Ch. 61 Thyroid Disorders and Pharmacology

What is the thyroid, Gland?

The thyroid is a small butterfly shaped endocrine gland located in front of the neck just below the voice box (larynx)

What does the thyroid do?

The thyroid produces hormones that regulate the body's metabolism, energy, HR, body temp, and growth.

What hormones do the thyroid produce?

Triiodothyronine (T3): A highly potent active thyroid hormone; its synthetic pharmaceutical equivalent is liothyronine.

Thyroxine (T4 or tetraiodothyronine): The primary circulating thyroid hormone; its synthetic pharmaceutical equivalent is levothyroxine.

Thyroid hormones have a profound effect on:

1. Metabolism 

2. Cardiac function 

3. Growth 

Thyroid hormones help promote maturation in infancy and childhood development. 

How does the thyroid process work?

Hypothalamus sends TRH (Thyroid-releasing-hormones)

Anterior Pituitary receives the message and sends TSH (Thyroid stimulating hormone)

Thyroid receives the stimulating message and makes T3 and T4 hormones

The cellular synthesis of T3 and T4 is directly stimulated by

low plasma levels of iodine and requires adequate dietary iodine uptake.

Negative Feedback:

As circulating plasma levels of T3 and T4 rise, they signal back to the anterior pituitary and hypothalamus to suppress further release of TSH and TRH

When dietary iodine intake is inadequate, the thyroid gland cannot synthesize sufficient amounts of T3 and T4. In response to low circulating thyroid hormone levels, the anterior pituitary attempts to compensate by

increasing TSH production.

continuous, elevated TSH stimulation causes TSH to accumulate at the thyroid gland, stimulating excessive cellular proliferation. This hyperstimulation results in

physical enlargement of the thyroid gland—a condition known as a goiter—and frequently leads to underactive thyroid function (hypothyroidism).

Serum thyroid-stimulating hormone (TSH) Thyroid function Test: 

• Screening and diagnosis of hypothyroidism 

• Elevated TSH is indication of hypothyroidism 

Thyroid function Tests: 

Serum T4 Test: Can measure total T4 or free T4 

Serum T3 Test: Can measure total T3 or free T3  

HYPOTHYROIDISM: 

Severe deficiency of thyroid hormone

Congenital Hypothyroidism (infancy) treatment

Replacement therapy with thyroid hormones

Severe form of hypothyroidism?

Myxedema (adults)

How is myxedema treated?

Replacement therapy with thyroid hormones; almost in all cases, treatment must continue lifelong.

Clinical presentation of hypothyroidism (adults) 

• Pale, puffy, and expressionless face 

• Cold and dry skin 

• Brittle hair or loss of hair 

• Heart rate and temperature are lowered 

• Lethargy and fatigue 

• Intolerance to cold 

• Impaired mentality 

Causes of hypothyroidism: 

• Usually due to malfunction of the thyroid 

• Hashimoto's disease: Chronic autoimmune thyroiditis 

• Insufficient iodine in the diet 

• Surgical removal of thyroid and destruction of thyroid with radioactive iodine 

• Adults: insufficient secretion of TSH and thyrotropin-releasing hormone (TRH) 

Standard treatment for hypothyroidism:

Levothyroxine (T4) is the standard, and Liothyronine (T3) is an Option

Hypothyroidism during pregnancy

In first trimester it can result in permanent neuropsychologic deficits in the child

Hypothyroidism in infancy

• May be permanent or transient (Temporary or lasting for a short period)

• Can cause mental retardation and derangement of growth

Two forms of Hyperthyroidism:

1. Graves' disease (most common cause)

2. Toxic nodular goiter (Plummer's disease)

Graves' disease

MOST COMMON FORM of hyperthyroidism

• Affects women 20-40 years old

• Causes exophthalmos (Abnormal bulging or protrusion of one or both eyes outward)

Toxic nodular goiter (Plummer's disease)

A condition where multiple nodules (lumps) develop in the thyroid gland and produce too much thyroid hormone)

Hyperthyroidism cause:

Thyroid-stimulating immunoglobulins (TSIs)

Hyperthyroidism treatment:

• Surgical removal of thyroid tissue

• Destruction of thyroid tissue

• Suppression of thyroid hormone synthesis

• Beta blockers (for example, propranolol)

• Nonradioactive iodine

Thyrotoxic Crisis (Thyroid Storm) Causes:

Patients with thyrotoxicosis undergo significant stress (Surgery, illness, etc.)

