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THE THYROID THE THYROID GLAND GLAND HYPERTYROIDISM HYPERTYROIDISM
56

THE THYROID GLAND

Jan 03, 2016

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Priscilla Hunt

THE THYROID GLAND. HYPERTYROIDISM. THE THYROID GLAND. The thyroid secretes primarily Thyroxine / T 4 / T 4 is probably not metabolically active until converted to T 3 (T 4 = prohormone) ~85% of T 3 is produced by monodeiodination of T 4. THE THYROID GLAND. - PowerPoint PPT Presentation
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Page 1: THE  THYROID  GLAND

THE THYROID THE THYROID GLANDGLAND

HYPERTYROIDISMHYPERTYROIDISM

Page 2: THE  THYROID  GLAND

THE THYROID GLANDTHE THYROID GLAND

The thyroid secretes primarilyThe thyroid secretes primarily

Thyroxine / TThyroxine / T4 4 //

TT4 is probably not metabolically active until 4 is probably not metabolically active until

converted to Tconverted to T33

(T(T44 = prohormone) = prohormone)

~85% of T~85% of T33 is produced by monodeiodination of T is produced by monodeiodination of T44

Page 3: THE  THYROID  GLAND

TT33 and T and T44 circulate in plasma are almost circulate in plasma are almost entirely (>99,9%) bound to transport entirely (>99,9%) bound to transport

proteins proteins (mainly TBG, less TBPA and albumins)(mainly TBG, less TBPA and albumins)

Only free hormones exert its metabolic Only free hormones exert its metabolic actionaction

It is better to measure the concentration It is better to measure the concentration

in plasma FTin plasma FT33 or FT or FT44

THE THYROID GLANDTHE THYROID GLAND

Page 4: THE  THYROID  GLAND

Patterns of thyroid function test results Patterns of thyroid function test results in patients with hyperthyroidismin patients with hyperthyroidism

Conventional hyperthyroidismConventional hyperthyroidism (95% of cases):(95% of cases):

FTFT44 ; FT; FT33 ; TSH ; TSH or undetectable or undetectable T3-hyperthyroidism T3-hyperthyroidism

(5% of cases):(5% of cases):

FTFT44 ↔↔; FT; FT33 ; TSH ; TSH or undetectable or undetectable Subclinical hyperthyroidism:Subclinical hyperthyroidism:

FTFT44 ↔;↔; FT FT33↔;↔; TSH TSH or undetectable or undetectable

NEGATIVE FEEDBACKNEGATIVE FEEDBACK

Page 5: THE  THYROID  GLAND

Not-thyroidal illness Not-thyroidal illness (e.g. myocardial infarction or pneumonia):(e.g. myocardial infarction or pneumonia):

Decreased peripherial conversion of TDecreased peripherial conversion of T44 to T to T3.3.

Alterations in the binding proteins.Alterations in the binding proteins.

Alterations in the affinity of binding proteins for Alterations in the affinity of binding proteins for

thyroid hormones.thyroid hormones.

↓↓TSH levels as a results of the illness itself or TSH levels as a results of the illness itself or

the use of drugs the use of drugs (e.g. dopamine or (e.g. dopamine or

corticosteroids).corticosteroids).

↑↑TSH into the hypothyroid range during TSH into the hypothyroid range during

convalescence.convalescence.

Page 6: THE  THYROID  GLAND

THYROTOXICOSISTHYROTOXICOSIS

Hypermetabolic state caused by thyroid Hypermetabolic state caused by thyroid hormone excess at the tissue levelhormone excess at the tissue level

HYPERTHYROIDISMHYPERTHYROIDISM

Increased thyroid hormones synthesis and Increased thyroid hormones synthesis and secretionsecretion

All patients with hyperthyroidism have thyreotoxicosis All patients with hyperthyroidism have thyreotoxicosis

Not all patients with thyreotoxicosis are hyperthyroidNot all patients with thyreotoxicosis are hyperthyroid

Page 7: THE  THYROID  GLAND

AETIOLOGYAETIOLOGY

It is important to identify the cause of It is important to identify the cause of hyperthyroidism in order to prescribe hyperthyroidism in order to prescribe

appropriate treatmentappropriate treatment

PREVALENCEPREVALENCE

Females:Females:

~20/1000~20/1000

Males:Males:

~4/1000~4/1000

Page 8: THE  THYROID  GLAND

Causes of thyrotoxicosisCauses of thyrotoxicosiscommon typescommon types

With high RAIUWith high RAIU Graves diseases (60-90%)Graves diseases (60-90%) Multinodular goitre (14%)Multinodular goitre (14%)

Autonomously Autonomously functioning solitary functioning solitary thyroid nodule (5%)thyroid nodule (5%) Iodine-induced Iodine-induced

thyrotoxicosisthyrotoxicosis

With low RAIUWith low RAIU ThyroiditisThyroiditis

subacute (3%)subacute (3%) silent (painless)silent (painless)

post-partumpost-partum Iodine-induced Iodine-induced

thyrotoxicosisthyrotoxicosis drugs (e.g. amiodarone)drugs (e.g. amiodarone)

radiografic contrast radiografic contrast mediamedia

iodine prophylaxis iodine prophylaxis programmeprogramme

Page 9: THE  THYROID  GLAND

Causes of thyrotoxicosisCauses of thyrotoxicosisuncommon typesuncommon types

With high RAIUWith high RAIU Congenital Congenital hyperthyroidismhyperthyroidism

TSH-induced TSH-induced hyperthyroidismhyperthyroidism

TSH-secreting adenomaTSH-secreting adenoma selective pituitary selective pituitary resistance to thyroid resistance to thyroid

hormonehormone Trophoblastic tumorsTrophoblastic tumors

With low RAIUWith low RAIU Thyrotoxicosis facticia Thyrotoxicosis facticia

(0.2%)(0.2%) Metastatic thyroid Metastatic thyroid

carcinoma (0.1%)carcinoma (0.1%) Struma ovariiStruma ovarii

Page 10: THE  THYROID  GLAND

Most signs and symptoms are common Most signs and symptoms are common to all types of thyreotoxicosis;to all types of thyreotoxicosis;

Some of them are specific to defined Some of them are specific to defined diseasedisease

for example:for example:

CLINICAL FEATURES OF CLINICAL FEATURES OF HYPERTHYROIDISMHYPERTHYROIDISM

ophthalmopathyophthalmopathypretibial myxoedemapretibial myxoedema

thyroid acropathythyroid acropathy

Graves’Graves’

diseasediseasethyroid painthyroid paintenderneestendernees

subacutesubacute

thyroiditisthyroiditis

Page 11: THE  THYROID  GLAND

CLINICAL FEATURES OF CLINICAL FEATURES OF HYPERTHYROIDISMHYPERTHYROIDISM

(according to frequency)(according to frequency)SYMPTOMSSYMPTOMS NervousnessNervousness PalptationsPalptations

Increased sweatingIncreased sweating Haet intoleranceHaet intolerance

FatigueFatigue Weight lossWeight loss

DyspneaDyspnea Increased appetiteIncreased appetite

Eye symptomsEye symptoms Friable hair and nailsFriable hair and nails

Increased bowel movementsIncreased bowel movements DiarrhoeaDiarrhoea

Menstrual disturbancesMenstrual disturbances

SIGNSSIGNS TachycardiaTachycardia

GoitreGoitre TremorsTremors

Skin changesSkin changes HyperkinesisHyperkinesis Thyroid bruitThyroid bruit

Lid lag and retractionLid lag and retraction OphthalmopathyOphthalmopathy Atrial fibrillationAtrial fibrillation

OnycholisisOnycholisis Localized (pretibial) myxedemaLocalized (pretibial) myxedema

VitiligoVitiligo AcropathyAcropathy

Page 12: THE  THYROID  GLAND

GRAVES’ DISEASEGRAVES’ DISEASEthe most frequent cause of the most frequent cause of

hyperthyroidismhyperthyroidism Graves’ disease is an autoimmune Graves’ disease is an autoimmune

thyroid disease, characterized by diffuse thyroid disease, characterized by diffuse thyroid enlargement, ophtalmopathy and thyroid enlargement, ophtalmopathy and

less frequently dermopathy (pretibial less frequently dermopathy (pretibial myxedema) and acropathy.myxedema) and acropathy. It can occur at any age It can occur at any age

