hyperthyroidism by dr. sarma

HYPERTHYROIDISMHYPERTHYROIDISMA Practical Approach to Dx. and Rx.A Practical Approach to Dx. and Rx.

Dr. R.V.S.N.Sarma., Dr. R.V.S.N.Sarma., M.D., M.Sc., M.D., M.Sc., (Canada)(Canada)

Consultant Physician and Chest Consultant Physician and Chest SpecialistSpecialist

www.drsarma.in

www.drsarma.inwww.drsarma.in

Clinical Exam. of ThyroidClinical Exam. of Thyroid

Have patient seated on a stool / chair Inspect neck before & after swallowing Examine with neck in relaxed position Palpate from behind the patient Remember the rule of finger tips Use the tips of fingers for palpation Palpate firmly down to trachea Pemberton’s sign for RSG

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

Clinical Anatomy of ThyroidClinical Anatomy of Thyroid

Clinical Exam of ThyroidClinical Exam of Thyroid

ThyromegalyThyromegaly

HyperthyroidismHyperthyroidism

A hyper metabolic biochemical stateA hyper metabolic biochemical state It is a multi system disease withIt is a multi system disease with Elevated levels of FTElevated levels of FT44 or FT or FT33 or both or both What is thyrotoxicosis ?What is thyrotoxicosis ? What is hyperthyroidism ?What is hyperthyroidism ? What are the various causes ?What are the various causes ? How to differentiate the causes ?How to differentiate the causes ? What is the appropriate treatment ?What is the appropriate treatment ?

Causes of HyperthyroidismCauses of Hyperthyroidism

1.1. Graves Disease – Diffuse Toxic GoiterGraves Disease – Diffuse Toxic Goiter

2.2. Plummer’s Disease – Toxic MNGPlummer’s Disease – Toxic MNG

3.3. Toxic phase of Sub Acute Thyroiditis - SATToxic phase of Sub Acute Thyroiditis - SAT

4.4. Toxic Single Adenoma – STAToxic Single Adenoma – STA

5.5. Pituitary Tumours – excess TSHPituitary Tumours – excess TSH

6.6. Molar pregnancy & Choriocarcinoma (↑↑ Molar pregnancy & Choriocarcinoma (↑↑ ββHCG)HCG)

7.7. Metastatic thyroid cancers (functioning)Metastatic thyroid cancers (functioning)

8.8. Struma Ovarii (Dermoid and Ovarian tumours)Struma Ovarii (Dermoid and Ovarian tumours)

9.9. Thyrotoxicosis Factitia ; INF, Amiodarone, SSRIsThyrotoxicosis Factitia ; INF, Amiodarone, SSRIs

Graves DiseaseGraves Disease

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

Thyroid Stimulating Immunoglobulin (TSI) or TSAThyroid Stimulating Immunoglobulin (TSI) or TSA TSI acts as proxy to TSH and stimulates TTSI acts as proxy to TSH and stimulates T44 and T and T33

• Anti thyro peroxidase (anti-TPO) antibodies Anti thyro peroxidase (anti-TPO) antibodies • Anti thyro globulin (anti-TG) Anti Microsomal and other Anti thyro globulin (anti-TG) Anti Microsomal and other • Autoimmune diseases - Pernicious Anemia, T1DM Autoimmune diseases - Pernicious Anemia, T1DM • RA, Myasthenia Gravis, Vitiligo, Adrenal insufficiency. RA, Myasthenia Gravis, Vitiligo, Adrenal insufficiency.

I 123 or TC 99m Normal v/s Graves

Toxic Multinodular Goiter Toxic Multinodular Goiter (TMG)(TMG)

TMG is the next most common hyperthyroidism - 20% TMG is the next most common hyperthyroidism - 20% More common in elderly individuals – long standing goiterMore common in elderly individuals – long standing goiter Lumpy bumpy thyroid glandLumpy bumpy thyroid gland Milder manifestations (apathetic hyperthyroidism)Milder manifestations (apathetic hyperthyroidism) Mild elevation of FTMild elevation of FT44 and FT and FT33

Progresses slowly over timeProgresses slowly over time Clinically multiple firm nodules (called Plummer’s disease)Clinically multiple firm nodules (called Plummer’s disease) Scintigraphy shows - hot and normal areasScintigraphy shows - hot and normal areas

