Thyroid Karina and Hope

Anatomy What is the blood supply to the thyroid gland? Arteries: Superior thyroid artery (external carotid), Inferior thyroid artery (thyrocervical trunk) and thyroid ima. Veins: superior, middle thyroid veins (into IJV) and inferior thyroid veins (brachiocephalic vein) What is its embryological origin? (Basic)… Pharyngeal arch (1st). Descends down the thyroglossal ducts which then disappear. NB: The thyroid moves on swallowing because it is in the pre-tracheal fascia.

Functions What three hormones does the thyroid gland secrete? – T3 (tri-iodothyroxine) – T4 (thyroxine) – Calcitonin What do they do? – T3/T4: Metabolism (increases BMR and O 2 consumption) Maturation & differentiation Neurological function (synapse formation, myelinogenesis and neuronal outgrowth) Growth – Calcitonin: Reduces calcium in the blood Cretinism

Histology Where is calcitonin produced? – Parafollicular C cells What happens in the follicle cell? – Thyroglobulin synthesis – Iodine trapping What is colloid? – Solution containing thyroglobulin + T3/T

What are the 6 steps of thyroid hormone synthesis? 1. Thyroglobulin synthesis 2. Uptake and concentration of iodide (I-) 3. Oxidation of iodide (I-) to iodine (I) 4. Iodination of thyroglobulin 5. Formation of MIT and DIT 6. Secretion Thyroglobulin synthesis Uptake and concentration of iodide (I- ) Oxidation of iodide (I-) to iodine (I) Iodination of thyroglobulin Formation of MIT and DIT Secretion

Blood What are the 6 steps in thyroid hormone synthesis? 1. Thyroglobulin synthesis NI S 2. I - Pendrin Colloid 3. I 0  I - TPO 3. I 0  I - TPO I I I I I I I I I I I I I I MIT DIT MIT DIT T3 T4 T3 T4 Follicle cells 6. I-I- I-I- I-I- I-I- I-I- I-I- I-I-

Questions on the production of thyroid hormone… What is thyroglobulin? – Binding protein produced by the follicular cell. Contains tyrosine residues which iodine binds to. Forming T3/T4. What side of the follicular cell would you find pendrin and NIS? – Basal NIS – Apical: pendrin What enzyme oxidises iodine to iodide? – TPO (thyroid peroxidase) T4 = ? + ? – T4 = DIT + DIT T3 = ? + ? – T3 = MIT + DIT

Outline the hypothalamo-pituitary- thyroid (HPT) axis What else is secreted from the anterior pituitary? FSH LH ACTH TSH GH Prolactin

Thyroid hormones in the blood How do T4 and T3 travel in the blood? – Lipophilic - cannot dissolve in the blood. – Must be associated with proteins. 70% thyroxin binding blobulin (TBG) 30% bound to albumin. Only the free T3/T4 can enter the cell.

How does thyroid hormone have an effect on target cells? T3/T4 have to enter cell via transporter MCT8 In order to have an effect - T4 must be converted to T3. There are 3 deiodinases which convert T4 to T3. – 1. Cell surface: T4--> T3 cell surface of most cells – 2. Intracellular: T4 --> T3 CNS and pituitary – 3. Extracellular: T4 --> rT3 (reverse) CNS and placenta Activation of receptors T3Ralpha and beta causes new protein synthesis via transcription and translation.

Hyperthyroidism Hypothyroidism Symptom sorter… HyperthyroidismHypothyroidism Heat ToleranceSlow/ lethargic Weight and muscle lossOverweight /obese Increased appetiteAlopecia (loss of lateral third of eyebrow) DiarrhoeaGoitre Nervous irritability Goitre

What is this symptom? 1.Iodine deficiency (low levels of T 4 : induces TSH secretion 2.Graves disease (high levels of T 4 ) autoimmune disease that produces thyroid stimulating immunoglobulin - acts as TSH 3.Tumours (benign or cancer) What are three causes of goitre?

Explain why goitre forms in Graves disease… Thyroid is overstimulated by TSI (thyroid stimulating immunoglobulin), therefore the gland increases in size in response in order to release more thyroid hormone.

How do both low and high T4 induce goitre?

TREATMENTHyperDrugsCarbimazole Radioactive iodine SurgeryHypoDrugsLevothyroxine What are the risks associated with thyroidectomy? (think Tunstall) External branch of superior laryngeal branch is at risk. Parathyroid gland damage Bleeding What condition in the hand is associated with a thyroid problem? Carpal tunnel (hypothyroidism) Treatment For hyperthyroidism? For hypothyroidism?