HYPERTHYROIDISM

Prevalence

Women 2%Men 0.2%15% of cases occur in

patients older than 60 years of age

Clinical Symptoms

Depends on Age of patient Magnitude of hormonal excess Presence of co-morbid condition

Mechanism of Clinical Symptoms

1. 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 Symptoms

Older 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 symptoms

Skin -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 disease

Thinning of hair Vitilago and alopecia areata

-mainly due to autoimmune disease Infilterative dermopathy

-Graves disease, most common on shins

Clinical symptoms

Eyes Stare Lid lag

*Due to sympathetic over activity *Only Grave’s disease has ophthalmopathy

-Inflammation of extraocular muscles, orbital fat and connective tissue.

-This results in exopthalmos -More common in smokers

Clinical symptoms

Eyes Impaired eye muscle function (Diplopia) Periorbital and conjunctival edema Gritty feeling or pain in the eyes Corneal ulceration due to lid lag and proptosis Optic neuritis and even blindness

Clinical symptoms

Cardiovascular System

Increased cardiac output (due to increased oxygen demand and increased cardiac contractibility.

Tachycardia Widened pulse pressure High output – heart failure

Clinical symptoms

Cardiovascular System

Atrial fibrillation, 10-20% of patients. More common in elderly

Atrial ectopy 60% of A-fib will convert to normal sinus

rhythm with treatment (4-months of becoming euthyroid)

Mitral valve problems LVH and cardiomyopathy

Serum Lipids

Low total cholesterol Low HDL Low total cholesterol/HDL ratio

Respiratory System Dyspnea on rest and with exertion Oxygen consumpation and CO2 production

increases. Hypoxemia and hypercapnea, which

stimulates ventilation Respiratory muscle weakness Decreased exercise capacity Tracheal obstruction May exacerbate asthma Increased pulmonary arterial pressure

Clinical symptoms

GI System -Weight loss due to increased calorigenesis -Hyperdefecation

-Malabsorption-Steatorrhea-Celiac Disease (in Grave’s Disease)-Hyperphagia (weight gain in younger patient)-Anorexia- weight loss in elderly-Dysphagia-Abnormal LFT especially phosphate

Clinical symptoms

Hematological System Normochromic normocytic anemia Serum ferritin may be high Grave’s disese

ITP Pernicious anemia Anti-neutrophiliac antibody

Clinical symptoms

GU System Urinary frequency and nocturia Enuresis is common in children

Clinical symptoms

GU SystemWomen Increased SHBG High serum estradiol Low free estradiol High LH Reduce mid-cycle LH surge Oligomenorrhea and amenorrhea Anovulatory infertility

Clinical symptoms

GU SystemMen High SHBG High total testosterone Low free testosterone High serum LH High serum estradiol Gynecomastia Decreased libido Erectile dysfunction Decreased or abnormal sperm

Clinical symptoms

Skeletal System Bone resorption Increased porosity of cortical bone Reduced volume of trabecular bone Serum alkaline phosphate is increased Increased osteoblasts Inhibit PTH secretions Decreased calcium absorption and increased

excretion Osteoporosis, Fractures

Clinical symptoms

Skeletal SystemGrave’s 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

Psychiatric Hyperactivity Emotional lability Anxiety Decreased concentration Insomnia

Clinical symptoms

Muscle Weakness

Proximal muscle weakness in 50% pts. Decreased muscle mass and strength May 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 Grave’s

disease.

Clinical symptoms

Endocrine Increased sensitivity of pancreatic beta cells to

glucose Increased insulin secretion Antagonism to peripheral action of insulin Latter effects usually predominate leading to

intolerance.

Etiology

1 Grave’s disease Autoimmune disease caused by antibodies to

TSH receptors Can be familial and associated with other

autoimmune diseases2 Toxic multi-nodular goiter 5% of all cases 10 times more common in iodine deficient

area Typically occurs in older than 40 with long

standing goiter

Etiology

3 Toxic adenoma More common in young patients Autonomically functioning nodule

Etiology

4 ThyroiditisSubacute Abrupt onset due to leakage of hormones Follows viral infection Resolves within eight months Can re-occurLymphatic and postpartum Transient inflammation Postpartum can occur in 5-10% cases in the

first 3-6 months Transient hypothyroidism occurs before

resolution

Etiology

5 Treatment Induced HyperthyroidismIodine Induced Excess iodine indirect Exposure to radiographic contrast media Medication Excess iodine increases synthesis and release of

thyroid hormone in iodine deficient and older patients with pre-existing goiters

Etiology

Amiodarone Induced Thyroiditis Up to 12% of patients, especially in iodine

deficient cases Most 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

Etiology

Thyroid Hormone Induced Factitious hyperthyroidism in accidental or

intentional ingestion to lose weight Tumors -Metastatic thyroid cancer -Ovarian tumor that produces thyriod

hormone (struma ovarii) -Trophoblastic tumor -TSH secreting tumor

Signs and symptoms of hyperthyroid

TSH level

Low TSHHigh TSH (rare)

Measure T4

High

Secondary hyperthyroidism

Image pituitary gland

Low TSH

Measure Free T4 Level

Normal High

Measure Free T3 Level

Normal High

-Subclinical hyperthyroidism

-Resolving Hyperthyroidism

-Medication

-Pregnancy

-New thyroid illness

T3 Toxicosis

Primary hyperthyroidism

Thyroid uptake

Low High

Measure thyroglobulin

decreased Increased

Exogenous ThyroiditisIodide exposureExrtraglandular production

DIffuse Nodular

hormone

Graves disease

Multiple areas

One “hot” area

Toxic multinodular goiter

Toxic adenoma

Etiology

Hyperthyroidism with high RIU - Grave’s disease - Toxic adenoma - Toxic multinodular goiter - TSH- producing pituitary adenoma - Hyperemesis gravidarum - Trophoblastic disease

Etiology

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

Treatment

Treatment 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.

Options Anti-thyroid drugs Radioactive iodine Surgery Beta-blocker and iodides are adjuncts to above

treatment

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

Grave’s 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 iodine—suppress 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 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 therapyDose 15-30 mg/day

Anti-thyroid Drugs

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 Grave’s 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 Grave’s 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 meds 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 48-72 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 Plasmaphoresis Percutaneous ethanol injection into toxic

nodule L-Carnitine supplementation may improve

symptoms and may prevent bone loss