Chapter 23 The Thyroid Gland

Congenital hypothyroidism occurs in

1 of 4,000 live births.

Thyroid Hormone Synthesis

1. Iodine 2. Follicles

(Protein Binding of Thyroid Hormone) Three major binding proteins:

1. Thyroxine-binding globulin (TBG)—can be elevated in individuals taking recurring regimens of androgens or anabolic steroids. 2. Thyroxine-binding prealbumin (TBPA) 3. Albumin

Protein Binding of Thyroid Hormone, Two active forms of thyroid hormone:

1. Triiodothyronine (T3) 2. Tetraiodothyronine (T4)

***Graves's Disease; Strong familial disposition

15% of patients have close relative with this condition.

TSH (most useful)

2nd- & 3rd-generation assays used in hormone replacement therapy & to screen for hyper- & hypothyroidism

Individuals should be tested for hypothyroidism beginning at age ________________________; more frequently if risk factors are present.

35 & every 5 years thereafter

In Graves's disease, Women are _____________more likely than men to develop it.

5 times

Thyroid Nodules; Common, Clinically apparent nodules are present in

6.4% of adult women & 1.5% of adult men

Iodine Intake of ___________ daily leads to hypothyroidism.

<50 mcg

Disorders of the Thyroid; Thyrotoxicosis:

A constellation of findings that result when peripheral tissues are presented with, & respond to, an excess of thyroid hormone

Nonthyroidal Illness

Abnormalities in thyroid function tests of hospitalized patients -especially critically ill patients. Central hypothyroidism & thyroid hormone-binding changes are associated with severe illness. Changes may be appropriate adaptations to illness.

Thyroglobulin test

An ideal tumor marker for thyroid cancer patients

TSH (thyroid stimulating hormone)

Circulates to thyroid gland & increases production & release of thyroid hormone

A 26-year-old man presents with a 3-cm, right lobe, thyroid nodule and a normal TSH. What is the next test that should be performed?

FNA of the nodule

Most accurate tool in evaluation of nodules (Thyroid Evaluation)

Fine needle aspiration (FNA)

The fetus

Is dependent on thyroid hormone for normal neurological development

Hypothyroidism

Low free T4 level with a normal or high TSH One of most common disorders of thyroid gland, occurring in 5-15% of women >65 years old Can lead to hyponatremia, anemia, hyperlipidemia

Graves's Disease

Most common cause of thyrotoxicosis An autoimmune disease in which antibodies are produced that activate TSH receptor

THE TRH STIMULATION TEST is useful in differentiating HYPOTHALAMIC HYPOTHYROIDISM from

PITUITARY HYPOTHYROIDISM

Thyroid Anatomy and Development

Positioned in lower anterior neck & shaped like a butterfly Made up of 2 lobes that rest on each side of trachea; band of thyroid tissue (isthmus) runs anterior to trachea & bridges lobes

Hypothalamic-pituitary-thyroid axis-slide

See pic

In cytoplasm, T4 is deiodinated into

T3

T3 leads to proteins that influence metabolism & development. Most active thyroid hormone will be elevated more than

T4 in hyperthyroidism

The thyroid gland depends on

TPO (Thyroid peroxidase) to permit iodination of the tyrosyl residues to make MIT( monoiodothyronine) and DIT(diiodothyronine)

Most useful Blood Test testing for Thyroid Evaluation

TSH

The primary serum test to screen for thyroid disease is

TSH

Thyroid Nodules

Thyroid ultrasound finds unsuspected nodules in 20-45% of women & 17-25% of men. 5-9% prove to be thyroid cancer.

All of the following statements about Iodine are true EXCEPT a. Radioactive iodine treatment of Graves disease is effective in less than 40% of patients treated with this agent. b. Iodine deficiency is one of the most common causes of hypothyroidism in the world c. T4 has four iodine molecules d. RAIU is often useful in determining the cause of thyrotoxicosis.

