Chapter 22: The Thyroid Gland

By Marissa Grotzke, Dev Abraham

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Thyroid
Produces 2 hormones

Thyroid hormone: critical in regulating body metabolism,

neurologic development, & other functions

Calcitonin: secreted by parafollicular C cells & involved in

calcium homeostasis

Conditions affecting thyroid hormone levels are much

more common than those affecting calcitonin.

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Thyroid (contd)

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

Parathyroid glands: posterior to thyroid; regulate serum calcium

levels & recurrent laryngeal nerves that innervate vocal cords

Thyroid hormone is critical to neurologic development of fetus.

Iodine is an essential component of thyroid hormone; iodine

deficiency leads to hypothyroidism, mental retardation, cretinism.

Congenital hypothyroidism occurs in 1 of 4,000 live births.

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Thyroid (contd)

Thyroid Hormone Synthesis

Iodine
Trace element & key component of thyroid hormone
Found in seafood, dairy products, breads, vitamins
Intake of <50 mcg daily leads to hypothyroidism.

Follicles
Site of thyroid hormone synthesis
Spheres of thyroid cells surrounding a colloid core
Inside thyroid cell, iodine is oxidized & bound with tyrosyl residues on
thyroglobulin to form thyroid hormone.

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Thyroid (contd)

Biosynthesis of thyroid hormone

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Thyroid (contd)

Protein Binding of Thyroid Hormone

Two active forms of thyroid hormone:

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

When released into circulation, only 0.04% of T 4 & 0.4% of T3 are

unbound by proteins & available for hormonal activity.

Three major binding proteins:

1. Thyroxine-binding globulin (TBG)
2. Thyroxine-binding prealbumin (TBPA)
3. Albumin

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Thyroid (contd)

Control of Thyroid Function

Hypothalamic-pituitary-thyroid axis regulates thyroid hormone

production

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)

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

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Thyroid (contd)

Hypothalamic-pituitary-thyroid axis

(Adapted from Surks MI, Sievert R. Drugs and thyroid function. N Engl J Med 1995;333:1688)
Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Thyroid (contd)

Actions of Thyroid Hormone

Thyroid hormone circulates in bloodstream.

In cytoplasm, T4 is deiodinated into T3 .

T3 leads to proteins that influence metabolism & development.

Effects of thyroid hormone:

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

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Tests for Thyroid Evaluation

Blood Tests

TSH (most useful)

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

Serum T4 & T3
Measured by radioimmunoassay or chemiluminometric assay

Thyroglobulin
An ideal tumor marker for thyroid cancer patients

Thyroid autoimmunity
Detects antibodies directed at thyroid tissue

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Other Tools for Thyroid Evaluation

Nuclear Medicine Evaluation

Radioactive 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.

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Other Tools for Thyroid Evaluation

(contd)
Thyroid Ultrasound

Has become more significant in past several years

Capable of detecting thyroid nodules of exceptionally small size

(<1 cm)

Fine-Needle Aspiration

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.

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Disorders of the Thyroid

Hypothyroidism

Low free T4 level with a normal or high TSH

One of most common disorders of thyroid gland, occurring in 515% of

women >65 years old

Can lead to hyponatremia, anemia, hyperlipidemia

Can be divided into primary, secondary, or tertiary disease

Most common cause in developed countries is chronic lymphocytic

thyroiditis.

Individuals should be tested beginning at age 35 & every 5 years

thereafter; more frequently if risk factors are present.

Treated with thyroid hormone replacement therapy

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Disorders of the Thyroid (contd)

Thyrotoxicosis

A constellation of findings that result when peripheral tissues are

presented with, & respond to, an excess of thyroid hormone

Possible causes
Excessive thyroid hormone ingestion
Leakage of stored thyroid hormone from thyroid follicles
Excessive thyroid gland production of thyroid hormone
(hyperthyroidism)

Symptoms: anxiety, emotional lability, weakness, tremor,

palpitations, heat intolerance, perspiration, weight loss

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Disorders of the Thyroid (contd)

Graves Disease

Most common cause of thyrotoxicosis

An autoimmune disease in which antibodies are produced that

activate TSH receptor

Features: thyrotoxicosis, goiter, ophthalmopathy, & dermopathy

Strong familial disposition: 15% of patients have close relative

with this condition.

Women are 5 times more likely than men to develop it.

Lab testing shows high free T4 and/or T3 level with undetectable

TSH.

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Disorders of the Thyroid (contd)

Graves Disease

Symptoms of ophthalmopathy: orbital soft tissue swelling, injection

of conjunctivae, proptosis, double vision, & corneal disease

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

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Disorders of the Thyroid (contd)

Toxic Adenoma and Multinodular Goiter

Caused by autonomously functioning thyroid tissue

Neither TSH nor TSH receptor-stimulating immunoglobulin is

required to stimulate thyroid hormone production.

Associated with receptor mutations in some toxic nodules

Occur in patients with hyperthyroidism & palpable nodules

Treatment: surgery, radioactive iodine, or medication

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Drug-Induced Thyroid Dysfunction

Amiodarone-Induced Thyroid Disease

Amiodarone
Used to treat cardiac arrhythmias
Fat-soluble with a long half-life (50 days)
37% of molecular weight is iodine.
Effects
Inhibits thyroid hormone production (Wolff-Chaikoff effect)
Blocks T4 to T3 conversion
Leads to hypothyroidism in 820% of patients & hyperthyroidism in
3%

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Drug-Induced Thyroid Dysfunction

(contd)
Subacute Thyroiditis

Characterized by transient changes in thyroid hormone levels

Associated with inflammation of thyroid gland, leakage of stored

thyroid hormone, repair of gland

Three classifications
Postpartum: occurs in 316% of women in postpartum
Painless: similar to postpartum type, except with no
associated pregnancy
Painful: characterized by neck pain, low-grade fever, myalgia,
tender diffuse goiter, swings in thyroid function test

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Nonthyroidal Illness
Abnormalities in thyroid function tests of hospitalized
patients (especially critically ill patients)
Characterized by low total T4, free T4, & TSH
Less T4 is converted to active T3, leading to decreased
levels of T3 and higher levels of reverse T3.
Central hypothyroidism & thyroid hormone-binding
changes are associated with severe illness.
Changes may be appropriate adaptations to illness.

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Thyroid Nodules
Common

Clinically apparent nodules are present in 6.4% of adult women

& 1.5% of adult men.

Thyroid ultrasound finds unsuspected nodules in 2045% of

women & 1725% of men.

59% prove to be thyroid cancer.

Fine-needle aspiration, with cytologic examination of
aspirate, is used to determine need for surgical removal.

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins