Hyperthyroidism

DR.HARDIK SHAHST.STEPHEN’S HOSPITAL

DELHI

• Hyperthyroidism results from excessive secretion of thyroid hormone.

• Graves disease is the most common cause of hyperthyroidism.

CAUSES OF HYPERTHYROIDISM

• CIRCULATING THYROID STIMULATORS: Graves disease Neonatal Graves disease Thyrotropin-secreting tumor (Pituitary adenoma) Choriocarcinoma• THYROIDAL AUTONOMY:• Toxic multinodular goiter• Toxic solitary adenoma• Congenital hyperthyroidism• Iodine-induced hyperthyroidism (Jod-Basedow)

• DESTRUCTION OF THYROID FOLLICLES (THYROIDITIS) Subacute thyroiditis Painless or postpartum thyroiditis Amiodarone-induced thyroiditis Acute (infectious) thyroiditis• EXOGENOUS THYROID HORMONE Iatrogenic Excess ingestion of thyroid hormone Factitious Excess ingestion of thyroid hormone Hamburger thyrotoxicosis• ECTOPIC THYROID TISSUE Struma ovarii - Ovarian teratoma containing thyroid tissue Metastatic follicular thyroid cancer Pituitary resistance to thyroid hormone

Graves Disease

• It is an autoimmune disorder; production of thyroid-stimulating immunoglobulin (TSI) results in diffuse toxic goiter.

• Graves disease occurs in approximately 0.02% of children (1 : 5,000).

• It has a peak incidence in the 11- to 15-yr old; there is a 5 : 1 female to male ratio.

• Most children with Graves disease have a positive family history of some form of autoimmune thyroid disease.

Etiology and Pathology:• Enlargement of the thymus, splenomegaly, lymphadenopathy, infiltration of the

thyroid gland and retro-orbital tissues with lymphocytes and plasma cells, and peripheral lymphocytosis are well-established findings in Graves disease.

• In the thyroid gland, T helper cells (CD4+) predominate in dense lymphoid aggregates; in areas of lower cell density, cytotoxic T cells (CD8+) predominate.

• The percentage of activated B lymphocytes infiltrating the thyroid is higher than in peripheral blood.

• A postulated failureof T suppressor cells allows expression of T helper cells, sensitized to the TSH antigen, which interact with B cells.

• These cells differentiate into plasma cells, which produce thyrotropin receptor–stimulating antibody (TRSAb).

• TRSAb binds to the receptor for TSH and stimulates cyclic adenosine monophosphate, resulting in thyroid hyperplasia and unregulated overproduction of thyroid hormone.

• In addition to TRSAb, thyrotropin receptor-blocking antibody (TRBAb) may also be produced, and the clinical course of the disease usually correlates with the ratio between the two antibodies.

• In whites, Graves disease is associated with HLA-B8 and HLA-DR3.

• Graves disease is also associated with other HLA-D3–related disorders such as Addison disease, type 1 diabetes mellitus, myasthenia gravis, and celiac disease.

• In family clusters, the conditions associated most commonly with Graves disease are autoimmune lymphocytic thyroiditis and hypothyroidism.

CLINICAL MANIFESTATIONS:• The earliest signs in children may be emotional

disturbances accompanied by motor hyperactivity. • The children become irritable and excitable, and they

cry easily because of emotional lability. • They are restless sleepers and tend to kick their covers

off. • Their schoolwork suffers as a result of a short attention

span and poor sleep. • Tremor of the fingers can be noticed if the arm is

extended. • There may be a voracious appetite combined with loss

of or no increase in weight. • Recent height measurements might show an

acceleration in growth velocity.

Symptoms:• Hyperactivity, irritability, altered mood, insomnia,

anxiety• Heat intolerance, increased sweating• Palpitations• Fatigue, weakness• Dyspnea• Weight loss with increased appetite (weight gain in 10%

of patients)• Pruritus• Increased stool frequency• Thirst and polyuria• Oligomenorrhea or amenorrhea

Signs:• Sinus tachycardia, atrial fibrillation (rare in children),

supraventricular• tachycardia• Fine tremor, hyperkinesis, hyperreflexia• Warm, moist skin• Palmar erythema, onycholysis• Hair loss• Osteoporosis• Muscle weakness and wasting• High-output heart failure• Chorea• Periodic (hypokalemic) paralysis (primarily in Asian men)• Psychosis (rare

MANIFESTATIONS OF GRAVES DISEASE• Diffuse goiter• Ophthalmopathy Upper eyelid retraction (the most common sign of Graves ophthalmopathy) Infrequent or incomplete blinking (Stellwag sign) Lid lag upon infraduction (Von Graefesign) or globe lag on supraduction (Kocher sign) Widened palpebral fissure during fixation (Dalrymple sign) Incapacity to close eyelids completely (lagophthalmos) Prominent stare (Binswanger sign) Inability to keep the eyeballs converged (Mobius sign) Limited extraocular gaze (especially upward) Blurred vision due to inadequate convergence and accommodation Swollen orbital contents and puffy lids Chemosis Globe pain Exophthalmos Enlarged lacrimal glands (visible on inspection and palpable) Dysfunctional lacrimal glands with decreased quantity and abnormal composition of tears Corneal injection, ulceration, punctate epithelial erosions, or superior limbic keratoconjunctivitis (rare) Decreased visual acuity due to papilledema, retinal edema, retinal hemorrhages, or optic nerve damage

(rare)• Localized dermopathy (rare in children)• Lymphoid hyperplasia• Thyroid acropachy (rare in children)

• Many scoring systems have been used to gauge the extent and activity of the orbital changes in Graves' disease.

