Thyroid Disorders Thyroid Disorders ––Pitfall of Diagnosis & Pitfall of Diagnosis & ManagementManagement

Dr. KW LoDr. KW LoDivision of Endocrinology Division of Endocrinology & & DiabetesDiabetesHK Sanatorium & HospitalHK Sanatorium & Hospital

What Is the ThyroidWhat Is the Thyroid

A small butterflyA small butterfly--shaped gland (~20 gm in shaped gland (~20 gm in an adult) located in the neck in front of the an adult) located in the neck in front of the tracheatracheaProducing thyroid hormones (T4 and T3), Producing thyroid hormones (T4 and T3), chemicals that travel through the blood to chemicals that travel through the blood to every part of the bodyevery part of the bodyThyroid hormones tell the body how many Thyroid hormones tell the body how many calories we burn, how warm we feel, and calories we burn, how warm we feel, and how much we weighhow much we weigh

Mechanism of ThyroidMechanism of Thyroid Hormones Hormones Action at the Cell LevelAction at the Cell Level

Binds to high affinity T3 nuclear receptor Binds to high affinity T3 nuclear receptor complex, which stimulates the formation complex, which stimulates the formation ofof mRNAmRNA sequences and subsequently sequences and subsequently brings about new protein synthesisbrings about new protein synthesisBinds to receptors for T3 at theBinds to receptors for T3 at themitochondrialmitochondrial level; stimulation of oxygen level; stimulation of oxygen consumption and increase in BMRconsumption and increase in BMREnhance sympathetic activitiesEnhance sympathetic activities

Physiological Effects of Physiological Effects of Thyroid Hormones (1)Thyroid Hormones (1)

Skin & connective tissue:Skin & connective tissue: important in the important in the integrity of the collagen, essential for normal integrity of the collagen, essential for normal hair growthhair growthRespiratory:Respiratory: regulation of ventilation, affect regulation of ventilation, affect respiratory muscle functionrespiratory muscle functionCVS:CVS: affect cardiac contractility, velocity of affect cardiac contractility, velocity of muscle shortening and the rate of isometric muscle shortening and the rate of isometric tension developmenttension developmentNeuromuscular:Neuromuscular: required for normal brain required for normal brain morphology andmorphology and histogenesishistogenesis, and deficiency in , and deficiency in neonatal life results in irreversible brain damageneonatal life results in irreversible brain damage

Physiological Effects of Physiological Effects of Thyroid Hormones (2)Thyroid Hormones (2)

GI and Kidney:GI and Kidney: affect the motility of the GI tract; affect the motility of the GI tract; inability to clear free water if no thyroid hormonesinability to clear free water if no thyroid hormonesEndocrine:Endocrine: affect growth and sexual development, affect growth and sexual development, control menstrual regularities and fertility, affect control menstrual regularities and fertility, affect metabolism of steroid hormones in the livermetabolism of steroid hormones in the liverIntermediary metabolism:Intermediary metabolism: stimulatestimulate lipolysislipolysis, , enhance hepaticenhance hepatic gluconeogenesisgluconeogenesis, stimulate protein , stimulate protein synthesis and breakdown, increase bone turn oversynthesis and breakdown, increase bone turn over

ErythropoiesisErythropoiesis:: enhance red cell formationenhance red cell formation

Production of TProduction of T4411 TT3311 and rTand rT33. The principal thyroid gland secretion is . The principal thyroid gland secretion is TT4411 85% of which is85% of which is monodeiodinatedmonodeiodinated by peripheral tissues to Tby peripheral tissues to T33 and and rTrT33. Under normal conditions only small amounts of T. Under normal conditions only small amounts of T33 and rTand rT33 are are derived from thyroidal secretion, a discovery that has led to thderived from thyroidal secretion, a discovery that has led to the e concept of Tconcept of T44 as aas a prohormoneprohormone. In. In nonthyroidalnonthyroidal illness peripheral illness peripheral conversion of Tconversion of T44 to rTto rT33 is enhanced leading to a reduction in serum Tis enhanced leading to a reduction in serum T33concentration (concentration (““sicksick euthyroideuthyroid””). The physiological significance of this ). The physiological significance of this shift in Tshift in T44 metabolism is not well understood.metabolism is not well understood.

