a func’onal approach to hypothyroidism – part 1 of 3 · • “sluggish” thyroid – poor...

AFunc'onalApproachtoHypothyroidism–Part1of3

JimPaole*,BSPharmacy,FAARFM,FIACP

Objec&ves

•  Reviewtheproduc/on,metabolism,andac/vi/esofthethyroidglandandthyroidhormones

•  Differen/atetypesofclinicalhypothyroidism•  Describethecauses,typesandsymptomsofhypothyroidism

LessThanOp&malThyroidFunc&on

•  Anumberofsitua/onscancontribute– Autoimmunereac/oninvolvingthethyroid–  Inadequateproduc/onofT4– PoorconversionfromT4toT3– Problemswiththecell’sabilitytotakeupT3– Problemswithreceptorfunc/on– Problemswithintracellulartransport

Thyroid Gland

T3

T4 Effects On Body (Symptoms)

TRH + Pituitary Gland

TSH +

Thyroid receptor in tissue cells

Thyroid Gland

T3

T4


TSH +

X X

Hypothyroidism

Thyroid Gland

T3

T4


TSH +

fT3 X

X

Functional Hypothyroidism

Thyroid Gland

T3

T4 Effects On Body (Symptoms)


TSH +

Thyroid receptor in tissue cells X

Functional Hypometabolism

Thyroid Hormone Resistance

Screening

•  Screeningtestreferstosimpletestthatvalidatesthatthereshouldbefurthermoreinvolvedtes/ng

•  Screeningitselfgivesnoinforma/ontodiagnoseortreat

•  BasalBodyTemperaturex3days•  AnkleReflex•  TSH•  Butthebest“screeningtest”is……Pa/entSymptoms

SymptomsofLowThyroidFunc&on

•  Fa/gue(especiallyevening)•  Lowstamina•  Coldextremi/es•  Intolerancetocold•  Headaches,esp.ina.m.•  Myxedema•  Swollen,puffyeyes•  Dryskin•  BriTlenails•  Dry,briTlehair•  Scalphairloss•  Cons/pa/on•  Weightgain

•  Depression•  Highcholesterol•  Anxiety•  Lowpulserate/bloodpressure•  Poorconcentra/on•  Memorylapses•  Heartpalpita/ons•  Lowlibido•  Infer/lity•  Fibromyalgia•  Generalachesandpains•  Slowwoundhealing•  Lossofoutermostpor/onofeyebrows

DecreasedThyroidFunc&on

•  Manyofthecondi/onsleadingtohypothyroidisminvolvelifestyleandnutri/on–  Irregularimmunefunc/on– Poorbloodsugarmetabolism– Adrenalissues– Gutinflamma/on/infec/ons– Hormoneimbalances

•  Correc/ngcausesusuallytakes/meandnoteasytoaccomplish

SubclinicalHypothyroidism

•  PlethoraofstudieshavedemonstratedSubclinicalHypothyroidismoXenassociatedwithsignificantsymptomsandincreasedriskformorbidityandmortality

•  Moreappropriateterm:MildThyroidFailure(MTF)

Mcdermott M.T., Ridgway C.: Subclinical hypothyroidism is mild thyroid failure and should be treated. J Clin Endocrinol Met 86. (10): 4585-4590.2001;

MildThyroidFailure

•  Non-treatmentresultsin–  Increasedcholesterollevels– Significantincreasedriskofcardiovascularevents

•  Endothelialdysfunc/onwithimpairedvasodila/on– Significantincreasedriskforarthrosclerosisandmyocardialinfarc/on

•  MTFisagreaterriskforMIthanhypercholesterolemia,hypertension,smokingorevendiabetes

•  MTFmaybecontribu/ngfactorin60%ofmyocardialinfarc/ons

MildThyroidFailure

•  MTFisassociatedwitha2.2foldincreasedriskofcoronaryarterydiseaseand1.5foldincreaseinriskofcardiovascularmortality

•  Treatmentcanresultin:– Significantreduc/onincholesterollevels– Loweringriskofarthrosclerosis,myocardialinfarc/on,coronaryarterydiseaseandcardiovascularmortality

•  TreatmentwarranteddespitenormalTSHandT4levels

Thyroid Gland

T3

T4


TSH +

X X

Hypothyroidism

CausesofOvertHypothyroidism

•  Thyroidfunc/ondecreaseswithage– Twotothreefoldincreaseinhypothyroidismincidencewithage

