

smallest stimulating peptide hormone, w/ nuclei of origin being medial portion of pvn nucleus

trh secretion is affected by

stimulated - noradrenaline

inhibitied - serotonin

neg feedback (peripherla Th)

tsh

g glycoprotein w/ a + b subunits

tsh type of secretion

pulsatile

circadian rhythm

thyroid autoregulation

1. synthesis t3 preferred, instead of t4 if I decreases

2. wolff-chaikof effect - excess amount iodine causes inhibition TH

increased susceptibility to wolff-chaikoff effect occurs in

autoimmune (hashimoto), fetal life, admnisitration radioactive iodine

what can result after admnisitration excess iodine

goiter, severe hypothyroidism

preop administration iodine is done to

reduce thyroid vasc

mechanisms of action of thyroid hormones

genomic - t3 interacts w/ nuclear r by binding to dna

non-genomic actions

hypothyroidism

reduction/absence th production

classification hypothyroidism

primary - agenesis/dysplasia/ectopy, disorders of synthesis/secretion th, transient

central

resistance - generalised or peripheral

pendred syndrome

congenital deafness and thyroid goiter (hypothyroidism)

subacute, silent and postpartum thyroiditis are what types of hypothyroidism

transient acquired

clinical signs at birth in first months of congenital myxedema (hypothyroidism)

breathing problems, lethargy, hypotonia, abundant lanugo, neonatal hair, disinterest in feeding, constipation, goiter, delay bone maturation

hypothyroidism during fetal/baby life can lead to

hypoplasia cortical neurons, delayed myelination, decreased cerebral flow → irreversible cns damage = slow neuromotor dev

clinical manifestations hypothyroidism in kids

growth retardation, short

decreased protein synthesis, secretion gh + igf-1

disproportionate dwarfism

delayed tooth eruption, enamel hypoplasia

clinical manifestations hypothyroidism in adults

slowing down metabolism - fatigue, feel cold, exp dyspnea, weight gain, constipation, bradycardia

gags accumulation in interstitum - dry skin, dysphonia, myalgia, myxedema, periorbital edema

cardiovasc manifestations hypothyroidism

reduced co, htn, cardiomegaly

resp manifestations hypothyroidism

rhinitis, pleurisy, exertional and expiratory dyspnea

digestive manifestations hypothyroidism

constipation, decreased gastric secretion + taste, weight gain

urogenital manifestations hypothyroidism

amenorrhea, metrorragia, decreased fertility in women

decreased libido in men

endocrine system manifestations of hypothyroidism

renin low

nervous system manifestations hypothyroidism

dementia, psych disorders

headache, paresthesias, carpal tunnel

paraclinicals for hypothyroidism

neonatal screning for congenital

thyroglobulin dosage

iodine uptake w/ tsg

bone age

anemia

mri

evolution untreated hypothyroidism

progressive deterioration metabolism, myxedematous coma

risk overdose, coronary artery disease

treatment hypothyroidism

levothyroxine

t3 in er + cancer

th replacement

dosage in treatment hypothyroidism

adults - full dose

old or w/ coronary disease - low dose, increasing

CO w/ acute MI

increased tl4 requirements in hypothyroidism treatment is in

substances that increase clearance - estrogens, carbamazepine

inhibition deiodinase - selenium deficiency, cirrhosis

decreased tl4 requirements in hypothyroidism treatment is in

age

androgen admnistritation in women

myxedematous coma

most severe complication hypothyroidism, from exposure cold, infections, trauma, mi, opioids

treatment myxedematous coma

th IV, lt4 iv, ext warming, hydrocortisone

clinical manifestations myxedema coma

asthenia, bradycardia, hypothermia, elevated tsh, lactesemia

indications treatment subclinical hypothyroidism

presence sumptoms (depression, constipation), pregnancy or infertility, dyslipidemia, high anti tpo + goiter

hypothyroidism teeated before pregnancy

increase l-thyroxine dose, monthlty monitoring tsh normalization

who may develop subclinical hypothyroidism in pegnancy + higher risk abortion

women with euthryoidism + positive anti tpo atb

hashimoto’s chronic thyroiditis (HCT)

most common cause hypothyroidism, in women

idiopathic myxedema

final stage of HCT, atrophy thyroid from destruction follicular parenchyma

etiopathogeny hct

massive lymphocytic and plasmacytic infiltration, enlarged follicular cells Hurthle, fibrosis

treatment hct

lt4 if goiter, hypothyroidism, pregnancy

if thyrotoxicosis - b blockers

clinical forms hct

silent (painless) thyroidits - elevated esr, evolution to hct + hypothyroidism

postpartum thyroiditis - do prophylaxis selenium

riedel thyroidits - w/ IgG4, sclerosing fibrosis, hard + compressive goiter, treat w/ steroids

euthyroid sick syndrome

severe non-thyroid disease needing intesive therapy, changes in peripheral th + tsh → less t3,t4,tsh if low t3, sick + bad prognosis if low t4