(unusual before puberty and most commonly (unusual before puberty and most commonly affects the 30-50- years-old age group)affects the 30-50- years-old age group)

the female/ male ratio the female/ male ratio ~7 : 1 ~7 : 1

Page 13: THE  THYROID  GLAND

Graves’ disease - pathogenesisGraves’ disease - pathogenesis

Thyroid antigen-specific T lymphocytesThyroid antigen-specific T lymphocytes

Humoral and cell-mediated immune Humoral and cell-mediated immune

reactionsreactions

Infiltration of the thyroid gland by Infiltration of the thyroid gland by

immune effector cellsimmune effector cells

Page 14: THE  THYROID  GLAND

Graves’ disease - pathogenesisGraves’ disease - pathogenesis

Genetic and environmental factorsGenetic and environmental factors

Production of IgG antibodiesProduction of IgG antibodies

(thyroid-stimulating immunoglobulins TSI(thyroid-stimulating immunoglobulins TSI

or TSH-receptor antibodies TRAb)or TSH-receptor antibodies TRAb)

Stimulation thyroid hormone production and Stimulation thyroid hormone production and

goitre formationgoitre formation

Page 15: THE  THYROID  GLAND

Graves’ disease - pathogenesisGraves’ disease - pathogenesis

Genetic factors:Genetic factors:

The familial predisposition.The familial predisposition.

The frequent finding of circulating autoantibodies The frequent finding of circulating autoantibodies

in relatives of Graves’ patients.in relatives of Graves’ patients.

The high concordance rate in monozygotic twins.The high concordance rate in monozygotic twins.

The positive association with haplotypes HLA-B8 The positive association with haplotypes HLA-B8

and DR3 (Caucasians), HLA-B35 (Japonese and DR3 (Caucasians), HLA-B35 (Japonese

population), and HLA-Bw46 (Chinese population).population), and HLA-Bw46 (Chinese population).

Female sex hormones.Female sex hormones.

Page 16: THE  THYROID  GLAND

Graves’ disease - pathogenesisGraves’ disease - pathogenesis

Environmental factors:Environmental factors:

IodineIodine

Immune-stimulant effectImmune-stimulant effect

(in areas of iodine defficiency thyroid autoimmune (in areas of iodine defficiency thyroid autoimmune

diseases are rare).diseases are rare).

CigarettesCigarettes

(assotiation with Graves’ ophtalmopathy (assotiation with Graves’ ophtalmopathy influence on immune-influence on immune-

competent cells?).competent cells?).

Page 17: THE  THYROID  GLAND

Graves’ disease - pathogenesisGraves’ disease - pathogenesis

Environmental factors:Environmental factors:

Escherichia coli and Yersinia enterocoliticaEscherichia coli and Yersinia enterocolitica

(antibodies to these microbial antigens(antibodies to these microbial antigens

cross-reaction with the TSH-receptorcross-reaction with the TSH-receptor

hyperthyroidism.hyperthyroidism.

StressStress

(relationship between the onset of hyperthyroidism (relationship between the onset of hyperthyroidism

and a major life event).and a major life event).

Page 18: THE  THYROID  GLAND

Graves’ disease - pathogenesisGraves’ disease - pathogenesis

Ophtalmopathy and dermopathy:Ophtalmopathy and dermopathy:

Pathogenesis is less well understood.Pathogenesis is less well understood.

Immunologically mediated but TRAb is not implicated.Immunologically mediated but TRAb is not implicated.

Proliferation of fibroblasts (adipocytes?) within the orbitProliferation of fibroblasts (adipocytes?) within the orbit