Serum Proteins that Transport Serum Proteins that Transport Thyroid Hormones*Thyroid Hormones*

ProteinsProteins TT44 Bound (%)Bound (%)

ThyroxineThyroxine--binding globulin (TBG)binding globulin (TBG) 7575

ThyroxineThyroxine--bindingbinding prealbuminprealbumin (TBPA)(TBPA) 2020

AlbuminAlbumin 55

*The amount of free and metabolically active hormone is extremely small, accounting for about 0.03% of circulating T4 and 0.3% of circulating T3

Thyroid Function Tests: The modern assay of TSH

Diagram of principles involved inDiagram of principles involved in immunoradiometricimmunoradiometric assay for assay for thyroidthyroid--stimulating hormone (TSH:stimulating hormone (TSH: thyrotropinthyrotropin). Assay ). Assay monoclonal antibody linked to a solid phase monoclonal antibody linked to a solid phase support.(Photograph courtesy of Bootssupport.(Photograph courtesy of Boots--CelltechCelltech Diagnostic, Diagnostic, Limited, Product Information, Slough, United Kingdom.)Limited, Product Information, Slough, United Kingdom.)

Proposed strategy for investigation of thyroid function in patieProposed strategy for investigation of thyroid function in patients nts with suspected thyroid disease. with suspected thyroid disease. FT3 FT3 = free= free triiodothyroninetriiodothyronine; fT4; fT4= free= free thyroxinethyroxine; ; IRMA IRMA == immunoradiometricimmunoradiometric assay; assay; TSHTSH ==thyrotropinthyrotropin. (From Caldwell G,. (From Caldwell G, KellettKellett HA,HA, GowGow SM. Beckett GJ,SM. Beckett GJ,SweetingSweeting VM, Seth J,VM, Seth J, ToftToft AD: A new strategy for thyroid function AD: A new strategy for thyroid function testing.testing. LaneetLaneet 1:11171:1117--1119, 1985. By permission.)1119, 1985. By permission.)

Interpretation of TSH and FT4 ResultsInterpretation of TSH and FT4 ResultsLow Normal High

High ••HyperthyroidismHyperthyroidism ••EuthyroidEuthyroid sick syndromesick syndrome••T4T4 autoantibodiesautoantibodies••Thyroid hormone Thyroid hormone resistance syndromeresistance syndrome••TSHTSH--secreting pituitary secreting pituitary

••Thyroid hormone Thyroid hormone resistance syndromeresistance syndrome••TSHTSH--secretingsecreting pitutarypitutaryadenomaadenoma

Normal

••SubclinicalSubclinical hyperthyroidismhyperthyroidism••T3T3 thyrotoxicosisthyrotoxicosis••Pregnancy (first trimester)Pregnancy (first trimester)••DrugsDrugs (eg(eg.. GlucocorticoidsGlucocorticoids, , dopamine,dopamine, amiodaroneamiodarone))

••EuthyroidismEuthyroidism ••SubclinicalSubclinical (compensated) (compensated) hypothyroidismhypothyroidism

Low ••Central hypothyroidismCentral hypothyroidism ••Central hypothyroidismCentral hypothyroidism••EuthyroidEuthyroid sick syndrome sick syndrome (more severe, uncommon)(more severe, uncommon)

••Primary Primary hypothyroidismhypothyroidism

FT

4(pm

mol

/l)

TSH (0.3-4.0) mIU/l

CauseCausess of anof an undetundetectectable/suppressed TSHable/suppressed TSH

•Thyrotoxicosis

•Transient hyperthyroxinemic state

•Hypopituitarism / central hypothyroidism

•Euthyroid patients in the first trimester of pregnancy

•Exophthalmic Graves’ disease

•Nodular goitre

•Early weeks and months following treatment of hyperthyroidism

•Nonthyroidal medical illness

•Psychiatric illness, e.g. Depressive disorders, schizophrenia

•Medications such as corticosteroids, dopamine

•Exogenous thyroxine

Prevalence ofPrevalence of Thyroglobulin Thyroglobulin Autoantibody (TGAbAutoantibody (TGAb) and Thyroid) and ThyroidPeroxidase Autoantibody (TPOAbPeroxidase Autoantibody (TPOAb))

TGAbTGAb TPOAbTPOAb

GravesGraves’’ diseasedisease 67%67% 87%87%

HashimotoHashimoto’’ss thyroiditisthyroiditis 9090--100%100% 9090--100%100%

NonNon--organ specific autoorgan specific auto--immune immune diseasedisease

35%35% 50%50%

Normal controlsNormal controls 1010--18%18% 1010--18%18%

Assessment of Thyroid Assessment of Thyroid Anatomy and StructureAnatomy and Structure

1.1. XX--Ray of the thoracic inlet Ray of the thoracic inlet –– trachea trachea compression and distortion,compression and distortion, retrosternalretrosternalextensionextension

2.2. Ultrasound Ultrasound –– size, texture, nodules, retrosize, texture, nodules, retro--orbital orbital changeschanges

3.3. Isotope scan (I Isotope scan (I 131131) /) / (Tc(Tc 99M99M) ) –– size, shape, size, shape, position, activity, nodulesposition, activity, nodules

