BENIGN DISEASES OF THE THYROID
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BENIGN DISEASES OF THE THYROID
Rivka Dresner Pollak M.D
Endocrinology.
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Thyroid gland- anatomyThyroid gland- anatomy
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Thyroid gland- anatomyThyroid gland- anatomy
sternocleidomastoidsternocleidomastoid
thyroidthyroid
esophagus
tracheatrachea
jugular v.
carotid a.carotid a.
strap musclesstrap muscles
vertebra
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Recommended and Typical Values for Dietary Iodine Intake
Recommended Daily Intake μg I/dayAdults 150During pregnancy 200Children 90-120
Typical Iodine intakesNorth America 75-300Europe (Germany, Belgium) 50-70Switzerland 130-160Chile <50-150
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Thyroid secretion
P
ProteinBound
Thyroidhormone
Free T4, T3 Tissue actionTissue action
Hormone metabolismHormone metabolism
Fecal excretionFecal excretion
Serum thyroid hormone bindingSerum thyroid hormone binding
Feedback controlFeedback control
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TBG = thyroxine binding globulinTTR = transthyretin% binding- mostly to TBGT4 - 99.5T3- 95
DEIODINASETYPE 1 & 2
THYROXINE BINDING GLOBULIN
Estrogen
Androgen =
Glucocorticoids =
Acute illness N
Chronic illness
Liver dis.
METABOLISM
TRANSPORT
THYROID HORMONES TRANSPORT AND METABOLISM
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Serum protein binding of thyroid hormonesSerum protein binding of thyroid hormones
Total TTotal T44
TBG T4T4T4
TBG T4T4 T4 T4T4
““Pill effect”Pill effect”
BoundBound Free Free
synthesisBy liver
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Regulation of Thyroid hormone secretionRegulation of Thyroid hormone secretion
Hypothalamus
TT44, T, T33
TSHTSH(-)(-) (+)(+)
TRHTRH(+)(+)(-)(-)
PituitaryPituitary
Thyroid
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Assessment of bioactive thyroid Assessment of bioactive thyroid hormoneshormones
Check free hormone levels:Check free hormone levels:Free TFree T44
Free TFree T33
Check thyroid hormone “biosensor’:Check thyroid hormone “biosensor’:TSH TSH
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Thyroid function testsThyroid function tests
Hypo HyperHypo Hyper Hypo HyperHypo Hyper 11oo Hypo 1 Hypo 1oo Hyper Hyper
TSHTSHFTFT33nmol/Lnmol/L
FTFT44
pmol/Lpmol/L
0.15
4
3.0
1.2
21
10
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Laboratory tests in thyroid diseaseLaboratory tests in thyroid disease
Anti-thyroid antibodies:Anti-thyroid peroxidase (TPO)
Thyroid stimulating antibodies:TSI-Thyroid stimulating imunoglobulinsTSH receptor Antibody
Thyroglobulin
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2. Thyroid scanning2. Thyroid scanning
Radioactive isotopes of I (Radioactive isotopes of I (131131I, I, 123123I)I)PertechnetatePertechnetate
Generates Data on:Generates Data on:- Anatomy- Anatomy- Physiology- Physiology
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Normal thyroid scanNormal thyroid scan
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““Hot nodule”Hot nodule”
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““Cold” noduleCold” nodule
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Multinodular goiter (MNG)Multinodular goiter (MNG)
Pertechnetate scanPertechnetate scan CHEST X-RAYCHEST X-RAY
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RRadio adio AActive ctive IIodine odine UUptake ptake ((RAIURAIU))
0 6 12 18 240
10
20
30
40
50
Time (hours)
HyperthroidismHyperthroidism
NormalNormal
Hyperthyroidism withHyperthyroidism withRapid turnoverRapid turnover
HypothroidismHypothroidism
2
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Thyroid abnormalitiesThyroid abnormalities
FunctionFunctionStructureStructure
Hyperthyroidism Hypothyroidism
EtiologyEtiology
RRXX
ThyroiditisThyroiditisGoiterGoiter
NodularNodular Diffuse Diffuse
BenignBenign MalignantMalignant Function nl Function nl
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Hyperthyroidism-EtiologyHyperthyroidism-Etiology