• The "NO SPECS" scheme is an acronym derived from the following eye changes:

0 = No signs or symptoms 1 = Only signs (lid retraction or lag), no symptoms 2 = Soft tissue involvement (periorbital edema) 3 = Proptosis (>22 mm) 4 = Extraocular muscle involvement (diplopia) 5 = Corneal involvement 6 = Sight loss

• Thyroid crisis, or thyroid storm, is a form of hyperthyroidism manifested by an acute onset, hyperthermia, severe tachycardia, heart failure, and restlessness.

• There may be rapid progression to delirium, coma, and death. Precipitating events include trauma infection, radioactive iodine treatment, or surgery.

• Apathetic, or masked, hyperthyroidism is another variety of hyperthyroidism characterized by extreme listlessness, apathy, and cachexia.

• A combination of both forms can occur. • These symptom complexes are rare in children.

LABORATORY FINDINGS• Serum levels of thyroxine (T4), triiodothyronine (T3), free T4, and

free T3 are elevated. • In some patients, levels of T3 may be more elevated than those

of T4. • Levels of TSH are suppressed to below the lower range of normal. • Antithyroid antibodies, including thyroid peroxidase antibodies,

are often present. • Most patients with newly diagnosed Graves disease have

measurable TRSAb;• Measurement of TSI or TBII is useful in confirming the diagnosis

of Graves disease. • Radioiodine is rapidly anddiffusely concentrated in the thyroid,

but this study is rarely necessary. • Children who experience an acceleration of growth might also

have advanced skeletal maturation. • Bone density may be reduced at diagnosis but returns to normal

with treatment.

TREATMENT:1. Antithyroid drugs2. Radioactive iodine (131I)3. Surgery

1. Antithyroid drugs 1. Propylthiouracil (PTU) and 2. Methimazole (Tapazole). • Both compounds inhibit incorporation of trapped inorganic iodide

into organic compounds, and they might also suppress TRSAb levels by directly affecting intrathyroidal autoimmunity.

• Methimazole is at least 10 times more potent than PTU, longer serum half-life (6-8 hr vs 0.5 hr); PTU generally is administered 3 times daily, but methimazole can be given once daily.

• Unlike methimazole, PTU is heavily protein bound and has a lesser ability to cross the placenta and to pass into breast milk; theoretically, PTU is the preferred drug during pregnancy and for nursing mothers.

• Due to reports of severe liver disease in patients treated with PTU, with some patients requiring liver transplant or potentially suffering a fatal outcome, the consensus is to use only methimazole to treat children with Graves disease.

• The initial dosage of methimazole is 0.25-1.0 mg/kg/24 hr given once or twice daily.

• Smaller initial dosages should be used in early childhood.

• Rising serum levels of TSH to greater than normal indicates overtreatment and leads to increased size of the goiter.

• Clinical response becomes apparent in 3-6 wk, and adequate control is evident in 3-4 mo.

• The dose is decreased to the minimal level required to maintain a euthyroid state.

• Transient granulocytopenia (<2,000/mm3) is common; it is asymptomatic .

• Transient urticarial rashes are common. • They may be managed by a short period off

therapy, and then restarting the antithyroid drug.

• The most severe reactions are hypersensitive and include agranulocytosis (0.1-0.5%), hepatitis (0.2-1%), a lupus-like polyarthritis syndrome, glomerulonephritis, and an ANCA-positive vasculitis involving the skin and other organs.

• Radioiodine treatment or surgery is indicated:

- when adequate cooperation for medical management is not possible,

- when adequate trial of medical management has failed to result in permanent remission, or

- when severe side effects preclude further use of antithyroid drugs.

2. Radioiodine• It is an effective, relatively safe first or alternative therapy for

Graves disease in children >10 yr of age. • Pretreatment with antithyroid drugs is unnecessary; if a

patient is taking them, they should be stopped a week before radioiodine administration.

• Many pediatric endocrinologists prefer to select a dose of radioiodine to ensure complete ablation of thyroid tissue.

• A dose of 300 μCi/g of thyroid tissue, or a total dose of approximately 15 mCi, will achieve this goal.

• Essentially all patients treated at this dose will become hypothyroid; the time course to hypothyroidism averages 11 wk, with a range of 9-28 wk.

• Because the full effects of treatment may not be complete for 1-6 mo, adjunctive therapy with a β-adrenergic antagonist and lower doses ofantithyroid drugs are recommended.

3. Surgery• Subtotal thyroidectomy, a safe procedure when performed by an

experienced team, is done only after the patient has been brought to a euthyroid state.

• This may be accomplished with methimazole over 2-3 mo. • After a euthyroid state has been attained, a saturated solution of

potassium iodide, 5 drops/24 hr, are added to the regimen for 2 wk before surgery to decrease the vascularity of the gland.

• Complications of surgical treatment are rare and include hypoparathyroidism (transient or permanent) and paralysis of the vocal cords.

• The incidence of residual or recurrent hyperthyroidism or hypothyroidism depends on the extent of the surgery.

• Most recommend near-total thyroidectomy. • The incidence of recurrence is low, and most patients

becomehypothyroid.

• A β-adrenergic blocking agent such as propranolol (0.5- 2.0 mg/kg/24 hr orally, divided 3 times daily) or atenolol (1-2 mg/ kg orally given once daily) is a useful supplement to antithyroid drugs in the management of severely toxic patients.