Increased interstitial fluid contentIncreased interstitial fluid content

Chronic inflammatory cel infiltrateChronic inflammatory cel infiltrate

Swelling of the extra-ocular muscles Swelling of the extra-ocular muscles

Rise in retrobulbar pressureRise in retrobulbar pressure

Page 19: THE  THYROID  GLAND

Graves’ disease - clinical findingsGraves’ disease - clinical findings

THYROID GLAND: THYROID GLAND: Symmetrically enlargedSymmetrically enlarged

FirmFirm

Thrills and bruitsThrills and bruits

Goiter is absent in 3% of causesGoiter is absent in 3% of causes

Page 20: THE  THYROID  GLAND

Graves’ disease – Graves’ disease – clinical findingsclinical findings

LOCALIZED MYXEDEMA: LOCALIZED MYXEDEMA: Pretibial regionPretibial region

Raised, light colored or yellow-reddish Raised, light colored or yellow-reddish

lesion with orange peel apperancelesion with orange peel apperance

Sometimes pruritusSometimes pruritus

Page 21: THE  THYROID  GLAND

Graves’ disease – Graves’ disease – clinical findingsclinical findings

THYROID ACROPATHY: THYROID ACROPATHY: Swelling and soft tissues of hands feetSwelling and soft tissues of hands feet

Clubbing of fingers and toesClubbing of fingers and toes

Page 22: THE  THYROID  GLAND

Soft tissue involvement:Soft tissue involvement:

Lacrimation Lacrimation Redness Redness

Burning sensation Burning sensation Photophobia Photophobia

Gritty sensationGritty sensation

Proptosis (exophtalmos) and lagophthalmosProptosis (exophtalmos) and lagophthalmos

keratitiskeratitis

Extra-ocular muscle dysfunctionExtra-ocular muscle dysfunction

diplopiadiplopia

Optic neuropathyOptic neuropathy

blidnessblidness

True ophtalmopathy is True ophtalmopathy is specific of Graves’ diseasespecific of Graves’ disease

Page 23: THE  THYROID  GLAND

Cardiovascular systemCardiovascular system

TachycardiaTachycardiaPalpitationsPalpitations

Blood pressure:Blood pressure:systolicsystolic diastolic diastolic

THYROCARDIAC SYNDROMETHYROCARDIAC SYNDROMEPremature heart beatsPremature heart beats

Atrial fibrillationAtrial fibrillationHeart failure and/or anginaHeart failure and/or angina

Page 24: THE  THYROID  GLAND

Alimentary systemAlimentary system

Increased appetiteIncreased appetite

but weight lossbut weight loss

Increased frequency of bowel Increased frequency of bowel

movements and diarrheamovements and diarrhea

Rarely Rarely liver dysfunctionliver dysfunction

Page 25: THE  THYROID  GLAND

Nervous systemNervous system NervousnessNervousness

AnxietyAnxiety

Emotional instabilityEmotional instability

HyperactivityHyperactivity

InsomniaInsomnia

Fine tremorsFine tremors

MusclesMuscles

Muscular weaknessMuscular weakness

In most severe cases In most severe cases muscular atrophymuscular atrophy

Page 26: THE  THYROID  GLAND

Skeletal systemSkeletal system

MetabolismMetabolism

Increased oxygen consumptionIncreased oxygen consumption

Diabetes mellitus may be exacerbatedDiabetes mellitus may be exacerbated

Serum cholesterol Serum cholesterol plasma triglycerides plasma triglycerides

ThyrotoxicosisThyrotoxicosis IncreasedIncreasedloss of boneloss of bone osteoporosisosteoporosis

Page 27: THE  THYROID  GLAND

GRAVES’ DISEASE –GRAVES’ DISEASE –DIAGNOSTIC PROCEDURESDIAGNOSTIC PROCEDURES

Labolatory investigationLabolatory investigation

important particularly in important particularly in

the absence of goitre the absence of goitre and eye diseaseand eye disease

Imaging studiesImaging studies

Important particularly in Important particularly in

diagnostic of Graves’ diagnostic of Graves’ ophtalmophathyophtalmophathy

Computed tommographyComputed tommography

Magnetic resonanceMagnetic resonance

Page 28: THE  THYROID  GLAND

LABORATORY INVESTIGNATIONLABORATORY INVESTIGNATION

HyperthyroidismHyperthyroidism

Serum concentrations of:Serum concentrations of: TSH: undetectable or TSH: undetectable or

FTFT44: : FTFT33: :

T3-toxicosis: T3-toxicosis: TSH: undetectable or TSH: undetectable or

FTFT33: :

