[excerpt starts]

Hyperthyroidism is indicated by an abnormally high radioactive iodine uptake (RAIU) of over 60% after 24 hours. On the other hand, hypothyroidism is indicated by an abnormally low RAIU of less than 5% after 24 hours. In individuals with Graves' disease-associated thyrotoxicosis, which involves extreme chronic stimulation of the thyroid, iodide is trapped, organified, and rapidly released as hormone. In such cases of elevated turnover, the 6-hour RAIU will be very high but the 24-hour RAIU will be lower. Various anions such as thiocyanate (CNS-), perchlorate (HClO4-), and pertechnetate (TcO4-) can competitively or non-competitively inhibit iodide transport via NIS. If iodide cannot be rapidly incorporated into tyrosine due to an organification defect, the administration of one of these anions will cause rapid release of iodide from the gland by blocking further iodide uptake. This release occurs as a result of the high thyroid-plasma concentration gradient.

To image the thyroid, a rectilinear scanner or gamma camera can be used after administering a tracer such as 123I, 131I, or pertechnetate (99mTc), which mimics iodine. This imaging technique allows the size and shape of the thyroid to be displayed, as well as any heterogeneities of active versus inactive tissue within the gland. These heterogeneities often result from the development of thyroid nodules, which are regions of enlarged follicles with evidence of regressive changes due to cycles of stimulation and involution. "Hot" nodules, which display high RAIU on imaging, are usually not cancerous but may lead to hyperthyroidism. On the other hand, "cold" nodules are 10 times more likely to be cancerous. Fine-needle aspiration biopsy can be performed to obtain a sample of such nodules for pathological analysis.

Ultrasonography can also be used to image the thyroid, offering superior resolution compared to RAIU imaging. This technique is particularly useful in guiding the physician during fine-needle aspiration biopsy of a nodule. For the highest resolution of the thyroid, magnetic resonance imaging (MRI) is the preferred method.

A B Colloid in endocytic vesicles Colloid in lumen of thyroid follicle Fig. 42.7 Before (A) and minutes after (B) rapid induction of thyroglobulin endocytosis by TSH. (From Wollman SH et al. J Cell Biol 1964;21:191.)

The concentration of thyroid-binding globulin (TBG) significantly affects total plasma T4 and T3 levels. TBG serves two important biological functions. Firstly, it maintains a large circulating reservoir of T4 that buffers any acute changes in thyroid gland function. Secondly, the binding of plasma T4 and T3 to proteins prevents the loss of these relatively small hormone molecules in urine, thereby helping conserve iodide. Transthyretin (TTR) transports T4 in cerebrospinal fluid and provides thyroid hormones to the central nervous system.

Regulation of Thyroid Function

[excerpt ends]
Fig.42.9 ).AbnormallyhighRAIU(>60%)after24hoursindicateshyperthyroidism.AbnormallylowRAIU(<5%)after24hoursindicateshypothyroidism.Inindividualswithextremechronicstimulationofthethyroid(Gravesdisease–associatedthyrotoxicosis),iodideistrapped,organified,andreleasedashormoneveryrapidly.Inthesecasesofelevatedturnover,6-hourRAIUwillbeveryhighbut24-hourRAIUwillbelower(see
Fig.42.8 ).Anumberofanions,suchasthiocyanate(CNS−),perchlorate(HClO4−),andpertechnetate(TcO4−),arecompetitiveornoncompetitiveinhibitorsofiodidetransportviaNIS.Ifiodidecannotberapidlyincorporatedintotyrosine(organification defect) afteritsuptakebythecell,administrationofoneoftheseanionswill,byblockingfurtheriodideuptake,causerapidreleaseofiodidefromthegland(see
Fig.42.9
Thisreleaseoccursasaresultofthehighthyroid-plasmaconcentrationgradient.
Thethyroidcanbeimagedwitharectilinearscannerorgammacameraafteradministrationofatracer,123I,131I,ortheiodine-mimicpertechnetate(99mTc).Imagingcandisplaythesizeandshapeofthethyroid(see
Fig.42.1C )aswellasheterogeneitiesofactiveversusinactivetissuewithinthethyroidgland.Suchheterogeneitiesareoftenduetothedevelopmentofthyroid nodules, whichareregionsofenlargedfollicleswithevidenceofregressivechangesduetocyclesofstimulationandinvolution.“Hot” nodules (i.e.,nodulesthatdisplayhighRAIUonimaging)arenotusuallycancerousbutmayleadtothyrotoxicosis(hyperthyroidism).“Cold” nodules are10timesmorelikelytobecancerous.Suchnodulescanbesampledforpathologicalanalysisbyfine-needle aspiration biopsy.
Thethyroidcanalsobeimagedbyultrasonography, whichissuperiorinresolutiontoRAIUimaging.Ultrasonographyisusedtoguidethephysicianduringfine-needleaspirationbiopsyofanodule.Thehighestresolutionofthethyroidisachievedwithmagnetic resonance imaging (MRI).
A B Colloid in endocytic vesicles Colloid in lumen of thyroid follicle •Fig. 42.7 Before(A)andminutesafter(B)rapidinductionofthy-roglobulinendocytosisbyTSH.(FromWollmanSHetal.J Cell Biol 1964;21:191.)
TBG concentration significantly affect total plasma T4 and T3 levels. Two important biological functions have been ascribed to TBG. First, it maintains a large circulating reservoir of T4 that buffers any acute changes in thyroid gland function. Second, binding of plasma T4 and T3 to proteins prevents loss of these relatively small hormone molecules in urine and thereby helps conserve iodide. TTR transports T4 in cerebrospinal fluid and provides thyroid hormones to the CNS.
Regulation of Thyroid Function