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

SAT is the next most common hyperthyroidism – 15%SAT is the next most common hyperthyroidism – 15%

TT4 4 and Tand T33 are extremely elevated in this condition are extremely elevated in this condition

Immune destruction of thyroid due to viral infectionImmune destruction of thyroid due to viral infection Destructive release of preformed thyroid hormoneDestructive release of preformed thyroid hormone Thyroid gland is Thyroid gland is painful painful and and tender tender on palpationon palpation

Nuclear Scintigraphy scan - no RIU in the glandNuclear Scintigraphy scan - no RIU in the gland Treatment is NSAIDs and CorticosteroidsTreatment is NSAIDs and Corticosteroids

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

TSA is a single hyper functioning follicular thyroid adenoma.TSA is a single hyper functioning follicular thyroid adenoma.

Benign monoclonal tumor that usually is larger than 2.5 cmBenign monoclonal tumor that usually is larger than 2.5 cm

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

Nuclear Scintigraphy scan shows only a single hot noduleNuclear Scintigraphy scan shows only a single hot nodule

TSH is suppressed by excess of thyroxines TSH is suppressed by excess of thyroxines

So the rest of the thyroid gland is suppressedSo the rest of the thyroid gland is suppressed

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

Nucleotide Scintigraphy

Age and SexAge and Sex

AgeAge Graves diseaseGraves disease 20 to 40 20 to 40 Toxic MNGToxic MNG > 50 yrs > 50 yrs Toxic Single AdenomaToxic Single Adenoma 35 to 50 35 to 50 Sub Acute ThyroiditisSub Acute Thyroiditis Any age Any age

Sex M : F ratioSex M : F ratio Graves DiseaseGraves Disease 1: 5 to 1:10 1: 5 to 1:10 Toxic MNGToxic MNG 1: 2 to 1: 4 1: 2 to 1: 4

Nucleotide ScintigraphyNucleotide Scintigraphy

Clinical FeaturesClinical Features

1.1. Those that occur with any type of thyrotoxicosisThose that occur with any type of thyrotoxicosis

2.2. Those that are specific to Graves diseaseThose that are specific to Graves disease

3.3. Non specific changes of hyper metabolismNon specific changes of hyper metabolism

Common SymptomsCommon Symptoms

1.1. NervousnessNervousness2.2. AnxietyAnxiety3.3. Increased perspirationIncreased perspiration4.4. Heat intoleranceHeat intolerance5.5. TremorTremor6.6. HyperactivityHyperactivity7.7. PalpitationsPalpitations8.8. Weight loss despite increased appetiteWeight loss despite increased appetite9.9. Reduction in menstrual flow or oligo-menorrhea Reduction in menstrual flow or oligo-menorrhea

Common SignsCommon Signs

1.1. Hyperactivity, Hyper kinesisHyperactivity, Hyper kinesis

2.2. Sinus tachycardia or atrial arrhythmia, AF, CHFSinus tachycardia or atrial arrhythmia, AF, CHF

3.3. Systolic hypertension, wide pulse pressureSystolic hypertension, wide pulse pressure

4.4. Warm, moist, soft and smooth skin- warm handshakeWarm, moist, soft and smooth skin- warm handshake

5.5. Excessive perspiration, palmar erythema, OnycholysisExcessive perspiration, palmar erythema, Onycholysis

6.6. Lid lag and stare (sympathetic over activity)Lid lag and stare (sympathetic over activity)

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

8.8. Large muscle weakness, Diarrhea, GynecomastiaLarge muscle weakness, Diarrhea, Gynecomastia

Specific to Graves DiseaseSpecific to Graves Disease

1.1. Diffuse Diffuse painlesspainless and firm enlargement of thyroid gland and firm enlargement of thyroid gland

2.2. Thyroid bruit is audible with the bell of stethoscopeThyroid bruit is audible with the bell of stethoscope

3.3. Ophthalmopathy – Eye manifestations – 50% of casesOphthalmopathy – Eye manifestations – 50% of cases Sand in eyes, periorbital edema, conjunctival edema Sand in eyes, periorbital edema, conjunctival edema

(chemosis), poor lid closure, extraocular muscle dysfunction, (chemosis), poor lid closure, extraocular muscle dysfunction, diplopia, pain on eye movements and proptosis.diplopia, pain on eye movements and proptosis.

