Measurementoftheserumconcentrationofthyrotropin(TSH),aglycoproteinwithamolecularweightof28,000daltonsandsecretedfromtheanteriorpituitary,isgenerallyre¬gardedasthemostsensitiveindicatoravailableforthediagnosisofprimaryandsecondary(pituitary)hypothyroidism(1,2).IncreaseinserumconcentrationsofTSH,whichisprimarilyresponsIBLeforthesynthesisandreleaseofthyroidhormones,isanearlyandsensitiveindicatorofdecreasethyroidreserveandinconjunctionwithdecreasedthyroxine(T4)concentrationsisdiagnosticofprimaryhypothyroidism.TheexpectedincreaseinTSHconcentrationsdemonstratestheclassicalnegativefeedbacksystembetweenthepituitaryandthyroidglands.Thatis,primarythyroidglandfailurereducessecretionofthethyroidhormones,whichinturnstimulatesthereleaseofTSHfromthepituitary.Additionally,TSHmeasurementsareequallyusefulindifferentiatingsecondaryandtertiary(hypothalamic)hypothyroidismfromtheprimarythyroiddisease.TSHreleasefromthepituitaryisregulatedbythyrotropinreleasingfactor(TRH),whichissecretedbythehypothalamus,andbydirectactionofT4andtriiodothyronine(T3),thethyroidhormones,atthepituitary.IncreaselevelsofT3andT4reducestheresponseofthepituitarytothestimulatoryeffectsofTRH.Insecondaryandtertiaryhypothyroidism,concentrationsofT4areusuallylowandTSHlevelsaregenerallylowornormal.EitherpituitaryTSHdeficiency(secondaryhypothyroidism)orinsufficiencyofstimulationofthepituitarybyTRH(tertiaryhypothyroidism)causesthis.TheTRHstimulationtestdifferentiatestheseconditions.Insecondaryhypothyroidism,TSHresponsetoTRHisbluntedwhileanormalordelayedresponseisobtainedintertiaryhypothyroidism.Further,theadventofimmunoenzymometricassayshasprovidedthelaboratorywithsufficientsensitivitytoenablethedifferentiatingofhyperthyroidismfromeuthyroidpopulationandextendingtheusefulnessofTSHmeasurements.Thismethodisasecond-generationassay,whichprovidethemeansfordiscriminationinthehyperthyroid-euthyroidrange.