4.4. CT scan / MRI of orbit CT scan / MRI of orbit –– infiltrativeinfiltrativeophthalmopathyophthalmopathy

5.5. PercutaneousPercutaneous biopsy biopsy –– fine needle aspiration fine needle aspiration (FNA) cytology,(FNA) cytology, trucuttrucut biopsybiopsy

Thyroid disease

Medical:•Hyperthyroidism(Thyrotoxicosis)

•Hypothyroidism•Thyroiditis

Surgical:•Goitre•Nodules•Cancer

Common Symptoms and Common Symptoms and Signs of HyperthyroidismSigns of HyperthyroidismSymptomsSymptoms

PalpitationsPalpitationsHeat intoleranceHeat intoleranceNervousnessNervousnessInsomniaInsomniaBreathlessnessBreathlessnessIncreases bowel Increases bowel movementsmovementsLight or absent Light or absent menstrual periodsmenstrual periodsFatigue

SignsSignsFast heart rateFast heart rateTrembling handsTrembling handsWeight lossWeight lossMuscle weaknessMuscle weaknessWarm moist skinWarm moist skinHair lossHair lossStaring gazeStaring gazeEnlarged thyroid glandEnlarged thyroid gland

Fatigue

Clinical Features of Hyperthyroidism (the most common features aClinical Features of Hyperthyroidism (the most common features are in italic)re in italic)

GeneralGeneral Ocular (5.3.2)Ocular (5.3.2)Heat intolerance, sweatingHeat intolerance, sweating Lid retraction, lid lagLid retraction, lid lagWeight loss despite increased appetiteWeight loss despite increased appetite Stare and photophobia*Stare and photophobia*FatigueFatigue IncreasedIncreased lacrimationlacrimation and grittiness of eyes*and grittiness of eyes*LymphadenopathyLymphadenopathy** PeriorbitalPeriorbital puffiness*puffiness*

Chemosis (conjunctival oedemaChemosis (conjunctival oedema)*)*CardiovascularCardiovascular ProptosisProptosis, corneal ulceration*, corneal ulceration*Palpitations,Palpitations, dyspnoeadyspnoea OphthalmoplegiaOphthalmoplegia,, diplopiadiplopia**SinusSinus tachycardiatachycardia,, atrialatrial fibrillationfibrillation PapilloedemaPapilloedema, loss of visual acuity*, loss of visual acuity*Systolic hypertension, collapsing pulse, flow murmursSystolic hypertension, collapsing pulse, flow murmursCardiac failureCardiac failure ReproductiveReproductive

OligoOligo--amenorrhoeaamenorrhoeaNeuromuscularNeuromuscular InfertilityInfertilityTremor,Tremor, choreoathetosischoreoathetosis ImpotenceImpotenceMuscle weakness, proximalMuscle weakness, proximal myopathymyopathy GynaecomastiaGynaecomastia

Periodic paralysisPeriodic paralysisMyasthenia gravis*Myasthenia gravis* DermatologicalDermatological

PruritusPruritusNeuropsychiatricNeuropsychiatric Palmar erythemaPalmar erythemaNervousness, agitationNervousness, agitation AnkleAnkle oedemaoedemaDepression, insomnia Depression, insomnia Thinning of hair,Thinning of hair, alopeciaalopeciaEmotionalEmotional labilitylability, poor concentration, poor concentration Brittle nails,Brittle nails, onycholysisonycholysisPsychosisPsychosis Finger clubbingFinger clubbing (acropachy(acropachy)*)*

Pretibial myxoedemaPretibial myxoedema (Figure 5.3.3)(Figure 5.3.3)GastrointestinalGastrointestinalIncreased frequency and softening of bowel motionsIncreased frequency and softening of bowel motions GoitreGoitreVomitingVomiting Diffuse with / without bruit*Diffuse with / without bruit*SplenomegalySplenomegaly** NodularNodular

Causes of HyperthyroidismCauses of HyperthyroidismNormal Normal / High / High RAIURAIU Low RAIULow RAIU

GravesGraves’’ diseasedisease Subacute thyroiditisSubacute thyroiditis

ToxicToxic multinodular goitremultinodular goitre Painless(silentPainless(silent)thyroiditis)thyroiditis

Solitary toxic noduleSolitary toxic nodule PostpartumPostpartum thyroiditisthyroiditis

ChoriocarcinomaChoriocarcinoma oror hydatiformhydatiformmolemole

Factitious hyperthyroidismFactitious hyperthyroidism

Hyperemesis gravidarumHyperemesis gravidarum(gestational hyperthyroidism)(gestational hyperthyroidism)

IodineIodine--induced hyperthyroidisminduced hyperthyroidism(Jod(Jod--BasedowBasedow))

