THE THYROID GLAND

Anatomical Structure

Gross Anatomy Located in neck –lobes –isthmus Relations –Larynx –Trachea –Recurrent laryngeal nerves –Parathyroid glands –Carotid sheath Blood supply –Sup. thyroidal a. –Inf. thyroidal a.

Embryology Thyroglossal duct Foramen caecum Thyroid cysts

Histology Thyroid follicles –Simple cuboidal- columnar Colloid – Thyroglobulin Rich vascularization Parafollicular cells

Thyroid Hormone 3-Monoiodotyrosine (MIT) 3,5-Diiodotyrosine (DIT) 3,5,3’-Triiodothyronine (T 3 ) Tyrosine 3,5,3’,5’-Tetraiodothyronine (T 4 ) 3,3’,5’-Triiodothyronine (Reverse T 3, rT 3 )

Thyroid Hormone Synthesis Tyrosine in Thyroglobulin CH 3 CH N C=O RC C=O RC OH-

Thyroid Hormone Synthesis Thyroperoxidase attaches Iodine to 3 position---MIT CH 3 CH N C=O RC C=O RC I OH-

Thyroid Hormone Synthesis Thyroperoxidase attaches Iodine to 5 position---DIT CH 3 CH N C=O RC C=O RC I I OH-

Thyroid Hormone Synthesis Thyroperoxidase attaches ring from one DIT to adjacent DIT = Thyroxine (T 4 ) CH 3 CH N C=O RC C=O RC I I O I I OH-

Thyroid Hormone Synthesis Thyroperoxidase attaches ring from one MIT to adjacent DIT = Triiodothyronine (T 3 ) CH 3 CH N C=O RC C=O RC I I O I OH-

Thyroid Hormone Synthesis Thyroperoxidase attaches ring from one DIT to adjacent MIT = Reverse T 3 CH 3 CH N C=O RC C=O RC I O I I OH-

Thyroid Hormone Biosynthesis Iodine pump/trap Thyroglobulin Iodination Thyronine Thyroglobulin pinocytosis Hormone release

Thyroid hormone transport Thyroid binding globulin (TBG) –Highest affinity Thyroid binding prealbumin –Intermediate affinity Albumin –Low affinity, High capacity

Thyroid Hormone T 3 is 3-8X more active than T 4 Thyroid Gland produces 10X T 4 to T 3 5’-deiodinase –Converts T 4 to T 3 in Target Tissues –Primarily responsible for circulating levels of T 3 T 4 probably a pro-hormone Thyroid hormone receptor –Nuclear

Physiological effects of thyroid hormone Increases oxygen consumption and heat production Positive chronotropic and inotropic effects on heart Increase sensitivity to adrenergic effectors –Up-regulates  -adrenergic receptors Increase gut motility Increase bone turnover

Physiological effects of thyroid hormone Increases reflex response Increase hepatic glycogenolysis and gluconeogenesis Stimulates lipolysis Developmental effects –Growth –Brain development

REGULATION OF THE THYROID GLAND THYROID GLAND ANTERIOR PITUITARY HYPOTHALAMUS TRH TSH T4T4 LONG-LOOP FEEDBACK T 3 & T 4 TSH SHORT-LOOP FEEDBACK BODY TEMP. EXPOSURE TO COLD STARVATION TSH- RECEPTOR ANTIBODIES THYROID AUTO REGULATION HIGH SERUM IODIDE HIGHER BRAIN CENTERS GOITROGENS

Endocrinopathies

Hyperthyroidism Level of the defect (1 , 2 , 3  ) Thyrotoxicosis Graves’ disease Toxic Adenoma Toxic Multinodular Goiter Chronic Thyroiditis

Hyperthyroidism Symptoms Tachycardia/arrhythmia Muscle tremors Hyperreflexia Increased core & skin temp./ Heat Intolerant Exophthalmos Muscle wasting Loose stool Osteoporosis Hair loss Oligo-/amenorrhea Irritability, Restlessness

Hypothyroidism 1 , 2 , 3  Newborn –Cretinism –Lack of myelination Children –Retarded Growth –Disproportionate

Hypothyroidism Adult –Muscle weakness –Mental slowness –Tired/fatigued –Cold –Slowed intestinal peristalsis –Impaired renal function –Anemia –Myxedema

Myxedema

Causes of Hypothyroidism Iodine deficiency Hashimoto’s Disease –Initially hyperthyroid Post-ablative 5’-Deiodinase Deficiency

Thyroid hormone resistance Mutation of the receptor. Characterized by high blood levels of both TSH and Thyroid hormones

Non-toxic goiter Iodine deficiency

Thyroiditis Subacute thyroiditis Chronic thyroiditis (Hashimoto’s Disease) –Autoimmune

Euthyroid Syndrome Patient presents and complains of hypothyroid type symptoms Levels of Thyroid hormones (free & total), & TSH in low normal range. May be due to a 5’-deiodinase deficiency

Allopathic treatments for thyroid disorders Hyperthyroidism –Goitrogens –Partial thyroidectomy –Radiothyroidectomy Hypothyroidism –Hormone Replacement