4.4. Dermoacropathy – Skin/limb manifestations – 20% of casesDermoacropathy – Skin/limb manifestations – 20% of cases Deposition of glycosamino glycans in the dermis of the lower Deposition of glycosamino glycans in the dermis of the lower

leg – non pitting edema, associated with erythema and leg – non pitting edema, associated with erythema and thickening of the skin, without pain or pruritus - called thickening of the skin, without pain or pruritus - called (pre tibial myxedema)(pre tibial myxedema)

Clinical PresentationsClinical Presentations

MNG and GravesMNG and Graves

Huge Toxic MNG Diffuse Graves Thyroid

Higher grades of GoiterHigher grades of Goiter

Toxic MNG (Diffuse) Graves

Grade IV Toxic MNGGrade IV Toxic MNG

Huge Toxic MNG Huge Toxic MNG

Proptosis

Lid lag

Thyroid OphthalmopathyThyroid Ophthalmopathy

Ophthalmopathy in GravesOphthalmopathy in Graves

Periorbital edema and chemosis

Ophthalmopathy in GravesOphthalmopathy in Graves

Occular muscle palsy Laka Laka Laka

Severe ExophthalmiaSevere Exophthalmia

Thyroid DermopathyThyroid Dermopathy

Pink and skin coloured papules, plaques on the shin

Graves with AcropathyGraves with Acropathy

Graves Goiter Acropathy

Clubbing and

Osteoarthropathy

Thyroid AcropathyThyroid Acropathy

OnycholysisOnycholysis

Non specific changesNon specific changes

1.1. Hyperglycemia, GlycosuriaHyperglycemia, Glycosuria

2.2. Osteoporosis and hypercalcemiaOsteoporosis and hypercalcemia

3.3. ↓ ↓ LDL and Total CholesterolsLDL and Total Cholesterols

4.4. Atrial fibrillation, LVH, ↑ LV EFAtrial fibrillation, LVH, ↑ LV EF

5.5. Hyper dynamic circulatory stateHyper dynamic circulatory state

6.6. High output heart failureHigh output heart failure

7.7. H/o excess Iodine, amiodarone, contrast dyesH/o excess Iodine, amiodarone, contrast dyes

LOW NORMAL HIGH

THYROID STIMULATING HORMONE - TSH

4 PRIMARYHYPERTHYROID

Nine Square ApproachNine Square Approach

LOW NORMAL HIGH

THYROID STIMULATING HORMONE - TSH

Nine Square ApproachNine Square Approach

SUB CLINICALHYPERTHYROID

DiagnosisDiagnosis

1.1. Typical clinical presentationTypical clinical presentation

2.2. Markedly Markedly suppressed suppressed TSH (<0.05 µIU/mL) TSH (<0.05 µIU/mL)

3.3. ElevatedElevated FT FT44 and FT and FT33 (Markedly in Graves) (Markedly in Graves)

4.4. Thyroid antibodies – by Elisa – anti-TPO, TSIThyroid antibodies – by Elisa – anti-TPO, TSI

5.5. ECG to demonstrate cardiac manifestationsECG to demonstrate cardiac manifestations

6.6. Nuclear Scintigraphy to differentiate the causesNuclear Scintigraphy to differentiate the causes

Algorithm for HyperthyroidismAlgorithm for Hyperthyroidism

Measure TSH and FT4

TSH, FT4

Measure FT3Primary (T4)

Thyrotoxicosis

Pituitary Adenoma FNAC, N Scan

Normal

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

T3 Toxicosis

Sub-clinical Hyper

Features of Grave’s

Rx. Grave’s

Single Adenoma, MNG

Low RAIU RAIU

Sub Acute Thyroiditis, I2, ↑ Thyroxine

F/u in 6-12 wks

Treatment OptionsTreatment Options

1.1. Symptom relief medicationsSymptom relief medications

2.2. Anti Thyroid Drugs – ATDAnti Thyroid Drugs – ATD Methimazole, CarbimazoleMethimazole, Carbimazole Propylthiouracil (PTU)Propylthiouracil (PTU)

