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Outline

Physiology of thyroid gland

Causes of thyrotoxicosis

Clinical features of hyperthyroidism

Diagnosis

Management

Thyroid storm

References

Thyroid gland

Wt 20-25g

parts

Pyramidal lobe in 50%

Rt &Lt. lobe

Isthmus

Blood supply

aa Sup. thyroid aa

Inf. thyroid aa (thyrocervical trunk)

Ima aa in 3%

veins Sup. thyroid vv

Middle thyroid vv

Inf. thyroid vv

Thyroid hormone

Characteristics

Anabolic hormone

Secreted in two forms : T3 and T4

Ratio to T4 to T3 : 20 to 1

T3 is more active than T4

Thyroid hormone synthesis

Begins with iodide

Iodide enters the thyroid follicular cells by

active transport

Thyroperoxidase catalyzes oxidation of iodide to

iodine

Peroxidase catalyzes iodination of thyroglobulin

Iodination of thyroglobulin ‘s tyrosine residue

yields 2 products

Monoiodotyrosine (MIT)

Diiodotyrosine (DIT)

Peroxidase also catalyzes coupling

2 DIT molecules= =T4

MIT +DIT + T3

Thyroid hormone regulation

Steps

Hypothalamus secretes TRH in to the

portal system

Pituitary thyrotrophs secrete TSH

Thyroid gland secretes T4 and T3

Thyroid hormones act as a negative

feedback to inhibit further secretion of

TRH and TSH

Thyroid hormone

Thyroid hormone function ( 4 B’s)

Brain maturation

Bone growth

Beta adrenergic effects

BMR

Hyperthyroidism

Thyrotoxicosis

symptom complex due to raised levels of thyroid

hormones

Hyperthyroidism

Reserved for disorders that result from sustained

overproduction and release of hormone by the thyroid

itself.

8/22/2015managment of hyperthyroidism

Causes of Thyrotoxicosis

Graves Disease (Basedow’s disease)

Characteristics

The most common cause of thyrotoxicosis (60-80 %)

auto-immune disease

The most important autoantibody is

Thyroid Stimulating Immunoglobulin (TSI) or TSA

Others - (anti-TPO) (anti-TG)

Symetrical enlargement of the thyroid

Hyper secretion of thyroid hormones

Patients tend to be young women

Toxic Multinodular Goiter(TMG) (Plummer ds)

Characteristics TMG is the next most common cause of hyperthyroidism - 20%

Caused by focal regions of hyper functioning follicular cells ( independent of TSH)

Due to mutation of the TSH receptor

Can be the result of chronic iodine deficiency

Excessive TSH stimulation induces

Focal hyperplasia

Subsequent necrosis and hemorrhage

Nodule formation

Cardiovascular manifestations tend to predominate

Toxic Single Adenoma (TSA) (Goetsch’s ds)

Characteristics

TSA is a single hyper functioning follicular thyroid adenoma.

Benign monoclonal tumor that usually is larger than 2.5 cm

It is the cause in 5% of patients who are thyrotoxic

Nuclear Scintigraphy scan shows only a single hot nodule

TSH is suppressed by excess of thyroxines

So the rest of the thyroid gland is suppressed

Clinical Features of hyperthyroidism

It is eight times more common in females.

Sex M : F ratio

Graves Disease 1: 5 to 1:10

Toxic MNG 1: 2 to 1: 4

Occurs in any age group.

Age

Graves disease 20 to 40

Toxic MNG > 50 yrs

Toxic Single Adenoma 35 to 50.

Clinical features can be grouped

those related to hyperthyroidism

Those that are specific to Graves disease

those related to hyperthyroidism

Specific to Graves Disease

1. Diffuse painless and firm enlargement of thyroid gland

2. Ophthalmopathy – Eye manifestations – 50% of cases

Classification of Eye Changes in Graves' Disease

0) No signs or symptoms.

1) Only signs, no symptoms. (Signs limited to upper lid retraction, stare, lid lag.)

2) Soft tissue involvement (symptoms and signs).

3) Proptosis (measured with Hertel exophthalmometer)

4) Extraocular muscle involvement.

5) Corneal involvement.

6 Sight loss (optic nerve involvement).

Eye Signs in Toxic Goitre

In early stages, may be unilateral but later may become bilateral.

Order of appearance of signs

Stellwag's sign : Absence of normal blinking—so staring look.

Von Graefe`s sign : Upper eye lid lags behind the eye ball as the patient is asked to look downwards.

Dalrymphe's sign : Upper sclera is visible due to retraction of upper eye lid.

Joffroy's sign : Absence wrinkling in the forehead on looking upwards with the face

inclined downwards.

Moebius sign : Inability or failure to converge the eye balls

Gifford's sign: Difficulty in eversion of the upper lid.

Specific to Graves Disease……..