• Diffuse toxic goiter (Graves’ disease)- most common in young people• Toxic adenoma (Plummers’ diesease)• Toxic mulitinodular goiter (MNG)• Subacute thyroiditis-Hyperthyroid phase• Hyperthyroid phase of Hashimotos’ thyroiditis• (“Hashitoxicosis)• Factitious hyperthyroidism• Rare causes: -TSHoma
-Hydatidiform mole/choriocarcinoma- Multiplex pregnancy- Struma ovarii
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Graves’ diseaseGraves’ disease• Diffuse toxic goiterDiffuse toxic goiter
• OpthalmopathyOpthalmopathy
• DermopathyDermopathy
•Acropathy Acropathy
(clubbing)(clubbing)Etiology: AutoimmuneAnti-TSH receptor antibodies (stimulating, blocking, neutral)Anti-thyroid antibodies expression of HLA-DR3 association with:
-diabetes mellitus-type 1 myasthenia gravis-Addison’s disease lupus- pernicious anemia
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• Epidemiology : incidence 0.3-1.5/1000
• Female: Male 5:1
• Most Common cause of hyperthyroidism
Graves’ diseaseGraves’ disease
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Thyroid and pituitary function in Thyroid and pituitary function in Graves’ diseaseGraves’ disease
TT44, , TT33 TSHTSH(+)(+) (-)(-)
(+)(+)
Thyroid Stimulating Thyroid Stimulating Immunoglobulins (TSI)Immunoglobulins (TSI)
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Graves’ disease- Graves’ disease- Clinical featuresClinical features
Symptoms:
Fatigue palpitationsWeight lossHeat intoleranceFrequent bowel movementsSweatinghyperkinesia
Signs:
TachycardiaMuscle wasting pulse pressureEye signsDiffuse goiterLymphadenopathySplenomegalyHyperreflexia
In the elderly: cardiovascular symptoms, myopathy
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Graves’ Disease- GoiterGraves’ Disease- Goiter
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Graves disease- Graves disease- OpthalmopathyOpthalmopathy
Extrathyroidal TSHR is present in retro-orbital adipocytes, muscle cells and fibroblasts
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Grave’s Opthalmopathy
• Class 0 — No symptoms or signs • Class I — Only signs, no symptoms (eg, lid
retraction, stare, lid lag) • Class II — Soft tissue involvement • Class III — Proptosis • Class IV — Extraocular muscle involvement • Class V — Corneal involvement • Class VI — Sight loss (optic nerve involvement)
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Graves’ disease dermopathyGraves’ disease dermopathy
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Graves disease- diagnosisGraves disease- diagnosis
• Clinical hyperthyroidism
• Biochemistry: FT4, TT3 , TSHcholesterol
• Serology: anti-TSH receptor antibodiesanti-thyroid antibodies
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Graves’ disease- therapyGraves’ disease- therapy1. Antithyroid drugs:
Thionamides- Propylthiouracil (PTU)Propylthiouracil (PTU)Methimazole (MMI)Methimazole (MMI)-blockers
3. Definitive therapy:131I- side effects:
hypothyroidism
Surgery- subtotal thyroidectomy
side effects: anesthesia morbidityhypoparathyroidismrecurrent laryngeal nerve damagehypothyroidism
Treat for 12 monthsTreat for 12 months
~30%remissionremission70%
RecurrenceOr non-remission
Follow-upFollow-up
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Anti-thyroid thionamide drugsAnti-thyroid thionamide drugs
PTU (propylthiouracil) MMI (methimazole)
Dosage: TID Once daily
Effect: T4, T3 synthesis T4, T3 synthesis
inhibits T4→T3(high dose) (slow)
Agranulocytosis*: Non-dose dependent Dose dependent
(> 40 mg/day)
> 40 yrs
Pregnancy: placental transfer placental
transfer
aplasia cutis
*occurrence 0.3-0.6%
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Treatment of Graves' Orbitopathy
• Treatment of patients with Graves' orbitopathy has three components:
• Reversal of hyperthyroidism, if present • Symptomatic treatment • Treatment with a glucocorticoid, orbital irradiation,
orbital decompression surgery to reduce inflammation in the periorbital tissues
• Anti thyroid drugs and thyroidectomy are safe; Radioactive iodine may worsen the situation.