– Decreaseinproduc/onoccursatages45-50innormalindividuals


•  Lackofcomponentsthatmakeupthyroidhormones–  Iodine

•  Iodinedeficiencyisthemostcommoncauseofhypothyroidismformostoftheworld’spopula/onpertheAmericanThyroidAssocia/on

•  Lackofiodinecausesincreaseinsizeofthyroidgland– Tyrosine

• WatchinVegans,VegetariansandBodyBuilders


•  “Sluggish”thyroid–poorrecoveryfollowingacutestress– Acutestressshutsdownthyroidfunc/on–  ThyroidglandfailstobouncebackaXerstressisrelieved

–  Lookforacutestressor6-18monthspriortoonsetofsymptoms

•  ThyroidGlanddestruc/on– Autoimmunereac/on,heavymetaltoxicity–  Cellsofglanddestroyed– WillmostoXenneedTRT

Overt(Primary)Hypothyroidism

•  Lackofproduc/on:measuredbestbyTT4•  Nutri/onalsupportincludesiodine,tyrosine,ashwagandha,VitaminA,VitaminD,seleniumandzinc

•  ThRTrequiredifnutri/onal/lifestylesupportdoesnotincreasethyroidhormoneproduc/onandaddresssymptoms

Overt(Primary)Hypothyroidism

•  TPO:enzymeresponsibleformakingthyroidhormone– Liberatesiodinethatisaddedtotyrosine

•  Cofactorsforthisprocessincludepyridoxal-5-phosphate,riboflavin,niacin,magnesium,selenium,zincandcopper

Thyroid Gland

T3

T4


TSH +

fT3 X

X

Functional Hypothyroidism

Func&onalHypothyroidism

•  Adequateproduc/onofhormonebutmetabolicpathwaysimpaired(euthyroid)– OXencanbeaddressedatleastpar/allywithlifestyleadjustmentsandnutri/onalsupport

– Testresultscanbewithin“normal”rangesbutpa/enthassymptoms

– Alsocouldbetermedeuthyroid– Thyroidglandisfine–produc/onisadequate– ThRTisnotrequired

CausesofFunc&onalHypothyroidism

•  ExcessivebindingofthyroidhormonesduetoincreasedTBGcausedby–  Estrogendominanceand/ortherapy

•  Pregnancy,OCs,ERT(especiallyoral)–  Thyroidreplacementtherapy– Delayedresponse

•  2-3monthsforneteffect–  Chronicsleepdisturbances

•  Note:decreasedTBG/bindingreported:– Androgens,glucocor/coids,Phenytoin,salicylates,malnutri/on

BindingofThyroidHormones

•  Morethan99%ofcircula/ngthyroidhormonesareboundtoserumproteins–  Thyroxine-bindingglobulin(TBG)–  Thyroxine-bindingprealbumin(TBPA)– Albumin(TBA)

•  T4ismoreextensivelyboundthanT3–  0.04%oftotalT4iffree–  0.4%oftotalT3isfree

•  AsmalldifferenceinTBGcanhaveamajoreffectonthepercentageofunboundhormone

CausesofFunc&onalHypothyroidism

•  DecreasedconversionofT4toT3– CreatesimbalanceoffT3andrT3

T2 (Active?)

5 deiodinase rT3 Reverse T3 (Inactive – Binds to T3 receptors)

T3 Triiodothyronine

(Active)

T4 Thyroxin (Inactive))

Normal T4 Conversion to T3 by the Enzyme 5’deiodinase.

T2 (Active?)

5 deiodinase rT3 Reverse T3 (Inactive – Binds to T3 receptors)

T3 Triiodothyronine

(Active)

T4 Thyroxin (Inactive))

Inhibition of T4 Conversion to T3 by the Enzyme 5’deiodinase.

T4toT3Conversion

•  Normally,T4isconvertedperipherallytoalmostequalpartsT3andreverseT3

•  DecreasedconversiontoT3isalwaysaccompaniedbyanincreasedconversiontoreverseT3

•  T4therapywithimbalancedconversionworsensthesitua/on

T4toT3Conversion

•  Theac/vehormoneisT3– T4isaninac/veprohormone– NoT4receptorshavebeeniden/fiedinthebody– Reportedrela/vestrengthsdeterminedbys.q.administra/onandmeasuringoutcomes

T4toT3Conversion

•  WheneverT4isadministered,youaredependingonproperconversiontoT3toobtaindesiredmetaboliceffects!

ThanksforListening!Emailques&onsto:

JimPaoleNjpaolel@power2prac/ce.com

a func’onal approach to hypothyroidism – part 1 of 3 · • “sluggish” thyroid – poor...

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