HipertiroidismeDepartemen ilmu kesehatan THT-KL

M. Fahmy H070100185

Anatomy of thyroid gland

Hypothalamus-

Pituitary- Thyroid Axis

Fisiologi hormon tiroid

Thyrotoxicosis and HyperthyroidismDefinitions

Thyrotoxicosis◦The clinical syndrome of hypermetabolism that results when the serum concentrations of free T4, T3, or both are increased

Hyperthyroidism◦Sustained increases in thyroid hormone biosynthesis and secretion by the thyroid gland

The 2 terms are not synonymousBraverman LE, et al. Werner & Ingbar’s The Thyroid. A

Fundamental and Clinical Text. 8th ed. 2000.

Prevalence of Thyrotoxicosis

In a cross-sectional study of urban and rural adults, the prevalence of thyrotoxicosis ranged from ◦ 1.9% to 2.7% in women◦ 0.16% to 0.23% in men

Tunbridge WMG, et al. Clin Endocrinol. 1977;7:481-493.

Tabel : Penyebab tirotoksikosis 7,8,9

Hipertiroidisme Primer Tirotoksikosis tanpa

hipertiroidisme

Hipertiroidisme Sekunder

Penyakit Graves

Gondok multinodula

toksik

Adenoma toksik

Obat : yodium, lithium

Karsinoma tiroid yang

berfungsi

Struma ovary (ektopik)

Mutasi TSH-r

Hormon tiroid berlebih

(tirotoksikosis faktisia)

Tiroiditis subakut

Silent thyroiditis

Destruksi kelenjar :

amiodaron

I-131, radiasi, adenoma,

infark

TSH secreting tumor

chGH secreting tumor

Tirotoksikosis gestasi

Resistensi hormon

tiroid

Common Signs and Symptoms of Thyrotoxicosis

Symptoms Signs Nervousness Hyperactivity Fatigue Tachycardia Weakness Systolic hypertension Increased perspiration Warm, moist, or

smooth skin Heat intolerance Stare and eyelid

retraction Tremor Tremor Hyperactivity Hyperreflexia Palpitations Muscle weakness Appetite/weight changes Menstrual disturbancesBraverman LE, et al. Werner & Ingbar’s The Thyroid. A

Fundamental and Clinical Text. 8th ed. 2000.

SYSTEMIC EFFECTSRESPIRATORYDyspnea, panting,

hyperventilation respiratory muscle weakness increased tissue carbon dioxide levels +/- congestive heart failure

SYSTEMIC EFFECTSCARDIOVASCULAR

Thyrotoxic cardiomyopathy◦ Hypermetabolic state◦ Systemic hypertension◦ Direct T3 and T4 action on heart

muscle LV hypertrophy, IVS hypertrophy,

RA and aortic dilation, enhanced contractility

1. Graves’ Disease (Toxic Diffuse Goiter)

The most common cause of hyperthyroidism ◦ Accounts for 60% to 90% of cases◦ Incidence in the United States estimated at

0.02% to 0.4% of the population◦ Affects more females than males, especially in

the reproductive age rangeGraves disease is an autoimmune disorder

possibly related to a defect in immune tolerance

Graves Disease

Autoimmune disorder◦ Production of TSH receptor autoantibodies◦ Stimulate thyroid hormone overproduction

Characterized by the presence of B- and T-lymphocytes in thyroid tissue◦ TSH receptor activation◦ Thyroglobulin and thyroid peroxidase antibodies◦ Sodium/iodide cotransporter (NIS) activity

enhanced (increased RAI)◦ Autoantigens

Abbott Laboratories Diagnostics Division Web site. Available at: et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.

2. Toxic Multinodular Goiter

More common in places with lower iodine intake◦ Accounts for less than 5% of thyrotoxicosis

cases in iodine-sufficient areasEvolution from sporadic diffuse goiter to

toxic multinodular goiter is gradualThyrotropin receptor mutations and TSH

mutations have been found in some patients with toxic multinodular goiters

Surgery or 131I is recommended treatment

Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.

Toxic Multinodular Goiter

MNG is an enlarged thyroid gland containing multiple nodules◦ The thyroid gland becomes more nodular with

increasing age◦ In MNG, nodules typically vary in size◦ Most MNGs are asymptomatic

MNG may be toxic or nontoxic◦ Toxic MNG occurs when multiple sites of autonomous

nodule hyperfunction develop, resulting in thyrotoxicosis

◦ Toxic MNG is more common in the elderly

3. Toxic AdenomaAutonomously functioning thyroid

nodule hypersecreting T3 and T4 resulting in thyrotoxicosis (Plummer’s disease)

Almost never malignantManage with antithyroid drugs

followed by either I-131 or surgery

Laboratory Testing in Thyroid DiseaseTSH:

◦ Pituitary hormone which stimulates thyroid◦ May rise transiently in recovery from other

illnessFree T4:

◦ direct measure of thyroxine activity◦ May be transiently suppressed in severe

acute illnessFree T3: suspect hyperthyroid but normal

FT4Thyroid peroxidase/thyroperoxidase

antibody:◦ Anti-TPO◦ High levels in Hashimoto’s (95%) & Graves◦ TSH receptor stimulating Ab measures

activity in Graves-use in pregnancy

Typical Thyroid Hormone Levels in Thyroid Disease

TSH T4

T3

Hypothyroidism High Low Low

Hyperthyroidism Low High High

Subclinical Hypothyroidsm High normal normal

Subclinical Hyperthyroidsm Low normal normal

Scans/Ultrasound

Radioiodine uptake (RAIU)Thyroid ScanUltrasoundFine needle Aspiration

Treatment of Hyperthyroidism

1. Antithyroid drugs

2. Surgical resection

3. Radioactive iodine therapy

Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.

1. Antithyroid Drug Therapy

Acute hyperthyroid symptomsGoal of therapy:

◦Inhibit peripheral conversion of T4 to T3◦Inhibit synthesis and release of T4 and

T3 from thyroid glandPropylthiouracil (PTU)Methimazole [generic] or Tapazole®

Antithyroid Drug TherapyA. PTU:

◦Inhibits peripheral conversion of T4 to T3◦Inhibits thyroid hormone synthesis and

release from thyroid glandB. Methimazole [generic]:

◦Inhibits thyroid hormone synthesis and release from thyroid gland

C. Beta-blocker therapy:◦Ameliorates tachycardia, sweating,

tremor, nervousness◦Propanolol: starting dose 20-40 mg

PO q6h◦Caution in patients with CHF or

bronchospasm

2. Subtotal ThyroidectomySurgical complications:

◦Vocal cord paralysis (1%)◦Hypothyroidism (up to 43% after 10

years)◦Hypoparathyroidism◦Recurrence of hyperthyroidism (10-

15%)

3. Radioactive Iodine 131[I] AblationTreatment of choice in patients >

21 years old with Graves’ DiseaseTreatment of choice in patients <

21 years old without remission after antithyroid drug therapy

Treatment of choice in patients with toxic multinodular goiter or toxic thyroid adenoma

Radioactive Iodine Ablation (cont’)

Single dose of 131[I] orally80% euthyroid after single dose> 50% of patients will develop

hypothyroidism◦Assay TSH every 3 months after

therapy

Radioactive Iodine Ablation (Cont’)

Levothyroxine therapy when patient becomes hypothyroid

Life-long Levothyroxine therapyRIA contraindicated in

pregnancy, lactation, iodine allergy◦Screen pre-menopausal women for

pregnancy prior to treatment

Thyroid StormA life-threatening crisis .Estimated mortality : 20-30% . the result of thyroid surgery .Caused more often by

antecedent Grave’s disease .

Precipitants of Thyroid StormSurgery .Radioiodine therapy .Iodinated contrast dyes .Thyroid hormone ingestion .Diabetic Ketoacidosis .Cerebrovascular accident .Pulmonary embolism and CHF .

Pathophysiology of Thyroid Storm1) An acute decrease in

thyroxine-binding globulin => high levels of free hormone .

2) Thyroid hormone increases the density of beta-adrenergic receptors & alters responsiveness to catecholamines at a postreceptor level .

Treatment of Thyroid StormBlock hormone synthesis with

either : a) Propylthiouracil 100-600 mg

loading PO or NG , 200-250 mg q4h for total daily dose of 1200-1500 mg ; or

b) methimazole 20 mg PO ( 10-40 mg range ) q 4h .

Treatment of Thyroid Storm ( continued )Inhibit hormone release : Iodides –Potassium iodide ( SSKI ) 5

drops PO Q6-8H , or Lugol’s solution 7-8 drops ( 1 mL PO

Q6H ) or Ipodate 1-3 g daily ( as 1 g Q8H for

24 hours , then 500 mg Q12H ) . If severe iodide allergy , lithium

carbonate 300 mg Q6H .

Treatment of Thyroid Storm ( continued )Glucocorticoids : Hydrocortisone (

300 mg IV , then 100 mg IV q8h ) ; dexamethasone ( 2 mg Q6H ) .

Adrenergic blockade : Propranolol ( 0.5-3 mg IV over 15 minutes slow IV , then 60-80 mg PO Q4H ) ; Esmolol ( 0.25-0.5 mcg/kg loading , infusion of 0.05-0.1 mcg/kg/min ) .

Adjunctive Therapy for Thyroid Storm Treat fever aggressively with

acetaminophen .IV fluid containing 10% dextrose

are recommended .Administer vitamin supplements ,

including thiamine .Treat CHF with conventional

methods .

Adjunctive Therapy for Thyroid Storm ( continued )Identify the precipitating event ,

including infection .Consider plasmapheresis ,

hemodialysis or peritoneal dialysis for removal of metabolically active hormone .

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