ThyroidThyroid

PhysiologyPhysiology

Seretion of thyroid hormonesSeretion of thyroid hormones – T – T3,3, T T4, 4,

calcitonincalcitoninee

Iodine: Iodine: 100 micrograme100 microgramess; 30% ; 30% absorbed in absorbed in digestive tractdigestive tract

CaptCapture in thyroid glandure in thyroid gland – oxida – oxidationtion (peroxidaze) – transport(peroxidaze) – transportation in ation in coloid coloid (t(thyhyroglobulinroglobulinee) – iod) – iodisation ofisation of t thhirozinirozinee – MIT, – MIT, DIT –TDIT –T33, T, T44 – – blood streamblood stream

TThyroid hormoneshyroid hormonesIncrease O2 consumption and metabolismIncrease O2 consumption and metabolism

Proteic metabolism: increase Proteic metabolism: increase catabolism and catabolism and anabolismanabolism (groth and development) (groth and development)

Lipid metabolism: Lipid metabolism: mobilization of lipidsmobilization of lipids from fatty from fatty tissue and stimulates oxidation at cellular level. tissue and stimulates oxidation at cellular level.

Glucidic metabolism: Glucidic metabolism: hhyyperglicemperglicemiaia (sinergi (sinergististic c with with adrenalineadrenaline - β-receptori), - β-receptori), diabetes: newly developed diabetes: newly developed or worsening or worsening

Essential for the normal brain development (stimulated Essential for the normal brain development (stimulated myelin production and neuronal ramifications) myelin production and neuronal ramifications) idiotismidiotism. .

ExcesExcess of s of T3 T3 andand T4 T4 –– tthyrotoxicosishyrotoxicosis

Hyper Hypo

Protidic metabolismCatabolism – loss of weight and

muscular tissuePozitiv nitrogen balance but

with anabolism

Lipidic metabolismLow cholesterol and TG High cholesterol-

ateroscolerosis

Gucidic metabolism Hyperglicemia Low intestinal absorbtion

H2O electolitesEdema Water retention and

depolimerization of MPZ = mixedema

Basal metabolismIncrease = heat production Decereased

Cardiovascular HyperkinesiaDeceresed cardiac output

(mixedematous infiltration of myocardial muscle)

Nervous systemHyperexcited, nervousness,

insomniaApatie, lentor, coma

Digestiv Diharrea Constipation

GOITERGOITERANY increase of ANY increase of volumevolume– BenignBenign– Malignant Malignant

Associated with Associated with ::– NormNormalal– HHyyperper-function-function– HHyypopo- function- function

Goiter Goiter structural changes in thyroid gland generated by structural changes in thyroid gland generated by the incapacity to inssure a normal plasmatic level of thyroid the incapacity to inssure a normal plasmatic level of thyroid hormoneshormones

A. A. Familial goiterFamilial goiter – geneti factors, many – geneti factors, many mambers on the same family mambers on the same family

B. B. Endemic goiterEndemic goiter – a significant number – a significant number of cases in the same arrea – low iodine in of cases in the same arrea – low iodine in the environmentthe environment

C. C. Sporadic –Sporadic – not always a clear cause. not always a clear cause.

Iodine deficit in thyroid Iodine deficit in thyroid glandgland

Deficit in synthesis or hormon excretion (normal iodine or excess of iodine)

Increased hormonal needs

Lack of iodine in waterLack of iodine in waterLack of intake Lack of intake Abnormal absorbtionAbnormal absorbtionExcessive loss (diarrhea, breast Excessive loss (diarrhea, breast feeding) feeding) Blocked transmembrane transport Blocked transmembrane transport of Iodine (perclorate, thyocianate of Iodine (perclorate, thyocianate intoxication)intoxication)

Genetic factors (under evaluation)Genetic factors (under evaluation)Iatrogenic (long term iodine, AINS, Iatrogenic (long term iodine, AINS, corticoids, synthetic antithyroid corticoids, synthetic antithyroid drugs)drugs)Endoscrine diseases (acromegaly)Endoscrine diseases (acromegaly)MenopauseMenopause

Puberty/Pregnancy/StressPuberty/Pregnancy/Stress

PathologyPathology

Difuse goiterDifuse goiterNodular goiterNodular goiterAdenomatous goiterAdenomatous goiterColoidal goiterColoidal goiterCystic goiterCystic goiterVascular goiterVascular goiterFibrotic goiterFibrotic goiterCalcified goiterCalcified goiter

GOITERGOITER

VOLUMVOLUM

TOPOGRAFTOPOGRAFYY– whole/lob/istmwhole/lob/istm

Pathological Pathological characteristiccharacteristic– Nodular, vascular, Nodular, vascular,

cystic..cystic..

CONSISTECONSISTENCENCE– Elastic, soft, hardElastic, soft, hard

MOBILITMOBILITYY

ASSOICIATED LNASSOICIATED LN

Clinical SignsClinical SignsHYPOHYPO

InfiltratedInfiltrated

Yellow-wax colourYellow-wax colour

Dry hair, lossDry hair, loss

Striated friable nailsStriated friable nails

Difuse altralgiaDifuse altralgia

BradipneeaBradipneea

Pleural efusionPleural efusion

HYPERHYPERMoist, warm, fineMoist, warm, fine

PruritusPruritus

EdemaEdema

Soft hair, lossSoft hair, loss

Nail destructionNail destruction

Osteoporosis with Osteoporosis with bone painbone pain

Scapulo-humeral Scapulo-humeral periarthritisperiarthritis

TachypneeaTachypneea

SkinSkin

Nail/hairNail/hair

Joint/bonesJoint/bones

RespiratoryRespiratory

Clinical SignsClinical SignsHYPOHYPO

CardiomegalyCardiomegalyPericardial effusionPericardial effusionAngorAngor

MacroglosiaMacroglosiaMeteorism/constipationMeteorism/constipation

Gallbladder diskinesia + Gallbladder diskinesia + stones stones

♀ ♀ amenorrea, abnormal amenorrea, abnormal bleedings, galactorea, bleedings, galactorea, frigidityfrigidity♂ ♂ sterility, impotencesterility, impotence

Intelectual deficitIntelectual deficitMemory problemsMemory problemsDepressionDepressionCarpian canal syndromeCarpian canal syndrome

HYPERHYPERTachycardia/arithmiaTachycardia/arithmiaHeart failureHeart failureAbnormal soundsAbnormal sounds

Incresed apetiteIncresed apetiteWeight lossWeight lossHypermotility + Hypermotility + DiarrheaDiarrhea

♀ ♀ oligo/amenorreaoligo/amenorrea♂ ♂ gynecomastia, gynecomastia, impotenceimpotence

FatigueFatigueNervousnessNervousnessFine tremour Fine tremour extremitiesextremities

Cardio-Cardio-vascularvascular

DigestivDigestiv

GenitalGenital

Nervous Nervous systemsystem

Nervous structuresNervous structures– Laryngeal recurrent nerve – butonal voiceLaryngeal recurrent nerve – butonal voice – Cervical sympathetic chain Cervical sympathetic chain (Claude-Bernard-Horner (Claude-Bernard-Horner

syndrome) syndrome) == enoftalmia, miozis, congestion of half of the enoftalmia, miozis, congestion of half of the face) face)

– HipoglosHipoglosal nerve – deviation of the tong on anterior al nerve – deviation of the tong on anterior projectionprojection