TSH TSH –– secreting pituitary secreting pituitary adenomaadenoma

Struma ovariiStruma ovarii

Pituitary selective thyroid Pituitary selective thyroid hormone resistance syndromehormone resistance syndrome

MetastaticMetastatic functioning thyroid functioning thyroid carcinomacarcinoma

RAIU = radioactive iodine uptake

A Case of Hyperthyroidism due A Case of Hyperthyroidism due to Gravesto Graves’’ DiseaseDisease

F/33, housewifeF/33, housewifec/o weight loss of 10 lbs in 2 months despite c/o weight loss of 10 lbs in 2 months despite good appetite, heat intolerance, increased good appetite, heat intolerance, increased sweating, palpitation and bad tempersweating, palpitation and bad temperPulse 100/min, sweaty palm, hand tremor, Pulse 100/min, sweaty palm, hand tremor, stare look, diffusestare look, diffuse goitregoitre with bruitwith bruitTSH < 0.01TSH < 0.01 mIUmIU/l, FT4 = 60.6/l, FT4 = 60.6 pmolpmol/l,/l, TgAbTgAb1/400,1/400, TPOAbTPOAb 1/1600, USS showed a diffuse1/1600, USS showed a diffusegoitregoitre

Thyroid Eye SignsThyroid Eye Signs

Lid retraction, lid lagLid retraction, lid lag (sympathetic overtone)(sympathetic overtone)

PeriorbitalPeriorbital puffinesspuffinessChemosisChemosisProptosisProptosis, corneal ulceration, corneal ulcerationOphthalmoplegiaOphthalmoplegiaOptic nerve compressionOptic nerve compression

Selection ofSelection of AntithyroidAntithyroid Treatment for Common Forms of Treatment for Common Forms of HyperthyroidismHyperthyroidism

AntithyroidAntithyroid drugsdrugs(thionamide(thionamide) (ATD)) (ATD)

RadioiodineRadioiodine (RAI)(RAI) SubtotalSubtotal thyroidectomythyroidectomy (SX)(SX)

Strongly Strongly indicatedindicated

••ThyrotoxicThyrotoxic crises or severecrises or severe••Preparation for RAI/SXPreparation for RAI/SX••PregnancyPregnancy••Young GravesYoung Graves’’ diseasedisease

••Relapse after SXRelapse after SX••ThyrotoxicThyrotoxic heart disease heart disease after stabilizationafter stabilization••Hyperthyroidism with Hyperthyroidism with concomitant disease or concomitant disease or complicationcomplication

••Large and/or nodularLarge and/or nodular goitregoitrewith pressure symptomswith pressure symptoms••Rapidly growingRapidly growing goitregoitre with with suspicion of cancersuspicion of cancer

Not Not recommendedrecommended

••As longAs long--term treatment in term treatment in toxic nodules or toxictoxic nodules or toxicmultinodular goitremultinodular goitre••For relapse of GravesFor relapse of Graves’’disease after first course of disease after first course of ATD or after SXATD or after SX••Large vascular and/or Large vascular and/or nodularnodular goitregoitre••Poor drug compliancePoor drug compliance

••““youngyoung”” patients (arbitrary patients (arbitrary limit < 20 years)limit < 20 years)••Large compressing and/orLarge compressing and/orretrosternal goitreretrosternal goitre••Unstable significant GravesUnstable significant Graves’’ophthalmopathyophthalmopathy

••Relapse after first operationRelapse after first operation••Patients relying on their voice Patients relying on their voice for their professionfor their profession

ContraindicatedContraindicated ••Known fatal allergy toKnown fatal allergy tothionamidesthionamides (blood(blooddyscrasiadyscrasia,, hepatotoxicityhepatotoxicity, , see text)see text)

••PregnancyPregnancy••ThyrotoxicThyrotoxic crisescrises

••ThyrotoxicosisThyrotoxicosis not yet not yet controlled by drugscontrolled by drugs

Example of ATD Regimen:Example of ATD Regimen:•One course of ATD varies from 9 months to 2 years, average 12 – 18 months.

