In adults who are not iodide deficient, the most common cause of hypothyroidism is Hashimoto's disease, which is an autoimmune disorder. Formerly known as lymphocytic thyroiditis, this condition involves the destruction of thyroid follicles and apoptosis of thyroid cells caused by thyroid autoantibodies against TPO, thyroglobulin, or the TSH receptor. These autoantibodies fix complement, leading to the lysis of thyroid cells and the release of thyroglobulin into the circulation. Both B and T lymphocytes infiltrate the thyroid gland, which may result in gland enlargement.

Other causes of hypothyroidism include iatrogenic factors (such as radiochemical damage or surgical removal for hyperthyroidism treatment), nodular goiters, and pituitary or hypothalamic disease. Treatment with the antiarrhythmic drug amiodarone, which contains a large amount of iodine, can also cause either hypo- or hyperthyroidism. It is crucial to carefully monitor thyroid function in patients taking this medication.

The clinical presentation of hypothyroidism in adults is essentially the opposite of hyperthyroidism. The lower-than-normal metabolic rate leads to weight gain without an increase in caloric intake. Decreased thermogenesis results in intolerance to cold, reduced sweating, and dry skin. Adrenergic activity is decreased, which can lead to bradycardia. Movement, speech, and thought processes are slowed, and lethargy, sleepiness, and ptosis (lowering of the upper eyelids) may occur. Accumulation of negatively charged mucopolysaccharides in connective tissues attracts sodium and fluid, leading to non-pitting myxedema. This condition causes puffy features, an enlarged tongue, hoarseness, joint stiffness, effusions in the pleural, pericardial, and peritoneal spaces, and pressure on peripheral and cranial nerves due to excess ground substance. Other signs include constipation, hair loss, menstrual dysfunction, and anemia. In individuals lacking thyroid hormone, positron emission tomography reveals a generalized reduction in cerebral blood flow and glucose metabolism. This abnormality may explain the psychomotor impairment and depressed affect observed in hypothyroid individuals.

In adults, replacement therapy with a daily dose of T4 that normalizes TSH levels is typically curative. In most cases, T3 supplementation is not necessary because it is generated as needed by peripheral D1 and D2 enzymes. Additionally, administering T3 can be complicated due to its high potency and short half-life, which requires frequent dosing and makes it difficult to maintain consistent physiological levels of T3.

Thyroid hormone also has significant effects on other parts of the endocrine system. Thyroid hormone increases pituitary production of growth hormone but decreases prolactin production. It stimulates adrenocortical secretion of cortisol and metabolic clearance of this hormone, although plasma free cortisol levels remain normal. The ratio of estrogen to androgens is increased in men, which may cause breast enlargement in cases of hyperthyroidism. Decreased production of both parathyroid hormone and 1,25-(OH)2-vitamin D is a compensatory consequence of the effects of thyroid hormone on bone resorption.
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