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CHAIRPERSON:DR.ARDAMAN SINGH

SPEAKER:DR.MANISH VINAYAK

APPROACHAPPROACH

Where to look for thyroid? How to examine thyroid? What are the normal steps in thyroid hormogenesis? What is thyrotoxicosis ? What is hyperthyroidism ? What are the various causes ? What test should we order? How to differentiate the causes ? What is the appropriate treatment ?

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Where to look for Thyroid ?Where to look for Thyroid ?

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Clinical Anatomy of ThyroidClinical Anatomy of Thyroid

How to examine Thyroid?How to examine Thyroid?

There is no consensus regarding which is the best way to examine thyroid.

Examination from front begins with examiner identifying the cricoid cartilage and then identifies the isthmus directly below this. Then left lobe is palpated with right hand, lateral to trachea and medial to sternocleidomastoid muscle. Similarly repeated on the other side.

Examination from back consists of simultaneously using fingers of both hands with neck in relaxed position.

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Clinical Exam of ThyroidClinical Exam of Thyroid

PSEUDOGOITRE: Apparent thyroidal enlargement when no true goiter is present, in thin patient when gland is located higher in neck, overlying the thyroid cartilage.

MODIGLIANI SYNDROME: Denotes illusion of goitre, seen when patient with long,curved necks have exaggerated cervical spine lordosis.

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WHO Classification of GoitreWHO Classification of Goitre

GRADE 0: No goitre presence is found.GRADE 1: Neck thickening not visible in the

normal position, however palpable.GRADE 2: Neck swelling visible when neck is

in normal position.

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Thyroid Regulation

PLASMA T4 + FT4

HYPOTHALAMUS - TRH

ANT. PITUITARY - TSH

THYROID T4 and T3

PLASMA T3 + FT3

TISSUES FT4 to FT3, rT3

TSH -R

Thyrotoxicosis/HyperthyroidismThyrotoxicosis/Hyperthyroidism

THYROTOXICOSIS refers to clinical syndrome of hypermetabolism and hyperactivity those results from excessive thyroid hormones.

HYPERTHYROIDISM denotes sustained increase in thyroid hormones biosynthesis and secretion by thyroid gland.

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While many patients with thyrotoxicosis have hyperthyroidism, it is not so in others such as- those in whom it is caused by thyroiditis or exogenous thyroid hormone administration.

Causes of thyrotoxicosis??Causes of thyrotoxicosis??

Primary Thyrotoxicosis Secondary

hyperthyoridism without hyperthyroidism hyperthyroidism

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Primary HyperthyroidismPrimary Hyperthyroidism

Graves disease (m.c cause) Toxic multinodular goitre Toxic adenoma Functioning thyroid metastasis Struma ovarii Activating mutation of TSH receptor Activating mutation of Gsa (McCune-Albright

syndrome) Drugs: iodine excess (Jod-Basedow phenomenon)

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Thryotoxicosis without Thryotoxicosis without hyperthyroidismhyperthyroidism

Subacute thyroiditisSilent thyroiditisThyrotoxicosis factitiaThyroid destruction: use of amiodarone,

lithium, interferon-alpha & beta, interleukin-2, radiation & infarction of adenoma

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Secondary hyperthyroidismSecondary hyperthyroidism

TSH-secreting pituitary adenoma Thyroid hormone resistance syndrome Chronic gonadotropin secreting tumors Gestational thyrotoxicosis. Testicular malignancies.

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Graves DiseaseGraves Disease The most common cause of thyrotoxicosis (50-60%). Organ specific auto-immune disease The most important autoantibody is

– Thyroid Stimulating Immunoglobulin (TSI) or TSA

– TSI acts as proxy to TSH and stimulates T4 and T3

Anti thyro peroxidase (anti-TPO) antibodies Anti thyro globulin (anti-TG) Autoimmune diseases - Pernicious Anemia, T1DM, RA,

Myasthenia Gravis, Vitiligo, Adrenal insufficiency. In long term, spontaneous hypothyroidism can develop in up to

15% of patients.17

Toxic Multinodular Goiter (TMG)Toxic Multinodular Goiter (TMG) TMG is the next most common hyperthyroidism -

20% More common in elderly individuals – long standing

goiter Mild elevation of FT4 and FT3

Progresses slowly over time Clinically multiple firm nodules (called Plummer’s

disease) Scintigraphy shows - hot and normal areas

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MNG and GravesMNG and Graves

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Huge Toxic MNG Diffuse Graves Thyroid

Sub Acute Thyroiditis (SAT)Sub Acute Thyroiditis (SAT)

Also called as De-Quervain Thyroiditis.

SAT is the next most common hyperthyroidism – 15%

T4 and T3 are extremely elevated in this condition

Immune destruction of thyroid due to viral infection

Destructive release of preformed thyroid hormone

Thyroid gland is painful and tender on palpation

Nuclear Scintigraphy scan - no RIU in the gland Hyperthyroidism (3-6 weeks) is followed by transient hypothyroid

phase(4-6 months) If the gland is non-tender, called as silent thyroiditis Disease is self limiting with 95% remission rate.

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Toxic Single Adenoma (TSA)Toxic Single Adenoma (TSA)

TSA is a single hyper functioning follicular thyroid adenoma.

Benign monoclonal tumor that usually is larger than 2.5 cm

It is the cause in 5% of patients who are thyrotoxic

Nuclear Scintigraphy scan shows only a single hot nodule

TSH is suppressed by excess of thyroxines

So the rest of the thyroid gland is suppressed

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Thyrotoxicosis FactitiaThyrotoxicosis Factitia

Excessive intake of Thyroxine causing thyrotoxicosis Patients usually deny – it is willful ingestion This is a primarily psychiatric disorder May lead to wrong diagnosis and wrong treatment They are clinically thyrotoxic without eye signs of Graves High doses of Thyroxine lead to TSH suppression This causes shrinkage of the thyroid, so impalpable thyroid gland Stop Thyroxine and give symptom relief drugs Epidemic of thyrotoxicosis has been caused by consumption of

ground beef contaminated with bovine thyroid gland.

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Hashimoto thyroiditisHashimoto thyroiditis

It may cause transient hyperthyroidism during the initial destructive phase.

Occurs due to release of stored thyroid hormone.

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Amiodarone Induced Amiodarone Induced Thyrotoxicosis (AIT)Thyrotoxicosis (AIT)

Drug resembles T4 and contains 37% of iodine by weight.

23% of patients receiving amiodarone can develop AIT.

It can occur 4 months to 3 yrs after initiation of amiodarone and may develop many months after amiodarone has been discontinued.

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Type 1 AITType 1 AIT

Type 1 AIT is caused by active elaboration of excessive thyroid hormone and may occur by either of two mechanisms:

1. Free iodine may cause toxic MNG in iodine deficient individuals with preexisting autonomous thyroid nodules (Jod-Basedow phenomenon)

2. Free iodine can trigger immunologic attack on thyroid causing Grave`s disease commonly with diffuse thyroid enlargement and anti TPO Ab`s.

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Type 2 AITType 2 AIT

It is destructive thyroiditis with release of preformed thyroid hormone. Hyperthyroidism can last for 1-3 months and may be followed by hypothyroidism.

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Clinical FeaturesClinical Features

1. Those that occur with any type of thyrotoxicosis

2. Those that are specific to Graves disease

In the elderly, features of thyrotoxicosis may be

subtle or masked, and patients may present with

fatigue and weight loss, known as APATHETIC

THYROTOXICOSIS. It can be mistaken for

depression in elderly.