•e.g. medications by titration method:

(carbimazole [CBZ] 10mg = propylthiouracil [PTU] 100mg)

DosageDosage Duration/FUDuration/FU

CBZ 10 CBZ 10 –– 15 mg15 mg tdstds / 15 mg/ 15 mgbdbd

4 4 –– 6 6 wkswks

1010mgmg bdbd 8 8 –– 10 10 wkswks

1515mg ODmg OD 10 10 –– 12 12 wkswks

10 10 mg ODmg OD 10 10 –– 12 12 wkswks

5 5 mg ODmg OD 10 10 –– 12 12 wkswks

Side Effects of ATDSide Effects of ATD

Side effectsSide effects ActionAction

Skin rash,Skin rash, prurituspruritus,,arthralgiasarthralgias

Try other alternative ATDTry other alternative ATD

AgranulocytosisAgranulocytosis Stop and never ATD again, Stop and never ATD again, may need admissionmay need admission

CholestaticCholestatic hepatitishepatitis Stop and evaluate, ? Try Stop and evaluate, ? Try other ATDother ATD

•It’s a good practice to mention and warn patients about these possible side effects (severs toxic reaction is extremely rare from our own experiences) when first starting ATD. Any doubt, check CBP, LFT

•PTU to be preferred during pregnancy

WBC &WBC & ThyrotoxicosisThyrotoxicosis

GravesGraves’’ thyrotoxicosisthyrotoxicosis may have low may have low WBC & platelet at presentationWBC & platelet at presentation0.5 to 1.0 % may develop0.5 to 1.0 % may developagraagranulnulocytosisocytosis after ATD, usually after ATD, usually abrupt presentationabrupt presentation, routine CBP , routine CBP surveillance not indicatedsurveillance not indicatedRoutine warning to patientsRoutine warning to patientsRecovery within 1 week, may be Recovery within 1 week, may be shortened with Gshortened with G--CSFCSF

Liver DerangementLiver Derangement &&ThyrotoxicosisThyrotoxicosis

Related directly to the state ofRelated directly to the state of thyrotoxicosisthyrotoxicosis ––mild mild ↑↑ ALT, ALT, ↑↑AlkAlk POPO4 4 (bone)(bone)ThyrotoxicThyrotoxic heart disease with CHF and heart disease with CHF and congested livercongested liverIdiosyncratic reaction toIdiosyncratic reaction to thionamides antithyroidthionamides antithyroidmedicationsmedicationsAetiologicallyAetiologically related to the underlying Gravesrelated to the underlying Graves’’disease disease –– autoimmune hepatitis, primaryautoimmune hepatitis, primary biliarybiliarycirrhosiscirrhosis

RadioiodineRadioiodine TherapyTherapy--Facts (1)Facts (1)

Nearly for all causes of hyperthyroidismNearly for all causes of hyperthyroidismSafely be given to patients of all ageSafely be given to patients of all age gpgp but but is less often given to children <10 yrs oldis less often given to children <10 yrs oldContraindicated in pregnancy and while Contraindicated in pregnancy and while breast feedingbreast feedingNo increased risk of thyroid cancer,No increased risk of thyroid cancer,leukaemialeukaemia, solid, solid tumourstumours,, teratogenicityteratogenicity and and chromosomechromosome damagedamage

RadioiodineRadioiodine TherapyTherapy--Facts (2)Facts (2)

The recommended strategy is to give an The recommended strategy is to give an activity sufficient to render the patient activity sufficient to render the patient rapidlyrapidly euthyroideuthyroid and maintain that state or and maintain that state or achieve no more than a low rate of achieve no more than a low rate of hypothyroidism in subsequent yearshypothyroidism in subsequent yearsA range of activity (300A range of activity (300--800800 MBqMBq) is ) is suggested depending on the clinical statesuggested depending on the clinical stateATD may be given before or after RAI (or ATD may be given before or after RAI (or both) if necessaryboth) if necessary

RadioiodineRadioiodine TherapyTherapy--Facts (3)Facts (3)

Administration of RAI must conform to Administration of RAI must conform to regulations and definitions as stated regulations and definitions as stated by government board by government board Full writFull writtten information should be en information should be given to the patient and written given to the patient and written consent obtainedconsent obtainedA structured FU should be used A structured FU should be used ensuring regular measurement of TSH ensuring regular measurement of TSH and FT4and FT4

RAIRAI--IndicationsIndications

Toxic nodularToxic nodular goitregoitre -- treatment of treatment of choicechoicePostPost--thyroidectomythyroidectomyGravesGraves’’ diseasedisease–– firstfirst--lineline–– relapserelapse–– compliancecompliance–– concommitantconcommitant clinical or social factorsclinical or social factors

Contraindications to RAIContraindications to RAI

Pregnancy and breast feedingPregnancy and breast feedingSituations where it is clear that the Situations where it is clear that the safety of other persons cannot be safety of other persons cannot be guaranteedguaranteedKnown allergy to iodineKnown allergy to iodineRelativeRelative -- egeg urinary incontinence urinary incontinence without a catheter, significantwithout a catheter, significantretrosternal goitreretrosternal goitre

RAIRAI -- other fother factors to actors to considerconsider

Patient age, gender and response to Patient age, gender and response to ATDATDCauses and severity of Causes and severity of hyperthyroidismhyperthyroidismPatient and doctor preference and Patient and doctor preference and access to RAIaccess to RAISafety Safety CostCost

