HYPERTHYROIDISM Medical & Surgical aspect

Presentation by : Dr Prabhakar Moderator : Dr S. Dam

Normal Thyroid State

Synthesis and release of thyroid hormone is controlled by TSH released from the anterior pituitary TSH is controlled by the release of thyroid releasing hormone (TRH) from the hypothalmus and a negative feedback loop to the pituitary Thyroid hormone production is dependent on adequate iodine intake

Normal Thyroid State

Thyroid hormone is reversibly bound to various proteins including thyroxine-binding globulin (TBG) Free unbound portions are biologically active T4 is the predominant circulating hormone T4 is deiodinated to T3 T3 is biologically more active than T4 but has a shorter half-life

Hyperthyroidism
Occurs in in all ages
Uncommon under the age of 15

10 times more common in women Graves disease is the most common etiology Toxic multinodular and toxic nodular goiters are the next most common etiologies

Thyrotoxicosis: Definition
Thyrotoxicosis :
Biochemical and physiologic complex when excessive serum levels of thyroid hormone

Hyperthyroidism
Thyrotoxicosis that results when thyroid gland overproduces thyroid hormones

Clinical features of thyrotoxicosis

Neuromuscular: Nervousness, irritability, emotional liability, psychosis Tremor Hyperreflexia, ill sustained clonus Muscle weakness, proximal myopathy, bulbar myopathy Reproductive: Amenorrhoea,Oligomenorrhoea Infertility, impotence

Thryotoxicosis..
Gastrointestinal: Weight loss despite increased appetite Hyperdefecation Diarrhoea and steatorrhoea Vomiting Cardiorespiratory: Palpitations, Sinus tachycardia, Atrial fibrillation Increased pulse pressure Dyspnea on exertion Angina, cardiomyopathy and heart failure

Thyrotoxicosis..
Others: Heat intolerance Increased sweating Fatigue Gynaecomastia Palmar erythema, Onycholysis

Nuclear thyroid scintigraphy iodine 123 (I-123) uptake and scan:

Common Forms (85-90% of cases)
Diffuse toxic goiter (Graves disease) Toxic multinodular goiter (Plummer disease) Thyrotoxic phase of subacute thyroiditis Toxic adenoma Radioactive iodine uptake over neck Increased Increased Decreased Increased

Less Common Forms Iodide-induced thyrotoxicosis

Excess human chorionic gonadotropin (molar pregnancy/choriocarcinoma) Thyrotoxicosis factitia

Variable
Decreased Decreased
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Hyperthyroidism Graves disease

Also known as Parrys or Basedows disease. Graves disease is a disorder with three major manifestations: 1)Hyperthyroidism with diffuse goitre 2)Ophthalmopathy and 3)Dermopathy. These three manifestations may not appear together.

Goiter
Is diffuse and toxic and maybe asymetric and lobular. There may be presence of bruit over the goiter

Ophthalmopathy
Signs of Gravess ophthalmopathy are divided into two components: 1) Spastic: Stare, lid lag and lid retraction which account for the frightened facies. 2) Mechanical: Proptosis of varying degrees,ophthalmoplegia,and congestive occulopathy characterized by chemosis,conjunctivitis,periorbital swelling and the potential complications of corneal ulceration,optic neuritis and optic atrophy.

Dermopathy
Usually occurs over the dorsum of the legs or feet and is termed localized or pretibial myxedema. It is usually a late phenomenon The affected area is usually demarcated from the normal skin by being raised and thickened and having a peau d orange appearance; it may be pruritic and hyperpigmented. The most common presentation is non pitting oedema, but lesions maybe plaque like, nodular or polypoid. Clubbing of the fingers and toes accompanies and is termed thyroid acropachy

Toxic multinodular goiter

Toxic multinodular goiter causes 5 percent of the cases of hyperthyroidism. It typically occurs in patients older than 40 years with a long-standing goiter.

Toxic adenoma
Toxic adenomas are autonomously functioning nodules that are found most commonly in younger patients and in iodine-deficient areas.
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Subacute thyroiditis
Soreness in the neck. It often follows a viral illness. Symptoms usually resolve within one year. This condition can be recurrent in some patients. ESR is markedly elevated.

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Subacute thyroiditis

Time course of changes in thyroid function tests in patients with Subacute thyroiditis.
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Amiodarone-induced
Amiodarone- (Cordarone-) induced hyperthyroidism can be found in up to 12 percent of treated patients. Type I - Because amiodarone contains 37 percent iodine, is an iodine induced hyperthyroidism. Type II is a thyroiditis that occurs in patients with normal thyroid glands. Medications such as interferon and interleukin-2 also can cause type II.

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Thyroid hormone-induced
Factitial hyperthyroidism is caused by the intentional or accidental ingestion of excess amounts of thyroid hormone. Some patients may take thyroid preparations to achieve weight loss.

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TREATMENT
The goal of therapy is to correct hyper-metabaolic state with few side effects and low incidence of hypothyroidism.

Beta Blockers
Prompt relief of adrenergic symptoms Propranolol widely used Any beta blocker can be used, but non-selectives have more direct effect on hyper-metabolism Start with 10-20 mg q6h Increase progressively until symptoms are controlled Most cases 80-320 mg qd is sufficient CCB can be used if beta blocker not tolerated or contraindicated

Iodides
Iodide blocks peripheral conversion of T4 to T3 and inhibits hormone release. These are used as adjunct therapy Before emergency non-thyroid surgery Beta blockers cannot curtail symptoms Decrease vascularity before surgery for Graves disease

Iodides
Iodides are not used for routine treatment because of paradoxical increase of hormone release with prolonged use Commonly used: Radiograph contrast agents -Iopanoic acid -Ipodate sodium Potassium iodide Dose 1 gram/ 12 weeks

Anti-thyroid Drugs
They interfere with organification of iodinesuppress thyroid hormone levels Two agents: - MMI (methimazole) - PTU (propylthiauracil)

Anti-thyroid Drugs
Remission rate: 60% when therapy continued for two years Relapse in 50% of cases. Relapse more common in -smokers -elevated TS antibodies at end of therapy

Anti-thyroid Drugs
Methimazole Drug of choice for non-pregnant patients because of : Low cost Long half life Lower incidence of side effects Can be given in conjunction with beta-blocker Beta-blockers can be tapered off after 4-8 weeks of therapy

Dose 15-30 mg/day

Methimazole Monthly Free T4 or T3 until euthyroid Maintenance dose 5-10 mg/day TSH levels may remain undetectable for months after euthyroid and not to be used to monitor the therapy

Anti-thyroid Drugs
Methimazole At one year if patient is clinically and biochemically euthyroid and TS antibodies are not detectable, therapy can be discontinued Monitor every three months for first year then annually Relapses are more common in the first year but can occur years later If relapse occurs, iodide or surgery although anti-thyroid drugs can be restarted

Anti-thyroid Drugs

PTU Prefered for pregnant patients Methimazole is associated with rare genetic abnormalities Dose 100 mg t.i.d Maintenance 100-200 mg/day Goal: Keep Free T4 at upper level of normal

Anti-thyroid Drugs
Complications Agranulocytosis up to 0.5% High with PTU Can occur suddenly Mostly reversible with supportive Tx Routine WBC monitoring controversial Some people monitor WBC every two weeks for first month then monthly Advised to stop drug if they develop sudden fever or sore throat

Radioactive Iodine
Treatment of choice for Graves disease and toxic nodular goiter Inexpensive Highly effective Easy to administer Safe Dose depends on estimated weight of gland Higher dose increases success rate but higher chance of hypothyroidism Some studies have shown increase of hypothyroidism irrespective of dose

Radioactive Iodine
Higher dose is favored in older patient Cardiac disease Other group needs prompt control Toxic nodular goiter or toxic adenoma

Radioactive Iodine
Side effects 50% of Graves ophthalmology can develop or worsen by use of radioactive iodine Use 40-50 mg Prednisone for at least three months can prevent or improve severe eye disease in 2/3 of patients Use lower dose in ophthalmology because post Tx hypothyroidism may be associated with exacerbation of eye disease Smoking makes ophthalmopathy worse.

Radioactive Iodine
Use of anti-thyroid drugs with iodine is not recommended in most cases May improve safety for severe or complicated cases Withdraw three days before iodine Tx Beta blockers used to control symptoms before radioactive iodine and can be combined throughout Tx Iodine containing medications need to be stopped several weeks before therapy

Radioactive Iodine
Safety Most radioactive iodine is eliminated in the urine, saliva and feces in 4-8 weeks. Have double flushing of toilet and frequent hand washing for several weeks No close contact with children and pregnant patients for 4872 hours Additional Tx may be needed after three months if indicated

Surgery
Radioactive iodine has replaced surgery for Tx of hyperthyroidism Subtotal thyroidectomy is most common This limits incidence of hypothyroidism to 25% Total thyroidectomy in large goiter or severe disease

New Treatment
Endoscopic subtotal thyroidectomy Embolization of thyroid arteries Plasmapheresis Percutaneous ethanol injection into toxic nodule L-Carnitine supplementation may improve symptoms and may prevent bone loss

Thyroid Storm
A life threatening hypermetabolic state due to hyperthyroidism Mortality rate is high (10-75%) despite treatment Usually occurs as a result of previously unrecognized or poorly treated hyperthyroidism Thyroid hormone levels do not help to differentiate between uncomplicated hyperthyroidism and thyroid storm

