MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Thyroid Gland

Anatomy Largest endocrine gland Located in the lower part of the neck, wrapped around trachea and larynx Composed of two cell types Follicular Make and secrete thyroxine (T4) and triodothyronine (T3) Clear 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 Iodide seafood, dairy products, vitamins and iodine-enriched breads

Synthesis of Thyroid Hormones

Thyroid Hormones Triiodothyronine (T3) Thyroxine (T4) Calcitonin Lowers plasma calcium Assists in calcium homeostasis Reverse T3 (rT3) Produced by the liver Inactive form of T3

Protein Binding of Thyroid Hormones Once released into circulation, only small amounts of T4 and T3 are unbound and available for hormone activity Binding Proteins 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 Tissue growth Brain maturation Increased heat production Increased oxygen comsumption

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 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 Tertiary Hypothalamus Hypothalamic

Thyrotoxicosis Causes 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 undetectable

Hyperthyroidism http://www.medicinenet.com/hyperthyroidism_pictures_slideshow/article.htm

Subacute Thyroiditis Condition where there is inflammation of the thyroid gland, leakage of stored thyroid hormone and repair of the gland Most common form is postpartum thyroiditis

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.

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.

Assessment of the Thyroid

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

Historical Procedures 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) Free thyroxine index( estimate of Free T4) Serological testing for antibodies to thyroid disease

Thyroid Testing Methods Competitive binding techniques RIA ELISA FIA

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

Thyroid Antibodies Microsomal antibodies Complement fixing IgG directed against a microsomal antigen within follicular cells Found in Hashimoto’s disease Thyrotoxicosis Primary myxedema