Chapter 23: The Thyroid Gland By Marissa Grotzke

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.

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.

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.

The Thyroid (cont’d) Biosynthesis of thyroid hormone

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

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)

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)

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

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

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.

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.

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

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

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.

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

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

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%

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

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. Page 499 - textbook

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. Page 499 in textbook