MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Thyroid Gland

Thyroid Anatomy Largest endocrine gland Located in the lower part of the neck, wrapped around trachea

Thyroid Cells Composed of two cell types Follicular Make and secrete thyroxine (T4) and triiodothyronine (T3) Parafollicular/ “C” cells Secrete calcitonin

Thyroid Hormone Synthesis Thyroid hormone is made up of iodine, primarily, so we must get iodine into the cell for thyroid function Daily intake of iodine should be 150 µg If < 50 µg/day: thyroid can not make thyroid hormone and leads to a deficiency Sources of Iodine seafood, dairy products, vitamins and iodine-enriched breads

Synthesis of Thyroid Hormones

Thyroid Hormones Triiodothyronine (T3) Active form of the hormone More potent than T4 Thyroxine (T4) Serves as a reservoir Reverse T3 (rT3) Found in the liver, kidney Inactive form of T3 Contributes to T3 circulating pool Calcitonin Lowers plasma calcium Assists in calcium homeostasis

Free Vs. Protein Binding of Thyroid Hormones Once released into circulation, only small amounts of T4 and T3 are unbound/FREE and available for hormone activity Binding Proteins Once bound- lacks biological function Affects TOTAL hormone levels Thyroxine-binding globulin (TBG) Thyroxine-binding prealbumin (TBPA) Albumin

Thyroid Hormone Regulation Regulation occurs via a feedback system between the thyroid gland, hypothalamus and anterior pituitary gland Hypothalamus produces TRH TRH asks the anterior pituitary to make and release TSH Free T3 and T4 hormones have a negative feedback effect to block TRH

Actions of Thyroid Hormone Regulation of body metabolism Body temperature Increases heat production Energy use Calorie burning Oxygen consumption Brain maturation Tissue growth

Disorders of the Thyroid Gland

Terms Euthyroid Goiter Normal thyroid gland function Condition where the thyroid gland grows larger than normal

Hypothyroidism Symptoms Lab features Vary depending on degree and cause Obesity, dry skin, dry lusterless hair, sluggishness of body functions and goiter Lab features Low free T4 level Normal to high TSH

Hypothyroidism Types Dysfunction Condition Primary Thyroid gland Hashimoto’s thyroiditis Treatment for toxic goiter Excessive iodine intake Subacute thyroiditis Secondary Pituitary gland/Hypopituitarism Adenoma Radiation therapy Pituitary destruction Tertiary Hypothalamus/Hypothalamic Rare

Thyrotoxicosis Causes of: Excessive thyroid hormone ingestion Leakage of stored thyroid hormone from thyroid follicles Excessive production of thyroid hormone (hyperthyroidism)

Thyrotoxicosis Signs Symptoms Tachycardia Tremor Warm, moist, flushed skin Goiter Muscle wasting and weakness Anxiety, nervousness Palpitations Weight loss Heat intolerance Prominence of eyes

Graves’ Disease Autoimmune Disease Familial Women more affected Antibodies activate TSH receptor Familial Women more affected Lab Features High free T4 and/or T3 level TSH low-undetectable

Thyroiditis Condition where there is inflammation of the thyroid gland Categories include acute, subacute, chronic

Nonthyroidal Illness Disorders linked to thyroid hormone excess or deficiency Less T4 is converted to active T3, leading to decreased levels of T3 and higher levels of reverse T3. Normal T4 Variable TSH

Assessment of the Thyroid

Thyroid Function Tests TSH= Thyroid Stimulating Hormone Responsible for directing the thyroid gland to make more thyroid hormone Best test to measure thyroid function Inversely related to thyroid status

Thyroid Function Tests Serum Total T4 and Total T3 Represents the total amount of T4 or T3 in the blood The higher the values- whether T4 or T3 indicate HYPERthyroidism The lower the values- whether T4 or T3 indicate HYPOthyroidism

Thyroid Function Tests Free T4/Thyroxine Usually ordered if TSH abnormal Measure free/unbound T4 Shows the level of hormone available for uptake & use Elevated in HYPERthyroidism Decreased in HYPOthyroidism

Thyroid Function Tests Free T3/ Triiodothyronine Measure free/unbound T3 Shows the level of hormone available for uptake & use

Thyroid FunctionTests Thyroglobulin Protein made and secreted by follicular cells Presence indicates thyroid tissue is present Used as a tumor marker for thyroid cancer

Historical Procedures Basal Metabolic Rate Measured rate of oxygen consumption over a 15 minute period Required careful patient preparation and precision of testing Radioactive iodine uptake test Measured the ability of the thyroid to take up and trap iodine Rate of absorption is determined by measuring increased radioactivity in the thyroid gland Protein bound iodine (PBI) Used to estimate the amount of thyroid T3 and T4 by measuring the amount of iodine contained in a protein precipitate of serum

Common Thyroid Function Tests TSH Total T3 and total T4 Free T3 and Free T4 T3 Uptake (for binding proteins) Serological testing for antibodies to thyroid disease

Thyroid Testing Methods Competitive immunoassay RIA ELISA FIA Noncompetitive immunoassay

Thyroid Antibodies Thyroglobulin antibodies Anti-thyroglobulin antibodies are mostly IgG and do not fix complement Found in Hashimoto’s thyroiditis Grave’s disease Subacute thyroiditis Thyroid cancer

References Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins. Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson .