1. Chapter 23: The Thyroid Gland
By Marissa Grotzke

2. 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.

3. The Thyroid 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 (stunted physical and mental growth).
Congenital hypothyroidism occurs in 1 of 4,000 live births.

4. The Thyroid 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.

5. The Thyroid (cont’d)
Biosynthesis of thyroid hormone

6. The Thyroid Protein Binding of Thyroid Hormone
Two active forms of thyroid hormone:
1. Triiodothyronine (T3) (3 Iodine)
2. Tetraiodothyronine (T4) aka Thyroxine (4 Iodine)
When released into circulation, only 0.04% of T4 & 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

7. The Thyroid Control of Thyroid Function
Hypothalamic-pituitary-thyroid axis regulates thyroid hormone production
Thyrotropin-releasing hormone (TRH) – made in hypothalamus
Synthesized by neurons in supraoptic & supraventricular nuclei of hypothalamus
When secreted, stimulates cells in anterior pituitary gland to manufacture & release thyrotropin (TSH)
TSH (made in pituitary)
Circulates to thyroid gland & increases production & release of thyroid hormone (T3 and T4)

8. The Thyroid (cont’d) Hypothalamic-pituitary-thyroid axis
(Adapted from Surks MI, Sievert R. Drugs and thyroid function. N Engl J Med 1995;333:1688)

9. The Thyroid 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 (thyroid hormones play role in body temp regulation)
Increased oxygen consumption

10. Thyroid Tests 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
Also used to assess/screen for hyper- & hypothyroidism
Thyroglobulin
An ideal tumor marker for thyroid cancer patients
Thyroid autoimmunity
Detects antibodies directed at thyroid tissue

11. Other Tools for Thyroid Evaluation
Nuclear Medicine Evaluation
Radioactive iodine
Given orally, a % of dose is taken up by thyroid gland.
Assesses metabolic activity of thyroid
Evaluates & treats thyroid cancer
High uptake suggests metabolic activity.
Low uptake suggests metabolic inactivity.
Because TSH stimulates iodine uptake, TSH levels must be taken into account.

12. Other Tools for Thyroid Evaluation (cont’d)
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.

13. 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 5–15% of women >65 years old
Can lead to hyponatremia, anemia, hyperlipidemia
Most common cause in developed countries is chronic lymphocytic thyroiditis (Hashimoto’s Thyroiditis)
Autoimmune disease targeting thyroid gland – enlarged gland or goiter often seen.
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
What do you think happens to the body (symptoms) of hypothyroidism?
Weight gain, lethargy/tiredness, cold

14. Disorders of the Thyroid
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 – opposite of hypothyroidism

15. Graves’ Disease Most common cause of thyrotoxicosis (hyperthyroidism)
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.

16. 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

17. Disorders of the Thyroid
Toxic Adenoma and Multinodular Goiter
Caused by autonomously (independently) 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

18. Drug-Induced Thyroid Dysfunction
Amiodarone-Induced Thyroid Disease
Amiodarone
Drug ssed to treat cardiac arrhythmias
Fat-soluble with a long half-life (50 days)
37% of molecular weight is iodine (which accounts for significant part of thyroid dysfunction seen)
Effects
Inhibits thyroid hormone production (Wolff-Chaikoff effect)
Blocks T4 to T3 conversion
Leads to hypothyroidism in 8–20% of patients & hyperthyroidism in 3%

19. Drug-Induced Thyroid Dysfunction
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 3–16% 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

20. 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.
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21. Thyroid Nodules Common 5–9% prove to be thyroid cancer.
Clinically apparent nodules are present in 6.4% of adult women & 1.5% of adult men.
Thyroid ultrasound finds unsuspected nodules in 20–45% of women & 17–25% of men.
5–9% prove to be thyroid cancer.
Fine-needle aspiration, with cytologic examination of aspirate, is used to determine need for surgical removal.
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