USMLE Step 1 Web Prep Thyroid Hormones

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Chapter 9: Thyroid Hormones

INTRODUCTION It is I- that is the form absorbed from the small intestine (I ion) Interior- pain staining proteinocious materials Thyroglobulin- attach thyroid hormone !ollicular lumen- e"tracellular compartment and surrounded by follicle cells (synthesi#e and secrete thyroid hormone)

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S!NTHESIS "ND SECRETION O# TH!ROID HOR$ONES

&ynthesis of thyroid hormones $ substrates to synthesi#e thyroid hormone: 1' I- - pump from circulation against concentration and electrical gradient (acti(e pumping) by inhibition of this pump it )ill slo) do)n the synthesis of thyroid hormone $' Thyroglobulin- synthesi#ed by the follicle cells a. Oxidation: I minus to I zero by peroxidase (probably facilitate 2 remained steps as well) b. Iodination: I zero stick to the surface of thyroglobulin (tyrosine residues can take up a

maximum two iodines (iodine is readily available) diiodtyrosine ! if " iodine monoiodtyrosine (deficiency of I) normally very little# $I% increases in iodine deficiency. c. Coupling: on the outer surface of the membrane: normally is formed &I% forms# &I% ' &I%( %) (normal end product) main end product &I% ' $I%( %* (normally very little# because $I% is less available) increases in I deficiency (more $I% synthesized) +ot all tyrosine residues will coupled# so you still have &I% and $I% attached to the thyroglobulin

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Str&'t&re of thyroid hormones

T3- more acti(e form I is missing from outer ring +e(erse T3- no acti(ity I is missing from inner ring

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Se'retion of thyroid hormone

3 step process: 1' endocytosis of small drop of thyroglobulin $' fusion )ith ly#osomes 3' digestion of thyroglobulin- release iodine containing compounds- only T3 and T% release into the circulation (mainly T%) ,ou release T% $0 times more than T3 (T%: T3- (:1) T% and T3 both are lipid-soluble (strong attached to protein)' &mall amount is free forms- acti(e form that can diffuse into the tissues and create negati(e feedbac.' In the circulation there is 50 times more T% than T3 form' T% has a higher affinity for binding protein and has a longer half-life than T3' &o it stays longer in the circulation and causes ratio of T% toT3 raises )(:1'

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TR"NS*ORT O# TH!ROID HOR$ONES IN +LOOD

/ormally there is 50" more T% than T3 T% has the higher affinity for binding proteins and a greater half-life than T 3 T% half-life - 0 days (the longest among all hormones) T3 half-life - 1 day

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"CTI-"TION "ND DE.R"D"TION O# TH!ROID HOR$ONES

T3 and T% bind to the same nuclear receptor but T3 binds more strongly than T% 2ecause it has greater affinity for the receptor T% is the more a'ti/e form of thyroid hormone T% 3 some consider it a prohormone of T3 3 not appropriate for step 1' 4any tissues can regulate the con(ersion of T % to either T3 or rT3 3 so they locally

regulate acti(ity the thyroid hormone ,ou deli(er mainly T4 and can change it to T3 or rT3

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*H!SIOLO.IC "CTIONS O# TH!ROID HOR$ONES

$eta1o2i' rate Increase metabolic rate 5o not directly affe't the metabolic rate of ner(ous tissue 6re absolutely ne'essary for normal 1rain maturation and essential for normal menstr&a2 cycles .ro3th and mat&ration !etal gro)th rates appear normal in the absence of thyroid hormone production 7ithout thyroid hormones in the perinatal period abnormalities de(elop in ner(ous system maturation Irre/ersi12e ne&ra2 'han4es 3i22 o''&r &n2ess rep2a'ement therapy is started soon after 1irth (re8uire thyroid screening for ne)borns)
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*H!SIOLO.IC "CTIONS O# TH!ROID HOR$ONE

9repubertal gro)th including bone ossification is retarded in the absence of thyroid hormones Thyroid hormone is re6&ired for norma2 synthesis and se'retion of 4ro3th hormone Thyroid- is a ma:or anabolic hormone Lipid meta1o2ism Thyroid hormones re8uired for con(ersion of 'arotene to -itamin " "&tonomi' system Thyroid hormone increases the number and affinity of -adrenergic receptors in the heart
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CONTROL O# TH!ROID HOR$ONE SECRETION

