Thyroiditis.ppt dg ffkjsnd.x.,jrei lvfdl

х

1. Thyroid Physiology and Thyroid Physiology and
ThyroiditisThyroiditis
Heidi Chamberlain Shea, MDHeidi Chamberlain Shea, MD
Endocrine Associates of DallasEndocrine Associates of Dallas

2. Case PresentationCase Presentation
23 year old female23 year old female

G2P2G2P2

6 months post partum6 months post partum

Palpitations that were Palpitations that were
intermittent for a couple of intermittent for a couple of
weeks and now resolvedweeks and now resolved

Now with 1 month of increased Now with 1 month of increased
fatigue, hair loss and 10 pound fatigue, hair loss and 10 pound
weight gain weight gain

3. Case PresentationCase Presentation
What is her diagnosis?What is her diagnosis?
Tests that should be done?Tests that should be done?
Pathophysiology of her disease process?Pathophysiology of her disease process?

4. Thyroid TriviaThyroid Trivia
““Bronchocele”Bronchocele”

Greek for tracheal Greek for tracheal
outpouchoutpouch
1500 AD described by 1500 AD described by
Leonardo da VinciLeonardo da Vinci
1656 AD “thyroid” 1656 AD “thyroid”

Thomas WhartonThomas Wharton

Shield shaped cartilageShield shaped cartilage

5. Thyroid TriviaThyroid Trivia
Largest endocrine Largest endocrine
glandgland

20 grams in adult20 grams in adult

Each lobe Each lobe
2-2.5cm in width and 2-2.5cm in width and
thicknessthickness
4cm in height4cm in height

IsthmusIsthmus
0.5cm thick0.5cm thick
2cm height and width2cm height and width

6. ThyroidThyroid
Derived from endoderm at Derived from endoderm at
base of tonguebase of tongue
Recognizable after 1 Recognizable after 1
month of fetal lifemonth of fetal life
Isthmus lies over 2Isthmus lies over 2
ndnd
and and
33
rdrd
tracheal rings tracheal rings
2cm wide x 2 cm height x 2cm wide x 2 cm height x
0.5cm thick0.5cm thick
Adult 15-20 gramsAdult 15-20 grams

7. ThyroidThyroid
Largest of the endocrine glandsLargest of the endocrine glands
Blood flow 5x the weight of the gland/minuteBlood flow 5x the weight of the gland/minute
Hormones producedHormones produced

93% thyroxine (T4)93% thyroxine (T4)

7% triiodothyronine (T3)7% triiodothyronine (T3)
4x the potency of thyroxine4x the potency of thyroxine
Responsible for the basal metabolic rateResponsible for the basal metabolic rate

Deficiency = 40-50% fall in metabolic rateDeficiency = 40-50% fall in metabolic rate

Excess = 60-100% increase in metabolic rateExcess = 60-100% increase in metabolic rate

8. Thyroid HistologyThyroid Histology
Multiple closed follicles Multiple closed follicles
(100-300 micrometers)(100-300 micrometers)
Cuboidal epithelial cells Cuboidal epithelial cells
secrete colloid into the secrete colloid into the
folliclesfollicles
Colloid = thyroglobulinColloid = thyroglobulin

Large glycoprotein with 70 Large glycoprotein with 70
tyrosine amino acidstyrosine amino acids

Endoplasmic reticulum Endoplasmic reticulum
and Golgi apparatus and Golgi apparatus
synthesize and secretesynthesize and secrete

9. TRH
(+)
HYPOTHALAMUS
ANTERIOR
PITUITARY
HYPOTHALAMIC-
PITUITARY
PORTAL SYSTEM
T4, T3 (T4 --> T3)
THYROID GLAND
TSH
POSTERIOR
PITUITARY
(-)
(-)

10. TRHTRH
Produced by HypothalamusProduced by Hypothalamus
Release is pulsatile, circadianRelease is pulsatile, circadian
Downregulated by TDownregulated by T
44, T, T
33
Travels through portal venous system to Travels through portal venous system to
adenohypophysisadenohypophysis
Stimulates TSH formationStimulates TSH formation

11. TSHTSH
Produced by Adenohypophysis ThyrotrophsProduced by Adenohypophysis Thyrotrophs
Upregulated by TRH Upregulated by TRH
Downregulated by TDownregulated by T
44, T, T
33
Travels through portal venous system to Travels through portal venous system to
cavernous sinus, body.cavernous sinus, body.
Stimulates several processesStimulates several processes

Iodine uptakeIodine uptake

Colloid endocytosisColloid endocytosis

Growth of thyroid gland Growth of thyroid gland

12. Thyroid PhysiologyThyroid Physiology
Uptake of Iodine by thyroidUptake of Iodine by thyroid
Coupling of Iodine to ThyroglobulinCoupling of Iodine to Thyroglobulin
Storage of MIT / DIT in follicular spaceStorage of MIT / DIT in follicular space
Re-absorption of MIT / DITRe-absorption of MIT / DIT
Formation of TFormation of T
33, T, T
44 from MIT / DIT from MIT / DIT
Release of TRelease of T
33, T, T
44 into serum into serum
Breakdown of TBreakdown of T
33, T, T
44 with release of Iodine with release of Iodine

13. Thyroid and IodineThyroid and Iodine
50 mg of iodides are needed per year50 mg of iodides are needed per year

1 mg/week1 mg/week

Iodized saltIodized salt
1 part Na iodide to 100,000 parts NaCl1 part Na iodide to 100,000 parts NaCl
Iodides are ingested and oxidized to iodine in Iodides are ingested and oxidized to iodine in
the thyroidthe thyroid

Nascent iodine(INascent iodine(I
oo
) or I) or I
33
--

Peroxidase enzyme (hydrogen peroxide)Peroxidase enzyme (hydrogen peroxide)
1/5 of ingested iodine utilized for hormone 1/5 of ingested iodine utilized for hormone
synthesissynthesis

14. Iodide CirculationIodide Circulation

15. Iodine uptakeIodine uptake
NaNa
++
/I/I
--
symport protein symport protein
controls serum Icontrols serum I
--

uptakeuptake
Based on NaBased on Na
++
/K/K
++

antiport potentialantiport potential
Stimulated by TSHStimulated by TSH
Inhibited by Inhibited by
PerchloratePerchlorate

16. Iodide PumpIodide Pump
Thyroid gland actively pumps iodide into Thyroid gland actively pumps iodide into
the cell via the basal membrane the cell via the basal membrane
(iodide trapping)(iodide trapping)

Iodide 30x the concentration of bloodIodide 30x the concentration of blood

Able to concentrate to 250x the concentration Able to concentrate to 250x the concentration
in bloodin blood
Rate of iodide trappingRate of iodide trapping

TSH dependentTSH dependent

17. Thyroid Hormone SynthesisThyroid Hormone Synthesis
Tyrosine backboneTyrosine backbone
IodineIodine

IodinaseIodinase enzyme (enzyme I) attaches iodine enzyme (enzyme I) attaches iodine
to thyroglobulinto thyroglobulin
Number of iodines determine activity of Number of iodines determine activity of
thyroid hormonethyroid hormone

Thyroxine (4 iodines)Thyroxine (4 iodines)

Triiodothyronine (3 iodines)Triiodothyronine (3 iodines)

18. MIT / DIT FormationMIT / DIT Formation
Thyroid Peroxidase (TPO)Thyroid Peroxidase (TPO)

Apical membrane proteinApical membrane protein

Catalyzes iodide oxidation to reactive iodine Catalyzes iodide oxidation to reactive iodine
Binds to Tyrosine residues of ThyroglobulinBinds to Tyrosine residues of Thyroglobulin

Antagonized by thionamidesAntagonized by thionamides

Coupling enzymeCoupling enzyme
MIT with DIT= T3MIT with DIT= T3
Two DIT’s= T4Two DIT’s= T4
Pre-hormones secreted into follicular spacePre-hormones secreted into follicular space

19. Transport of T3 and T4Transport of T3 and T4
When in circulationWhen in circulation

93% thyroxine and 7% triiodothyronine93% thyroxine and 7% triiodothyronine

Conversion to active (T3) is by slow Conversion to active (T3) is by slow
deiodination processdeiodination process