Side Effects of RAISide Effects of RAINo documented allergic reactions to No documented allergic reactions to RAIRAIRadiation gastritisRadiation gastritisRadiationRadiation thyroiditisthyroiditis–– anterior neck painanterior neck pain–– transient exacerbation oftransient exacerbation of thyrotoxicosisthyrotoxicosis–– ? increased compressive? increased compressive symtomssymtomsSubsequent development or worsening Subsequent development or worsening of infiltrativeof infiltrative ophthalmopathyophthalmopathy

Common Symptoms and Common Symptoms and Signs of HypothyroidismSigns of HypothyroidismSymptomsSymptoms

FatigueFatigueFeeling slow or tiredFeeling slow or tiredCold intoleranceCold intoleranceMuscle aching and Muscle aching and crampscrampsMemory lossMemory lossDepressionDepressionConstipationConstipationHeavy menstrual flowHeavy menstrual flowDecreased libido, Decreased libido, infertility

SignsSignsSlow heart rateSlow heart rateDry, coarse, yellowish Dry, coarse, yellowish skinskinWeight gainWeight gainFacial and hand Facial and hand puffinesspuffinessHusky voiceHusky voiceThinning hairThinning hairIn children, short In children, short staturestatureEnlarged thyroid glandEnlarged thyroid glandinfertility

Clinical Features of Hypothyroidism (the most common Clinical Features of Hypothyroidism (the most common features are in italic)features are in italic)GeneralGeneral••TirednessTiredness••Weight gainWeight gain••Cold intoleranceCold intolerance••HypothermiaHypothermia••GoitreGoitre••HyperlipidaemiaHyperlipidaemia

CardiovascularCardiovascular••BradycardiaBradycardia••AnginaAngina••Heart failureHeart failure••HypertensionHypertension••Pericardial effusionsPericardial effusions

RespiratoryRespiratory••DyspnoeaDyspnoea••ReducedReduced inspiratoryinspiratory efforteffort••Pleural effusionsPleural effusions

NeuromuscularNeuromuscular••Aches and painsAches and pains••MyalgiaMyalgia and muscle crampand muscle cramp••Joint stiffnessJoint stiffness••ParesthesiasParesthesias••Carpel tunnel syndromeCarpel tunnel syndrome••HoarsenessHoarseness

••DeafnessDeafness••CerebellarCerebellar ataxiaataxia••MyotoniaMyotonia••Delayed relaxation of reflexesDelayed relaxation of reflexes

NeuropsychiatricNeuropsychiatric••LethargyLethargy••FatiabilityFatiability••SleepinessSleepiness••DeliriumDelirium••DementiaDementia••DepressionDepression••PsychosisPsychosis••((““myxoedemamyxoedema madnessmadness””))

HaematologicalHaematological••Iron deficiencyIron deficiency anaemiaanaemia••Macrocytic anaemiaMacrocytic anaemia••PerniciousPernicious anaemiaanaemia••Normochromic normocytic anaemiaNormochromic normocytic anaemia

DermatologicalDermatological••Dry cool skinDry cool skin••Brittle nailsBrittle nails••Coarse hairCoarse hair••AlopeciaAlopecia••OedemaOedema

••MyxoedemaMyxoedema (especially facial and(especially facial andperiorbital tissresperiorbital tissres))••VitiligoVitiligo••Erythema ab igneErythema ab igne

ReproductiveReproductive••InfertilityInfertility••ImpotenceImpotence••MenorrhagiaMenorrhagia••GalactorrhoeaGalactorrhoea andand hyperprolactinaemiahyperprolactinaemia

GastrointestinalGastrointestinal••ConstipationConstipation••IleusIleus, rarely toxic, rarely toxic megacolonmegacolon••Abdominal distensionAbdominal distension

DevelopmentalDevelopmental••Growth retardationGrowth retardation••Mental retardationMental retardation••Short statureShort stature••Delayed pubertyDelayed puberty

What Causes What Causes HypothyroidismHypothyroidism

One common cause of thyroid gland failure One common cause of thyroid gland failure is Hashimotois Hashimoto’’ss thyroiditisthyroiditis, a painless disease , a painless disease of the immune system that runs in families.of the immune system that runs in families.Thyroid surgery or radioactive iodine Thyroid surgery or radioactive iodine treatment may cause hypothyroidismtreatment may cause hypothyroidismOne out of every 4000One out of every 4000--6000 infants is born 6000 infants is born with hypothyroidism. If the problem is not with hypothyroidism. If the problem is not corrected promptly, the child will become corrected promptly, the child will become mentally and physically retardedmentally and physically retarded

