THE THYROID THE THYROID GLANDGLAND
HYPERTYROIDISMHYPERTYROIDISM
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
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
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
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.
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
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
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
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
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
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
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
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
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
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.
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?).
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).
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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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
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
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
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
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
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
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
PARTIAL THYROIDECTOMYPARTIAL THYROIDECTOMY
GoalGoal
thyroid ablation, i.e. hypothyroidismthyroid ablation, i.e. hypothyroidism
ContraindicationsContraindications
systemic contraindications to surgerysystemic contraindications to surgery
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
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
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
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)
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
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)
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.
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
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
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%
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
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
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.
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
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
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
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