3. Thyroid dermopathy

consists of thickening of the skin, particularly over the lower

tibia, due to accumulation of glycosaminoglycans

(pre tibial myxedema)

Is usually bilateral

4. Thyroid Acropachy

Thyroid acropachy is clubbing of fingers and toes in primary

thyrotoxicosis.

diagnosis

Examinations, symptoms

Thyroid blood tests

Thyroid function tests TSH , T4,T3

Thyrroid antibodies TSI, ANTI TPO, ANTI Tg

Other — nonspecific laboratory findings.

low serum total, LDL, and (HDL) cholesterol concentrations

normochromic, normocytic anemia

Serum alkaline phosphatase

Diagnosis……………….

Thyroid imaging

Radionuclide imaging

Size, shape & function of gland assessed

Increased uptake=“hot", less risk of malignancy,<5%

Decreased uptake=“cold" higher risk of malignancy,15-20%

Ultrasound

CT/ MRI good for assessment of retrosternal extension.

pathology

www.drsarma.in

Algorithm for Hyperthyroidism

Measure 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

MANAGEMENT

approaches

•Anti thyroid drugs,beta blockers

•Radioactive Iodine I131

•surgery

Choice Of Therapy

•Type of thyrotoxicosis

•Age of the patient

•Co existing medical illness

•Severity of thyrotoxicosis

•Goitre size

•Presence of ophtalmopathy

•Patient preference

Factors influencing

ANTITHYROID DRUGS

Indications for antithyroid drugs:

Patients with high likelihood of remission

the elderly or others with comorbidities increasing

surgical risk or with limited life expectancy

Toxicity in pregnant women

moderate to severe active Graves’

ophthalmopathy (GO)

Before surgery, to make the patient euthyroid

Soon after starting radioactive I131therapy for 6 to

12 weeks

Anti Thyroid Drugs (ATD)

Medications known to inhbit thyroid hormone are

Propylthrouracil

Drug class : thioamides

Metimazole

How long to give ATD ?

Most patients have improved symptoms in 2 weeks and become euthyroid

in about 6 weeks

Check TSH and FT4 every 4 to 6 weeks

In Graves, many go into remission after 12-18 months

Once ATD therapy is discontinued, the patient should be monitored every

three months for the first year, and then annually

40% experience recurrence in 1 yr.

MNG and Toxic Adenoma will not get cured by ATD.

adjuvants

Beta blockers

Inhibit adrenergic effects

Indications

Prompt control of symptoms;

treatment of choice for thyroiditis;

first-line therapy before surgery, radioactive iodine, and antithyroid

drugs;

Contraindications

Use with caution in older patients and in patients with pre-existing

heart disease, chronic obstructive pulmonary disease, or asthma

Propranolol is the most commonly prescribed medication in doses of

about 20 to 40 mg four times daily

Adjuvants ….

Iodides

Block the conversion of T4to T3 and inhibit hormone release

Indications

preoperatively when other medications are ineffective or contraindicated;

to reduce gland vascularity before surgery for Graves’ disease

during preg-nancy when antithyroid drugs are not tolerated;

Complications

Paradoxical increases in hormone release with prolonged use;

common side effects of sialadenitis, conjunctivitis, or acneform rash;

RADIOIODINE THERAPY

Radioactive iodine

Concentrates in the thyroid gland and destroys thyroid tissue

High cure rates with single-dose treatment (80 percent);

treatment of choice for

Graves’ disease in the United States,

Multi nodular goitre, toxic nodules in patients older than 40 years, and

In recurrent thyrotoxicosis

It is effective, safe, and does not require hospitalization.

Given orally as a single dose in a capsule or liquid form.

RADIOIODINE THERAPY………

Drawbacks

Delayed control of symptoms;

post treatment hypothyroidism in majority of patients with Graves’

disease regardless of dosage (82 percent after 25 years);

contraindicated in patients who are pregnant or breastfeeding;

can cause transient neck soreness, flushing, and decreased taste;

radiation thyroiditis in 1 percent of patients;

may exacerbate Graves’ ophthalmopathy;

may require pre treatment with antithyroid drugs in older or cardiac

patients

Surgical Treatment

Surgical treatment is reserved

patient preference

Pregnant women who can’t tolerate ATD

child or adolescent intolerant of ATDs

large goiter, with or without compressive symptoms

severe Graves’ ophthalmopathy

the presence of suspicious nodules

Preoperative Preparation

Standard preparation

make the patient euthyroid/ near euthyroid using antythyroid drugs

Alternative method

rapid control of thyroid status can be achieved with a combination of

thionamides, SSKI, dexamethasone (1 to 2 mg twice daily), and beta

blockers

very rapid control=> operation within a week

Lugol’s iodide solution or saturated potassium iodide( three

drops twice daily) for 7 to 10 days

SURGICAL TECHNIQUE

Extent of thyroidectomy

controversial, and determined by the desired outcome

Risk of recurrence Vs hypothyroid, and surgeons experience

Total or near thyroidectomy

for patients with coexistent thyroid cancer, sever ophthalmopathy,

life treating reactions to antythyroid drugs

Subtotal thyroidectomy is recommended for the rest

bilateral subtotal thyroidectomy in which 1–2 grams of thyroid tissue is left on both sides.