99% of T4 and T3 bound to plasma proteins99% of T4 and T3 bound to plasma proteins
Causes slow release of hormone to tissueCauses slow release of hormone to tissue
Thyroxine-binding globulin (TBG)Thyroxine-binding globulin (TBG)
Tyroxine-binding prealbumin and albuminTyroxine-binding prealbumin and albumin

20. Secretion of Thyroid HormoneSecretion of Thyroid Hormone
Stimulated by TSHStimulated by TSH
Endocytosis of colloid on apical membraneEndocytosis of colloid on apical membrane
Coupling of MIT & DIT residuesCoupling of MIT & DIT residues

Catalyzed by TPOCatalyzed by TPO
MIT + DIT = TMIT + DIT = T
33
DIT + DIT = TDIT + DIT = T
44
Hydrolysis of ThyroglobulinHydrolysis of Thyroglobulin
Release of TRelease of T
33, T, T
44
Release inhibited by LithiumRelease inhibited by Lithium

21. Thyroid HormonesThyroid Hormones

22. Thyroglobulin StorageThyroglobulin Storage
Thyroglobulin moleculeThyroglobulin molecule

30 thyroxine molecules30 thyroxine molecules

Few triiodothyronineFew triiodothyronine
Sufficient supply for 2-3 Sufficient supply for 2-3
monthsmonths
Deiodinase enzyme Deiodinase enzyme
recycles iodine when recycles iodine when
thyroglobulin utilizedthyroglobulin utilized

23. Thyroid Hormone Thyroid Hormone
Metabolic effect of thyroxine noticed 2-3 Metabolic effect of thyroxine noticed 2-3
days after releasedays after release
Steady state of thyroid hormone 10-12 Steady state of thyroid hormone 10-12
days after ingestiondays after ingestion
Half life of 15 daysHalf life of 15 days
Due to steady state, thyroid hormone is Due to steady state, thyroid hormone is
typically adjusted every 4-6 weekstypically adjusted every 4-6 weeks

Check T4 vs. TSH in the short term Check T4 vs. TSH in the short term
assessmentassessment

24. Thyroid HormoneThyroid Hormone

Majority of circulating hormone is TMajority of circulating hormone is T
44
98.5% T98.5% T
44
1.5% T1.5% T
33

Total Hormone load is influenced by serum Total Hormone load is influenced by serum
binding proteins binding proteins
Thyroid Binding Globulin 70%Thyroid Binding Globulin 70%
Albumin 15%Albumin 15%
Transthyretin 10%Transthyretin 10%

Regulation is based on the free component of Regulation is based on the free component of
thyroid hormonethyroid hormone

25. Hormone Binding FactorsHormone Binding Factors
Increased TBGIncreased TBG

High estrogen states (pregnancy, OCP, HRT, Tamoxifen)High estrogen states (pregnancy, OCP, HRT, Tamoxifen)

Liver disease (early)Liver disease (early)
Decreased TBGDecreased TBG

Androgens or anabolic steroidsAndrogens or anabolic steroids

Liver disease (late)Liver disease (late)
Binding Site CompetitionBinding Site Competition

NSAID’sNSAID’s

Furosemide IVFurosemide IV

Anticonvulsants (Phenytoin, Carbamazepine)Anticonvulsants (Phenytoin, Carbamazepine)

26. Hormone DegradationHormone Degradation
TT
44 is converted to T is converted to T
33 (active) by (active) by 5’ deiodinase5’ deiodinase
TT
44 can be converted to rT can be converted to rT
33 (inactive) by (inactive) by 5 deiodinase5 deiodinase
TT
33 is converted to rT is converted to rT
22 (inactive)by (inactive)by 5 deiodinase5 deiodinase
rTrT
33 is inactive but measured by serum tests is inactive but measured by serum tests

27. Hypothyroidism Hypothyroidism
SymptomsSymptoms
Nervous systemNervous system

Forgetfulness and Forgetfulness and
mental slowingmental slowing

ParesthesiasParesthesias

Carpal tunnelCarpal tunnel

Ataxia and decreased Ataxia and decreased
hearinghearing

Tendon jerk slowed Tendon jerk slowed
with prolonged with prolonged
relaxation phaserelaxation phase
CardiovascularCardiovascular

BradycardiaBradycardia

Decreased cardiac Decreased cardiac
outputoutput

Pericardial effusionPericardial effusion

Reduced voltage on Reduced voltage on
EKG and flat T wavesEKG and flat T waves

Dependent edemaDependent edema

28. HypothyroidismHypothyroidism
SymptomsSymptoms
GastrointestinalGastrointestinal

ConstipationConstipation

Achlorhydria with Achlorhydria with
pernicious anemiapernicious anemia

Ascitic fluid with high Ascitic fluid with high
proteinprotein
Renal Renal

Reduced excretion of Reduced excretion of
water loadwater load
HyponatremiaHyponatremia

Decreased renal blood Decreased renal blood
flow and glomerular flow and glomerular
filtrationfiltration
PulmonaryPulmonary

Responses to hypoxia and Responses to hypoxia and
hypercapnia are decreasedhypercapnia are decreased

Pleural effusions high Pleural effusions high
proteinprotein
MusculoskeletalMusculoskeletal

ArthralgiaArthralgia

Joint effusionsJoint effusions

Muscle crampsMuscle cramps

CK can be elevatedCK can be elevated
AnemiaAnemia

Normochromic normocyticNormochromic normocytic

MegaloblasticMegaloblastic
Pernicious anemiaPernicious anemia

29. HypothyroidismHypothyroidism
SymptomsSymptoms
Skin and hairSkin and hair

Loss of lateral eye browsLoss of lateral eye brows

Dry, cool skinDry, cool skin

Facial featuresFacial features
Coarse and puffyCoarse and puffy

Orange skinOrange skin
CaroteneCarotene
Reproductive systemReproductive system

Menorrhagia from Menorrhagia from
anovulatory cyclesanovulatory cycles

HyperprolactinemiaHyperprolactinemia
No inhibition of thyroid No inhibition of thyroid
hormonehormone
MetabolismMetabolism

HypothermiaHypothermia

Intolerance to coldIntolerance to cold

Increased cholesterol Increased cholesterol
and triglycerideand triglyceride
Decreased lipoprotein Decreased lipoprotein
receptorsreceptors

Weight gainWeight gain

30. Thyroid HormoneThyroid Hormone
Metabolic effect of thyroxine noticed 2-3 Metabolic effect of thyroxine noticed 2-3
days after releasedays after release
Steady state of thyroid hormone 10-12 Steady state of thyroid hormone 10-12
days after ingestiondays after ingestion
Half life of 15 daysHalf life of 15 days
Due to steady state, thyroid hormone is Due to steady state, thyroid hormone is
typically adjusted every 4-6 weekstypically adjusted every 4-6 weeks

Check T4 vs TSH in the short term Check T4 vs TSH in the short term
assessmentassessment

31. HypothyroidismHypothyroidism
EtiologiesEtiologies
ThyroiditisThyroiditis
Thyroid ablationThyroid ablation
External radiotherapyExternal radiotherapy
Pharmacologic agentsPharmacologic agents
Infiltrative disordersInfiltrative disorders
Embryologic variantsEmbryologic variants

32. ThyroiditisThyroiditis
Decreased uptake on Decreased uptake on
uptake scanuptake scan
TransientTransient

Euthyroidism returns with Euthyroidism returns with
time time

Lead to chronic thyroid Lead to chronic thyroid
dysfunctiondysfunction
EtiologyEtiology

InfectiousInfectious

Post-partumPost-partum

Auto-immuneAuto-immune
TransientTransient
ChronicChronic

DrugDrug

33. ThyroiditisThyroiditis
Thyrotoxic phaseThyrotoxic phase

Short phaseShort phase

Increased T3 and T4Increased T3 and T4

Symptoms of Symptoms of
hyperthyroidismhyperthyroidism

Thionamides not Thionamides not
effectiveeffective
Thyroid synthesis lowThyroid synthesis low