– Frenic Frenic ( (hickuphickup), spinal (), spinal (palsy of SCM and trapezius)palsy of SCM and trapezius), , – VagusVagus ( (digestive changes)digestive changes);;

VascularVascular: veno: venousus ( (venous ectasia) arterial (cerebral venous ectasia) arterial (cerebral irrigation) irrigation) EEsofagsofagus: disphagiaus: disphagiaTrachea: dispnoea, radiologic changes – deviation of Trachea: dispnoea, radiologic changes – deviation of the trachea (mostly lateral deviation)the trachea (mostly lateral deviation)

Clinica Signs- local Clinica Signs- local compressioncompression

Goiter – simple/non-toxicGoiter – simple/non-toxic

Iodine deficitIodine deficit

SSyymptomemptomess– NNone one →compresion signs→compresion signs

ParaclinicalParaclinical– T3, T4; TSHT3, T4; TSH– Echo, CT, RMN, Echo, CT, RMN, ENT ENT

exploration exploration

Goiter - simpleGoiter - simple

SCINTIGRASCINTIGRAMM

Diagnostic – organ of originDiagnostic – organ of origin : : – Thyroid in clinical examination – all signsThyroid in clinical examination – all signs– ScintigrafScintigrafy y - I - I131131 capture in tumor capture in tumor ..

DiagnosticDiagnostic - goiter - goiter– AnamneAnamnesis – endemic areasis – endemic area– Clinical examinationClinical examination:: caracter caracteristics of tumoristics of tumor– Paraclinical examination - imagisticsParaclinical examination - imagistics

DiagnosticDiagnostic - functional - functional– Thyroid hormonal functionThyroid hormonal function

Differential diagnosticDifferential diagnosticCervica tumors:Cervica tumors:– ThyThyreogloreoglotic cysttic cyst – Dermoid tumorsDermoid tumors / Branchial arch derived tumors / Branchial arch derived tumors– Cervical adenopathtCervical adenopatht– Benign tumorsBenign tumors:: lipolipomama, , sebaceus cysts, angioma sebaceus cysts, angioma – Malignant tumorsMalignant tumors Hodgkin,Hodgkin, LN, sracomas LN, sracomas

Other thyroid diseases Other thyroid diseases – FFuncţionaluncţional hypertrophy (puberty, gestational, menstruation) hypertrophy (puberty, gestational, menstruation) – Acute thyroiditis Acute thyroiditis – Subacute thyroiditis -Subacute thyroiditis - de Quervain de Quervain – Chronic lymphocytic thyroiditis – HashimotoChronic lymphocytic thyroiditis – Hashimoto – RiedlRiedl chornic thyroiditis chornic thyroiditis – Specific chronic thyroiditis: Specific chronic thyroiditis: sifilis, tbc, actinomicosifilis, tbc, actinomicosissis– HipertrofHipertrofy associated to y associated to hhyypertperthyroidismhyroidism t thyhyreotoxicreotoxic syndrome syndrome – Thyroid cancerThyroid cancer

Abnormal positionsAbnormal positionsEctopic goiterEctopic goiter – Intrathoracic goiter: abnormal thyroid tissue developed in the thorax – Intrathoracic goiter: abnormal thyroid tissue developed in the thorax –

vasculature from thoracic cavityvasculature from thoracic cavity– Lateral cervical goiter: abnormal thiroid tissue developed in the lateral Lateral cervical goiter: abnormal thiroid tissue developed in the lateral

cervical areacervical area– Lingual – defect in migration of tissues in emriogenesis: the thyroid gland Lingual – defect in migration of tissues in emriogenesis: the thyroid gland

is stuck at the level of foramen cecumis stuck at the level of foramen cecum– Intratracheal goiter: first segments: produces obstruction Intratracheal goiter: first segments: produces obstruction – Intraesophageal goiter: rarity ~ esophageal tumorIntraesophageal goiter: rarity ~ esophageal tumor– Ovarina goiter: abnormal thyroid tissue in the ovary Ovarina goiter: abnormal thyroid tissue in the ovary

(disembrioplastic/metastasis)(disembrioplastic/metastasis)

Cervical-mediastinal goiter:Cervical-mediastinal goiter: cervical origin but aspirated in the cervical origin but aspirated in the upper part of thoracic cavity: feeding vessels are normal from upper part of thoracic cavity: feeding vessels are normal from cervical sources.cervical sources.

TreatmentTreatment

L-THYROXINEL-THYROXINE– 50% reduction in volume in 30% of cases50% reduction in volume in 30% of cases

IODINE THERAPY IODINE THERAPY

RADIRADIO-IODINE THERAPYO-IODINE THERAPY– 50-60% reduction in ~1-1.5 y50-60% reduction in ~1-1.5 y

SURGERYSURGERY– TiroidectomTiroidectomyy subtotal subtotal/total/total + + L-ThyroxineL-Thyroxine

Surgical treatment – WHEN?Surgical treatment – WHEN?

Failure of other modalitiesFailure of other modalities

Multinodular goiter or cold nodules on scintigrafy Multinodular goiter or cold nodules on scintigrafy

Goiter with lesions which are most probably Goiter with lesions which are most probably irreversible: fibrosis, recurrent cysts) irreversible: fibrosis, recurrent cysts)

Complicated goiter: hyperthyroidism, Complicated goiter: hyperthyroidism, inflammation, intracystic bleeding, compression inflammation, intracystic bleeding, compression syndrome syndrome

Esthetic indications Esthetic indications

TTHYHYROTOXICOROTOXICOSISSIS

Hypermetabolic condition Hypermetabolic condition characterised by increased levels characterised by increased levels of of FT3 FT3 and/orand/or FT4 FT4

– HHyperthyroidismyperthyroidism

– Subacute thyroiditisSubacute thyroiditis

– Exogenous administration of thyroid Exogenous administration of thyroid hormoneshormones

HHYYPERTPERTHYHYROIDIROIDISMSM

Excess synthesis and discharge of Excess synthesis and discharge of hormones in the circulationhormones in the circulation– Graves 50-60%Graves 50-60%

AutoimunAutoimunee conditioncondition

– Multinodular goiterMultinodular goiter 15-20% 15-20%Long lasting goiterLong lasting goiter

– Toxic adenomaToxic adenoma 3-5% 3-5%

PATHOGENYPATHOGENYGraves DiseaseGraves Disease – Ig GIg G acting aginst Thyroid gland , including effect against acting aginst Thyroid gland , including effect against

TSH receptor in a stimulatory fashion: activation of cAMP = TSH receptor in a stimulatory fashion: activation of cAMP = increase the volume of the gland, vascular pattern and increase the volume of the gland, vascular pattern and hypersecretion of thyroid hormones. hypersecretion of thyroid hormones.

LATS LATS - - Long Acting Thyroid StimulatorLong Acting Thyroid Stimulator

TSI TSI - - Thyroid Stimulating ImmunoglobulinsThyroid Stimulating Immunoglobulins

Nodular Goiter associated with hyperthyroidismNodular Goiter associated with hyperthyroidism::– Nodules producing high levels of hormone secretionNodules producing high levels of hormone secretion

Toxic adenoma: Toxic adenoma: – Thyroid nodule completely independent (bening in majority Thyroid nodule completely independent (bening in majority

of cases) without feed back inhibition = administration of of cases) without feed back inhibition = administration of T3/T4 does not produce suppression. T3/T4 does not produce suppression.

HHYYPERTPERTHYHYROIDROIDISMISMNeurological Neurological problemsproblems

Fine tremourFine tremour

ExoExophphtthhalmiaalmia

Neurovegetative Neurovegetative imbalance: imbalance: – Excessive Excessive

sweeteningsweetening– Low level feverLow level fever

Thyroid hypertrophyThyroid hypertrophy

Hyperthyroidism Hyperthyroidism syndrome syndrome depending on T3/T4 depending on T3/T4 levelslevels

HHYYPERTPERTHYHYROIDROIDISMISMSkinSkin– Warm, fine, moist, Warm, fine, moist,

intense dermographismintense dermographismNailsNails– Thin, fragileThin, fragile

Infiltrative demopathy Infiltrative demopathy – Pretibial mixedemaPretibial mixedema

Thyrotoxic myopathyThyrotoxic myopathy– Loss of muscular massLoss of muscular mass– HypotoniaHypotonia– Muscular painMuscular pain– FatigueFatigue

All systems are affectedAll systems are affected– CardiovascularCardiovascular– RespiratorRespirator– DigestivDigestiv– Genital Genital

HIPERTHIPERTHYHYROIDIROIDISMSM

LABLAB– Low Low TSH TSH – High High FT3, FT4FT3, FT4– TSI, LATSTSI, LATS

SCINTIGRASCINTIGRAPHYPHY

Increased Increased RICRIC

Imaging the glandImaging the gland– UltrasoundUltrasound– CTCT– RMNRMN– FNAFNA

TREATMENTTREATMENT

Symptomatic treatment:Symptomatic treatment:– Beta-blockersBeta-blockers– SedativesSedatives

Inhibitors of hormone synthesis- Inhibitors of hormone synthesis- synthetic antithyroid drugs synthetic antithyroid drugs ((propiltiouracil, methimazolpropiltiouracil, methimazol, carbimazol), carbimazol) – Block the oxidation of iodine with Block the oxidation of iodine with

sequential block in iodothyrozine sequential block in iodothyrozine synthesis synthesis

– Produces a secondary goiter Produces a secondary goiter development due to rises in TSHdevelopment due to rises in TSH

– Normal thyroid hormone levels in 6-Normal thyroid hormone levels in 6-12 weeks12 weeks

– Major side effects: AgranulocitosisMajor side effects: Agranulocitosis, , liver toxicity, LES, alopecia, nefrotic liver toxicity, LES, alopecia, nefrotic syndrome, poliarthritis, syndrome, poliarthritis, poliradiculonevritis. poliradiculonevritis.

IIodine – odine – Lugol solutionLugol solution – Reduce the volume and Reduce the volume and

vascular pattern of the thyroid vascular pattern of the thyroid gland. Effect is maximal in 10 gland. Effect is maximal in 10 days, maintained 2-3 weeks, days, maintained 2-3 weeks, then the gland escapes then the gland escapes suppresion. suppresion.

– Preopertaive or in Preopertaive or in thyrotoxicosis associated with thyrotoxicosis associated with syntehetic antithyroid drugs. syntehetic antithyroid drugs.

CorticosteroiziiCorticosteroizii– Lower T secretionLower T secretion– Inhance urinary lossInhance urinary loss– Prevent and treat thyrotoxicosis Prevent and treat thyrotoxicosis

cresc ioduriacresc ioduria

RADIOACTIVRADIOACTIV IODINE IODINE– Thyroid tissue destruction – Thyroid tissue destruction –

aiming to transform all patients aiming to transform all patients in hypothyroid patients. in hypothyroid patients.

TREATMENTTREATMENT

SURGERYSURGERY– TTHYROIDECTOMY: HYROIDECTOMY: subtotal,subtotal, quasi quasitotal, total,

totaltotal– Correct preoperative preparation – normal Correct preoperative preparation – normal

thyroid hormone levels + sedationthyroid hormone levels + sedation– Postoperative complicationsPostoperative complications

HemorHemorrhagerhageThyrotoxic crisesThyrotoxic crisesRecurrent nerve palsyRecurrent nerve palsyHHypoparathyroidismypoparathyroidism

THYROTOXIC CRISIS – major THYROTOXIC CRISIS – major emergency emergency

Acute augmentation of hyperthyroid statusAcute augmentation of hyperthyroid status

May develop in the first 24-48 hours postoperative, May develop in the first 24-48 hours postoperative, more often after incomplete preparationmore often after incomplete preparation

Stage I : Stage I : tatacchicardihicardia >a >130/minut130/minutee, hipert, hiperthhermiermia, massive sweating, a, massive sweating, dehydration, intense tremour. dehydration, intense tremour.

Stage II: adds desorientation, stupor and somnolence. Stage II: adds desorientation, stupor and somnolence.

Stage III: coma Stage III: coma

Treatment: Treatment: Large doses of synthetic antithyroid drugsLarge doses of synthetic antithyroid drugs

Mineral iodine (KCl or Lugol) Mineral iodine (KCl or Lugol)

Symptomatic treatment: corticoids and beta-blockersSymptomatic treatment: corticoids and beta-blockers

Lower body temperature – refrigerationLower body temperature – refrigeration

Intensive care: O2, ionic balanceIntensive care: O2, ionic balance

INFLAMMATORY INFLAMMATORY DISEASES = DISEASES = THYROIDITISTHYROIDITIS

Classification Classification ACUTEACUTE

SUBACUTE – granulomatous SUBACUTE – granulomatous DeQuervainDeQuervain

CCHHRONICRONIC– NNonspecificonspecific

LimfoLimfocyticcytic Hashimoto Hashimoto

FibrFibroticotic Riedel Riedel

– SpecificSpecificTBC, TBC, sifilis, actinomycosissifilis, actinomycosis

ACUTE THYROIDITISACUTE THYROIDITIS<1% <1% of all thyroid pathology, frequently preexisting goiterof all thyroid pathology, frequently preexisting goiter

PATPATHHOGENOGENYYGermeGermess – abscess formation (aggressive germs + low – abscess formation (aggressive germs + low immunity)immunity)– BacteriBacteriaa – streptococ – streptococcuscus, stafilococ, stafilococcuscus, pneumococ, pneumococcuscus, G-, G-bacilibacili– VirusViruseses – – influenzainfluenza,,– Fungs: Fungs: – – CCandidaandida– ParaziParazitictic

Contamination:Contamination:– HematogenHematogenous,ous, l lyymfatic, mfatic, directdirect

SSooururcece– Close contactClose contact– Distant source with hematogenic circulation Distant source with hematogenic circulation

CLINICAL EXAMINATIONCLINICAL EXAMINATION

AnamnesisAnamnesis – Sudden onsetSudden onset– Local inflammatory signsLocal inflammatory signs– Fever high (38.5-40), chills Fever high (38.5-40), chills

and tachicardiaand tachicardia– Anterior cervical painAnterior cervical pain

Pressure sensationPressure sensationRadiating: mandible, earRadiating: mandible, earIntensifies with swallowingIntensifies with swallowingAntalgic positionAntalgic position

– DysphagiaDysphagia– DyspnoeaDyspnoea– DysphoniaDysphonia– Irritative coughing Irritative coughing

Clinical examination Clinical examination – T gland enlarged (whoe or T gland enlarged (whoe or

part) and very painfulpart) and very painful– All inflammatory signs in the All inflammatory signs in the

anterior cervical area (skin)anterior cervical area (skin)– Abscess formation can Abscess formation can

produce fluctuence.produce fluctuence.– Inflammatory LN in the latero-Inflammatory LN in the latero-

cervical areacervical area

LAB EVALUATIONLAB EVALUATION

High WBC with % PMN High WBC with % PMN

Vey high ESRVey high ESRThyroid scintigram: a cold difuse area (no iodine Thyroid scintigram: a cold difuse area (no iodine capture) capture)

US: hypoecoic i the begining, transsonic if absecess is US: hypoecoic i the begining, transsonic if absecess is formed. formed.

Blood cultures – isolation of bacteriaBlood cultures – isolation of bacteria

RIC may be normal/lower then normal.RIC may be normal/lower then normal.

In cases of abscess: puncture and culture of In cases of abscess: puncture and culture of pathogenic germpathogenic germ

TREATMENTTREATMENT

Prognostic: very good if rapidly diagnosed and Prognostic: very good if rapidly diagnosed and treatment is adequatetreatment is adequate

Complications without proper treatment: Complications without proper treatment: – SepticSeptic:: local (mediastinitis, fistula formation – skin, local (mediastinitis, fistula formation – skin,

esophagus, trachea), or metastatic. esophagus, trachea), or metastatic. – MMecechhanicanic:: large abscess behaves like a tumor large abscess behaves like a tumor – VVascularascular: : thrombosis of adjacent veinsthrombosis of adjacent veins– EEndocrinendocrine: : very unusualvery unusual

TREATMENT - earlyTREATMENT - early

Medical Medical – Antibiotics: empirical + culturesAntibiotics: empirical + cultures– NSAIDNSAID– Antialgic medicationAntialgic medication

Surgical Surgical – Abscess – drainageAbscess – drainage– Partial thyroidectomy +/-Partial thyroidectomy +/-

SUBACUTE THYROIDITISSUBACUTE THYROIDITIS

Granulomatous thyroiditisGranulomatous thyroiditis

DeQuervain thyroiditisDeQuervain thyroiditis

PATHOGENYPATHOGENY

5% 5% of all T pathologyof all T pathology

F>F>MM 20 – 40 20 – 40yy

EthiologyEthiologyunknownunknown

Known:Known:– Viral (urlian, influenza)Viral (urlian, influenza)– Bacteria (streptococcus, entorobacteriacea)Bacteria (streptococcus, entorobacteriacea)– Genetic predispositionGenetic predisposition

Pathogeni: destruction of folicular epithelium:Pathogeni: destruction of folicular epithelium:Immediate release of thryoid hormonesImmediate release of thryoid hormones

Lowers capacity to produce hormones in timeLowers capacity to produce hormones in time

Pathological changesPathological changes

MacroscopicMacroscopic – T is increased in size (2-3x), harder, yelowishT is increased in size (2-3x), harder, yelowish

Mycroscopic Mycroscopic – Multifocal granulomatous inflammatory Multifocal granulomatous inflammatory

reaction, limfocityc and plasma cells reaction, limfocityc and plasma cells infiltration + interstitialinfiltration + interstitial

DIAGNOSTICDIAGNOSTIC

Past medical history: Past medical history: 50% 50% cases cases 2-6 weeks before2-6 weeks before respiratory infection, rhinopharinx, respiratory infection, rhinopharinx, sometimes easy to forget about. sometimes easy to forget about.

AnamnesisAnamnesis+/- Sudden onset+/- Sudden onsetFever (High), chills, malaiseFever (High), chills, malaiseCervical pain aggravated by swallowing, cough and head Cervical pain aggravated by swallowing, cough and head movements.movements.

Clinical evaluationClinical evaluation T gland enlarged, asymetrical, ferm and painful. T gland enlarged, asymetrical, ferm and painful. No palpable LNNo palpable LNSignsSigns of moderate hyperthyroidism in 20% of cases of moderate hyperthyroidism in 20% of cases

LAB EVALUATIONLAB EVALUATION

High WBC – lymphocitesHigh WBC – lymphocitesHigh ESR High ESR High T3 – T4, thyroglobulin in early stages of High T3 – T4, thyroglobulin in early stages of inflammation, while TSH and RIC are inflammation, while TSH and RIC are diminished. diminished. Increses levels of antyT antibody ~3 weeks Increses levels of antyT antibody ~3 weeks after onset. after onset. US – diffuse hypoechigenity US – diffuse hypoechigenity ScintigrScintigram – inhomogeneous fixationam – inhomogeneous fixation with cold with cold areas, but will become normal with healingareas, but will become normal with healingGigantic multinuclear cells on FACGigantic multinuclear cells on FAC

DIAGNOSTICDIAGNOSTIC

POZITIVPOZITIV

PainPain

Local and Local and general general inflammatory inflammatory signssigns

Very low RICVery low RIC

CytologyCytology

antyT antibodyantyT antibody

DifferentialDifferential

Acute Acute thyroiditis thyroiditis

Hashimoto Hashimoto

Graves Graves

CarcinomaCarcinoma

PROGRESSIONPROGRESSION

Self healing conditionSelf healing condition– 1-3 1-3 monthsmonths– No sequels No sequels

Transform in chronic inflammationTransform in chronic inflammation– RiedelRiedel// Hashimoto Hashimoto

HipotHipothhiroidismiroidism - - 10% 10%

RecRecurrent condition – very rareurrent condition – very rare

TREATMENTTREATMENT

NSAID/ CORTICOSTEROIDSNSAID/ CORTICOSTEROIDS

Hormonal – hyper or hypo functionHormonal – hyper or hypo function

Surgical – an exceptionSurgical – an exception– LobectomLobectomyy, t, thyhyroidectomroidectomyy– When a nodular hypertrophy persistsWhen a nodular hypertrophy persists

CRONIC LYMPHOCYTIC CRONIC LYMPHOCYTIC THYROIDITISTHYROIDITIS

Hashimoto thyroiditisHashimoto thyroiditis

PATHOGENYPATHOGENY

The most common type of inflammatory The most common type of inflammatory disease of T glanddisease of T gland

The most common cause of hypothyroidismThe most common cause of hypothyroidism

F>B; 40-50F>B; 40-50yy

CAUSECAUSE– AutoimAutoimmune aggression: ATB against mune aggression: ATB against

Thyroglubuline, Mycrosomes. Thyroglubuline, Mycrosomes.

Histology Histology

MACROMACRO– Hypertrophy with accentuated lobulationHypertrophy with accentuated lobulation– Ferm, pale, grey, reduced vascular pattern.Ferm, pale, grey, reduced vascular pattern.

