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) – Active form of the hormone – 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 1. 2. 3. 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 – Normal thyroid gland function • Goiter – Condition where the thyroid gland grows larger than normal Hypothyroidism • Symptoms – 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 • Tachycardia • Tremor • Warm, moist, flushed skin • Goiter • Muscle wasting and weakness Symptoms • Anxiety, nervousness • Palpitations • Weight loss • Heat intolerance • Prominence of eyes Graves’ Disease • Autoimmune Disease – 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 .