Thyroid Histology - Vanderbilt University Medical Center 2006...Alvin C. Powers, M.D. 1/27/06 Thyroid Disease Clinical Management Course 1 Thyroid Histology Photos from University

Alvin C. Powers, M.D. 1/27/06

Thyroid DiseaseClinical Management Course 1

Thyroid Histology

Photos from University of Manchester and tutorial created by Dr.James Crimando, GateWay Community College

ColloidThyroid Follicles-200-400 uM

Parafollicularor C-cells

Follicular CellsApical lumenECF side



Thyroid Follicular CellThyroid Follicular Cell

TSHTSH TSH TSH ReceptorReceptor

TT44, T, T33 Thyroglobulin Thyroglobulin

ThyroidPeroxidase

Iodine++

II__

Apical LumenApical Lumen(Colloid)(Colloid)

ECFECF(Plasma)(Plasma)

IodotyrosineIodotyrosine

ThyroidPeroxidase

II+*+*HH22OO22





21 year old female is referred from her21 year old female is referred from hercardiologist for treatment of hyperthyroidism.cardiologist for treatment of hyperthyroidism.She is followed for asymptomatic aorticShe is followed for asymptomatic aorticinsufficiency.insufficiency.

Total T4 = 15.6 (Total T4 = 15.6 (nl nl = 4-12)= 4-12) Free T4 = 1.35 (Free T4 = 1.35 (nl nl = 0.8-1.9)= 0.8-1.9) TSH = 1.2 (TSH = 1.2 (nl nl = 0.4-5.0)= 0.4-5.0)

Thyroid Function TestsThyroid Function Tests

Total TTotal T44

Total TTotal T33

Free TFree T44

TSHTSH



Thyroxine MetabolismThyroxine Metabolism

Transport and Metabolism ofTransport and Metabolism ofThyroid HormonesThyroid Hormones

Adapted by Adapted by UptoDate UptoDate from from UtigerUtiger, Endocrinology and Metabolism, , Endocrinology and Metabolism, FeligFelig, Baxter, , Baxter, FrohmanFrohman, 1995, 1995

T4T4

T3T3

Total TTotal T44

Major circulating thyroid hormone hormoneMajor circulating thyroid hormone hormone Over 99% bound to proteins in serumOver 99% bound to proteins in serum

Unbound TUnbound T44 is converted to T is converted to T3 3 and should beand should beconsidered a prohormoneconsidered a prohormone

Levels affected by drugs and non-thyroidalLevels affected by drugs and non-thyroidalillnessesillnesses



Free T4Free T4

Reflection of bioactive hormoneReflection of bioactive hormone Either measured directly or calculatedEither measured directly or calculated Calculated Free T4 (using Total T4 and an estimateCalculated Free T4 (using Total T4 and an estimate

of thyroid hormone binding capacity, the resin T3of thyroid hormone binding capacity, the resin T3uptake) is called a Free T4 indexuptake) is called a Free T4 index

Should order a Free T4 and not a total T4.Should order a Free T4 and not a total T4.

Total TTotal T33

Results from peripheral conversion from TResults from peripheral conversion from T4 4 andandthyroid production of Tthyroid production of T33

Bioactive hormone and is the major ligand for theBioactive hormone and is the major ligand for thethyroid hormone receptorthyroid hormone receptor

Always elevated in hyperthyroidismAlways elevated in hyperthyroidism Often normal in hypothyroidismOften normal in hypothyroidism

Thyroid Stimulating HormoneThyroid Stimulating Hormone

Gold standard-best overall indicator ofGold standard-best overall indicator ofthyroid diseasethyroid disease

Capable of separating hyperthyroid,Capable of separating hyperthyroid,euthyroid, and hypothyroid stateseuthyroid, and hypothyroid states



TSH Levels inTSH Levels inThyroid DiseaseThyroid Disease

11oo

HypothyroidismHypothyroidism22oo HyperthyroidismHyperthyroidismNormalNormal

100100

5050

2020

1010

55

2211

0.50.5

0.20.2

<0.01<0.01

Misleading TSH ValuesMisleading TSH Values

Patients with hypothalamic or pituitaryPatients with hypothalamic or pituitarydiseasedisease

Patients hospitalizedPatients hospitalized––PsychiatricPsychiatric

–– Intensive care unitsIntensive care units During transition phase of hyperthyroidismDuring transition phase of hyperthyroidism

Summary of Summary of TFTTFT’’ss

TT4TT4 FT4FT4 T3T3 TSHTSH

HyperthyroidismHyperthyroidism ↑↑ ↑↑ ↑↑ ↓↓

Primary HypothyroidismPrimary Hypothyroidism ↓↓ ↓↓ ↑↑

Secondary HypothyroidismSecondary Hypothyroidism ↓↓ ↓↓ ↓↓

Non-thyroid diseaseNon-thyroid disease ↓↓ nlnl ↓↓ nlnl



Suggested Use of ThyroidSuggested Use of ThyroidFunction TestsFunction Tests

Suspect thyroid diseaseSuspect thyroid disease -Free T4 and TSH -Free T4 and TSH Monitor T4 replacementMonitor T4 replacement -TSH -TSH If pituitary disease is presentIf pituitary disease is present -Free T4 -Free T4

48 year old man from Shelbyville is referred48 year old man from Shelbyville is referredby his primary care physician for weightby his primary care physician for weightloss, tachycardia, and tremor.loss, tachycardia, and tremor.

Free T4 = 4.2 (Free T4 = 4.2 (nl nl = 0.8-1.9)= 0.8-1.9)

TSH < 0.001 (TSH < 0.001 (nl nl = 0.4-5.0)= 0.4-5.0)

How would you evaluate him?How would you evaluate him?

Normal Thyroid ScanNormal Thyroid Scan



Thyroid Scan in GravesThyroid Scan in Graves’’ Disease Disease

Graves DiseaseGraves Disease

HyperthyroidismHyperthyroidism OphthalmopathyOphthalmopathy

Dermopathy Dermopathy (pre-(pre-tibial tibial myxedema)myxedema)

TSHTSHTSHReceptorTSHReceptor

IodineIodine IodineIodine IodotyrosineIodotyrosine

ThyroglobulinThyroglobulin T4T4

Thyroid PeroxidaseThyroid Peroxidase

++TSITSI

Thyroid Follicular CellThyroid Follicular Cell



A 34 year old woman, who is 4 months post-A 34 year old woman, who is 4 months post-partum (twin boys), reports a month longpartum (twin boys), reports a month longhistory of trouble sleeping, emotionalhistory of trouble sleeping, emotionallability, fatigue, and neck swelling. Onlability, fatigue, and neck swelling. Onexamination, she is mildly tachycardiac andexamination, she is mildly tachycardiac andhas a diffusely enlarged thyroid. She has nohas a diffusely enlarged thyroid. She has noeye findings to suggest Graveseye findings to suggest Graves’’ Disease. Disease.

Free T4 = 2.8 (normal 0.9 - 1.9)Free T4 = 2.8 (normal 0.9 - 1.9)

TSH = <0.05 (normal 0.3 - 4.0)TSH = <0.05 (normal 0.3 - 4.0)HOW WOULD YOU EVALUTE HER?HOW WOULD YOU EVALUTE HER?

Low Uptake on Thyroid ScanLow Uptake on Thyroid Scan

Causes of ThyrotoxicosisCauses of Thyrotoxicosis Normal or Increased Activity on Thyroid ScanNormal or Increased Activity on Thyroid Scan–– Graves DiseaseGraves Disease–– Multinodular Multinodular Goiter or Hot NoduleGoiter or Hot Nodule

Decreased Activity on Thyroid ScanDecreased Activity on Thyroid Scan–– ThyroiditisThyroiditis–– Iodine-induced thyrotoxicosis (Iodine-induced thyrotoxicosis (amiodaroneamiodarone))–– Exogenous thyroid hormone useExogenous thyroid hormone use



Multinodular Multinodular GoiterGoiter

A 71 year old man comes for theA 71 year old man comes for theevaluation of weight loss, poor appetite,evaluation of weight loss, poor appetite,and new-onset congestive heart failureand new-onset congestive heart failure(mild). His thyroid function tests show:(mild). His thyroid function tests show:

Free T4 = 1.9 (normal 0.9 - 1.9)Free T4 = 1.9 (normal 0.9 - 1.9)

TSH = <0.05 (normal 0.2 - 4.0)TSH = <0.05 (normal 0.2 - 4.0)

IS HE HYPERTHYROID?IS HE HYPERTHYROID?

TSHTSH

TT44

NormalNormal

NormalNormalBA

B = Develops hypothyroidismB = Develops hypothyroidismB

A

A = Develops hyperthyroidismA = Develops hyperthyroidism

Individualized Set Point for TIndividualized Set Point for T44



Treatment of HyperthyroidismTreatment of Hyperthyroidism

Antithyroid Antithyroid DrugsDrugs

Radioactive Radioactive IodineIodine

SurgerySurgery

74 year old woman is brought74 year old woman is broughtby her son who has noticed:by her son who has noticed:

Decreased memoryDecreased memory FatigueFatigue

ConstipationConstipation

She has the heat on in her house in theShe has the heat on in her house in thesummer.summer.



