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Dr: Wael H.Mansy, MDAssistant Professor

College of Pharmacy

King Saud University

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There are two main hormones produced by the thyroid

gland:

1. Thyroxin (T4) and

2. Triiodothyronine (T3). Both hormones are derived from the amino acid

Tyrosine and contain Iodine that is extracted from the

blood. The release of thyroid hormones from the thyroid is

regulated by TRH secreted from the anterior pituitary

gland.

Function of the thyroid gland

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T4 versus T3• T3 ~5X as active as T4• T4 secreted solely form thyroid gland• <20% T3 secreted from the thyroid gland• Majority of T3 from breakdown of T4(de-iodination) in peripheral tissue• Mostly liver and kidneys

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The main actions of T3 and T4

1. Increased basal metabolic rate

2. Maintenance of normal metabolic function.

3. Normal physical, mental and sexual development.

4. Development of the nervous system in the fetus

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Definitions• Goiter– Enlargement of the thyroid gland• Hypothyroidism– Inadequate thyroid hormone production• Thyroiditis– Inflammation of the thyroid gland• Thyrotoxicosisa term that is used to describe the “toxic” effects of excess thyroid hormones on the body.– State resulting from excess production/exposure to thyroidhormone• Hyperthyroidism– Thyrotoxicosis caused by a hyperfunctioning thyroid gland– Excludes thyroiditis or excessive exogenous thyroid hormone

Thyroid Diseases

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Common causes of Hypothyroidism• Thyroiditis: Hashimoto’s thyroiditis in which antibodies are produced against the tissue of the thyroid. Although the exact etiology of this autoimmune disorder is unknown, it can lead to progressive destruction of the thyroid gland and loss of thyroid function.

• Thyroid Surgery or Irradiation

• Iodine deficiency (Goiter)–Most common cause of hypothyroidism worldwide

Hypothyroidism

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Hashimoto’s Thyroiditis• Most common cause of hypothyroidism• Women 30-50 years of age• HLA-DR5 +• Autoimmune thyroiditis– Antimicrosomal antibodies• Against peroxidase– Antithyroglobulin antibodies• Against thyroglobulin– Autoantibodies against TSH receptor• Net effect is prevent TSH stimulation of gland

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Nontoxic goiter:1. Hypertrophy of the thyroid gland that is not accompanied by

excess secretion of thyroid hormones.

2. May occur as a result of dietary iodine deficiency, during

pregnancy and at puberty.

3. Symptoms are those of hypothyroidism.

Toxic goiter :1. Hypertrophy of the thyroid that is accompanied by excess thyroid

production.

2. May be associated with Graves’ disease.

3. Symptoms are those of hyperthyroidism.

Goiter

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GOITER

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Hypothyroidism that occurs during

fetal development

May occur as a result of a

congenital defect in thyroid

development

Severe mental retardation due to

poor development of the brain

Poor overall development and

growth retardation

Hypothyroidism

Cretinism

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Hypothyroidism in the adult

May result from autoimmune destruction of the thyroid or

thyroid injury or removal

Presents with signs of hypometabolism including: Cold intolerance

Weight gain

Fatigue

Bradycardia

Cool, dry skin

Anorexia

Constipation

Edema of the face (swelling around the eyes), hands

and ankles; drooping eyelids.

Hypothyroidism Myxedema

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Possible long-term complications of untreated

hypothyroidism:

cardiac hypertrophy, heart failure, and myxedema coma,

which presents with hypothermia, seizures and

respiratory depression.

Treatment

Thyroid hormone replacement therapy. A variety of

synthetic and natural T3/T4 preparations are available for

use orally.

Hypothyroidism

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Increased synthesis and release of T3 and T4, Hyperthyroidism is

also referred to as Thyrotoxicosis.

Hyperthyroidism may be

1. A primary condition that results from an overactive thyroid

gland.

2. Secondary to excessive stimulation of the thyroid by TSH from

the pituitary.

3. Grave’s disease: the most common causes of hyperthyroidism

4. Plummer’s disease: toxic goiter not associated with Grave’s

disease.

5. a tumor of the thyroid. In rare cases carcinomas arising

outside of the thyroid may produce thyroid hormone or TSH.

Hyperthyroidism

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*Patients with Graves’ disease produce (Thyroid

Stimulating Immunoglobulin) antibodies that bind

TSH receptors on the thyroid and mimic the actions

of TSH leading to excess production of thyroid

hormones.

Hyperthyroidism

Graves’ disease

*Classic Triad (15-20%):Diffuse goiter, Hyperthyroidism, and Ophthalmopathy (exophthalmos)

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The manifestations of hyperthyroidism are essentially the same

regardless of the cause of the hyperthyroidism:

1. Increased basal metabolic rate

2. Increased heat production, patient always feels “hot”

3. Tachycardia

4. Increased catecholamine sensitivity; patients are at risk for

cardiac arrhythmias

5. Increased appetite

6. Weight loss

7. Enhanced bowel activity

8. Behavioral changes : nervousness and hyperactivity

Hyperthyroidism

Manifestations

Laboratory tests to evaluate thyroid function• Serum total thyroxine (total)• Unbound or serum free thyroxine• Serum total triiodothyronine• Serum TSH• Serum thyroglobulin• Antibodies

Thyroid Antibodies• Antithyroglobulin and Antiperoxidase– Markers for Hashimoto’s but not specific

• Thyroid stimulating immunoglobulin—TSI– Against the TSH receptor– The cause of Graves’ disease– Predict neonatal hyperthyroidism

Thyroid Scan

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β-Blocking drugs to blunt the effects of excess adrenergic

stimulation.

Antithyroid drugs (propylthiouracil, carbimazole, methimazole)

that block production of thyroid hormone.

Surgical ablation of a portion of the thyroid may be used.

Following surgery, patients may likewise become hypothyroid and require

thyroid hormone replacement therapy.

Hyperthyroidism

Treatment

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Radioiodine: Given orally and taken up by hormone-producing

cells of the thyroid as if it were normal iodine. The cytotoxic actions

of the β and γ radiation destroy the hormone-producing cells of the

thyroid. After treatment the patient usually becomes hypothyroid and

must be managed with thyroid hormone replacement therapy.

Radioactive iodine should not be used in patients of childbearing

age due to the possible effects on offspring.

Hyperthyroidism

Treatment

Hyperthyroid emergenciesThyroid Storm

• Rare complication of hyperthyroidism where manifestations of thyrotoxicosis become life threatening. Also may be termed Thyrotoxic Crisis.

Precipitating factors:• Infection• Trauma/Surgery• Parturition• DKA• MI• CVA• PE• Withdrawal of thyroid meds• 20-25% cases no precipitant found

• Fever >38.5• Sinus tachycardia out of proportion to fever.• SVT or dysrhythmias with or without CHF• GI symptoms (nausea, vomiting, diarrhea, rarely jaundice)• Volume depletion.• CNS dysfunction (agitation, confusion, delirium, stupor, coma, seizure)

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