Thyroid Storm
Precipitants of Thyroid Storm
Infection DKA CVA Surgery Iodine administration Ingestion of thyroid hormone Trauma MI PE Withdrawal of thyroid med Palpation of thyroid gland Unknown etiology (2025%)

Thyroid Storm
Clinical features
The most common signs are fever, tachycardia out of proportion to the fever, altered mental status, and diaphoresis Clues include a history of hyperthyroidism, exophthalmoses, widened pulse pressure and a palpable goiter Patients may present with signs of CHF

Thyroid Storm
Clinical features cont.
Common GI symptoms include diarrhea and hyperdefecation Apathetic thyrotoxicosis is a distinct presentation seen in the elderly
Characteristic symptoms include lethargy, slowed mentation, and apathetic facies Goiter, weight loss , and proximal muscle weakness also present

Thyroid Storm
Diagnosis
Thyroid storm is a clinical diagnosis based upon suspicion and treated empirically Lab work is non specific and may include Leukocytosis, hyperglycemia, elevated transaminase and elevated bilirubin

Thyroid Storm
Treatment
Initial stabilization includes airway protection, oxygenation, fluids and cardiac monitoring Treatment can then be divided into 5 areas:
General supportive care Inhibition of thyroid hormone synthesis Retardation of thyroid hormone release Blockade of peripheral thyroid hormone effects Identification and treatment of precipitating events

Thyroid Storm
Drug Treatment of Thyroid Storm
Decrease de novo synthesis:
Porpythiouracil Methimazole
Iodine then Lugol Lithuim

Prevent releases of hormone (after synthesis blockade intiated)

600-1000mg PO initially, followed by 200-250 mg q 4 hrs 40 mg PO initial dose, then 25 mg PO q6h

Iaponoric acid (Telepaque) 1 gm IV q8h for the first 24 h, 500 mg bid or Potassium iodide (SSKI) 5 drops PO q6h or solution 8-10 drops PO q6h 800-1200 mg PO every day Propanolol (IV) titrate 1-2 mg q 5min prn (may need 240PO q day) or Esmolol (IV) 500 mcg/kg IV bolus, then 50-200 mcg/kg per min maintenance 30-40 mg PO q 6 h 2.5-5 mg IM q4-6h Hydrocortisone 100 mg IV q 8 h or dexamethosone 2 mg IV q 6 hr Cooling blanket acteaminophen 650 mg PO q 4-6h

Prevent peripheral effects:

B-Blocker 480mg Guanethidine Reserpine

Other consideration:
Corticosteroids Antipyretics

Thyroid Storm
Treatment cont
Propranolol has the additional effects of blocking peripheral conversion of T4-T3 Avoid Salicylates because it may displace T4 from TBG If the patient continues to deteriorate despite appropriate therapy circulating thyroid hormone may be removed by plasma transfusion, plasmapheresis, charcoal plasmaperfusion Remember not to administer iodine until the synthetic pathway has been blocked

HYPERTHYROIDISM IN PREGNANCY

Physiologic Changes in Pregnancy

Free thyroxine levels remain within the normal range during pregnancy (though total thyroxine levels are increased secondary to increased TBG.) TSH decreases slightly in first trimester. The thyroid gland increases slightly in size during pregnancy.

Hyperthyroidism
95% of hyperthyroidism in pregnancy is secondary to Graves Disease. A good pregnancy outcome can be expected in patients with good control.

Hyperthyroidism
Untreated hyperthyroidism is associated with decreased fertility, an increased rate of miscarriage, intrauterine growth retardation (IUGR), premature labor, and perinatal mortality. Poorly controlled thyrotoxicosis is associated with thyroid storm especially at labor and delivery.

DIAGNOSIS
The diagnosis of hyperthyroidism in pregnant women should be based primarily on a serum TSH value <0.01 mU/L and also a high serum free T4 value. Free T3 measurements may be useful in women with suppressed serum TSH concentrations and normal or minimally elevated free T4 values. High serum hCG concentrations during early pregnancy, found in women with hyperemesis gravidarum or multiple pregnancies, may result in transient subclinical or rarely overt hyperthyroidism

FT4
Treatment indicated if FT4 > 2.0 ng/dl PTU 50 100 mg q12 hrs in patient with minimal symptoms (doses > 200 mg of PTU can result in fetal goitre & hypothyroidism Patient with large goitre & long disease duration may require larger initial doses 100 150 mg tid. Clinical improvement (weight gain & HR) is noted in the first 2 6 wks, with FT4 improvement in the first 2 wks. Once clinical improvement occcurs the dose of PTU is by half. Goal to keep FT4 at the upper limit of normal, with least amount of medication In 30% of pt PTU may be D/Ced in the last 4 8 wks of pregnancy

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