MICROMICRO– Lymphocytic infiltrationLymphocytic infiltration– – even formation of even formation of

germinative centersgerminative centers– Follicular epithelium destructionFollicular epithelium destruction – – large oxiphilic large oxiphilic

cells cells AskenazyAskenazy cells cells ( (diagnosticdiagnostic))– FibroFibrosissis

PRESENTATIONPRESENTATION

Past medical history: Past medical history: – Other autoimmune diseases (LES, rheumatoid Other autoimmune diseases (LES, rheumatoid

arthritis, dermatomiositis) arthritis, dermatomiositis)

GGOITEROITER– Insidious onsetInsidious onset– Not very largeNot very large– DifuDifuse, asymmetrical, no signs of compressionse, asymmetrical, no signs of compression– Thyroid function can be high, normal or lowThyroid function can be high, normal or low– FatigueFatigue

LAB WORKLAB WORKNonspecific inflammatory reaction Nonspecific inflammatory reaction (normal (normal WBC, increased ESR) WBC, increased ESR)

ImmunologyImmunology– Antimicrosomal antibodies 100%Antimicrosomal antibodies 100% – Antithyroglobulin antibodie 90% Antithyroglobulin antibodie 90% ii

Thyroid functionThyroid functionIniInittialial: : hyperfunction without increased production (RIC hyperfunction without increased production (RIC increased, basal metabolism increased) increased, basal metabolism increased)

Late: Late: hhyypopofunctiondue to destruction of parenchime (RIC functiondue to destruction of parenchime (RIC bellow normal, decresed basal metabolism)bellow normal, decresed basal metabolism)

DIAGNOSTICDIAGNOSTIC

POZITIVPOZITIV– Goiter Goiter – Antibodies + biopsyAntibodies + biopsy

DIFFERENTIALDIFFERENTIAL– ClinicClinical – can mimic anythingal – can mimic anything– DeQuervainDeQuervain– GoiterGoiter– CancerCancer

COMPLICACOMPLICATIONSTIONS– HHyypotpothyhyroidism – 50-80%roidism – 50-80%

PROGNOSTICPROGNOSTIC– Slow progression with periods of long Slow progression with periods of long

stagnation (years) followed y progressionstagnation (years) followed y progression– Rapid progression - unusualRapid progression - unusual

TREATMENTTREATMENT

Hormonal Hormonal – Hormonal replacementHormonal replacement

SurgicalSurgical – CompressionCompression– Questionable diagnostic (Lymphoma/Cancer)Questionable diagnostic (Lymphoma/Cancer)

FIBROTIC THYROIDITISFIBROTIC THYROIDITIS

Riedel wood-hard thyroiditisRiedel wood-hard thyroiditis

PATHOGENYPATHOGENY

Chronic inflammation with Chronic inflammation with fibrotic transformation of fibrotic transformation of T gland and surrounding T gland and surrounding tissue tissue

Can be associated with Can be associated with other fibrotic diseases:other fibrotic diseases:– Retroperitoneal fibrosisRetroperitoneal fibrosis– Mediastinal fibrosisMediastinal fibrosis– Parotid gland fibrosis, Parotid gland fibrosis,

salivary/lacrimal gland salivary/lacrimal gland fibrosisfibrosis

– Sclerosing cholangitis Sclerosing cholangitis

HLA-DR3HLA-DR3 – genetic – genetic determinationdeterminationAAntimicrosomal ntimicrosomal antibodies : antibodies : autoimmune autoimmune mechanismmechanism

Mycroscopy: fibrosis + Mycroscopy: fibrosis + lymphocytic infiltrationlymphocytic infiltrationUnknown causeUnknown causeFinal stage of any Final stage of any autoimmune thyroiditis.autoimmune thyroiditis.

PATHOLOGYPATHOLOGY

One lobe or whole glandOne lobe or whole gland

Fibrotic, white tissueFibrotic, white tissue

Fibrosis extends outside T gland: there are Fibrosis extends outside T gland: there are no cleavage plans and structures can not no cleavage plans and structures can not be identifiedbe identified

CLINICAL PRESENTATIONCLINICAL PRESENTATION

Females: 30-60y ageFemales: 30-60y age

AnamnesisAnamnesis– signs of diffuse hypertrophy + compression of signs of diffuse hypertrophy + compression of

adjacent organsadjacent organs

Clinical examinationClinical examination– wood-hard consistency wood-hard consistency – TenderTender– T gland fixed to all plans T gland fixed to all plans – T gland does not invade skinT gland does not invade skinHormonal status: Hormonal status: normal (most cases) or hyponormal (most cases) or hypo

LAB WORKLAB WORK

Slight inflammatory responseSlight inflammatory responseNormal or low T hormonesNormal or low T hormonesSometimes: low levels of antyThyroid Sometimes: low levels of antyThyroid antibodiesantibodiesUS: hypoechoic + invasion in adjacent US: hypoechoic + invasion in adjacent structuresstructuresScintigram: inhomogenous fixation with Scintigram: inhomogenous fixation with areas with non-fixation of iodineareas with non-fixation of iodine

DIAGNOSTICDIAGNOSTIC

Pozitiv: Pozitiv: pathologic examinationpathologic examination

DifferentialDifferential– cancercancer– HashimotoHashimoto– DeQuervainDeQuervain

COMPLICACOMPLICATIONSTIONS– CompresCompressionsion

ProgressionProgression– Very slow: years until compression is significantVery slow: years until compression is significant

TREATMENTTREATMENT

HormonalHormonal– Replacement for hypothyroidismReplacement for hypothyroidism– May reduce progression to fibrosisMay reduce progression to fibrosis

SurgicalSurgical– TThyhyroidectomroidectomyy– Limited excision for decompressionLimited excision for decompression

THYROID CANCERTHYROID CANCER

MOST COMMON ENDOCRINE MOST COMMON ENDOCRINE CANCERCANCER

1% OF ALL CANCERS 1% OF ALL CANCERS Occurs mainly in patients 25-65 yearsOccurs mainly in patients 25-65 yearsAnnual incidence 20-70 new cases/10Annual incidence 20-70 new cases/1066

Annual mortality ~4/10Annual mortality ~4/1066

Most carcinomas – favorable prognosisMost carcinomas – favorable prognosisNecroptic incedence much higher and Necroptic incedence much higher and with significant variations:with significant variations:– USA ~1.8%; Honolulu~15%; Hiroshima 25%USA ~1.8%; Honolulu~15%; Hiroshima 25%

RISK FACTORSRISK FACTORS

Iodine supplements increase the incidence Iodine supplements increase the incidence of papillary carcinoma (<T, well of papillary carcinoma (<T, well differentiated, overall increases survival) differentiated, overall increases survival)

External irradiation External irradiation – in human the only proven carcinogenic factor in human the only proven carcinogenic factor

for thyroid carcinoma for thyroid carcinoma – children with neck irradiation develop papillary children with neck irradiation develop papillary

carcinoma carcinoma

RISK FACTORSRISK FACTORS– 1986 Cernobil effect- steady increase 1986 Cernobil effect- steady increase (Pacini (Pacini

1997)1997)Peak 3x in 1992-1994 ; Peak 3x in 1992-1994 ;

~80% children <14 years of age~80% children <14 years of age

PATHOLOGYPATHOLOGY- follicular cells-- follicular cells-

FOLlICULAR

CELLS

HYPOFUNCTIONAL ADENOMA

FOLLICULAR

CARCINOMA

PAPILLARY CARCINOMA

HYPERFUNCTIONAL ADENOMA

ANAPLASTIC

CARCINOMA

PATHOLOGYPATHOLOGYessential in classificationessential in classification

Papillary carcinoma 80% Papillary carcinoma 80% – from follicular cellsfrom follicular cells– usually well differentiatedusually well differentiated– but very frequently but very frequently multifocalmultifocal– mixed forms are includedmixed forms are included– slow growing – excellent prognosisslow growing – excellent prognosis

SpreadingSpreading: tends to spread locally into : tends to spread locally into lymph nodes and adjacent structures lymph nodes and adjacent structures

PATHOLOGYPATHOLOGY

Invasion in the local lymph nodes is not Invasion in the local lymph nodes is not associated with a worse prognosis associated with a worse prognosis

Poor prognosis:Poor prognosis:– Male genderMale gender– >50 years>50 years– Less differentiated Less differentiated

Metastases: lungs, rarely to bonesMetastases: lungs, rarely to bones

– Tumors larger then 4 cmTumors larger then 4 cm– Local invasion or distant Local invasion or distant

metastasesmetastases

PATHOLOGYPATHOLOGYFollicular carcinoma 10%Follicular carcinoma 10%

HIGHER FREQUENCY IN IODINE DEFICIENT AREASHIGHER FREQUENCY IN IODINE DEFICIENT AREAS

– from follicular cellsfrom follicular cells– usually well differentiated usually well differentiated – slow growing – good prognosisslow growing – good prognosis– closely resemble folicular adenomas closely resemble folicular adenomas – capsular and/or vascular invasion is defining the capsular and/or vascular invasion is defining the

malignant statusmalignant status– tends to take up radioactive iodine. tends to take up radioactive iodine. – 10% chance of being multifocal.10% chance of being multifocal.

PATHOLOGYPATHOLOGYSpreadingSpreading: tends to spread through the blood : tends to spread through the blood

stream making it more difficult to control and also stream making it more difficult to control and also grows into adjacent structures.grows into adjacent structures.Metastases Metastases – lung and bonelung and bone– usually concentrate iodineusually concentrate iodinePoor prognosis associated with:Poor prognosis associated with:– Age >45 yearsAge >45 years– Local extracapsular invasionLocal extracapsular invasion– Distant metastases Distant metastases

PATHOLOGYPATHOLOGY

Hürthle Cell carcinoma 3.6%Hürthle Cell carcinoma 3.6%– composed of "modified follicular cells" composed of "modified follicular cells" – very similar to follicular carcinoma very similar to follicular carcinoma – 25% chance of being 25% chance of being multifocalmultifocal– does not tend to take up radioactive iodinedoes not tend to take up radioactive iodine– has a prognosis similar to that of follicular has a prognosis similar to that of follicular

carcinoma.carcinoma.

PATHOLOGYPATHOLOGY

Medullary carcinoma 2.7%Medullary carcinoma 2.7%– from the parafollicular C cells from the parafollicular C cells – There are two types There are two types

Genetic disposition – AD MUTATIONS- Genetic disposition – AD MUTATIONS- represents about 20% of all patients with represents about 20% of all patients with medullary carcinoma medullary carcinoma

USUALLY PRESENT IN BOTH LOBESUSUALLY PRESENT IN BOTH LOBES

Sporadic – occurs randomly and represents Sporadic – occurs randomly and represents 80% of medullary carcinoma80% of medullary carcinoma

USUALLY PRESENTS UNILATERAL USUALLY PRESENTS UNILATERAL

PATHOLOGY - CMTPATHOLOGY - CMT

Worse prognosis compared with Worse prognosis compared with previous forms: 50% survive at 10 yearsprevious forms: 50% survive at 10 yearsOccult tumors discovered in families at Occult tumors discovered in families at risk – 95% cure raterisk – 95% cure rate– Detection by screening for calcitonin basal Detection by screening for calcitonin basal

and/or pentagastrin infusion testand/or pentagastrin infusion testTUMOR PRESUMED – 95% cureTUMOR PRESUMED – 95% cureTUMOR PALPABLE – 17% cureTUMOR PALPABLE – 17% cure

SPREADING: blood born metastases SPREADING: blood born metastases and lymphnodes and lymphnodes

PATHOLOGYPATHOLOGYAnaplastic carcinoma 1.7%Anaplastic carcinoma 1.7%– develops from follicular cells develops from follicular cells – poorly differentiated poorly differentiated – aggressive and rapidly growing. aggressive and rapidly growing. – poor prognosis <2 yearspoor prognosis <2 yearsSpreadingSpreading: rapidly in the adjacent structures and also sends : rapidly in the adjacent structures and also sends

blood born metastasis – STAGE IV blood born metastasis – STAGE IV

Others rare tumors that may develop in the thyroid Others rare tumors that may develop in the thyroid gland are gland are – LymphomaLymphoma– Sarcoma – originating in the connective tissue Sarcoma – originating in the connective tissue – Carcinosarcoma - composed of both malignant thyroid cells Carcinosarcoma - composed of both malignant thyroid cells

and connective tissueand connective tissue

Metastatic tumorsMetastatic tumors

SIGNIFICANT MICROSCOPICSIGNIFICANT MICROSCOPICFEATURESFEATURES

1.1. Differentiation levelDifferentiation level2.2. Capsular or vascular invasion (in Capsular or vascular invasion (in

follicular and Hürthle cell carcinomas follicular and Hürthle cell carcinomas invasion is needed to prove the tumor invasion is needed to prove the tumor malignantmalignant

3.3. Regional lymph node involvementRegional lymph node involvement4. Invasion of adjacent structures 4. Invasion of adjacent structures

(extracapsular invasion)(extracapsular invasion)

DIAGNOSTICDIAGNOSTICclinical examinationclinical examination

Evaluation of the neck Evaluation of the neck NODULENODULEAssesment of nodulesAssesment of nodules– FirmnessFirmness– MobilityMobility– MultipleMultiple

Evaluation of typical Evaluation of typical metastatic sitesmetastatic sites– Cervical nodesCervical nodes– BonesBones– LungsLungs

DIAGNOSTICDIAGNOSTICanatomical evaluationanatomical evaluationULTRASOUND SCANULTRASOUND SCAN– Confirm - thyroid glandConfirm - thyroid gland– Solid/cysticSolid/cystic– Unic/multicentricUnic/multicentric– LymphnodesLymphnodes– Guides FNB Guides FNB – DopplerDoppler

NON INVASIVE - SCREENING

DIAGNOSTICDIAGNOSTICanatomical testanatomical test

Scintiscan:Scintiscan:– Evaluate the capacity to Evaluate the capacity to

concentrate iodineconcentrate iodine– Cold nodules – 15-20% are Cold nodules – 15-20% are

malignantmalignant– Essential in postoperative Essential in postoperative

follow-upfollow-upEstimate the remnant thyroid tissueEstimate the remnant thyroid tissue

Diagnose iodine concentrating Diagnose iodine concentrating metastatic tumormetastatic tumor

WBS - Diagnose bone metastasesWBS - Diagnose bone metastases

DIAGNOSTICDIAGNOSTICanatomical testanatomical test

CAT scan and chest X-RayCAT scan and chest X-Ray– Lung metastasesLung metastases– Restrosternal goitersRestrosternal goiters

FUNCTIONAL EVALUATIONFUNCTIONAL EVALUATION

Is mostly used in the follow-upIs mostly used in the follow-up

Thyroglobuline Thyroglobuline – >5ng/ml after total thyroidectomy>5ng/ml after total thyroidectomy– >10ng/ml after total thyroidectomy>10ng/ml after total thyroidectomy

Calcitonine (Pg-CT)Calcitonine (Pg-CT)– marker for the diagnosis of MTC in high risk marker for the diagnosis of MTC in high risk

populations (nodule + CT(+) the most populations (nodule + CT(+) the most significant association) significant association)

– Marker for postoperative follow-up Marker for postoperative follow-up

CYTOLOGIC DIAGNOSISCYTOLOGIC DIAGNOSIS

Fine needle aspiration cytology – most important Fine needle aspiration cytology – most important study in evaluating thyroid nodulesstudy in evaluating thyroid nodules

Core biopsy – larger sample but higher riskCore biopsy – larger sample but higher risk– HISTOLOGIC DIAGNOSISHISTOLOGIC DIAGNOSIS– Preoperative diagnosis of most thyroid cancersPreoperative diagnosis of most thyroid cancers– Help to plan the extent of surgical resectionHelp to plan the extent of surgical resection– Selection of cases which will not benefit from surgical Selection of cases which will not benefit from surgical

managementmanagement

CYTOLOGIC DIAGNOSISCYTOLOGIC DIAGNOSIS

ResultsResults– NondiagnosticNondiagnostic– IndeterminateIndeterminate– MalignantMalignant

GENETIC STUDIESGENETIC STUDIES

Numerous mutations are associated with Numerous mutations are associated with thyroid cancerthyroid cancer

MTCMTC– Germinal cells RET mutations associated with Germinal cells RET mutations associated with

early onset and multicentric tumorsearly onset and multicentric tumors– MEN II (A and B) MEN II (A and B) – Profilactic thyroidectomyProfilactic thyroidectomy

TREATMENTTREATMENT

SURGICAL RESECTION IS SURGICAL RESECTION IS THE STANDARD THERAPYTHE STANDARD THERAPY

EXTENT OF SURGICAL EXTENT OF SURGICAL RESECTIONRESECTION

Depends primarily on Depends primarily on HISTOLOGICAL typeHISTOLOGICAL type

Age Age

Capsular/extracapsular invasionCapsular/extracapsular invasion

Invasion in adjacent structuresInvasion in adjacent structures

ESSENTIAL – PREOPERATIVE ACCURATE DIAGNOSIS – FNB AND INTRAOPERATIVE

FROZEN SECTIONS

SURGICAL TREATMENTSURGICAL TREATMENT

PAPILLARY CARCINOMAPAPILLARY CARCINOMA

CONSERVATIVECONSERVATIVE– Lobectomy +/- istmusectomyLobectomy +/- istmusectomy– Macroscopic - unic noduleMacroscopic - unic nodule– Permanent TSH supression is Permanent TSH supression is

essentialessential– Acceptable if poor prognostic Acceptable if poor prognostic

factors ar absentfactors ar absent– 5-10% will develop recurrences5-10% will develop recurrences

SURGICAL TREATMENTSURGICAL TREATMENT

PAPILLARY CARCINOMAPAPILLARY CARCINOMAAGGRESSIVE APPROACHAGGRESSIVE APPROACH– Near total/total Near total/total

thyroidectomythyroidectomy– For macroscopic multifocal + For macroscopic multifocal +

lymph-nodes involvementlymph-nodes involvement– Lymph-node dissection – Lymph-node dissection –

primary drainage arrea primary drainage arrea

SURGICAL TREATMENT

FOLLICULAR CARCINOMAFOLLICULAR CARCINOMADg. suspected on FNB and Dg. suspected on FNB and CONFIRMED on frozen sectionCONFIRMED on frozen section

Total/near total thyroidectomyTotal/near total thyroidectomy

Total thyroidectomy Total thyroidectomy – makes metastases visiblemakes metastases visible– 5-10% recur in residual tissue5-10% recur in residual tissue

SURGICAL TREATMENTSURGICAL TREATMENT

ANAPLASTIC ANAPLASTIC TUMORSTUMORS– Old age patients– usually Old age patients– usually

is of no benefitis of no benefit– Middle age – total Middle age – total

thyoidectomy may be thyoidectomy may be tried, but little benefittried, but little benefit

– Istmusectomy – pressure Istmusectomy – pressure on the trachea (similar on the trachea (similar results with radiotherapy)results with radiotherapy)

– 1 year survival rate ~01 year survival rate ~0

SURGICAL TREATMENTSURGICAL TREATMENT

MEDULLARY CARCINOMAMEDULLARY CARCINOMA– Total thyroidectomyTotal thyroidectomy

Frequent multicentric (both forms)Frequent multicentric (both forms)Lymphadenectomy in the primary drainage area – Lymphadenectomy in the primary drainage area – essential. 75% of cases demonstrate MTS in nodes from essential. 75% of cases demonstrate MTS in nodes from the central compartmentthe central compartmentNodes in the secondary drainage area should be Nodes in the secondary drainage area should be sampled - if involved RADICAL NECK DISSECTIONsampled - if involved RADICAL NECK DISSECTION

Pheocromocytoma and parathyroid tumors Pheocromocytoma and parathyroid tumors should be checked and solved prior to total should be checked and solved prior to total thyroidectomythyroidectomy

COMPLICATIONSCOMPLICATIONS

recurrent laryngeal nerve damage 2-8%recurrent laryngeal nerve damage 2-8%permanent hypoparathyroidism 1-3% ; permanent hypoparathyroidism 1-3% ; 5-10% in difficult resections5-10% in difficult resectionshematoma formationhematoma formationwound infectionwound infectionkeloid formation in the scarkeloid formation in the scarairway compromise (anaplastic airway compromise (anaplastic carcinoma)carcinoma)

POSTOPERATIVE POSTOPERATIVE TREATMENTTREATMENT

radioactive iodineradioactive iodine

thyroid suppressionthyroid suppression

external radiotherapy (exceptional) –external radiotherapy (exceptional) –– locally advanced papillary carcinoma and locally advanced papillary carcinoma and

metastatic sitesmetastatic sites

external beam radiotherapyexternal beam radiotherapy

cytotoxic chemotherapycytotoxic chemotherapy

FOLLOW-UPFOLLOW-UP

Differentiated Differentiated carcinomas thyroglobulin carcinomas thyroglobulin measurement + WBSmeasurement + WBS

Medullary carcinoma - Medullary carcinoma - calcitonincalcitonin

PROGNOSISPROGNOSIS

OVERALL PROGNOSIS IS OVERALL PROGNOSIS IS GOOD WITH > 94% LONG GOOD WITH > 94% LONG

TERM SURVIVALTERM SURVIVAL

PARATHYROID GLANDSPARATHYROID GLANDS

Disorders of the Parathyroid Disorders of the Parathyroid GlandsGlands

Maintenance of calcium, phosphate and Maintenance of calcium, phosphate and magnesium homeostasis is under the magnesium homeostasis is under the influence of two polypeptide hormones;influence of two polypeptide hormones;

* * parathyroid hormone(PTH)parathyroid hormone(PTH)

* * calcitonincalcitonin (CT),(CT),

* * sterol hormone, 1,25sterol hormone, 1,25 dihydroxy dihydroxy cholecalciferol (1,25 (OH)cholecalciferol (1,25 (OH)22DD33..

Parathyroid GlandsParathyroid Glands

These hormones regulate the flow of These hormones regulate the flow of minerals in and out of the extracellular minerals in and out of the extracellular fluid compartments through their actions fluid compartments through their actions on on intestine, kidneys, and bonesintestine, kidneys, and bones..

Normal functionNormal function

The PTH acts directly on the bones and kidneys The PTH acts directly on the bones and kidneys and indirectly on the intestine through its effect and indirectly on the intestine through its effect on the synthesis of 1,25 (OH)on the synthesis of 1,25 (OH)22DD33. .

Its production is regulated by the concentration Its production is regulated by the concentration of serum ionized calcium. of serum ionized calcium.