/egati(e feedbac.- at the le(el of anterior pituitary and hypothalamus: main circulating form is T% so the T4- creates most of ne4ati/e feed1a'7 1 T3- 1 T% in negati(e feedbac. but you ha(e 50 T% for 1 T3' T4 ta.en up by thyrotrophs 'on/erted into T% before it creates negati(e feedbac.' T3 creates negati(e feedbac. but that T3 is deri(ed from T% ;o)-T3- syndrome 3 circulating T3 goes do)n- decreases metabolic rate 2ut T% is unchanged< you ha(e the same le(el of negati(e feedbac.' &o you don=t ha(e significant change in the circulating T&> In:ection of large dose T3- increase negati(e feedbac. and decrease T&> ?s- @bese pt=s gi(e thyroid hormone to cause )eight loss' 7ould it be better to gi(e T% or T3' It is better to gi(e T% (smaller dose of T3 )ill increase more metabolic rate)so it=s less increase in negati(e feedbac. and less decrease T&> If T%- the larger dose greater negati(e feedbac. and greater T&>'
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O/era22 effe'ts of thyrotropin 8TSH9 on the thyroid:

T&> tends to increase rapidly all steps in the synthesis and degradation of thyroid hormones Increased hypertrophy of the thyroid cells )hich initially leads to increased si#e of the gland 6 goiter is simply an enlarged thyroid and does not desi4nate functional stat&s There is no 'orre2ation 1et3een thyroid si;e and f&n'tion
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*atho2o4i'a2 Chan4es in Thyroid Hormone Se'retion

Table IA *-1 sho)s the changes in feedbac. relationships in se(eral disorders T4 1' B9rimary hypothyroidism $' 9ituitary hypothyroidism (secondary) 3 no T&> 3' >ypothalamic hypothyroidism (tertiary) 3 no T+> 3' 9ituitary hyperthyroidism (secondary)- increase T&> %' Cra(e=s disease (autoimmune) TSH TRH (small)

*rimary hypothyroid -Thyroid not secrete T% ?s- pt=s primary hypothyroid- more sensiti/e indi'ator- increase in TSH 2ecause T&> is a )ater-soluble (free in plasma) if you measure total T% in plasmayou measure bound-fraction (not a good inde" of circulating acti(ity) ?s- if you measure free T% in plasma- it=s sensiti(e inde" of thyroid hormone ?s- you treat for primary hypothyroid ho) to chec. a right dose for thyroid hormone: you should measure TSH: /ormal T&> - enough T% hormone< T&> belo) normal - too much T% T&> abo(e normal- not enough T% .R"-E<s disease- autoimmune - directly stimulate thyroid tissue - increases T%hyperthyroid (early stage)- suppress T&> (do)n) and suppress T+>
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Thyroida2 response to 2o3 inta7e of iodine:

In most cases if iodine is deficient in the diet but not absent the indi(idual )ill remain euthyroid but )ill de(elop a goiter 4ore T3 produced T% go do)n (do)n the negati(e feedbac.)' &o T&> increases- cause of goiter

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Chara'teristi's of hypothyroid ad&2ts

5ecreased basal metabolic rate and o"ygen consumption 6n ele(ated T&> is more diagnostic than the decrease in T % in primary hypothyroidism 5ecreased mental capacity' Thought and speed are slo) and memory is poor 9lasma cholesterol and other blood lipids tend to be ele(ated (indi(iduals are slightly o(er)eight) Domple" of protein hyaluronic acid and chondroitin sulfate (mucopolysaccharide) accumulate *ro2on4ed re2a=ation phase of deep tendon ref2e=es (stret'h ref2e=) 9hysiological :aundice (carotene accumulation) hoarse (oice constipation anemia
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Chara'teristi's of hyperthyroid ad&2ts

Increased metabolic rate and o"ygen consumption In spite of increased appetite there is generally )eight loss protein )asting and muscle )ea.ness (thyroto"ic myopathy) F"citability irritability restlessness Ta'hy'ardia and in'reased 'ardia' o&tp&t (increased >adrener4i' stimulation) F"ophthalmos (Cra(e=s disease)