HYPERTHYROIDISM PrevalenceWomen 2%Men 0.2%15% of cases occur in patients older than 60 years of age

Clinical Symptoms

Depends onAge of patientMagnitude of hormonal excessPresence of co-morbid condition

Mechanism of Clinical Symptoms1. Catabolism2. Enhancement of sensitivity to catecholamines

Clinical Symptoms

Clinical manifestations of hyperthyroidism are largely independent of its cause.However, causing disorder may have other effects.

Clinical SymptomsOlder patient presents with lack of clinical signs and symptoms, which makes diagnosis more difficult

Thyroid storm is a rare presentation, occurs after stressful illness in under treated or untreated patient. Characteristics -Delirium -Dehydration -Severe tachycardia -Vomiting -Fever -Diarrhea

Clinical symptomsSkin -Warm -May be erythematous (due to increased blood flow) -Smooth- due to decrease in keratin-Sweaty and heat intolerance-Onycholysis softening of nails and loosening of nail beds

Clinical symptoms

Hyperpigmentation -Due the patient increase ACTH secretion Pruritis -mainly in graves diseaseThinning of hairVitilago and alopecia areata-mainly due to autoimmune diseaseInfilterative dermopathy-Graves disease, most common on shins

Clinical symptoms

Eyes Stare Lid lag *Due to sympathetic over activity *Only Graves disease has ophthalmopathy-Inflammation of extraocular muscles, orbital fat and connective tissue. -This results in exopthalmos -More common in smokers

Clinical symptoms

EyesImpaired eye muscle function (Diplopia)Periorbital and conjunctival edemaGritty feeling or pain in the eyesCorneal ulceration due to lid lag and proptosisOptic neuritis and even blindness

Clinical symptoms

Cardiovascular System

Increased cardiac output (due to increased oxygen demand and increased cardiac contractibility. TachycardiaWidened pulse pressureHigh output heart failure

Clinical symptoms

Cardiovascular System

Atrial fibrillation, 10-20% of patients. More common in elderlyAtrial ectopy60% of A-fib will convert to normal sinus rhythm with treatment (4-months of becoming euthyroid)Mitral valve problemsLVH and cardiomyopathy

Serum LipidsLow total cholesterol Low HDLLow total cholesterol/HDL ratio

Respiratory SystemDyspnea on rest and with exertionOxygen consumpation and CO2 production increases. Hypoxemia and hypercapnea, which stimulates ventilationRespiratory muscle weaknessDecreased exercise capacityTracheal obstructionMay exacerbate asthmaIncreased pulmonary arterial pressure

Clinical symptoms

GI System -Weight loss due to increased calorigenesis -Hyperdefecation-Malabsorption-Steatorrhea-Celiac Disease (in Graves Disease)-Hyperphagia (weight gain in younger patient)-Anorexia- weight loss in elderly-Dysphagia-Abnormal LFT especially phosphate

Clinical symptoms

Hematological SystemNormochromic normocytic anemiaSerum ferritin may be highGraves diseseITPPernicious anemiaAnti-neutrophiliac antibody

Clinical symptoms

GU System Urinary frequency and nocturiaEnuresis is common in children

Clinical symptoms

GU SystemWomenIncreased SHBGHigh serum estradiolLow free estradiol High LHReduce mid-cycle LH surgeOligomenorrhea and amenorrheaAnovulatory infertility

Clinical symptoms

GU SystemMenHigh SHBGHigh total testosteroneLow free testosteroneHigh serum LHHigh serum estradiolGynecomastiaDecreased libidoErectile dysfunctionDecreased or abnormal sperm

Clinical symptoms

Skeletal SystemBone resorptionIncreased porosity of cortical boneReduced volume of trabecular boneSerum alkaline phosphate is increasedIncreased osteoblastsInhibit PTH secretionsDecreased calcium absorption and increased excretionOsteoporosis, Fractures

Clinical symptoms

Skeletal SystemGraves disease is associated with thyroid acropathy-Clubbing of nails-Periosteal bone formation in metacarpal bone or phalanges

Clinical symptoms

Neuromuscular System

Tremors-outstretched hand and tongue Hyperactive tendon reflexes

Clinical symptoms

PsychiatricHyperactivityEmotional labilityAnxietyDecreased concentrationInsomnia

Clinical symptoms

Muscle Weakness

Proximal muscle weakness in 50% pts.Decreased muscle mass and strengthMay take up to six months after euthyroid state to gain strength Hypokelemic periodic paralysis especially in Asian men (cause is not known)Myesthenia Gravis, especially in Graves disease.

Clinical symptoms

EndocrineIncreased sensitivity of pancreatic beta cells to glucoseIncreased insulin secretionAntagonism to peripheral action of insulinLatter effects usually predominate leading to intolerance.

Etiology

1 Graves diseaseAutoimmune disease caused by antibodies to TSH receptorsCan be familial and associated with other autoimmune diseases2 Toxic multi-nodular goiter5% of all cases 10 times more common in iodine deficient areaTypically occurs in older than 40 with long standing goiter

Etiology

3 Toxic adenoma More common in young patientsAutonomically functioning nodule

Etiology4 ThyroiditisSubacuteAbrupt onset due to leakage of hormonesFollows viral infectionResolves within eight monthsCan re-occurLymphatic and postpartumTransient inflammationPostpartum can occur in 5-10% cases in the first 3-6 monthsTransient hypothyroidism occurs before resolution

Etiology5 Treatment Induced HyperthyroidismIodine InducedExcess iodine indirectExposure to radiographic contrast mediaMedication Excess iodine increases synthesis and release of thyroid hormone in iodine deficient and older patients with pre-existing goiters