Lowering of the serum calcium levels will induce Lowering of the serum calcium levels will induce an increased rate of parathyroid hormone an increased rate of parathyroid hormone secretionsecretion

Normal functionNormal function

Calcitonin is released by the “C” cells Calcitonin is released by the “C” cells (parafollicular cells in the thyroid gland) (parafollicular cells in the thyroid gland)

Secretion in response to small increases Secretion in response to small increases in plasma ionic calcium. It acts on the in plasma ionic calcium. It acts on the kidney and bones to restore the level of kidney and bones to restore the level of calciumcalcium

PTH and calcitonin are antagonisticPTH and calcitonin are antagonistic

Disorders of the Parathyroid FunctionDisorders of the Parathyroid Function

Excessive PTH from one/more glands Excessive PTH from one/more glands which are hyperfunctional.which are hyperfunctional.

HyperCa that fails to inhibit in normal feed-HyperCa that fails to inhibit in normal feed-back loop. back loop.

Cause? – possible genetic (multiple Cause? – possible genetic (multiple adenomas are frequent) . Carcinoma<1%adenomas are frequent) . Carcinoma<1%

Primary HyperparathyroidismPrimary Hyperparathyroidism

Clinical FeaturesClinical Features

KidneysKidneys: renal stones or nephrocalcinosis : renal stones or nephrocalcinosis (diffuse deposition of CaPO4.(diffuse deposition of CaPO4.SkeletonSkeleton: : osteitis fibrosa cysticaosteitis fibrosa cystica

Massive subperiostal resorbtion of boneMassive subperiostal resorbtion of boneBone cysts and brown tumors of long bonesBone cysts and brown tumors of long bones

Other: muscle weakness, easy fatigability, Other: muscle weakness, easy fatigability, peptic ulcer disease, pancreatitis, peptic ulcer disease, pancreatitis, hypertension, gout and pseudogout as hypertension, gout and pseudogout as well as anemia and depression well as anemia and depression 90% cases diagnosed before that on 90% cases diagnosed before that on screening for calciumscreening for calcium

DiagnosisDiagnosis

hypercalcaemia in more than one serum hypercalcaemia in more than one serum measuremenmeasuremen

elevated immunoreactive PTH is elevated immunoreactive PTH is characteristic (iPTH)characteristic (iPTH)

LAB WorkLAB Work

Serum phosphate is usually low but may Serum phosphate is usually low but may be normal. be normal. Hypercalcaemia is common Hypercalcaemia is common alkaline phosphatase (of bone origin)- highalkaline phosphatase (of bone origin)- highurinary hydroxyproline concentrations are urinary hydroxyproline concentrations are commonly elevated when the bones are commonly elevated when the bones are involved. involved. Negative glucocoticoid supression test Negative glucocoticoid supression test (supression indicates no adenoma)(supression indicates no adenoma)

RADIOLOGYRADIOLOGY

subperiosteal bone resorption usually on subperiosteal bone resorption usually on the radial surfacy of the distal phalanx with the radial surfacy of the distal phalanx with distal phalangeal tuftingdistal phalangeal tufting

cysts formation and generalized cysts formation and generalized osteopenia.osteopenia.

UltrasonographyUltrasonography

MRIMRI

CTCT

Thallium Thallium 201201 – Tehcnichum – Tehcnichum99m99m scan scan (subtraction study)(subtraction study)

Pre-operative localization of the abnormal Pre-operative localization of the abnormal parathyroid gland(s):parathyroid gland(s):

TreatmentTreatmentVery often “biochemical” hyperPTH. Very often “biochemical” hyperPTH.

Resection of the parathyroid lesion is curative Resection of the parathyroid lesion is curative with recurrences observed mainly in the multiple with recurrences observed mainly in the multiple glandular disease.glandular disease.

TumorTumor

31/2 of all hyperplastic tissue31/2 of all hyperplastic tissue

Medical management of hypercalcemiaMedical management of hypercalcemia– GlucocorticoidsGlucocorticoids - Diuresis- Diuresis– MithramycinMithramycin - Calcitonin- Calcitonin– BisphosphonatesBisphosphonates - Phosphates- Phosphates– EstrogenEstrogen

Secondary hyperparathyroidismSecondary hyperparathyroidism

chronic stimulation of the parathyroid chronic stimulation of the parathyroid glands by a chronic decrease in the ionic glands by a chronic decrease in the ionic calcium level in the bloodcalcium level in the blood

Major causesMajor causes

Dietary deficiency of vitamin D or calciumDietary deficiency of vitamin D or calciumDecreased intestinal absorption of vitamin Decreased intestinal absorption of vitamin D or calcium due to primary small bowel D or calcium due to primary small bowel disease, short bowel syndrome, and post-disease, short bowel syndrome, and post-gastrectomy syndrome.gastrectomy syndrome.Drugs that cause rickets or osteomalacia Drugs that cause rickets or osteomalacia such as phenytoin, phenobarbital, such as phenytoin, phenobarbital, cholestyramine, and laxative.cholestyramine, and laxative.

Major causes of chronic hypocalcemiaMajor causes of chronic hypocalcemia

States of tissue resistance to vitamin DStates of tissue resistance to vitamin D

Excessive intake of inorganic phosphate Excessive intake of inorganic phosphate compundscompunds

PsudohypoparathyroidismPsudohypoparathyroidism

Severe hypomagnesemiaSevere hypomagnesemia

Chronic renal failureChronic renal failure

HypoparathyroidismHypoparathyroidism

Deficient secretion of PTHDeficient secretion of PTH which which manifests itself biochemically by manifests itself biochemically by hypocalcemia, hyperphospatemia hypocalcemia, hyperphospatemia diminished or absent circulating iPTH and diminished or absent circulating iPTH and clinically the symptoms of neuromuscular clinically the symptoms of neuromuscular hyperactivity.hyperactivity.

HypoparathyroidismHypoparathyroidism

Surgical hypoparathyroidismSurgical hypoparathyroidism – the – the commonestcommonest

Idiopathic hypoparathyroidismIdiopathic hypoparathyroidism– GeneticGenetic– Autoimmune Autoimmune – Functional (associated with hypoMg – PTH Functional (associated with hypoMg – PTH

can not be released in this condition)can not be released in this condition)

Causes:Causes:

Clinical featuresClinical features

Neuromuscular:Neuromuscular:

CardiovascularCardiovascular

CataractCataract

Dental problemsDental problems

MalabsorbtionMalabsorbtion

– ParesthesiaParesthesia– TetanyTetany– HyperventilationHyperventilation– Adrenergic symptomsAdrenergic symptoms– Convulsion Convulsion – Signs of latent tetanySigns of latent tetany

- Prolonged QT interval in Prolonged QT interval in the ECGthe ECG

- Resistance to digitalisResistance to digitalis- HypotensionHypotension- Refractory heart failureRefractory heart failure

In the absence of renal failureIn the absence of renal failure

hypocalcaemia with hypocalcaemia with hyperphosphataemia is virtually hyperphosphataemia is virtually diagnostic of hypoparathyroidism.diagnostic of hypoparathyroidism.

Undetectable serum iPTH confirms the Undetectable serum iPTH confirms the diagnosis or it can be detectable if the diagnosis or it can be detectable if the assay is very sensitive. assay is very sensitive.

DiagnosisDiagnosis

TREATMENTTREATMENT

Prevention – surgical traumaPrevention – surgical trauma

Oral calcium with pharmacological doses Oral calcium with pharmacological doses of vitamin D or its potent analogues.of vitamin D or its potent analogues.

Phosphate restriction in diet may also be Phosphate restriction in diet may also be useful with or without aluminum useful with or without aluminum hydroxide gel to lower serum phosphate hydroxide gel to lower serum phosphate level.level.