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Common SymptomsCommon Symptoms

1. Nervousness, anxiety

2. Heat intolerance

3. Tremor

4. Hyperactivity

5. Palpitations

6. Weight loss despite increased appetite

7. Oligo-menorrhea, loss of libido

8. Diarrhea, polyuria

9. Fatigue and weakness28

Common SignsCommon Signs

1. Sinus tachycardia or PAC, AF, Thyrotoxic cardiomyopathy, ppt of CHF

2. Systolic hypertension, wide pulse pressure

3. Goitre

4. Warm, moist skin

5. Fine hair & Onycholysis

6. Fine tremor of out stretched hands – format's sign

7. Hyperreflexia, proximal myopathy, chorea

8. Hypokalemic periodic paralysis

9. Gynecomastia29

Common Eye SignsCommon Eye Signs

Dalrymple sign- Upper eyelid retractionVon Graefe sign- lid lag with downward gazeKocher sign- staring appearance

These signs can occur with thyrotoxicosis of any etiology

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Specific to Graves DiseaseSpecific to Graves Disease

1. Diffuse painless goitre with audible bruit.

2. Ophthalmopathy – Eye manifestations – 20-40% of cases Sense of sand in eyes, periorbital edema, conjunctival edema

(chemosis), proptosis , extraocular muscle dysfunction leading to diplopia

Weakness of upward gaze ( Stellwag sign ) Weakness of convergence ( Moebius sign ) Optic nerve compression leading to pappiledema, field defect

and permanent loss of vision

Eye changes are unilateral in 10% of cases.

Severity of eye disease does not correlate with severity of thyrotoxicosis. some cases are EUTHYROID.

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REMEMBER, diplopia in Grave disease can be caused by exophthalmos or by coexistent ocular myasthenia gravis, which is usually mild, often with selective eye involvement.

AChR Ab levels are elevated in only 36% of such patients and thymoma is present in 9% only.

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Thyroid OphthalmopathyThyroid Ophthalmopathy

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Proptosis Staring appearance

Ophthalmopathy in GravesOphthalmopathy in Graves

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Graves DermopathyGraves Dermopathy

Deposition of glycosamino glycans in the dermis of the lower leg – non pitting edema, associated with erythema and thickening of the skin, without pain or pruritus - called as pre tibial myxedema

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Thyroid DermopathyThyroid Dermopathy

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Pink and skin coloured papules, plaques on the shin

Thyroid AcropachyThyroid Acropachy

Presents with clubbing & swelling of fingers and toes.

It is so strongly associated with thyroid dermopathy that an alternative cause of clubbing sholud be sought in Graves patient without coincident skin and orbital involvement.

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Thyroid AcropathyThyroid Acropathy

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Clubbing and Osteoarthropathy

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LOW NORMAL HIGH

THYROID STIMULATING HORMONE - TSH

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BASIC THYROID EVALUATION

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EUTHYROID

LOW NORMAL HIGH

THYROID STIMULATING HORMONE - TSH

BASIC THYROID EVALUATION

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LOW NORMAL HIGH

THYROID STIMULATING HORMONE - TSH

BASIC THYROID EVALUATION

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SECONDARYHYPERTHYROID

LOW NORMAL HIGH

THYROID STIMULATING HORMONE - TSH

BASIC THYROID EVALUATION

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SUB-CLINICALHYPERTHYROID

LOW NORMAL HIGH

THYROID STIMULATING HORMONE - TSH

BASIC THYROID EVALUATION

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THYROID HORMONES

TEST REFERENCE RANGE

TSH Normal Range 0.3 - 4.0 mU/L

Free T4 Normal Range 0.7-2.1 ng/dL

TSH upper limit will soon be revised to 2.5 mU/L

T3/T4 RATIOT3/T4 RATIO

Graves disease and toxic nodular goitre typically present with increased T3 production, with T3/T4 ratio greater than 20.

While thyrotoxicosis caused by thyroiditis, iodine exposure or exogenous levothyroxine intake, T4 is the predominant hormone and T3/T4 ratio is usually less than 20.