Can use beta-blockersCan use beta-blockers
Hypothyroid phaseHypothyroid phase

Transient or permanentTransient or permanent

Symptomatic patients Symptomatic patients
need replacementneed replacement

Can check for recovery Can check for recovery
with stopping after 3-6 with stopping after 3-6
monthsmonths

34. ThyroiditisThyroiditis
Time CourseTime Course
Williams Text of Endocrinology, Fig 11.50

35. Infectious ThyroiditisInfectious Thyroiditis
EtiologyEtiology

Bacterial 90%Bacterial 90%

FungalFungal

MycobacterialMycobacterial

ParasiticParasitic

SyphiliticSyphilitic
SymptomsSymptoms

Thyroid pain and Thyroid pain and
tendernesstenderness

FeverFever

DysphagiaDysphagia

Dysphonia Dysphonia
TreatmentTreatment

Treat the infectionTreat the infection

36. Autoimmune ThyroiditisAutoimmune Thyroiditis
Chronic LymphocyticChronic Lymphocytic

Silent ThyroiditisSilent Thyroiditis

Hashimoto’sHashimoto’s
Women 3.5/1000Women 3.5/1000
Men 0.8/1000Men 0.8/1000
Frequency increases with Frequency increases with
ageage
Familial historyFamilial history
Associated with Associated with
autoimmune diseasesautoimmune diseases
AntibodiesAntibodies

Thyroid peroxidaseThyroid peroxidase
More specificMore specific

ThyroglobulinThyroglobulin
Elevated in many types of Elevated in many types of
thyroid inflammationthyroid inflammation

37. ThyroiditisThyroiditis
Postpartum thyroiditisPostpartum thyroiditis

2-21% of pregnancies2-21% of pregnancies

Can occur up to one Can occur up to one
year post partumyear post partum

Usually transient and Usually transient and
returns to euthyroid returns to euthyroid
statestate

Treat Treat
HypothyroidismHypothyroidism
Symptoms with Symptoms with
‘hyperthyroidism’‘hyperthyroidism’
Presence of TPO AB Presence of TPO AB
increases risk of long increases risk of long
term hypothyroidismterm hypothyroidism

38. Transient/Destructive ThyroiditisTransient/Destructive Thyroiditis
SubacuteSubacute

20% of thyrotoxic cases20% of thyrotoxic cases

De Quervain’s thyroiditisDe Quervain’s thyroiditis

Giant cell thyroiditisGiant cell thyroiditis

Pseudogranulomatous Pseudogranulomatous
thyroiditisthyroiditis

Subacute painful thyroiditisSubacute painful thyroiditis
SymptomsSymptoms

PainPain

FeverFever

Increased ESRIncreased ESR

Hoarseness or dysphagiaHoarseness or dysphagia
TreatmentTreatment

ASA, NSAIDASA, NSAID

Steroid rarelySteroid rarely

39. Comparison of ThyroiditisComparison of Thyroiditis
CharacteristicCharacteristicSilent thyroiditisSilent thyroiditisSubacute thyroiditisSubacute thyroiditis
Age of onset (yr)Age of onset (yr) 5-935-93 20-6020-60
Sex ratio (F:M)Sex ratio (F:M) 2:12:1 5:15:1
EtiologyEtiology AutoimmuneAutoimmune ViralViral
PathologyPathology Lymphocytic infiltrationLymphocytic infiltrationGiant cells, granulomasGiant cells, granulomas
ProdromeProdrome PregnancyPregnancy Viral illnessViral illness
GoiterGoiter Non-painfulNon-painful PainfulPainful
Fever/malaiseFever/malaise NoNo YesYes
TPO/thyroglobulin ABTPO/thyroglobulin AB High and risingHigh and rising Low, absent or transientLow, absent or transient
ESRESR NormalNormal HighHigh
RAIURAIU <5%<5% <5%<5%
RelapseRelapse CommonCommon RareRare
Permanent Permanent
hypothyroidismhypothyroidism
CommonCommon InfrequentInfrequent