FTFT44: : ↔↔

Graves’ disease:Graves’ disease: TRAb TRAb

TPO TPO ATG ATG

Page 29: THE  THYROID  GLAND

Imaging studiesImaging studies

24-hour thyroidal radioactive iodine uptake:24-hour thyroidal radioactive iodine uptake: increasedincreased

thyroid scan thyroid scan diffuse, homogenous goitrediffuse, homogenous goitre Thyroid ultrasound:Thyroid ultrasound:

enlarged glandenlarged gland hypoechoic patternhypoechoic pattern

increased blood flowincreased blood flow Computed tomography and magnetic Computed tomography and magnetic

resonanceresonance

Page 30: THE  THYROID  GLAND

GRAVES’ DISEASE – GRAVES’ DISEASE – TREATMENTTREATMENT

General principles of treatment General principles of treatment

Treatments availableTreatments available for Graves’ diseasefor Graves’ disease

MEDICALMEDICAL SURGICALSURGICAL

RADIOIODINERADIOIODINE

Most treatment regiments are directed at the thyroid, but there is Most treatment regiments are directed at the thyroid, but there is a small place for peripherally acting drugs such as propranolol a small place for peripherally acting drugs such as propranolol

and ipodate.and ipodate.

Page 31: THE  THYROID  GLAND

GRAVES’ DISEASE – GRAVES’ DISEASE – TREATMENTTREATMENT

Patient preferencePatient preference Small goitreSmall goitre Mild diseaseMild disease

Other diseasesOther diseases ChildrenChildren

PregnancyPregnancy

OphtalmopathyOphtalmopathy PreoperativePreoperative

Pre-radioiodinePre-radioiodine Thyrotoxic crisisThyrotoxic crisis

Relapse after Relapse after thyroidectomythyroidectomy

Indications for medical treatmentIndications for medical treatment

Page 32: THE  THYROID  GLAND

ANTITHYROID DRUGSANTITHYROID DRUGS

THIONAMIDES:THIONAMIDES:

Methimazole, Carbimazole, PropylthiouracilMethimazole, Carbimazole, Propylthiouracil

Mechanism of actions:Mechanism of actions:

Inhibition of thyroid hormone synthesis Inhibition of thyroid hormone synthesis

and secretionand secretion

PTUPTUinhibition of peripheral conversion inhibition of peripheral conversion

of Tof T44 to T to T33

Page 33: THE  THYROID  GLAND

THIONAMIDESTHIONAMIDES

Goal:Goal: Permanent remission of Permanent remission of

hyperthyroidismhyperthyroidism

Limitations:Limitations: High recurrence rate of High recurrence rate of

hyperthyroidismhyperthyroidism

Possible side effectsPossible side effects

Page 34: THE  THYROID  GLAND

Factors that may influance antithyroid drug therapyFactors that may influance antithyroid drug therapy

associated with remissionassociated with remission

ClinicalClinical Small goitreSmall goitre Mild diseaseMild disease

Rapid responce to Rapid responce to antithyroid drugsantithyroid drugs

Small maintenance doseSmall maintenance dose Female sexFemale sex

Low iodine intakeLow iodine intake

LaboratoryLaboratory Modest elevation of Modest elevation of

thyroid hormonesthyroid hormones Low urinary iodine Low urinary iodine

excretionexcretion Low or absent TSH-R9s) Low or absent TSH-R9s)

antibodies at end of antibodies at end of therapytherapy

Normal responce to TRH at Normal responce to TRH at end of therapyend of therapy

Normal suppression of Normal suppression of thyroidal radioiodine thyroidal radioiodine

uptake at end of therapyuptake at end of therapy

Page 35: THE  THYROID  GLAND

Factors that may influance antithyroid drug therapyFactors that may influance antithyroid drug therapy

associated with relapseassociated with relapse

ClinicalClinical Large goitreLarge goitre

Vascular goitreVascular goitre Severe diseaseSevere disease

Slow responce to Slow responce to antithyroid drugsantithyroid drugs

Large maintenance doseLarge maintenance dose Male sexMale sex

High iodine intakeHigh iodine intake

LaboratoryLaboratory Major elevation of thyroid Major elevation of thyroid

hormoneshormones High urinary iodine High urinary iodine

excretionexcretion Raised TSH-R(s) Raised TSH-R(s) antibodies at end of antibodies at end of

therapytherapy Absent responce to TRH at Absent responce to TRH at

end of therapyend of therapy Impaired or absent Impaired or absent suppression of thyroidal suppression of thyroidal radioiodine uptake at end radioiodine uptake at end

of therapyof therapy

Page 36: THE  THYROID  GLAND

THIONAMIDESTHIONAMIDES

NauseaNausea VomitingVomiting PruritisPruritis

Skin rashSkin rash UrticariaUrticaria

Loss of tasteLoss of taste

Side effectsSide effects(overall frequency <5%)(overall frequency <5%)