Iodine Deficiency Iodine Deficiency Disorders Disorders

About 100 million people around the world About 100 million people around the world (usually inland mountainous area) don(usually inland mountainous area) don’’t get t get enough iodine in their diets.enough iodine in their diets.Iodine is a chemical which the thyroid uses Iodine is a chemical which the thyroid uses to produce its hormonesto produce its hormonesAdding iodine to salt as a national policy Adding iodine to salt as a national policy could solve the problem for endemic iodine could solve the problem for endemic iodine deficiency areadeficiency area

Causes of HypothyroidismCauses of HypothyroidismPrimary hypothyroidismPrimary hypothyroidism Secondary hypothyroidism (pituitary)Secondary hypothyroidism (pituitary)••Thyroid agenesis /Thyroid agenesis / dysgenesisdysgenesis••Thyroid gland destructionThyroid gland destruction

HashimotoHashimoto’’ss thyroiditisthyroiditisPostPost--thyroidectomythyroidectomyPostPost--radioiodineradioiodine/neck irradiation/neck irradiationPostPost--subacutesubacute/silent/silent thyroiditisthyroiditis

••Thyroid gland atrophyThyroid gland atrophyAtrophicAtrophic thyroiditisthyroiditis/primary/primary

agoitrousagoitrous••Disorders of thyroid hormone Disorders of thyroid hormone synthesissynthesis

Iodine deficiencyIodine deficiencyDrugsDrugs (thionamides(thionamides, lithium, iodide,, lithium, iodide,

amiodaroneamiodarone))DyshormonogenesisDyshormonogenesis (inherited (inherited

enzyme deficiencies)enzyme deficiencies)

••PituitaryPituitary tumourtumour (primary or(primary ormetastaticmetastatic))••AutoimmuneAutoimmune hypophysitishypophysitis••Pituitary irradiation or surgeryPituitary irradiation or surgery

Tertiary hypothyroidism (hypothalamic)Tertiary hypothyroidism (hypothalamic)••HypothalamicHypothalamic tumourtumour or destructionor destruction

Generalized or peripheral thyroid Generalized or peripheral thyroid hormone resistancehormone resistance

A Case of Hypothyroidism due to A Case of Hypothyroidism due to HashimotoHashimoto’’ss ThyroiditisThyroiditis

F/16, studentF/16, studentc/o weight gain of 10 lbs in 3 months, cold c/o weight gain of 10 lbs in 3 months, cold intolerance, feeling slow and tired, drowsy during intolerance, feeling slow and tired, drowsy during the day, heavy menstrual flowthe day, heavy menstrual flowPulse 60/min, dry, cold hand with yellowish skin, Pulse 60/min, dry, cold hand with yellowish skin, puffy face, small diffuse firmpuffy face, small diffuse firm goitregoitreTSH = 85TSH = 85 mIUmIU/l, FT4 = 3.2/l, FT4 = 3.2 pmolpmol/l,/l, TgAbTgAb 1/100,1/100,TPOAbTPOAb 1/25,600, USS showed a diffuse1/25,600, USS showed a diffuse goitregoitre

Treatment Treatment Daily LDaily L--thyroxinethyroxine replacementreplacementTitrateTitrate according to TSHaccording to TSH (0.10 mg daily for (0.10 mg daily for average adult, or 0.016average adult, or 0.016--0.018 mg/kg daily), 0.018 mg/kg daily), allow >6 weeks before monitorallow >6 weeks before monitorCaution in patients with IHD or elderly, start Caution in patients with IHD or elderly, start at low doseat low doseIf suspect adrenal insufficiency orIf suspect adrenal insufficiency orhypopituitarismhypopituitarism, must replace steroids , must replace steroids beforebefore thyroxinethyroxine

Thyroid enlargement(Goitre)

•Diffuse or nodular•Single nodule or multinodular•Cystic or solid•Benign or malignant•Any pressure effects

•Simple euthyroid•Hyperthyroid•Hypothyroid•?Autoimmunity

•Examination•TFTs•TGAb & TPOAb

•Neck palpation•Thyroid scintiscan•Ultrasound•FNA

Etiology of Simple GoiterEtiology of Simple Goiter

1. Iodine deficiency1. Iodine deficiency

2. Iodine excess2. Iodine excess

3.3. GoitrogenicGoitrogenic agentsagentsa. Drugsa. Drugsb. Food stuffsb. Food stuffs

4.4. DyshormonogenesisDyshormonogenesis

5.5. Autoimmunizing thyroiditisAutoimmunizing thyroiditis

6. Ionizing radiation6. Ionizing radiation

Nomenclature ofNomenclature of thyroiditisthyroiditis according to the according to the American Thyroid Association (WERNER 1969)American Thyroid Association (WERNER 1969)

American Thyroid Association SynonymsAmerican Thyroid Association Synonyms

SubacuteSubacute or acuteor acutenonsuppurative thyroiditisnonsuppurative thyroiditis

Granulomatous thyroiditisGranulomatous thyroiditisGiant cellGiant cell thyroiditisthyroiditisDeDe QuervainQuervain’’ss thyroiditisthyroiditis

ChronicChronic lymphocytic thyroiditislymphocytic thyroiditis HashimoloHashimolo’’ss thyroiditisthyroiditisStruma lymphomatosaStruma lymphomatosaAutoimmuneAutoimmune thyroiditisthyroiditis

Chronic invasive fibrousChronic invasive fibrousthyroiditisthyroiditis

RiedelRiedel’’ss thyroiditisthyroiditis

AcuteAcute suppurative thyroiditissuppurative thyroiditis

ChronicChronic nonsuppurative nonsuppurative thyroiditisthyroiditis due to specific due to specific infection (tuberculosis, syphilis)infection (tuberculosis, syphilis)

DeDe QuervainQuervain’’ss thyroiditisthyroiditisSSpontaneouslypontaneously remitting inflammatory remitting inflammatory disease of the thyroid glanddisease of the thyroid glandBBelievedelieved to be viral into be viral in aetiologyaetiology

Incidence : Incidence : not an uncommon disease,not an uncommon disease,WoolnerWoolner et al collected 162 cases over 5 et al collected 162 cases over 5 years, approximate oneyears, approximate one--eighth the eighth the incidence of Gravesincidence of Graves’’ disease and 50 times disease and 50 times more frequently than Riedelmore frequently than Riedel’’ss thyroiditisthyroiditis

DeDe QuervainQuervain’’ss thyroiditisthyroiditis

Clinical featuresClinical features::

PPainain and tenderness in thyroid and tenderness in thyroid regionregionMMalaisealaise , fatigue with fever (PUO), fatigue with fever (PUO)TTypicallyypically gradual onset over 1 to 2 gradual onset over 1 to 2 weeks , continues with fluctuating weeks , continues with fluctuating intensity for 3 to 6 weeksintensity for 3 to 6 weeks

DeDe QuervainQuervain’’ss thyroiditisthyroiditisAApproximatelypproximately one half of the patient one half of the patient present in first week with symptoms ofpresent in first week with symptoms ofthyrotoxicosisthyrotoxicosisHoffman HS (US) andHoffman HS (US) and HarefuahHarefuah (Israel) (Israel) reported 2 cases presented as PUO similar reported 2 cases presented as PUO similar to our to our local experienceslocal experiencesDDemonstratedemonstrated association with HLAassociation with HLA--B35 B35 and B67 byand B67 by OhsakoOhsako (Japan) in (Japan) in 19199595

DeDe QuervainQuervain’’ss thyroiditisthyroiditis

DDiagnosisiagnosis : clinical, with striking : clinical, with striking elevation in ESR , elevation in ESR , mildmild leucocytosis leucocytosis and high serum T4, T3 leveland high serum T4, T3 levelLLowow thyroidal RAIUthyroidal RAIUBirchallBirchall , Chow and, Chow and MetreweliMetreweli in in 191990 demonstrated the ultrasonic 90 demonstrated the ultrasonic features and striking volume features and striking volume change after treatment of 2 cases change after treatment of 2 cases of Deof De QuervainQuervain’’ss thyroiditisthyroiditis in HKin HK

DeDe QuervainQuervain’’ss thyroiditisthyroiditis

Treatment : Treatment : some patients do some patients do not need treatment, most of them need not need treatment, most of them need NSAID as analgesic, if this fails : NSAID as analgesic, if this fails : 1 short 1 short course course steroidsteroid for 3for 3--6 weeks6 weeks

Prognosis :Prognosis : 90% with complete 90% with complete and spontaneous recovery and return to and spontaneous recovery and return to normal thyroid function.normal thyroid function. LitakaLitaka (Japan) (Japan) evaluated 3344 patients, at least recur evaluated 3344 patients, at least recur in 2% of patients and exhibited in 2% of patients and exhibited relatively mild clinical manifestationrelatively mild clinical manifestation

Other topics of interestOther topics of interest

Pregnancy related thyroid disordersPregnancy related thyroid disorders–– Hyper & HypothyroidismHyper & Hypothyroidism–– PostpartumPostpartum thyroiditisthyroiditis

ThyrotoxicThyrotoxic heart diseaseheart diseaseThyrotoxicThyrotoxic periodic paralysisperiodic paralysisThyroid Disorders in the ElderlyThyroid Disorders in the Elderly