BENIGN DISEASES OF THE THYROID

Rivka Dresner Pollak M.D

Endocrinology.

Thyroid gland- anatomyThyroid gland- anatomy

Thyroid gland- anatomyThyroid gland- anatomy

sternocleidomastoidsternocleidomastoid

thyroidthyroid

esophagus

tracheatrachea

jugular v.

carotid a.carotid a.

strap musclesstrap muscles

vertebra

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

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

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

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

Regulation of Thyroid hormone secretionRegulation of Thyroid hormone secretion

Hypothalamus

TT44, T, T33

TSHTSH(-)(-) (+)(+)

TRHTRH(+)(+)(-)(-)

PituitaryPituitary

Thyroid

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

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

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

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

Normal thyroid scanNormal thyroid scan

““Hot nodule”Hot nodule”

““Cold” noduleCold” nodule

Multinodular goiter (MNG)Multinodular goiter (MNG)

Pertechnetate scanPertechnetate scan CHEST X-RAYCHEST X-RAY

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

Thyroid abnormalitiesThyroid abnormalities

FunctionFunctionStructureStructure

Hyperthyroidism Hypothyroidism

EtiologyEtiology

RRXX

ThyroiditisThyroiditisGoiterGoiter

NodularNodular Diffuse Diffuse

BenignBenign MalignantMalignant Function nl Function nl

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

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

• Epidemiology : incidence 0.3-1.5/1000

• Female: Male 5:1

• Most Common cause of hyperthyroidism

Graves’ diseaseGraves’ disease

Thyroid and pituitary function in Thyroid and pituitary function in Graves’ diseaseGraves’ disease

TT44, , TT33 TSHTSH(+)(+) (-)(-)

(+)(+)

Thyroid Stimulating Thyroid Stimulating Immunoglobulins (TSI)Immunoglobulins (TSI)

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

Graves’ Disease- GoiterGraves’ Disease- Goiter

Graves disease- Graves disease- OpthalmopathyOpthalmopathy

Extrathyroidal TSHR is present in retro-orbital adipocytes, muscle cells and fibroblasts

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)

Graves’ disease dermopathyGraves’ disease dermopathy

Graves disease- diagnosisGraves disease- diagnosis

• Clinical hyperthyroidism

• Biochemistry: FT4, TT3 , TSHcholesterol

• Serology: anti-TSH receptor antibodiesanti-thyroid antibodies

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

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%

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.

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:

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)

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

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)

Hypothyroidism- Hypothyroidism- clinical featuresclinical features

Symptoms:

Fatigue WeaknessWeight gainCold intoleranceConstipationCrampsParesthesias (carpal tunnel)

Signs:

Coarse featuresBradycardiaMyxedemaAnemia

Laboratory: serum thyroid hormones, cholesterolanemia (iron def., megaloblastic)

HypothyroidismHypothyroidism

Hypothyroidism- myxedemaHypothyroidism- myxedema

Hypothyroidism-Hypothyroidism- differential diagnosis differential diagnosis

Serum FT4 andTSH

FT4, TSH

Primary hypothyroidism

FT4, TSH normal/low

Secondary hypothyroidism

TRH test

Excessive response

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”

Hypothyroidism- treatmentHypothyroidism- treatment

Before After

Thyroid Storm and Myxedema Coma – rare endocrine emergencies

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

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)

Myxedema ComaMyxedema ComaExtreme hypothyroidism:

• Coma• Hypothermia• Hypoventilation• Hypoglycemia• Hyponatremia• Bradycardia

Laboratory: FT4 , FT3, TSHCo2 retention

Myxedema Coma- therapyMyxedema Coma- therapy

Treat:

Ventilation

Precipitating factors

T4 or T3 I.V.Corticosteroids-50-100mg hydrocortisoneevery 8 hours

Subclinical Hypothyroidism

TSH FT4 AND FT3 NORMAL

Biochemical definition

WHEN TO TREAT?WHEN TSH > 10AND WHAT ABOUT 4.5<TSH<10????

TSH 4.5-10

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

Always repeat the test

before initiating

therapy!

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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