3.3. Radio Active Iodine treatment – RAI Rx.Radio Active Iodine treatment – RAI Rx.

4.4. Thyroidectomy – Subtotal or TotalThyroidectomy – Subtotal or Total

5.5. NSAIDs and Corticosteroids – for SATNSAIDs and Corticosteroids – for SAT

Symptom ReliefSymptom Relief

1.1. Rehydration is the first stepRehydration is the first step

2.2. ββ – blockers to decrease the sympathetic excess – blockers to decrease the sympathetic excess Propranalol, Atenelol, MetoprololPropranalol, Atenelol, Metoprolol

3.3. Rate limiting CCBs if Rate limiting CCBs if ββ – blockers contraindicated – blockers contraindicated

4.4. Treatment of CHF, ArrhythmiasTreatment of CHF, Arrhythmias

5.5. Calcium supplementationCalcium supplementation

6.6. SSKI or Lugol solution for ↓ vascularity of the glandSSKI or Lugol solution for ↓ vascularity of the gland

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

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

Reduction of thyroid hormones takes 2-8 weeksReduction of thyroid hormones takes 2-8 weeks Check TSH and FTCheck TSH and FT44 every 4 to 6 weeks every 4 to 6 weeks

In Graves, many go into remission after 12-18 monthsIn Graves, many go into remission after 12-18 months In such pts ATD may be discontinued and followed upIn such pts ATD may be discontinued and followed up 40% experience recurrence in 1 yr. Re treat for 3 yrs.40% experience recurrence in 1 yr. Re treat for 3 yrs. Treatment is not life long. Graves Treatment is not life long. Graves seldom needsseldom needs surgery surgery MNG and Toxic Adenoma will not get cured by ATD. MNG and Toxic Adenoma will not get cured by ATD. For them ATD is not the best. Treat with RAI.For them ATD is not the best. Treat with RAI.

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

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

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

II123123 is used for Nuclear Scintigraphy (Dx.) is used for Nuclear Scintigraphy (Dx.) II131131 is given for RAI Rx. (6 to 8 milliCuries) is given for RAI Rx. (6 to 8 milliCuries) Goal is to make the patient hypothyroidGoal is to make the patient hypothyroid No effects such as Thyroid Ca or other malignanciesNo effects such as Thyroid Ca or other malignancies Never given for children and pregnant/ lactating womenNever given for children and pregnant/ lactating women Not recommended with patients of severe OphthalmopathyNot recommended with patients of severe Ophthalmopathy Not advisable in chronic smokersNot advisable in chronic smokers

Surgical TreatmentSurgical Treatment Subtotal Thyroidectomy, Total ThyroidectomySubtotal Thyroidectomy, Total Thyroidectomy Hemi Thyroidectomy with contra-lateral subtotal Hemi Thyroidectomy with contra-lateral subtotal ATD and RAI Rx are very efficacious and easy – soATD and RAI Rx are very efficacious and easy – so Surgical treatment is Surgical treatment is reservedreserved for MNG with for MNG with

1.1. Severe hyperthyroidism in childrenSevere hyperthyroidism in children

2.2. Pregnant women who can’t tolerate ATD Pregnant women who can’t tolerate ATD

3.3. Large goiters with severe OphthalmopathyLarge goiters with severe Ophthalmopathy

4.4. Large MNGs with pressure symptomsLarge MNGs with pressure symptoms

5.5. Who require quick normalization of thyroid functionWho require quick normalization of thyroid function

Preoperative PreparationPreoperative Preparation

ATD to reduce hyper function before surgeryATD to reduce hyper function before surgery ββeta blockers to titrate pulse rate to 80/mineta blockers to titrate pulse rate to 80/min SSKI 1 to 2 drops bid for 14 days SSKI 1 to 2 drops bid for 14 days This will reduce thyroid blood flowThis will reduce thyroid blood flow And there by reduce per operative bleedingAnd there by reduce per operative bleeding Recurrent laryngeal nerve damageRecurrent laryngeal nerve damage Hypo parathyroidism are complicationsHypo parathyroidism are complications

Dietary Advice Dietary Advice

Avoid Iodized salt, Sea foodsAvoid Iodized salt, Sea foods Excess amounts of iodide in someExcess amounts of iodide in some

Expectorants, x-ray contrast dyes, Expectorants, x-ray contrast dyes, Seaweed tablets, and health food Seaweed tablets, and health food

supplementssupplements These should be avoided becauseThese should be avoided because The iodide interferes with or complicates the The iodide interferes with or complicates the

management of both ATD and RAI Rx.management of both ATD and RAI Rx.

