Thyroid Flashcards
Thyroid hormone synthesis
1) I taken up via active transport into thyroid follicular cells (Na/I) stimulated by TSH
2) Transported across apical membrane into the colloid by pendrin
3) I added to tyrosine in thyroglobulin by thyroid peroxidase to form monoiodotyrosine and diiodotyrosine
4) TPO joins two iodonated tyrosines to form T4, T3, or reverse T3, still attached to TG. Two iodonated tyrosines linked by an ether linkage
5) TSH stimulation: colloid taken up by surrounding follicular cells, fused with lysosomes –> TG cleaved - T3, T4 rT3 into circulation. Most released as T4
Action of TSH on the thyroid gland
Follicular cell growth
Na/I transporter
Transcription of TG and TPO
endocytosis of colloid
Regulation of thyroid hormone secretion
1) Neurons from hypothalamus TRH –> portal veins to anterior lobe cells
2) Thyrotropes in anterior pituitary secrete TSH into pituitary venous system
3) follicular cells stimulated by TSH, secrete TH to target or back to hypothalamus/pituitary
4) Target: nucleus thyroid receptor (TR)/T3 bind to thyroid response elements, regulate gene transcription
5) negative feedback: serum T3/T4 regulate TRH and TSH - decrease TRH receptor gene expression
- excess iodide inhibits NIS (sodium iodine symporter), TG iodination and TH release
Factors that regulate TH
Circadian rhythm and cold stimulate TRH Estrogen stimulates TSH GCs inhibit TSH Chronic illness inhibits TSH Autoimmune Ab against TSH receptors on the thyroid - stimulate or block Iodide excess downregulates TH
TH action on growth
normal growth in children and young animals
intertwined with GH action
skeletal maturation in the fetus
TH action on development
early brain development
TH action on CV system
increase HR increase contractility and CO promotes v/d, enhance bloodflow increase rate of diastolic relaxation increase expression of more rapidly contractile isoforms of myosin heavy chains in the heart
TH action on lipid metabolism
stimulate fat mobilization, leading to increased concentrations of FA in plasma
enhance oxidation of FA in many tissues
plasma concentrations of cholesterol and TG inversely correlated with thyroid hormone levels (increased blood cholesterol can be a diagnostic indication for hypothyroidism)
TH action on carb metabolism
enhancement of insulin-dependent entry of glucose into cells
Increased gluconeogenesis and glycogenolysis to generate free glucose
Stimulate Na/K ATPase in most tissues -> increase basal metabolic rate, O2 consumption and heat production
TH action on respiratory system
maintain ventilatory response to hypoxia and hypercapnia
TH action on CNS
both decreased and increased concentrations of thyroid hormones –> mental state
Too little = sluggish
too much = anxiety, nervousness
TH action on reproduction
Hypothyroidism associated with infertility
Deficiency –> decreased GH in children, delayed puberty through decreased GnRH, increased prolactin through increased TRH
Hyperthyroidism in adults –> can impair normal GNRH release leading to infertility and amenorrhea
TH effect on MSK
stimulate bone turnover
Excess: hypercalcuria and osteoporosis
Hyperthyroidism: hyperreflexia, fine hand tremor
Hpothyroidism: delayed relaxation phase of reflexes
TH increases protein turnover in muscle and hyperthyroidism can lead to proximal myopathy
Miscelanneous TH effects
Increased sensitivity to catecholamines by increasing number of beta receptors
Increase erythropoesis through increased O2 demand
Increases gut motility
Hyperthyroidism: hyperdefecation
Hypothyroid: constipation
TSH tests
screen for hyper/hypothyroidism