40. Drug Induced Thyroid DysfunctionDrug Induced Thyroid Dysfunction
LithiumLithium

Inhibits thyroid hormone Inhibits thyroid hormone
secretionsecretion

HypothyroidismHypothyroidism

3.4% prevalence3.4% prevalence
Interferon-Interferon-αα

Hyper/HypothyroidismHyper/Hypothyroidism

Transient thyroiditisTransient thyroiditis

TPO AB increases risk of TPO AB increases risk of
thyroid dysfunctionthyroid dysfunction
Interleukin-2Interleukin-2
AminoglutethimideAminoglutethimide
EthionamideEthionamide
SulfonamidesSulfonamides

41. Drug Induced Thyroid DysfunctionDrug Induced Thyroid Dysfunction
AmiodaroneAmiodarone

75 mg iodine/200 mg75 mg iodine/200 mg

HypothyroidismHypothyroidism

ThyrotoxicosisThyrotoxicosis
Type I and Type IIType I and Type II

Increased blood flow vs. Increased blood flow vs.
decreased blood flowdecreased blood flow
Not responsive to thionamidesNot responsive to thionamides

42. HypothyroidismHypothyroidism
Infiltrative DisordersInfiltrative Disorders
Riedel’s thyroiditisRiedel’s thyroiditis

Invasive Fibrous ThyroiditisInvasive Fibrous Thyroiditis

Thyroid tissue replaced by Thyroid tissue replaced by
fibrous tissuefibrous tissue

Rapidly enlarging neck Rapidly enlarging neck
massmass

Compressive symptomsCompressive symptoms

Surgical removalSurgical removal

Steroids and tamoxifenSteroids and tamoxifen
AmyloidosisAmyloidosis
SarcoidosisSarcoidosis
HemochromatosisHemochromatosis
CystinosisCystinosis
Pneumocystis cariniiPneumocystis carinii
LymphomaLymphoma

43. Thyroid Hormone ReplacementThyroid Hormone Replacement
1.3 ug/kg/day1.3 ug/kg/day

75-100 ug per day75-100 ug per day
Elderly or patients with Elderly or patients with
anginaangina

12.5-25 ug/day 12.5-25 ug/day
Carefully increase every Carefully increase every
monthmonth
IV dosingIV dosing

Use 60% of oral doseUse 60% of oral dose
LevothyroxineLevothyroxine

SynthroidSynthroid

LevoxylLevoxyl

UnithroidUnithroid
Armour ThyroidArmour Thyroid

T3/T4 preparationT3/T4 preparation

Dessicated pig thyroidDessicated pig thyroid

Not a consistent amount of Not a consistent amount of
T3/T4T3/T4
Most T3 preparations give Most T3 preparations give
higher than 1:11 ratio of higher than 1:11 ratio of
T3:T4T3:T4

44. Case PresentationCase Presentation
23 year old female23 year old female

G1P1G1P1

6 months post partum6 months post partum

Palpitations that were Palpitations that were
intermittent for a intermittent for a
couple of weeks and couple of weeks and
now resolvednow resolved

Now with 1 month of Now with 1 month of
increased fatigue, hair increased fatigue, hair
loss and 10 pound loss and 10 pound
weight gain weight gain

45. Case PresentationCase Presentation
What is her diagnosis?What is her diagnosis?

Post partum thyroiditisPost partum thyroiditis
Tests that should be done?Tests that should be done?

TSH 15 uIU/ml, Free T4 1.2 ng/dlTSH 15 uIU/ml, Free T4 1.2 ng/dl

TPO AB negativeTPO AB negative
Pathophysiology of her disease process?Pathophysiology of her disease process?

TransientTransient
TreatmentTreatment

Levothyroxine therapyLevothyroxine therapy

Recheck every 6-8 monthsRecheck every 6-8 months

After 3-6 months may be able to wean replacementAfter 3-6 months may be able to wean replacement

46. Post Partum ThyroiditisPost Partum Thyroiditis
Time CourseTime Course
Williams Text of Endocrinology, Fig 11.51
Changes in free T4

47. Williams Text of Endocrinology, Fig 12.6