Summary of Summary of HyperthyroidismHyperthyroidism

Hyperthyroidism Age % Enlarged Pain RAIU Treatment

Graves (TSI Ab

eye, dermo, bruit)20 - 40 60% Diffuse None ↑↑ ATD – 18 m

Toxic MNG > 50 20% Lumpy Pressure ↑ RAI, Surgery

Single Adenoma 35 - 50 5% Single None ± RAI, ATD

S Acute Thyroiditis

Any age 15% None Yes ↓↓ NSAID, Ster.

TSH is markedly low, FT4 is elevated

Thyrotoxicosis FactitiaThyrotoxicosis Factitia

Excessive intake of Thyroxine causing thyrotoxicosis Excessive intake of Thyroxine causing thyrotoxicosis Patients usually deny – it is willful ingestion Patients usually deny – it is willful ingestion This primarily psychiatric disorder This primarily psychiatric disorder May lead to wrong diagnosis and wrong treatment May lead to wrong diagnosis and wrong treatment They are clinically thyrotoxic without eye signs of Graves They are clinically thyrotoxic without eye signs of Graves High doses of Thyroxine lead to TSH suppressionHigh doses of Thyroxine lead to TSH suppression This causes shrinkage of the thyroidThis causes shrinkage of the thyroid Stop Thyroxine and give symptom relief drugsStop Thyroxine and give symptom relief drugs

Algorithm for Thyroid Algorithm for Thyroid NoduleNodule

Thyroid Nodule

Low TSH Normal TSH

TC 99 Nuclear Scan

FNAC or US guided biopsyHot Nodule Cold Nodule

RAI Ablation, Surgery or ATD

Non diagnostic – repeat FNAC

Surgery or Cytology

CystBenign

T4 suppression

Suspicious or follicular Ca

Malignant

Surgery

4% 10% 69% 17%

Case # 1Case # 1

A patient complains of “sandy” sensation in his eyes,weight loss, and a tremor. His extraocular muscles are inflammed. His thyroid is diffusely enlarged and non tender.

The most likely diagnosis is

a. Iodine deficiency

b. Sub-acute thyroiditis

c. Multinodular goiter

d. Graves’ disease

e. Silent thyroiditis

Case # 2Case # 2 A 55 year old woman is anxious, irritable, frequent semi

solid stools and she reports weight loss of 5 kgs in the past six months. She was having a lumpy bumpy painless swelling in her neck for past 20 years.

The most likely diagnosis isa. Iodine deficiency goiterb. Sub-acute thyroiditisc. Multinodular goiterd. Graves’ diseasee. Solitary toxic adenoma

Case # 3Case # 3 A 60 year patient from a mountain region complains of

constipation. He has a heart rate of 60, dry thick skin,

and a tongue that has scalloped edges from teeth

indentation. He has a goiter.

The most likely diagnosis is

a. Iodine deficiency

b. Subacute thyroiditis

c. Graves’ disease

d. Silent thyroiditis

Case # 4Case # 4 A 25 year old woman is three months pregnant. She has

a large goiter. Her exam is otherwise normal. Her thyroid tests are normal.

You recommend

a. Cassava five times weekly

b. Fish three times weekly

c. Formula milk for the baby when it is born

d. A very low salt diet

Case # 5Case # 5 A 72 year old man complains of tremor and inability to

concentrate. On exam, he has a heart rate of 100 beatsper minute. He has a large goiter with many nodules. Hehas a fine tremor. His serum T4 is very high and TSH isvery low.Treatments that are likely to improve his symptoms are

a. Iodine therapyb. Ethanol injection of his thyroid (PEI)c. 6 weeks of Methimazoled. Radio Active Iodine therapy

Case # 6Case # 6

In Nuclear Scintigraphy Scan I123 uptake is very high in

the thyroid of patients with

a. Silent thyroiditis

b. Single functional adenoma

c. Sub-acute thyroiditis

d. Acute ingestion of animal thyroid extract

e. Graves’ disease

Let us start applyingLet us start applying

hyperthyroidism by dr. sarma

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