mbs127 slide hyperthyroidism 1

HYPERTHYROIDISMHYPERTHYROIDISM

Dharma Lindarto

Div. Endokrin-Metabolisme dan Diabetes. Dep Ilmu Penyakit Dalam FK USU / RSUP HAM Medan

Anatomy of the Thyroid Gland

Tiroid Disease

Aspect

fungtion morphology

Multi N

fungtion morphology

eutiroid, hypertiroid, hypotiroid

normal, atrophic, nodule, diffus

HypothalamusHypothalamus--

PituitaryPituitary-- Thyroid AxisThyroid Axis

Typical Thyroid Hormone Levels

in Thyroid Disease

TSH T4 T3

Hypothyroidism High Low Low

Hyperthyroidism Low High HighHyperthyroidism Low High High

Subclinical Hypothyroidsm High normal normal

Subclinical Hyperthyroidsm Low normal normal

Thyrotoxicosis and Hyperthyroidism

Definitions

• Thyrotoxicosis–The clinical syndrome of hypermetabolism that

results when the serum concentrations of free T4, T3, or both are increasedT4, 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 & Ingbar’s The Thyroid. A

Fundamental and Clinical Text. 8th ed. 2000.

• Thyroid Storm Rare complication of hyperthyroidism where manifestations of thyrotoxicosis become life threatening. Also may be termed Thyrotoxic Crisis.

• Apathetic Thyrotoxicosis Rare form usually occurring in the elderly. Often presents as single organ failure (CHF). Patient may develop thyroid storm without the typical manifestations.

Prevalence of Thyrotoxicosis

• In a cross-sectional study of urban and rural adults, the prevalence of thyrotoxicosis ranged from 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.

Hyperthyroidism Etiology

• Graves’ disease

• Multinodular goiter

• Autonomous nodule• Autonomous nodule

• Exogenous thyroid hormone

• Transient—subacute thyroiditis, postpartum thyroiditis

• Drugs—amiodarone

Causes of Thyrotoxicosis

Divided by Degree of Radioiodine Uptake

High I123 Uptake

Graves’ diseaseToxic nodular goiterTSH-mediated thyrotoxicosis

Pituitary tumor

I123

Low I123 UptakeSubacute thyroiditisHashitoxicosisDrug-induced

Iodide

I123

Pituitary tumorPituitary resistance tothyroid hormone

HCG-mediated thyrotoxicosisHydatidiform moleChoriocarcinomaOther HCG-secreting tumors

Thyroid carcinoma (very rare)

Iodide Thyroid hormone

Struma ovariiFactitious

Common Signs and Symptoms

of Thyrotoxicosis

Symptoms Signs� Nervousness � Hyperactivity

� Fatigue � Tachycardia

� Weakness � Systolic hypertension

� Increased perspiration � Warm, moist, or smooth skin� Increased perspiration � Warm, moist, or smooth skin

� Heat intolerance � Stare and eyelid retraction

� Tremor � Tremor

� Hyperactivity � Hyperreflexia

� Palpitations � Muscle weakness

� Appetite/weight changes

� Menstrual disturbances

Braverman LE, et al. Werner & Ingbar’s The Thyroid. A

Fundamental and Clinical Text. 8th ed. 2000.

SYSTEMIC EFFECTSRESPIRATORY

• Dyspnea, panting, hyperventalation• 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 musclemuscle

• 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 population0.4% 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 T-lymphocytes in thyroid tissuelymphocytes in thyroid tissue– TSH receptor activation

– Thyroglobulin and thyroid peroxidase antibodies

– Sodium/iodide cotransporter (NIS) activity enhanced (increased RAI)

– AutoantigensAbbott Laboratories Diagnostics Division Web site. Available at: et al. Werner & Ingbar’s The

Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.

Graves' Disease

�Goiter

�HyperthyroidismHyperthyroidism

�Exophthalmos

�Localized myxedema

�Thyroid acropachy

�Thyroid stimulating immunoglobulins

Clinical Characteristics of Goiter

in Graves’ Disease

�Diffuse increase in thyroid gland size

�Soft to slightly firm

�Non-nodular�Non-nodular

�Bruit and/or thrill

�Mobile

�Non-tender

�Without prominent adenopathy

Graves’ Disease - Localized Myxedema

Margins sharply

demarcated

Margins sharply

demarcated

Thickened skin

Nodularity

demarcated

Graves’ Ophthalmopathy

• Class one: spasm of upper lids with thyrotoxicosis

• Class two: periorbital edema and chemosis

• Class three: proptosis• Class three: proptosis

• Class four: extraocular muscle involvement

• Class five: corneal involvement

• Class six: loss of vision due to optic nerve involvement

DIAGNOSTICS

• Endocrine Testing

– Total T4: 5-10% will be normal

– Total T3: 30% will be normal– Total T3: 30% will be normal

– Free T4: false negative with NTI and

shipping

– fT4 better

– T3 supression

– TRH stimulation and TSH response

DIAGNOSTICSRADIONUCLIDE IMAGING

• Pertechnetate imaging• extent of involvement

• detect metastasis to other gland

• no palpable enlargement (within thorax)

• Carcinoma metastasis• Carcinoma metastasis

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

• Th/ 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– 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 (Plummer’s resulting in thyrotoxicosis (Plummer’s 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:• 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 Hashimoto’s (95%) & Graves

– TSH receptor stimulating Ab measures activity in Graves-use in pregnancy

Scans/Ultrasound

• Radioiodine uptake (RAIU)

• Thyroid Scan

• Ultrasound• Ultrasound

• Fine needle Aspiration

Treatment of Hyperthyroidism

1. Antithyroid drugs

2. Surgical resection

3. Radioactive iodine therapy3. 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 symptoms

• Goal of therapy:

– Inhibit peripheral conversion of T4 to T3

– Inhibit synthesis and release of T4 and 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,

nervousnessnervousness

– 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)– 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 • 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 • > 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• 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 .the result of thyroid surgery .

• Caused more often by antecedent Grave’s disease .

Precipitants of Thyroid Storm

• Surgery .

• Radioiodine therapy .

• Iodinated contrast dyes .• Iodinated contrast dyes .

• Thyroid hormone ingestion .

• Diabetic Ketoacidosis .

• Cerebrovascular accident .

• Pulmonary embolism and CHF .

Pathophysiology of Thyroid Storm

• 1) An acute decrease in thyroxine-binding globulin => high levels of free hormone .hormone .

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

Laboratory Diagnosis of Thyroid Storm

• A combination of low TSH and elevated free T4 => makes the diagnosis .

• If TSH is lower than normal and free T4 • If TSH is lower than normal and free T4 is normal => free T3 testing is recommended .

ED measurement of thyroglobulin or thyroid antibodies : No indication .

Treatment of Thyroid Storm

• Block hormone synthesis with either :

a) Propylthiouracil 100-600 mg loading PO or NG , 200-250 mg q4h for total 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 ) .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 • 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 , • Consider plasmapheresis , hemodialysis or peritoneal dialysis for removal of metabolically active hormone .

Thyrotoxic Periodic Paralysis

� Most common cause of hypokalemic periodic

paralysis

� Flaccid paralysis

� Lower extremities affected most often

� Ocular and bulbar muscles uninvolved, � Ocular and bulbar muscles uninvolved,

respiratory muscles rarely involved

� Most often starts during sleep

� Precipitated following exercise, high salt intake or

high carbohydrate diet

� Hypokalemia during the paralysis

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