EtiologyAmiodarone Induced ThyroiditisUp to 12% of patients, especially in iodine deficient casesMost common cause of iodine excess in US. Two types: *Type I - due to excess iodine Amiodarone contains 37% iodine. *Type II occurs in normal thyroid

EtiologyThyroid Hormone InducedFactitious hyperthyroidism in accidental or intentional ingestion to lose weightTumors -Metastatic thyroid cancer -Ovarian tumor that produces thyriod hormone (struma ovarii) -Trophoblastic tumor -TSH secreting tumor

Signs and symptoms of hyperthyroidTSH levelLow TSHHigh TSH (rare)Measure T4HighSecondary hyperthyroidismImage pituitary gland

Low TSH

Measure Free T4 LevelNormalHighMeasure Free T3 LevelNormalHigh-Subclinical hyperthyroidism-Resolving Hyperthyroidism -Medication-Pregnancy -New thyroid illnessT3 ToxicosisPrimary hyperthyroidismThyroid uptakeLowHighMeasure thyroglobulindecreasedIncreased Exogenous ThyroiditisIodide exposureExrtraglandular productionDIffuseNodularhormoneGraves diseaseMultiple areasOne hot areaToxic multinodular goiterToxic adenoma

EtiologyHyperthyroidism with high RIU - Graves disease - Toxic adenoma - Toxic multinodular goiter - TSH- producing pituitary adenoma - Hyperemesis gravidarum - Trophoblastic disease

EtiologyHyperthyroidism with low RIU - Subacute thyroiditis - Exogenous harmone intake - Ectopic ovarii - Metastatic follicular thyroid CA - Radiation thyroiditis - palpation thyroiditis - Amiodarone induced

TreatmentTreatment depends upon -Cause and severity of disease -Patients age -Goiter size -Comorbid condition -Treatment desired

Treatment

The goal of therapy is to correct hyper-metabaolic state with fewest side effects and lowest incidence of hypothyroidism.

OptionsAnti-thyroid drugsRadioactive iodineSurgeryBeta-blocker and iodides are adjuncts to above treatment

Beta BlockersPrompt relief of adrenergic symptomsPropranolol widely usedAny beta blocker can be used, but non-selectives have more direct effect on hyper-metabolismStart with 10-20 mg q6hIncrease progressively until symptoms are controlledMost cases 80-320 mg qd is sufficientCCB can be used if beta blocker not tolerated or contraindicated

IodidesIodide blocks peripheral conversion of T4 to T3 and inhibits hormone release. These are used as adjunct therapyBefore emergency non-thyroid surgeryBeta blockers cannot curtail symptomsDecrease vascularity before surgery for Graves disease

IodidesIodides are not used for routine treatment because of paradoxical increase of hormone release with prolonged useCommonly used: Radiograph contrast agents -Iopanoic acid -Ipodate sodiumPotassium iodide Dose 1 gram/ 12 weeks

Anti-thyroid DrugsThey interfere with organification of iodinesuppress thyroid hormone levels

Two agents: -Tapazole (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 DrugsMethimazole

Drug of choice for non-pregnant patients because of :Low costLong half lifeLower incidence of side effects Can be given in conjunction with beta-blockerBeta-blockers can be tapered off after 4-8 weeks of therapyDose 15-30 mg/day

Anti-thyroid Drugs

MethimazoleMonthly Free T4 or T3 until euthyroidMaintenance dose 5-10 mg/dayTSH levels may remain undetectable for months after euthyroid and not to be used to monitor the therapy

Anti-thyroid DrugsMethimazoleAt 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 annuallyRelapses 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

PTUPrefered for pregnant patientsMethimazole 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 DrugsComplicationsAgranulocytosis up to 0.5%High with PTUCan occur suddenlyMostly reversible with supportive TxRoutine WBC monitoring controversialSome people monitor WBC every two weeks for first month then monthlyAdvised to stop drug if they develop sudden fever or sore throat

Radioactive IodineTreatment of choice for Graves disease and toxic nodular goiterInexpensiveHighly effectiveEasy to administerSafeDose depends on estimated weight of glandHigher dose increases success rate but higher chance of hypothyroidismSome studies have shown increase of hypothyroidism irrespective of dose

Radioactive IodineHigher dose is favored in older patientCardiac diseaseOther group needs prompt controlToxic nodular goiter or toxic adenoma

Radioactive IodineSide effects50% of Graves ophthalmology can develop or worsen by use of radioactive iodineUse 40-50 mg Prednisone for at least three months can prevent or improve severe eye disease in 2/3 of patientsUse lower dose in ophthalmology because post Tx hypothyroidism may be associated with exacerbation of eye diseaseSmoking makes ophthalmopathy worse.

Radioactive IodineUse of anti-thyroid drugs with iodine is not recommended in most casesMay improve safety for severe or complicated casesWithdraw three days before iodine TxBeta blockers used to control symptoms before radioactive iodine and can be combined throughout TxIodine containing meds need to be stopped several weeks before therapy

Radioactive IodineSafetyMost 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 weeksNo close contact with children and pregnant patients for 48-72 hoursAdditional Tx may be needed after three months if indicated

SurgeryRadioactive iodine has replaced surgery for Tx of hyperthyroidismSubtotal thyroidectomy is most commonThis limits incidence of hypothyroidism to 25%Total thyroidectomy in large goiter or severe disease

New TreatmentEndoscopic subtotal thyroidectomyEmbolization of thyroid arteries PlasmaphoresisPercutaneous ethanol injection into toxic noduleL-Carnitine supplementation may improve symptoms and may prevent bone loss

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