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The effect of high- dose PTUThe effect of high- dose PTU
0 1 2 3 4 5 620
25
30
35
40
45
50 FT4
FT3
012345678910
Days
12001200 600600PTU dose mg/day:
Upper limit of normal
Normalrange
140
120
100
80
Pulse rate:
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Subacute thyroiditisSubacute thyroiditis
Etiology: (Post) viral inflammation of thyroid
Symptoms & signs: HyperthyroidismPainful swelling of thyroidPain irradiation to earFeverSometimes “silent”
Laboratory: ESR acute phase reactants (CRP)
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Subacute thyroiditis- therapySubacute thyroiditis- therapy
A self limited disease
Therapy depends on symptoms/signs
Non-steroid anti-inflammatory agents (NSAIDS)
-blockers
Corticosteroids
Outcome - in 6 months 90% euthytroid
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Hypothyroidism- classificationHypothyroidism- classification
1. Hashimoto’s thyroiditis2. Post 131I therapy for Grave’s disease3. Post thyroidectomy4. Excessive I intake (amiodarone-procor)
Primary - TSH↑
Secondary TSH ↓ or normal:Hypopituitarism due to adenoma, destructive lesion, ablationTSH↓
Tertiary:Hypothalamic dysfunction (rare)
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Hypothyroidism- Hypothyroidism- clinical featuresclinical features
Symptoms:
Fatigue WeaknessWeight gainCold intoleranceConstipationCrampsParesthesias (carpal tunnel)
Signs:
Coarse featuresBradycardiaMyxedemaAnemia
Laboratory: serum thyroid hormones, cholesterolanemia (iron def., megaloblastic)
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HypothyroidismHypothyroidism
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Hypothyroidism- myxedemaHypothyroidism- myxedema
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Hypothyroidism-Hypothyroidism- differential diagnosis differential diagnosis
Serum FT4 andTSH
FT4, TSH
Primary hypothyroidism
FT4, TSH normal/low
Secondary hypothyroidism
TRH test
Excessive response
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Hypothyroidism- therapyHypothyroidism- therapy
• Levothyroxine 0.05-0.3 mg/day
• Combined L-T4 and L-T3 may be beneficial with
respect to well-being
• In elderly patients (at high risk for CVD),
“go low, go slow”
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Hypothyroidism- treatmentHypothyroidism- treatment
Before After
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Thyroid Storm and Myxedema Coma – rare endocrine emergencies
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THYROID STORM
Clinical setting
History of Graves’ disease and discontinuation of medications/
previously undiagnosed hyperthyroidism.
Acute onset of hyperpyrexia (over 40 ˚C)
Sweating
Marked tachycardia, often with atrial fibrillation
Nausea, vomiting, diarrhea
Agitation, tremulousness, delirium
Occasionally “apathetic” – without restlessness and agitation, but with
weakness, confusion, and cardio-vascular dysfunction.
Acute life threatening exacerbation of thyrotoxicosis
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THYROID STORMDIAGNOSIS:
Largely based on the clinical findings and clinical suspicion.
Elevated serum FT4, FT3.
Low TSH
MANAGEMENT
1. Supportive care
Fluids, Oxygen, Cooling blanket,cetaminophen
2. Specific measuresPropranolol, 40-80 mg every 6 hours.Antithyroid drugs – PTU. Glucocorticoids - Dexamethasone, 2 mg every 6 hours (due to reduction in glucocorticoids half life)
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Myxedema ComaMyxedema ComaExtreme hypothyroidism:
• Coma• Hypothermia• Hypoventilation• Hypoglycemia• Hyponatremia• Bradycardia
Laboratory: FT4 , FT3, TSHCo2 retention
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Myxedema Coma- therapyMyxedema Coma- therapy
Treat:
Ventilation
Precipitating factors
T4 or T3 I.V.Corticosteroids-50-100mg hydrocortisoneevery 8 hours
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Subclinical Hypothyroidism
TSH FT4 AND FT3 NORMAL
Biochemical definition
WHEN TO TREAT?WHEN TSH > 10AND WHAT ABOUT 4.5<TSH<10????
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TSH 4.5-10
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Subclinical hyperthyroidism• TSH below lower limit of normal (<0.3)
• Free T3 & Free T4 – normal
• Make sure not over treatment of hypothyroidism
• Associated with increased risk of atrial fibrillation in subjects > age 60 and accelerated bone loss in postmenopausal women
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Always repeat the test
before initiating
therapy!
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Amiodarone (Procor)-induced thyroid dysfunction
• Each Procor tablet (200 mg) has 75 mg Iodine• Procor can cause: hypothyroidism- does not require discontinue the
medication (thyroxine can be added)Hyperthyroidism- anti thyroid drugs have limited
efficacy; radioactive iodine doesn’t workThyroiditis- may require steroids
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