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Thyroid AntibodiesThyroid Antibodies

Anti thyroid peroxidase (TPO)Anti thyroglobulinTSH-R antibodiesTSH-R Ab are helpful in diagnosis & management

of grave`s disease.It also helps in prediction of post-partum grave`s

disease % neonatal thyrotoxicosis.Helps in identification of orbitopathy in absence of

features of thyrotoxicosis.47

Nucleotide Scintigraphy

CAUSE OF THYROTOXICOSIS

Grave`s disease Toxic nodular goitre (uni or

multinodular) Subacute thyroiditis Silent thyroiditis Iodine induced & factitious

thyrotoxicosis Struma ovarii Follicular carcinoma TSH induced thyrotoxicosis

PATTERN OF DISTRIBUTION

Homogenous Restricted to region of

autonomy No uptake No uptake No uptake

Uptake in ovary Uptake in tumour metastasis Homogenous

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Nucleotide ScintigraphyNucleotide Scintigraphy

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Algorithm for HyperthyroidismAlgorithm for Hyperthyroidism

Measure TSH and FT4

TSH, FT4

Measure FT3Primary (T4)

Thyrotoxicosis

High

Pituitary Adenoma FNAC, N Scan

Normal

TSH, FT4 N TSH, FT4 N TSH, FT4 N

T3 Toxicosis

Sub-clinical Hyper

Features of Grave’s

Yes

Rx. Grave’s

No

Single Adenoma, MNG

Low RAIU RAIU

Sub Acute Thyroiditis, I2, ↑ Thyroxine

F/u in 6-12 wks

Treatment OptionsTreatment Options

1. Symptom relief medications (β-blockers)

2. Anti Thyroid Drugs – ATD

Methimazole, Carbimazole

Propylthiouracil (PTU)

3. Other agents- iodine, potassium perchlorate, lithium, cholestyramine.

4. Radio Active Iodine treatment – RAI Rx.

5. Thyroidectomy – Subtotal or Total

6. NSAIDs and Corticosteroids – for SAT51

Anti Thyroid Drugs (ATD)Anti Thyroid Drugs (ATD)

Imp. considerationsImp. considerations Methimazole Methimazole PropylthiouracilPropylthiouracil

EfficacyEfficacy Very potentVery potent PotentPotent

Duration of actionDuration of action Long acting BID/ODLong acting BID/OD Short acting QID/TIDShort acting QID/TID

In pregnancyIn pregnancy ContraindicatedContraindicated Safely can be givenSafely can be given

Mechanism of actionMechanism of action Iodination, CouplingIodination, Coupling Iodination, CouplingIodination, Coupling

Conversion of TConversion of T44 to T to T33 No actionNo action Inhibits conversionInhibits conversion

Adverse reactionsAdverse reactions Rashes, NeutropeniaRashes, Neutropenia Rashes, ↑NeutropeniaRashes, ↑Neutropenia

DosageDosage 20 to 40 mg/ OD PO20 to 40 mg/ OD PO 100 to 150mg qid PO100 to 150mg qid PO

Adverse effects of ThionamidesAdverse effects of Thionamides

Abnormal taste, arthralgias, pruritis, urticariaAgranulocytosis- usually occurs in first three

months, related to dose of methimazole (>30mg/day) and not of PTU.

Routine assessment of blood counts has not been useful and is not recommended.

HepatitisVasculitis, SLE like syndrome

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ββ – Blocking Drugs – Blocking Drugs

Control cardiovascular and hyperadrenergic manifestations.

There is also rapid metabolism of propranolol in thyrotoxicosis hence larger doses are needed.

In addition to β blocking effect, propranolol in doses greater than 160mg/day decreases T3 generation by inhibiting 5-monodeiodinase enzyme.

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Role of IodineRole of Iodine

Iodine in high concentrations, blocks release of pre-stored hormone and dec iodide transport and oxidation called as WOLF-CHAIKOFF EFFECT.

But this effect is transient and within 1-2 weeks complete escape from inhibition occurs.