a

Of the following, which will MOST likely interfere with quantitation of thyroglobulin? a. Antithyroglobulin autoantibodies b. Thyroid-stimulating antibodies c. TSH receptor antibodies d. Thyroid peroxide antibodies

a. Antithyroglobulin autoantibodies

A 65-year-old woman presents with fatigue, hypothermia, pericardial effusions, hair loss. Her thyroid function test show a significantly elevated TSH and a low free T4. All of the following laboratory test abnormalities may be associated with her underlying condition EXCEPT a. Elevated WBC b. An elevated cholesterol level c. Anemia d. Elevated CPK levels

a. Elevated WBC

A 34-year-old woman presents with goiter, tachycardia, and weight loss of 2 months duration. TSH is undetectable and free T4 is high . All of the following tests are useful in diagnosing the cause of the hyperthyroidism EXCEPT a. FNA biopsy of the thyroid gland b. TSH receptor antibodies c. RAIU d. TSH

a. FNA biopsy of the thyroid gland

All of the following abnormalities might be expected in a severely ill patient EXCEPT a. Low rT3 b. Low T4 c. Low T4 d. Low TSH

a. Low rT3

The thyroid gland produces all of the following EXCEPT a. TSH b. Thyroglobulin c. T3 d.T4

a. TSH

Hypothyroidism is generally associated with all of the following EXCEPT a. TSH receptor antibodies b. Depression c. An elevation of TSH levels d. TPO antobodies

a. TSH receptor antibodies

The following are treatment options for hyperthyroidism associated with Graves's disease EXCEPT a. Thyroid hormone b. PTU c. Beta-blockers d. Radioactive iodine

a. Thyroid hormone

Thyrotoxicosis; Symptoms:

anxiety, emotional lability, weakness, tremor, palpitations, heat intolerance, perspiration, weight loss

Graves' Disease Treatments; Medication:

beta-blockers, propylthiouracil, methimazole

Thyroxine-binding globulin (TBG)

can be elevated in individuals taking recurring regimens of androgens or anabolic steroids.

Painful sub-acute Thyroiditis:

characterized by neck pain, low-grade fever, myalgia, tender diffuse goiter, swings in thyroid function test

Most common cause of Hypothyroidism in developed countries is

chronic lymphocytic thyroiditis (Hashimoto's disease)

Of the following thyroid hormones, which is considered the most biologically active? a. T3 bound to TBG b. T4 bound to TBG c. Free T4 d. Free T3 e. rT3

d. Free T3

In Nonthyroidal Illness, Less T4 is converted to active T3, leading to

decreased levels of T3 and higher levels of reverse T3.

Graves' Disease Treatments; Radioactive iodine:

destruction of thyroid tissue to make patient hypothyroid; lifelong treatment with thyroid replacement therapy is usually required

Thyroid autoimmunity

detects antibodies directed at thyroid tissue

The old T3 resin test has been replaced with a

direct assay for T3

Graves' Disease. Lab testing shows _____________________ with undetectable TSH.

high free T4 and/or T3 level

Amiodarone-Induced Thyroid Disease leads to

hypothyroidism in 8-20% of patients hyperthyroidism in 3%

Iodine is an essential component of thyroid hormone; iodine deficiency leads to

hypothyroidism, mental retardation, cretinism.

Because TSH stimulates __________________, TSH levels must be taken into account.

iodine uptake

Nonthyroidal Illness is Characterized by

low total T4, free T4, & TSH

High uptake of Radioactive iodine suggests

metabolic activity

Low uptake of Radioactive iodine suggests

metabolic inactivity

Thyroid hormone is critical to

neurologic development of fetus.

Graves' Disease Symptoms of ophthalmopathy:

orbital soft tissue swelling, injection of conjunctivae, proptosis, double vision, & corneal disease

Toxic Adenoma and Multinodular Goiter occur in

patients with hyperthyroidism & palpable nodules

Parathyroid glands:

posterior to thyroid; regulate serum calcium levels & recurrent laryngeal nerves that innervate vocal cords

Graves' Disease Treatments; Surgery:

preferred in cases of thyroid cancer or to avoid eye problems associated with radioactive iodine treatment

Hypothyroidism can be divided into

primary, secondary, or tertiary disease

Biosynthesis of Thyroid Hormones slide

see pic

Toxic Adenoma and Multinodular Goiter; ***Treatment:

surgery, radioactive iodine, or medication

Conditions affecting thyroid hormone levels are much more common than

those affecting calcitonin.

Hypothyroidism is Treated with

thyroid hormone replacement therapy

***Features of Graves' Disease

thyrotoxicosis, goiter, ophthalmopathy, & dermopathy

(Protein Binding of Thyroid Hormone) When released into circulation, only 0.04% of T4 & 0.4% of T3 are

unbound by proteins & available for hormonal activity.

