Hipertiroidisme

Departemen ilmu kesehatan THT-KL M. Fahmy H 070100185

Anatomy of thyroid gland

HypothalamusPituitary- Thyroid Axis

Fisiologi hormon tiroid

Thyrotoxicosis and Hyperthyroidism Definitions

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 synonymous

Braverman LE, et al. Werner & Ingbars 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 toksik multinodula

Hormon tiroid berlebih (tirotoksikosis faktisia) Tiroiditis subakut

TSH secreting tumor chGH secreting tumor

Adenoma toksik
Obat : yodium, lithium Karsinoma tiroid yang berfungsi

Tirotoksikosis gestasi

Silent thyroiditis
Destruksi amiodaron I-131, radiasi, adenoma, kelenjar :

Resistensi
tiroid

hormon

Struma ovary (ektopik)

Mutasi TSH-r

infark

Common Signs and Symptoms of Thyrotoxicosis

Symptoms
Nervousness Fatigue Weakness Increased perspiration Heat intolerance Tremor Hyperactivity Palpitations Appetite/weight changes Menstrual disturbances

Signs
Hyperactivity Tachycardia Systolic hypertension Warm, moist, or smooth skin Stare and eyelid retraction Tremor Hyperreflexia Muscle weakness

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

SYSTEMIC EFFECTS
RESPIRATORY

Dyspnea, panting, hyperventilation

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

SYSTEMIC EFFECTS
CARDIOVASCULAR

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 range

Graves 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 Tlymphocytes 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 & Ingbars 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 areas

Evolution from sporadic diffuse goiter to toxic multinodular goiter is gradual Thyrotropin 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 & Ingbars 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 Adenoma
Autonomously functioning thyroid nodule hypersecreting T3 and T4 resulting in thyrotoxicosis (Plummers disease) Almost never malignant Manage with antithyroid drugs followed by either I-131 or surgery

Laboratory Testing in Thyroid Disease

TSH:
Pituitary hormone which stimulates thyroid May rise transiently in recovery from other illness

Free T4:

direct measure of thyroxine activity May be transiently suppressed in severe acute illness Free T3: suspect hyperthyroid but normal FT4

Thyroid peroxidase/thyroperoxidase antibody:

Anti-TPO High levels in Hashimotos (95%) & Graves TSH receptor stimulating Ab measures activity in Graves-use in pregnancy

Typical Thyroid Hormone Levels in Thyroid Disease

TSH Hypothyroidism High Hyperthyroidism Low Subclinical Hypothyroidsm High Subclinical Hyperthyroidsm Low

T4

T3

Low Low High High normal normal normal normal

Scans/Ultrasound
Radioiodine uptake (RAIU) Thyroid Scan Ultrasound Fine needle Aspiration

Treatment of Hyperthyroidism
1. Antithyroid drugs 2. Surgical resection 3. Radioactive iodine therapy

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

1. Antithyroid Drug Therapy

Acute hyperthyroid symptoms Goal of therapy:

Inhibit peripheral conversion of T4 to T3 Inhibit synthesis and release of T4 and T3 from thyroid gland

Propylthiouracil (PTU) Methimazole [generic] or Tapazole

Antithyroid Drug Therapy

A. PTU:
Inhibits peripheral conversion of T4 to T3 Inhibits thyroid hormone synthesis and release from thyroid gland

B. 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 Thyroidectomy

Surgical complications:
Vocal cord paralysis (1%) Hypothyroidism (up to 43% after 10 years) Hypoparathyroidism Recurrence of hyperthyroidism (10-15%)

3. Radioactive Iodine 131[I] Ablation

Treatment of choice in patients > 21 years old with Graves Disease Treatment 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] orally 80% 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 therapy RIA contraindicated in pregnancy, lactation, iodine allergy

Screen pre-menopausal women for pregnancy prior to treatment

Thyroid Storm
A life-threatening crisis . Estimated mortality : 20-30% . the result of thyroid surgery . Caused more often by antecedent Graves disease .

Precipitants of Thyroid Storm

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

Pathophysiology of Thyroid Storm

1) An acute decrease in thyroxinebinding 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 Storm

Block 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 Lugols 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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