Hartley Dunhill procedure

SURGICAL………..

GRAVES DISEASE

near-total or total thyroidectomy is the procedure of choice

TMNG

near- total or total thyroidectomy should be performed

TOXIC ADENOMA

an ipsilateral thyroid lobectomy, or

isthmusectomy

In patients with coexisting eye disease,

total thyroidectomy

Surgical optionsFeatures

Control of toxicity

Return to euthyroid state

Recurrence

Thyroid failure

Hypoparathyroidism

Followup

Total Thyroidectomy

Immediate

Immediate

None

100%

5%

Minimal

Subtotal thyroidectomy

Immediate

Variable

5%

25%

1%

lifelong

Postoperative management

Following surgery, thyroid hormone replacement should be started

TSH should be measured every 1–2 months until stable, and then annually

RAIT should be used for retreatment of persistent or recurrent

hyperthyroidism following inadequate surgery

Following thyroidectomy, serum calcium hormone levels be measured, and

oral calcium supplementation be administered based on these results

novel minimally invasive therapies

Percutaneous Ethanol Injection (PEI) for Nodules

Injections of ethanol can be administered directly to toxic

thyroid nodules, cysts and large nontoxic thyroid nodules

Ultrasound-Guided Laser Thermal Ablation (LTA) for

Nodules

Percutaneous laser thermal ablation is used to reduce both

hyperfunctioning and compressive nodule

Treatments Under Investigation

Arterial Embolization

Indicated in patients with severe hyperthyroidism who cannot tolerate or

who prefer not to use conventional treatment methods

The Novel Molecule

a small-molecule antagonist that directly inhibits or prevents TSI antibodies from

activating the TSH receptor.

The small-molecule antagonist has not yet been studied in clinical trials

Therapeutic Peptides

antagonistic peptides that interfere with the action of TSH receptor antibodies

as well as peptides that bind to TSH receptor antibodies, preventing them from

reacting with the TSH receptor

Choice of therapy

Diffuse toxic goitre

over 45 years, radioiodine.

under 45 years,

surgery for the large goitre and

anti-thyroid drugs or radioiodine

for the small goitre

Toxic nodular goitre

Surgery

Toxic nodule

Surgery or radioiodine(>45)

Recurrent thyrotoxicosis after surgery

radioiodine is the treatment of choice, but anti-

thyroid drugs may be used in young women

intending to havechildren. Further surgery has

little place.

8/22/2015managment of hyperthyroidism

Thyroid storm

Is a life threatening emergency

Characterized by sudden appearance of clinical signs of hyperthyroidism

due to the abrupt release of T4 and T3 into circulation.

Mortality is as high as 25% to 30%.

Commonly associated with Grave's disease.

Thyroid storm……….

Predisposing conditions:

Medical factors :

Infection ,

Fever

Uncontrolled toxicity

Irregular drug intake

Pregnancy,

Radio iodine therapy

DKA.

Surgical factors

Anxious and nervous patient

before surgery,

Too much handling of gland just

before surgery.

Thyroid storm……….

Clinical features :

Fever ranges from 38 to 41°C

Tachycardia: arrhythmias commonly atrial fibrillation

CHF - initially high output failure, Later may go for Low output failure.

Shock - cardiogenic/hypovolemic

Electrolyte imbalance

Hypo/hyperglycemia may also be present.

Marked anxiety, agitation, psychosis.

TREATMENT

References

HYPERTHYROIDISM AND OTHER CAUSES OF THYROTOXICOSIS: MANAGEMENT GUIDELINES OF THE ATA AND AACE Baskin HJ, Cobin RH, Duick DS, et al (American Association of Clinical Endocrinologists) 2011

Klein I, Becker D, Levey GS.Treatment of hyperthyroid disease. Ann Int Med.1994;121:281-288.

Schwartz’s Principles of Surgery, 9th ed.

William’s Text Book Of Endocrinology, 11th ed.

Bailey & Loves’ Short Practice of Surgery, 25th ed.

Greenspan’s Basic & Clinical Endocrinology, 8th ed.

Uptodate

Thank you

Tips for Coping with Hyperthyroidism

Small measures can be taken to alleviate and reduce

hyperthyroidism symptoms

Try to:

Reduce stress by listening to music, taking a long bath or

meditating in a quiet place

Avoid caffeine and other stimulants as they may worsen

certain symptoms

Ice packs on the throat can help to reduce inflammation

Stay away from refined foods, shellfish, wheat, and alcohol

Avoid food and supplements containing iodine