So while treating thyrotoxicosis with iodine, addition of thionamides is essential to prevent aggravation of symptoms with loss of Wolf-chaikoff effect.

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Potassium perchloratePotassium perchlorate

Inhibits iodine uptakeUsed orally in doses of 500mg twice daily.S/E include aplastic anaemia & nephritic

syndrome.Use of this agent is in initial stages for about 1

month with doses not greater than 1gm/day.Particularly useful in amiodarone induced

thyrotoxicosis.

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LithiumLithium

Inhibits coupling and also decreases thyroid hormone release.

Doses of 300 mg 8 hrly.Lithium toxicity has to be avoided by

monitoring serum levels and maintaining them below 1 mEq/L.

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CholestyramineCholestyramine

Decreases reabsorption of thyroid hormones from the enterohepatic circulation.

Used orally at rate of 4g four times daily, in combination with methimazole or PTU.

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How long to give ATD ?How long to give ATD ?

Reduction of thyroid hormones takes 2-8 weeks

Check TSH and FT4 every 4 to 6 weeks

In Graves, once patient is rendered euthyroid options include use of ATD for 12-18 weeks or definitive treatment with RAI or surgery.

After cessation of therapy, close follow up for 3-6 months is required to detect relapse.

40% experience recurrence in 1 yr. in such situation RAI or surgery has to be considered.

MNG and Toxic Adenoma will not get cured by ATD. For them ATD is not the best. Treat with RAI.

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Radio Active Iodine (RAI Rx.)Radio Active Iodine (RAI Rx.)

In women who are not pregnant In cases of Toxic MNG and TSA Graves disease not remitting with ATD RAI Rx is the best treatment of hyperthyroidism in adults The effect is less rapid than ATD or Thyroidectomy It is effective, safe, and does not require hospitalization. Given orally as a single dose in a capsule or liquid form. Very few adverse effects as no other tissue absorbs RAI

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Radio Active Iodine (RAI Rx.)Radio Active Iodine (RAI Rx.)

I123 is used for Nuclear Scintigraphy (Dx.)

I131 is given for RAI Rx. (6 to 8 milliCuries)

Goal is to make the patient hypothyroid

No effects such as Thyroid Ca or other malignancies

Never given for children and pregnant/ lactating women

Not recommended with patients of severe Ophthalmopathy

Not advisable in chronic smokers

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Surgical TreatmentSurgical Treatment

ATD and RAI Rx are very efficacious and easy – so Surgical treatment is reserved for MNG with

1. Severe hyperthyroidism in children

2. Pregnant women who can’t tolerate ATD

3. Large goiters with severe Ophthalmopathy

4. Large MNGs with pressure symptoms

5. Who require quick normalization of thyroid function

6. Suspicious of biopsy proven malignant nodules

7. Co-morbidity requiring surgery like hyperparathyroidism.

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Management of AITManagement of AIT

Colour flow doppler ultrasound may reveal hypervascularity in type 1 disease and in type 2 reduced blood flow might be apparent.

Drug should be discontinuedType 1 is treated with high doses of ATD with

addition of potassium perchlorate to prevent further uptake of iodine.

Type 2 responds to high dose corticosteroids (prednisolone 20-40 mg/day)

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Thyrotoxic Crisis/StormThyrotoxic Crisis/Storm

Ppt factors- infection, stress, thyroid surgery, radio iodine therapy, DKA, parturition, vigorous palpation of thyroid

Presents with fever, tachyarrhythmia, CCF psychosis, adrenocortical failure leading to hypotension, coma.

Treat dehydration and hyperpyrexia.Glucorticoids indicated.

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Excessive thyroid hormones can be treated with iodides, given as potassium iodide 15 mg 6 hrly orally or i.v

Alternatively iodinated X-Ray contrast media can be given to inhibit peripheral conversion of T4 to T3 in dosage of 1gm/day.

Use propranolol 80 mg 6hrly to counteract increased catecholamine activity.

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THANKS66