HypothyroidisminadultswhoarenotiodidedeficientmostoftenresultsfromanotherautoimmunedisorderknownasHashimoto’s disease (formerlycalledlymphocytic thyroiditis).IncontrasttothestimulatoryeffectofautoantibodiesseeninGravesdisease,thyroidautoantibodiesinHashimoto’sdisease(againstTPO,thyroglobulin,orTSHreceptor)causeapoptosisofthyroidcellsanddestructionofthyroidfollicles.Theseantibodiesfixcomplementandpromotelysisofthyroidcells,causingreleaseofthyroglobulinintothecirculation.ThethyroidglandbecomesinfiltratedbybothBandTlymphocytes,whichmaycauseenlargementofthegland.
Othercausesofhypothyroidismincludeiatrogeniccauses(e.g.,radiochemicaldamageorsurgicalremovalfortreatmentofhyperthyroidism),nodulargoiters,andpituitaryorhypothalamicdisease.Treatmentofpatientswiththeantiarrhythmicdrugamiodarone,whichcontainsalargeamountofiodine,maycauseeitherhypo-orhyperthyroidism.Thyroidfunctionmustbecarefullymonitoredinpatientstakingthismedication.
Theclinicalpictureofhypothyroidisminadultsisinmanyrespectstheexactoppositeofthatseeninhyperthyroidism.Thelower-than-normalmetabolicrateleadstoweightgainwithoutanappreciableincreaseincaloricintake.Thedecreasedthermogenesislowersbodytemperatureandcausesintolerancetocold,decreasedsweating,anddryskin.Adrenergicactivityisdecreased,andthereforebradycardiamayoccur.Movement,speech,andthoughtareallslowed,andlethargy,sleepiness,andloweringoftheuppereyelids(ptosis)occur.Accumulationofnegativelychargedmucopolysaccharidesinconnectivetissuesattractssodiumandfluid.Theresultingnonpittingmyxedema producespuffyfeatures,anenlargedtongue,hoarseness,jointstiffness,effusionsinthepleural,pericardial,andperitonealspaces,andpressureonperipheralandcranialnervesentrappedbyexcessgroundsubstance.Constipation,lossofhair,menstrualdysfunction,andanemiaareothersigns.Inadultslackingthyroidhormone,positronemissiontomographydemonstratesageneralizedreductionincerebralbloodflowandglucosemetabolism.Thisabnormalitymayexplainthepsychomotorimpairmentanddepressedaffectofhypothyroidindividuals.
ReplacementtherapywithadailydoseofT4thatnormalizesTSHlevelsisusuallycurativeinadults.Inmostpatients,T3isnotneededbecauseitisgeneratedasneededbyperipheralD1andD2.Furthermore,administrationofT3iscomplicatedbyitshighpotencyandshorthalf-life,requiringfrequentdosingandcausingdifficultyinmaintainingconsistentphysiologicallevelsofT3.
Thyroidhormonealsohassignificanteffectsonotherpartsoftheendocrinesystem.Pituitaryproductionofgrowthhormoneisincreasedbythyroidhormone,whereasthatofprolactinisdecreased.Adrenocorticalsecretionofcortisol(see )aswellasmetabolicclearanceofthishormoneisstimulated,butplasmafreecortisollevelsremainnormal.Theratioofestrogenstoandrogens(see )isincreasedinmen(inwhombreastenlargementmayoccurwithhyperthyroidism).Decreasesinbothparathyroidhormoneand1,25-(OH)2-vitaminDproductionarecompensatoryconsequencesoftheeffectsofthyroidhormoneonboneresorption(see