Mild leukopenia (12 – 25%)Mild leukopenia (12 – 25%) Agranulocytosis (0.1 – 0.5%)Agranulocytosis (0.1 – 0.5%)

Aplastic anemiaAplastic anemia ThrombocytopeniaThrombocytopenia

CholestasisCholestasis Hepatocellular necrosisHepatocellular necrosis Lupus-like syndromeLupus-like syndrome Nephrotic syndromeNephrotic syndrome

Page 37: THE  THYROID  GLAND

GRAVES’ DISEASE – GRAVES’ DISEASE – TREATMENTTREATMENT

Experienced thyroid Experienced thyroid surgeon avaliablesurgeon avaliable

Patient preferencePatient preference Adults up to 40 Adults up to 40

yearsyears Severe diseaseSevere disease

Nodular goitreNodular goitre Large goitreLarge goitre

Relapse after drug Relapse after drug treatmenttreatment

Indications for surgical treatmentIndications for surgical treatment

Page 38: THE  THYROID  GLAND

SURGICAL TREATMENTSURGICAL TREATMENT

PARTIAL THYROIDECTOMYPARTIAL THYROIDECTOMY

Mechanism of actionMechanism of action

removal of tissue responsible for removal of tissue responsible for

excessive thyroid hormone synthesisexcessive thyroid hormone synthesis

Page 39: THE  THYROID  GLAND

PARTIAL THYROIDECTOMYPARTIAL THYROIDECTOMY

GoalGoal

thyroid ablation, i.e. hypothyroidismthyroid ablation, i.e. hypothyroidism

ContraindicationsContraindications

systemic contraindications to surgerysystemic contraindications to surgery

Page 40: THE  THYROID  GLAND

PARTIAL THYROIDECTOMYPARTIAL THYROIDECTOMY- COMPLICATIONS- COMPLICATIONS

EARLYEARLY Recurrent laryngeal nerve Recurrent laryngeal nerve

palsypalsy Superior laryngeal nerve Superior laryngeal nerve

palsypalsy HaemorrhageHaemorrhage

HypoparathyroidismHypoparathyroidism PneumothoraxPneumothorax Thyroid crisisThyroid crisis

Damage to thoracic drugDamage to thoracic drug Damage to carotic arteryDamage to carotic artery Damage to jugular veinDamage to jugular vein

LATELATE Cheloid scarCheloid scar

Tethered scarTethered scar HypothyroidismHypothyroidism Recurrence of Recurrence of

hyperthyroidismhyperthyroidism Recurrent upper pole Recurrent upper pole

nodulesnodules

Page 41: THE  THYROID  GLAND

GRAVES’ DISEASE – GRAVES’ DISEASE – TREATMENTTREATMENT

Patient preferencePatient preference Poor-compliance Poor-compliance

with antithyroid with antithyroid drugsdrugs

Patients over 40 Patients over 40 yearsyears

Recurrence after Recurrence after thyroidectomythyroidectomy

Severe uncontrolled Severe uncontrolled diseasedisease

Large goitreLarge goitre Unco-operative Unco-operative

patientspatients Presence of other Presence of other

disease(s)disease(s)

Indications for radioiodine therapyIndications for radioiodine therapy

Page 42: THE  THYROID  GLAND

RADIOIODINE THERAPYRADIOIODINE THERAPYMechanism of actionMechanism of action

Destruction of thyrocytes by Destruction of thyrocytes by ββ-radiation-radiation

GoalGoal

thyroid ablation, i.e. hypothyroidismthyroid ablation, i.e. hypothyroidism

ContraindicationsContraindications

pregnancypregnancy

Page 43: THE  THYROID  GLAND

RADIOIODINE THERAPYRADIOIODINE THERAPY

ComplcationsComplcations Permanent hypothyroidismPermanent hypothyroidism Transient hypothyroidismTransient hypothyroidism

