Thyroid in Health and Disease Richard B. Horenstein, MD Assistant Professor Department of Medicine Division of Endocrinology Diabetes & Nutrition

The structural and functional unit of the thyroid is the follicle, a closed sac filled with colloid, a protein rich fluid which contains the hormones (T 4 and T 3 ) made by thyroid follicular cells. Thyroid follicular cells line the wall of the follicle and secrete thyroid hormones into the colloid. Thyroid Microscopic Anatomy: The thyroid Follicle Colloid Follicular cells

Hormones Produced by the Thyroid Thyroxine (T 4 ) Triiodothyronine (T 3 ) –“T” stands for Thyroid –The numbers ‘4’ and ‘3’ refer to the number of iodine residues which are found in each hormone –We need iodine in our diet to make thyroid hormone

The Thyroid in Health –Produces hormones (thyroid hormones) which travel from the thyroid into the blood stream –Thyroid hormones bind to receptors in all cells (like a key into a lock) –Thyroid hormones help regulate metabolism (energy use), and temperature

Thyroxine T 4 Triiodothyronine T 3

Normal Regulation of Thyroid Function The thyroid itself acts in response to a hormone (Thyroid Stimulating Hormone) produced by a part of the brain TSH (Thyroid Stimulating Hormone) levels are what doctors measure most commonly to check thyroid function If the thyroid is making too little hormone, TSH levels rise; if the thyroid makes too much hormone (or if one takes too much of a thyroid hormone supplement), TSH levels falls

Thyroid Hormone Regulation The hypothalamic – pituitary – thyroid axis

Thyroid Hormone Regulation

Iodine Deficiency and Goiter Prevalent in many mountainous regions, central Africa, central South America, and norther Asia Goiter (enlargement of the thyroid) is found in areas of relative iodine deficiency The thyroid is able to take up dietary iodine efficiently To prevent iodine deficiency, our salt and bread has iodine added (Wonder, Stroehman, Pepperidge Farm); so do prenatal vitamins

US efforts to prevent iodine deficiency

Iodine and Development Decreased iodine in the diet, leading to insufficient thyroid hormone, results in lower IQ levels in children, pointing to the import of iodine and thyroid hormone to normal development When iodine deficiency is severe and children are not treated with iodine or thyroid hormones, cretinism, a disorder characterized by mental and growth retardation, results

Common Thyroid Diseases Hypothyroidism – the condition where the thyroid does not make enough thyroid hormone Hyperthyroidism – the condition where the thyroid makes too much thyroid hormone Thyroid Nodules – disordered growth of thyroid follicles Thyroid Cancer – uncontrolled growth and spread of thyroid follicular cells (most commonly)

Hyperthyroidism - Symptoms Fatigue Heat intolerance Sweating Nervousness Restlessness Frequent bowel movements Weight loss despite increased appetite

Hyperthyroidism - Signs Rapid Heart Rate Warm moist skin Tremor Eye lid retraction Proximal muscle weakness Diffuse enlargement of the thyroid is possible

Eye Lid Retraction in Hyperthyroidism

Patients with Graves' Ophthalmopathy Bahn RS. N Engl J Med 2010;362:

Graves' Hyperthyroidism Iraci GS, Fux-Otta C. N Engl J Med 2009;360:e31.

Hyperthyroidism - laboratory findings Elevated Free T4 and Free T3 levels Depressed TSH level

Hyperthyroidism - Causes Iodine excess Antibodies directed against the thyroid (Graves’ Disease) Inflammation of the thyroid (thyroiditis) due to infection or trauma Toxic Nodule (clone of thyroid cells which produce too much thyroid hormone) Ingesting too much thyroid hormone

Hyperthyroidism - T reatment Use of medications which slow the incorporation of iodine into new thyroid hormone –Methimazole –PTU (propylthiouracil) Use of radioactive iodine (I-131) to destroy a focus of increased thyroid hormone production Surgery to remove the overactive thyroid Stop use of excess thyroid hormone

Hyperthyroidism - T reatment Treat with methimazole or PTU until the TSH levels rise into the normal range If the thyroid gland is removed in whole or in part, treat with thyroid hormone replacement (Synthroid, levothyroxine)

Hypothyroidism – Causes Inflammation due to immune factors (autoimmune thyroid disease) Previous medical treatment with radiation to the head and neck Congenital (birth without a thyroid gland) Previous treatment of hyperthyroidism with radioactive iodine (I-131) Surgery to remove part or the entire gland Viral illness (thyroiditis) Infiltration of the gland by other proteins, metals (iron) or by other cancers Drugs prescribed for other diseases (lithium, amiodarone)

Hypothyroidism - Symptoms Being more sensitive to cold Constipation Depression Fatigue or feeling slowed down Lower extremity edema Increased menstrual flow Joint or muscle pain Weakness Thin, brittle hair or fingernails Unintentional weight gain

Hypothyroidism - Signs Slow pulse Cool extremities Dry, coarse skin Puffy face, hands, and feet Lower extremity edema Delayed tendon reflex relaxation

Hypothyroidism - T reatment Provide the patient with thyroid hormone supplementation –Synthroid, levothyroxine Treat so that the TSH level falls into the normal range (the brain senses that the thyroid hormone levels are normal)

Imaging Techniques to Evaluate the Thyroid Nuclear medicine studies Radiology Studies –Ultrasound –MRI –CT Scan

Image of normal thyroid on nuclear medicine iodine scan

Ultrasound image of well circumscribed thyroid nodule

Thyroid Cancer - Treatment Surgery to remove the entire thyroid Treatment with higher doses of radioactive iodine (I-131) to destroy remaining thyroid cells Treatment with Synthroid (levothyroxine) at levels which are high enough to suppress TSH

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