Lecture 19: Thyroid Flashcards
HPT axis
PVN -> TRH -> TSH -> T3, T4
- T3/T4 neg. fb on TRH/TSH
- TRH stim. by: stress, cold, fed, circadian
- TRH inhib. by: T4/T3, fasting/starvation
Thyrotrope also forms some T3 -> downreg. TRH receptors
Thyroid hormone forms
rT3 = inactive T3 form
T4 = longer blood half life due to transporter affinity
T3 = more active form; often T4 -> T3 by target tissue
Thyroid gland structure
Follicles w/ central glycoprotein colloid core; follicular epithelial cells apically face colloid, basolateral towards blood
Thyroid hormone synthesis process
- Derived from Tyr, iodine
1. [Rate limit.] dietary I- taken up from blood via follicular symporter - TSH stim. Na/I symporter
2. Thyroglobulin synth. + glycosylation + secretion to colloid - Tyr source
3. Iodide oxidation via Thyroid Peroxidase (TPO), H2O2; w/ I- secretion via pendrin transporter
4/5. Tyr iodination + coupling; DIT + MIT coupled to T3, T4. Also TPO catalyzed.
6/7. Reabsorption + secretion. TG endocytosis to lysosomes; proteases release T3/T4/rT3 (blood secretion), MIT/DIT (recycle).
Wolff-Chaikoff effect
Very high iodide levels transient. inhib. thyroglobulin iodination and TH synth.; also adaptation to chronic high iodide by NISymporter downreg.
Thyroid hormone transport
Thyroxine binding globulin (TBG), albumin, transthyretin
- T4 has higher affinity (longer half life)
Intracellular TH deiodination
Modulates activity.
Step up = T4 outer ring -> T3
Step down = T4 inner ring -> rT3
Ultimately deiodin. to T2 or excreted
T3 receptor action
Binds nuclear receptor TR -> heterodimer. w/ retinoid X receptor (RXR) -> down/upreg TH target genes
Thyroid hormone cellular effects
Increase metabolic rate by upreg.:
- Na/K ATPase
- Mt/respiration enzymes
- Growth/maturation proteins
- Beta adrenergic receptors; permissive effect for symp. NS
Whole body thyroid hormone effects
Increase ventilation/cardiac output, appetite, energy mobilization; thus increased:
- CO2
- Urea
- Renal func.
- Thermogen.
- Sweating
Downreg. muscle/fat
Thyroid hormone somatotrope synergy
TH -> increased GHRH response by increasing somatotrope receptors
Fetal thyroid dependency
Fetus relies on mom’s TH in 1st trimester; risk of I- deficit or TH excess
Post-partum thyroiditis
- Hyperthyroid phase due to inflam.
- Hypothyroid phase after supply is depleted
- Euthyroid restoration
Hyperthyroidism effects
Increased BMR:
- CNS symptoms
- Vision change
- Goiter
- Increased GI motility
- Sweating
- Tachycardia
- Weight loss
- Heat intolerance
Graves’ Disease
Autoimmun. Abs activate TSH receptor -> excess TH w/ tropic + trophic effects (goiter); eye bulging inflam. response
Hypothyroidism effects
Decreased BMR:
- CNS
- Mood/sleep
- Dry skin
- Goiter
- Cold intolerance
- Increased cholesterol
- Constipation
- Weakness
Usually caused by iodide deficiency
Hashimoto’s thyroiditis
Autoimmunity vs thyroglobulin and/or TPO -> decreased TH
Goiter caused by lymphocyte infiltration
TH endocrine emergencies
- Myxedema coma
- Thyroid storm
Myxedema coma
Sever hypothyroid. -> hypovent., cardiac failure, coma; occurs w/ initiating event e.g. infection
Thyroid storm
Acute extreme hyperthyroidism; high fever/cardiac load, initiated by infection or stopping anti-TH medication