ThyroiditisThyroiditis SialadenitisSialadenitis

Thyrotoxic crisisThyrotoxic crisis Nodule formationNodule formation

Possible exacerbation of ophtalmopathy Possible exacerbation of ophtalmopathy

(preventable by glucocorticoids)(preventable by glucocorticoids)

Page 44: THE  THYROID  GLAND

GRAVES’ DISEASE – GRAVES’ DISEASE – TREATMENTTREATMENT

ΒΒ-adrenergic -adrenergic antagonists antagonists

(e.g. Propranolol)(e.g. Propranolol) Inorganic iodideInorganic iodide

Potassium Potassium

perchlorateperchlorate

GlucocorticoidsGlucocorticoids

Other drugsOther drugs

Page 45: THE  THYROID  GLAND

GRAVES’ DISEASE – GRAVES’ DISEASE – TREATMENT OF OPHTHALMOPATHYTREATMENT OF OPHTHALMOPATHY

Mild ophthalmopathyMild ophthalmopathy Guanethidine or Guanethidine or ββ-adrenergic eye drops -adrenergic eye drops

(lid retraction)(lid retraction) Methylcellulose eye drops Methylcellulose eye drops

(lacrimation, burning sensation)(lacrimation, burning sensation) Sunglasses Sunglasses

(photophobia)(photophobia) Nighttime tapering of eyes Nighttime tapering of eyes

(lagophthalmos)(lagophthalmos) Prisms Prisms

(mild diplopia)(mild diplopia)

Page 46: THE  THYROID  GLAND

Severe ophthalmopathySevere ophthalmopathy High-dose glucocorticoidsHigh-dose glucocorticoids

(active ophthalmopathy)(active ophthalmopathy)

Orbital radiotherapyOrbital radiotherapy

(active ophthalmopathy)(active ophthalmopathy)

Orbital decompresionOrbital decompresion

(active or inactive ophthalmopathy)(active or inactive ophthalmopathy)

Rehabilitative surgery: eye muscles, eyelids Rehabilitative surgery: eye muscles, eyelids

(to be performed at least 6 months after rendering (to be performed at least 6 months after rendering

ophthalmopathy stable and inactive with other ophthalmopathy stable and inactive with other

treatments)treatments)

Immunosuppressive drugs, somatostatin analogues, Immunosuppressive drugs, somatostatin analogues,

intravenous immunoglobulins, plasmapheresis. intravenous immunoglobulins, plasmapheresis.

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THYROTOXIC STORMTHYROTOXIC STORM

RARE BUT VERY SERIOUS COMPLICATION RARE BUT VERY SERIOUS COMPLICATION OF HYPERTHYROIDISMOF HYPERTHYROIDISM

Severe manifestations of hypermetabolicSevere manifestations of hypermetabolic(fever, profound sweating, dehydration, (fever, profound sweating, dehydration,

restlessness, insomnia)restlessness, insomnia) In patients with not diagnosed or In patients with not diagnosed or inadeguately treated hyperthyroidisminadeguately treated hyperthyroidism

SURGERYSURGERY

INFECTIONSINFECTIONS

TRAUMASTRAUMASTHYROTOXIC STORMTHYROTOXIC STORM

Page 48: THE  THYROID  GLAND

THYROTOXIC STORM - THYROTOXIC STORM - TREATMENTTREATMENT

High doses of High doses of thionamidethionamide

Iodide or iodinated Iodide or iodinated contrast agentscontrast agents

Glucocorticoids Glucocorticoids ββ-adrenergic -adrenergic

antagonists antagonists

The treatmnent of The treatmnent of underlying non-underlying non-thyroidal illnessthyroidal illness Correction of Correction of

dehydrationdehydration Normalisation of body Normalisation of body

temperaturetemperature Plasmapheresis or Plasmapheresis or

peritoneal dialysisperitoneal dialysis

Page 49: THE  THYROID  GLAND

TOXIC ADENOMATOXIC ADENOMAAn autonomously functioning, benign An autonomously functioning, benign

thyroid nodule causing thyrotoxicosisthyroid nodule causing thyrotoxicosis

FREQUECYFREQUECY

Iodine-deficientIodine-deficientareasareas

Iodine-sufficient Iodine-sufficient areasareas

≤≤10%10%

>10%>10%

Page 50: THE  THYROID  GLAND

TOXIC ADENOMATOXIC ADENOMA

otherwise normal otherwise normal thyroid glandthyroid gland

goitergoiter

Solitary nodule Solitary nodule

in:in:

Pathogenesis:Pathogenesis:

Somatic mutations in the gene encoding the TSH receptorSomatic mutations in the gene encoding the TSH receptor

constitutive activation of TSH receptorconstitutive activation of TSH receptor

Page 51: THE  THYROID  GLAND

TOXIC ADENOMATOXIC ADENOMASmptoms and signs of thyrotoxicosis Smptoms and signs of thyrotoxicosis

Ophthalmopathy, localized myxedema and Ophthalmopathy, localized myxedema and acropachy are absentacropachy are absent

Thyroid scanThyroid scan

Prevalent tracer uptake in the nodulePrevalent tracer uptake in the nodule(„hot nodule”)(„hot nodule”)

TreatmentTreatmentRadioiodine or surgeryRadioiodine or surgery

Antithyroid drugs only for preparation of definitive Antithyroid drugs only for preparation of definitive treatmenttreatment

Page 52: THE  THYROID  GLAND

TOXIC MULTINODULAR GOITERTOXIC MULTINODULAR GOITER

Multiple hyperfunctioning thyroid Multiple hyperfunctioning thyroid nodules nodules

or areas of autonomously functioning or areas of autonomously functioning thyroid folliclesthyroid follicles

Commonly found in older patients with Commonly found in older patients with long-standing multinodular goiter.long-standing multinodular goiter.

Page 53: THE  THYROID  GLAND

UNUSUAL FORMS OF THYROTOXICOSISUNUSUAL FORMS OF THYROTOXICOSIS

TSH-secreting TSH-secreting

pituitary adenomapituitary adenoma(280 cases so far described)(280 cases so far described)

TSH TSH or or ↔; ↔; FTFT44 ; ;

FTFT33

TSH TSH αα-subunit -subunit TSH TSH αα-subunit / TSH>1-subunit / TSH>1

Selective pituitary Selective pituitary resistenceresistence

TSH TSH or or ↔; ↔; FTFT44 ; ;

FTFT33

TSH TSH αα-subunit ↔-subunit ↔

TSH TSH αα-subunit / TSH<1-subunit / TSH<1

TSH-INDUCED HYPERTHYROIDISMTSH-INDUCED HYPERTHYROIDISM

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UNUSUAL FORMS OF THYROTOXICOSISUNUSUAL FORMS OF THYROTOXICOSIS

Thyrotoxicosis factitiaThyrotoxicosis factitia

Clinical and biochemical Clinical and biochemical

picture is typical of picture is typical of

thyrotoxicosisthyrotoxicosis

Goiter is absentGoiter is absent

RAIU is very low/suppressedRAIU is very low/suppressed

Serum thyroglobulin – very Serum thyroglobulin – very

low or undetectablelow or undetectable

Congenital hyperthyroidismCongenital hyperthyroidism

Germline mutations of the Germline mutations of the

TSH-R geneTSH-R gene

Constitutional activation in all Constitutional activation in all

thyroid follicular cellsthyroid follicular cells

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UNUSUAL FORMS OF THYROTOXICOSISUNUSUAL FORMS OF THYROTOXICOSIS

Metastatic thyroid Metastatic thyroid

carcinomacarcinoma

Follicular thyroid arcinomaFollicular thyroid arcinoma

Metastases to lung and boneMetastases to lung and bone

Thyrotoxicosis (rarely)Thyrotoxicosis (rarely)

Struma ovariiStruma ovarii

Functioning thyroid tissue Functioning thyroid tissue

within an ovarian within an ovarian

teratoma or dermoidteratoma or dermoid

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UNUSUAL FORMS OF THYROTOXICOSISUNUSUAL FORMS OF THYROTOXICOSIS

Trophoblastic tumorsTrophoblastic tumors

High serum and urine concentrations High serum and urine concentrations

of of ββ-subunit of chorionic gonadotropin-subunit of chorionic gonadotropin

stimulation of TSH receptorstimulation of TSH receptor