It causes High levels of thyroid hormones (TOO MUCH)

Cannot be identified by laboratory testing

Signs Thyrotoxic Crisis (Thyroid Storm):

Hyperthermia (105f or higher), severe tachycardia, restlessness, agitation, tremor, unconsciousness, coma, hypotension, heart failure

Thyrotoxic Crisis (Thyroid Storm) treatment

• Potassium iodide

• Methimazole

• Beta blockers

• Sedation

• Cooling

• Glucocorticoids

• IV fluids

Firstline drug for hyperthyroidism

Hyperthyroidism Methimazole (Tapazole)

Prototype of the thioamides

Hyperthyroidism Methimazole (Tapazole)

Does not cause the liver damage associated with PTU

Does no destroy existing storage of thyroid hormone

May take 3-12 weeks for euthyroid state

More dangerous than PTSU during lactation and during the first trimester of pregnancy.

Applications of Methimazole (Tapazole) in hyperthyroidism:

• Can be used alone for graves' disease

• Adjunct (Something that can be used alongside) to radiation therapy until effects of radiation become manifest

• Suppress thyroid hormone synthesis in preparation for thyroid gland surgery (subtotal thyroidectomy)

• PTs experiencing thyrotoxic crisis (Although PTU is preferred)

Methimazole is considered a

hazardous agent, handle with caution

Thyroid Hormone Preparations Levothyroxine (Synthroid)

• Synthetic preparation of thyroxine (T4) and drug of choice for hypothyroidism

• Conversion to T3

• Half-life: 7 days

• Used for all forms of hypothyroidism

Levothyroxine (Synthroid) Should be taken in the

morning at least 30 to 60 minutes Before breakfast.

Adverse effects: Levothyroxine (Synthroid)

• Tachycardia

• Angina

• Tremors

• Can intensify effects of warfarin

Levothyroxine (Synthroid) Drug interactions:

• Drugs that reduce levothyroxine absorption

• Drugs that accelerate levothyroxine metabolism

• Warfarin

• Catecholamines

Propylthiouracil (PTU)

Inhibits thyroid hormone synthesis. Second-line drug for Graves’ disease. Short half-life (about 90 minutes). Full benefits may take 6–12 months

Therapeutic uses: Propylthiouracil (PTU)

• Graves’ disease

• Adjunct to radiation therapy

• Preparation for thyroid gland surgery

• Thyrotoxic crisis

Adverse effects: Propylthiouracil (PTU)

•Agranulocytosis (most serious)

•Hypothyroidism

•Pregnancy and lactation

•Can cause severe liver damage

PTU (propylthiouracil) vs. Methimazole

• PTU can cause severe liver injury, whereas methimazole does not.

• PTU has a shorter half-life than methimazole (90 minutes vs. 6 to 13 • hours), hence it requires two or three daily doses rather than one.

• PTU crosses the placenta less readily than does methimazole and achieves lower concentrations in breast milk.

• PTU blocks conversion of T4 to T3 in the periphery, whereas methimazole does not.

Radioactive Iodine-131 (131I)

• Radioactive isotope of stable iodine

• Emits gamma and beta rays

• Half-life: 8 days

• 2–3 months for full effect

Used in Graves’ disease

Radioactive Iodine-131 (131I) Effect on the thyroid:

Destroys the overactive thyroid cells (tissue) with beta and gamma rays

Advantages and disadvantages of 131I therapy:

- Contraindicated in pregnancy/breast feeding

- Destroys overactive thyroid cells and decreases T3 and T4 production

- May destroy too many thyroid cells, causing underactive thyroid, hypothyroidism

Nonradioactive Iodine Lugol’s Solution

• Strong iodine solution (Lugol’s solution)

• Used to suppress thyroid function in preparation for thyroidectomy

Nonradioactive Iodine Lugol’s Solution Adverse effects:

Could be mild toxicity: Brassy taste, Burning sensation in the mouth and throat, Soreness of the teeth and gums, GI Injury

Beta Blockers

• Can suppress tachycardia and other symptoms of Graves’ disease.

• Benefits derive from beta-adrenergic blockade, not from reducing levels of T3 or T4.

• Beneficial in thyrotoxic crisis