Patient withPatient withHypothyroidismHypothyroidism

HypothyroidismHypothyroidism

TSH is best indicatorTSH is best indicator May or may not have a goiterMay or may not have a goiter

Thyroid scanning or ultrasound is notThyroid scanning or ultrasound is notnecessarynecessary

Autoimmune or post-surgical are the mostAutoimmune or post-surgical are the mostcommon causescommon causes





““You know the thyroid gland in your throat-theYou know the thyroid gland in your throat-theone that stokes the engine and keeps the oldone that stokes the engine and keeps the oldbrain working. In some people the thingbrain working. In some people the thingdoesndoesn’’t work properly and they turn out to bet work properly and they turn out to becretinous imbecilescretinous imbeciles…….., but feed .., but feed ‘‘em the stuffem the stuffand they come out absolutely all rightand they come out absolutely all right……....””

Lord Peter Wimsey in Dorothy SayersLord Peter Wimsey in Dorothy Sayers’’ HangmanHangman’’s Holidays Holiday, 1933, 1933

Treatment of HypothyroidismTreatment of Hypothyroidism

Thyroid Hormone SupplementsThyroid Hormone Supplements Well-tolerated; well-absorbed from GI tractWell-tolerated; well-absorbed from GI tract One of most commonly prescribed medicationsOne of most commonly prescribed medications Current preparations consist of synthetic TCurrent preparations consist of synthetic T44

((EuthyroxEuthyrox, , LevothyroidLevothyroid, , LevoxylLevoxyl, Synthroid,, Synthroid,UnithroidUnithroid) and/or T) and/or T33

New evidence does not support replacement withNew evidence does not support replacement withTT44 and T and T33

TT33 results from T results from T44 metabolism and is not routinely metabolism and is not routinelyprescribed.prescribed.



Thyroid Hormone SupplementsThyroid Hormone Supplements

Dose should be titrated to achieve a normal TSHDose should be titrated to achieve a normal TSHlevel.level.

Recheck TSH 4-6 weeks after a dose changeRecheck TSH 4-6 weeks after a dose changebecause of the long half-life of T4 (7 days).because of the long half-life of T4 (7 days).

Excessive levels (as evidenced by a suppressedExcessive levels (as evidenced by a suppressedTSH) cause iatrogenic hyperthyroidism andTSH) cause iatrogenic hyperthyroidism andaccelerated bone loss.accelerated bone loss.

Drugs that Affect Thyroid FunctionDrugs that Affect Thyroid Function

Drugs that cause hypothyroidismDrugs that cause hypothyroidism Inhibit T4 synthesis/release (lithium, perchlorate,Inhibit T4 synthesis/release (lithium, perchlorate,

iodine-containing drugs)iodine-containing drugs) AmiodaroneAmiodarone Decrease T4 absorptionDecrease T4 absorption

Drugs that cause hyperthyroidismDrugs that cause hyperthyroidism AmiodaroneAmiodarone/interferon-alpha/interferon-alpha

IodidesIodides Inhibit thyroid hormone synthesisInhibit thyroid hormone synthesis

(autoregulation)(autoregulation)

Adjunctive therapy for severe hyperthyroidismAdjunctive therapy for severe hyperthyroidism



SSaturated aturated SSolutions ofolutions ofPPotassium otassium IIodideodide(SSKI) is most(SSKI) is mostcommon preparation;common preparation;some countries havesome countries haveemergency stores ofemergency stores ofthis in case of athis in case of anuclear accident.nuclear accident.

IodidesIodides

19 year old Vanderbilt undergraduate is19 year old Vanderbilt undergraduate isreferred for a left sided thyroid nodule thatreferred for a left sided thyroid nodule thatwas found in Student Health when she waswas found in Student Health when she wasseen for a sore throat.seen for a sore throat.

TFTTFT’’s s normalnormal

Thyroid NodulesThyroid Nodules

Most are benign.Most are benign. Hot nodules are benign; thyroid cancer is coldHot nodules are benign; thyroid cancer is cold

on scanning.on scanning. Most are cold on thyroid scanningMost are cold on thyroid scanning Ultrasound cannot confirm or excludeUltrasound cannot confirm or exclude

malignancy.malignancy. FNA is required for all cold nodules.FNA is required for all cold nodules.



Documents

Thyroid Histology - Vanderbilt University Medical Center 2006...Alvin C. Powers, M.D. 1/27/06 Thyroid Disease Clinical Management Course 1 Thyroid Histology Photos from University