Thyroid Ultrasound

●Has become more significant in past several years ●Capable of detecting thyroid nodules of exceptionally small size (<1 cm)

Control of Thyroid Function

●Hypothalamic-pituitary-thyroid axis regulates thyroid hormone production ●Thyrotropin-releasing hormone (TRH) ●TSH

Amiodarone-Induced Thyroid Disease; Effects

●Inhibits thyroid hormone production -Wolff-Chaikoff effect- ●Blocks T4 to T3 conversion

Fine needle aspiration (FNA) (Other Tools for Thyroid Evaluation)

●Often the first step & most accurate tool in evaluation of nodules ●Routine use allows prompt identification & treatment of malignancies & avoids unnecessary surgery in benign cases. ●Small-gauge needle is inserted into nodule & cells are aspirated.

Thyrotropin-releasing hormone (TRH)

●Synthesized by neurons in supraoptic & supraventricular nuclei of hypothalamus & stored in median eminence ●When secreted, stimulates cells in anterior pituitary gland to manufacture & release thyrotropin (TSH)

Actions of Thyroid Hormone

●Thyroid hormone circulates in bloodstream. ●In cytoplasm, T4 is deiodinated into T3 . ●T3 leads to proteins that influence metabolism & development. Most active thyroid hormone will be elevated more than T4 in hyperthyroidism

Effects of thyroid hormone:

●Tissue growth ●Brain maturation ●Increased heat production ●Increased oxygen consumption ●Increased number of beta-adrenergic receptors

(Drug-Induced Thyroid Dysfunction) Amiodarone-Induced Thyroid Disease

ꙮAmiodarone ●Used to treat cardiac arrhythmias ●Fat-soluble with a long half-life (50 days) ●37% of molecular weight is iodine.

Toxic Adenoma and Multinodular Goiter

ꙮCaused by autonomously functioning thyroid tissue ꙮNeither TSH nor TSH receptor-stimulating immunoglobulin is required to stimulate thyroid hormone production. ꙮAssociated with receptor mutations in some toxic nodules

Subacute Thyroiditis

ꙮCharacterized by transient changes in thyroid hormone levels ꙮAssociated with inflammation of thyroid gland, leakage of stored thyroid hormone, repair of gland

Thyrotoxicosis; Possible causes

ꙮExcessive thyroid hormone ingestion ꙮLeakage of stored thyroid hormone from thyroid follicles ꙮExcessive thyroid gland production of thyroid hormone (hyperthyroidism)

Serum T4 and T3

ꙮMeasured by radioimmunoassay or chemiluminometric assay ꙮThe old T3 resin test has been replaced with a direct assay for T3

Graves' Disease Treatments

ꙮMedication: beta-blockers, propylthiouracil, methimazole ꙮRadioactive iodine: destruction of thyroid tissue to make patient hypothyroid; lifelong treatment with thyroid replacement therapy is usually required ꙮSurgery: preferred in cases of thyroid cancer or to avoid eye problems associated with radioactive iodine treatment

Drug-Induced Thyroid Dysfunction; Three classifications of sub-acute Thyroiditis:

ꙮPostpartum: occurs in 3-16% of women in postpartum ꙮPainless: similar to postpartum type, except with no associated pregnancy ꙮPainful: characterized by neck pain, low-grade fever, myalgia, tender diffuse goiter, swings in thyroid function test

Nuclear Medicine Evaluation

ꙮRadioactive iodine ●Assesses metabolic activity of thyroid ●Evaluates & treats thyroid cancer ●Given orally, a % of dose is taken up by thyroid gland. ●High uptake suggests metabolic activity. ●Low uptake suggests metabolic inactivity. ●Because TSH stimulates iodine uptake, TSH levels must be taken into account.

Follicles (Thyroid Hormone Synthesis)

ꙮSite of thyroid hormone synthesis ꙮSpheres of thyroid cells surrounding a colloid core ꙮInside thyroid cell, iodine is oxidized & bound with tyrosyl residues on thyroglobulin to form thyroid hormone.

Tests for Thyroid Evaluation Blood Tests

ꙮTSH (most useful) ꙮSerum T4 & T3 ꙮThyroglobulin ꙮThyroid autoimmunity

The Thyroid Produces 2 hormones

ꙮThyroid hormone: critical in regulating body metabolism, neurologic development, & other functions ꙮCalcitonin: secreted by parafollicular C cells & involved in calcium homeostasis

Iodine

ꙮTrace element & key component of thyroid hormone ꙮMajor fraction of organic iodine circulating in the blood is T4 ꙮFound in seafood, dairy products, breads, vitamins ꙮIntake of <50 mcg daily leads to hypothyroidism.