HYPERTHYROIDISM

Mh.GOZASHTI

ENDOCRINOLOGIST Kerman medical university

Case # 1A patient complains of “sandy” sensation in his

eyes,weight loss, and a tremor. His extraocular muscles are inflammed. His thyroid is diffusely enlarged and non tender.

The most likely diagnosis is

a. Iodine deficiency

b. Sub-acute thyroiditis

c. Multinodular goiter

d. Graves’ disease

e. Silent thyroiditis

Case # 2A 72 year old man complains of tremor and inability to concentrate. On exam, he has a heart rate of 100 beats per minute. He has a large goiter with many nodules. He has a fine tremor. His serum T4 is very high and TSH isvery low.Treatments that are likely to improve his symptoms are

a. Iodine therapyb. Ethanol injection of his thyroid (PEI)c. 6 weeks of Methimazoled. Radio Active Iodine therapy

HYPERTHYROIDISM

PrevalenceWomen 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

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

Thyroid storm:- Rare - occurs after stressful illness- Both in untreated and in patients who are under

treatment.

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-Diapharesis & heat intolerance-Onycholysis –softening of nails and looseningof nail beds

Clinical symptoms

Hyperpigmentation-Due to increase ACTH secretion

Pruritis-mainly in graves disease

Thinning of hair Vitiligo and alopecia areata

-mainly due to autoimmune disease Infilterative dermopathy

-Graves disease, most common on shins

Clinical symptoms

EyesStareLid 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 catabolism-Hyperdefecation-Malabsorption-Steatorrhea-Celiac Disease (in Grave’s Disease)-Hyperphagia (weight gain in younger patient)-Anorexia- weight loss in elderly-Dysphagia-Abnormal LFT especially Alk-ph

Clinical symptoms

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

ITP Pernicious anemia Anti-neutrophilic 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 Hypokalemic 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 Insulin resistance 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

www.drsarma.in

Algorithm for HyperthyroidismMeasure TSH and FT4

↓ TSH, ↑ FT4

Measure FT3Primary (T4)

Thyrotoxicosis

High

Pituitary Adenoma FNAC, N Scan

Normal

↓ TSH, FT4 N ↑ TSH, ↑ FT4 N TSH, FT4 N

T3 Toxicosis

Sub-clinical Hyper

Features of Grave’s

Yes

Rx. Grave’s

No

Single Adenoma, MNG

Low RAIU↑ RAIU

Sub Acute Thyroiditis, I2, ↑ Thyroxine

F/u in 6-12 wks

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 hormone 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 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 propylthiouracil’s well-known rare but serious side

effect of hepatic failure in June 2009 the U.S. Food and Drug

Administration (FDA) issued an advisory that propylthiouracil should not be used as a first-line agent for hyperthyroidism in adults or children

Dose 100 – 200 mg t.i.d Maintenance 50-100 mg/dayGoal: Keep Free T4 at upper level of normal

Its use is still recommended in the: first trimester of pregnancy thyroid storm those who are intolerant of

methimazole

In general, improvement within the first 2 weeks includes decreased nervousness and palpitations, increased strength, and weight gain.

Usually, the metabolic state becomes normal within about 6 weeks.

During treatment, the size of the thyroid gland decreases in one third to one half of the patients.

In the remainder, it may remain unchanged or even enlarge

Clinical criteria are not the main guidelines by which adequacy of treatment can be judged.

Adequacy of therapy is assessed by measurement of free T4 in the first several months, when the serum TSH level usually remains suppressed, and then subsequently by TSH assessment.

Predicting the Response to Drug Withdrawal

Remission rates are reported to be lower in:

men older patients smokers those with more active Graves disease

(including those with higher titers of TRAbs and larger goiters)

Anti-thyroid drug therapy usually should be continued for 12 to 18 months and then withdrawn if the serum TSH level returns to normal.

Therapeutic duration longer than 18 months does not increase remission rates, according to a meta-analysis.

About 75% of relapses occur during the first 3 months after withdrawal of therapy, and most of the remainderoccur during the subsequent 6 months.

Suppression of the TSH concentration below normal levels is the first signalof relapse, even in the presence of a normal serum T4 level.

about one third of patients experience a lasting remission.

Anti-thyroid Drugs

Complications Agranulocytosis up to 0.5% High with PTU Can occur suddenly Mostly reversible with supportive Tx Routine WBC monitoring controversial 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

the age limit for use of radioiodinehas been lowered progressively by some physicians, from the initial lower limit of 40 years to age 10 or less

However, in childhood, anti-thyroid drugs continue to be the first treatment of choice, and the use of radioiodine inwomen of reproductive age remains unpopular

Radioiodine use is contraindicated during pregnancy, and fetuses exposed to 131I after 10 weeks of gestation may be born athyreotic.

131I should not be administered for at least 8 weeks after cessation of lactation because it is concentrated in breast milk.

Preparation before Radioiodine Therapy

use of anti-thyroid drugs before radioiodine treatment:

considered especially in older patients with ischemic heart disease

Anti-thyroid drugs may also prevent the increase in thyroid autoantibodies that occurs after radioiodine therapy and may affect ophthalmopathy

Normally, such drugs are withdrawn 3to 7 days before treatment; if needed, they can be reintroduced 7 days after treatment.

Treatment after Radioiodine Therapy

Although exacerbation of thyrotoxicosis after radioiodine therapy is rare methimazole use should be considered for patients with severe hyperthyroidism and other comorbidities

Patients are seen at 4-week intervals after 131I administration and monitored by measurements of serum T4 and TSH levels

Women who are planning to become pregnant are advised to wait for an arbitrary period of 4 to 6 monthsafter 131I therapy

If, after 6 months, hyperthyroidism is still present :

the treatment is repeated, usually with about 1.5 times the initial dose of 131I or an ablative amount.

Complications of Radioiodine Therapy

Thyroid Cancer from Low-Level Exposure

Mortality after Radioiodine Hypothyroidism after Radioiodine Radiation Thyroiditis Orbitopathy and Radioiodine

One regimen involves prednisone, 0.4 to 0.5 mg/kg given 1 month before 131I treatment, with a gradual tapering over 3 to 4 months

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

Surgery

current surgical procedure of choice for treatment of Graves’ disease is a neartotal thyroidectomy.

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

Complications of Surgery

Apart from direct request by the patient, surgery is recommended only when the shortcomings of other modes of therapy are of particular importance,

such as in patients with: allergy to anti-thyroid drugs, a coincident cold nodule, a very large goiter need for a rapid return to normal.

TOXIC MULTINODULAR GOITER

Radioiodine may be the treatment of choice

Surgical therapy is often recommended in patients with obstructive manifestations.

TOXIC ADENOMA

Hyperfunctioning adenomas may eventually cause clinicalhyperthyroidism, but many do so slowly, and others not at all

Clinically euthyroid subjects who wish to avoid both surgery and radioiodine therapy may be monitored withannual TSH measurements

suppression of TSH below normal, particularly to less than 0.1 mU/L, indicates hyperthyroidism, and therapy may be warranted

Radioiodine For the patient older than 18 years of

age with a nodule 5 cm in diameter or smaller

Surgery

Summary of HyperthyroidismHyperthyroidism Age % Enlarged Pain RAIU Treatment

Graves (TSI Abeye, dermo, bruit)

20 - 40 60% Diffuse None ↑↑ ATD – 18 m

Toxic MNG > 50 20% Lumpy Pressure ↑ RAI, Surgery

Single Adenoma 35 - 50 5% Single None ± RAI, ATD

S Acute Thyroiditis Any age 15% None Yes ↓↓ NSAID, Ster.

TSH is markedly low, FT4 is elevated

CP1273670-70