A Func’onal Approach to Hypothyroidism – Part 1 of 3 Jim Paole*, BS Pharmacy, FAARFM, FIACP
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
TRH + Pituitary Gland
TSH +
X X
Hypothyroidism
Thyroid Gland
T3
T4
TRH + Pituitary Gland
TSH +
fT3 X
X
Functional Hypothyroidism
Thyroid Gland
T3
T4 Effects On Body (Symptoms)
TRH + Pituitary Gland
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
TRH + Pituitary Gland
TSH +
X X
Hypothyroidism
CausesofOvertHypothyroidism
• Thyroidfunc/ondecreaseswithage– Twotothreefoldincreaseinhypothyroidismincidencewithage
– Decreaseinproduc/onoccursatages45-50innormalindividuals
CausesofOvertHypothyroidism
• Lackofcomponentsthatmakeupthyroidhormones– Iodine
• Iodinedeficiencyisthemostcommoncauseofhypothyroidismformostoftheworld’spopula/onpertheAmericanThyroidAssocia/on
• Lackofiodinecausesincreaseinsizeofthyroidgland– Tyrosine
• WatchinVegans,VegetariansandBodyBuilders
CausesofOvertHypothyroidism
• “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
TRH + Pituitary Gland
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