1. Thyroid Anatomy Physiology Examination Pathologies Hamburger thyrotoxicosis Presenting complaints Pharmacology Investigations Embryology Epidemiology Evolution Ethics Social determinants

2. THYROID HORMONE Hypothalamus Anterior Pituitary THYROID GLAND + TRH + TSH T 3 : Triiodothyronine (more active) T 4: Thyroxine) - ?-?- Foetal development – enhances CNS & skeletal growth Metabolism -  O 2 consumption & heat production (  MR) plus  hepatic glucogneogenesis, glycogenolysis and cholesterol synthesis & degradation CV – Positive inotropic & chronotropic effects (  HR and force of contraction   CO) Sympathetic – increase sensitivity to Ad (more receptors in heart, muscle, adipose, lymphocytes) Pulmonary – Maintain normal hypoxic & hypercapnic drive in the respiratory centre Haematopoietic -  EPO due to increased O 2 consumption GI – Gut motility,  intestinal glucose absorption Skeletal -  bone turnover, growth (enhances GH/IGF-1 effects) Endocrine – increases metabolic turnover (cortisol, sex hormones – infertility) - Stress + Cold, infants

3. WTF so complex? (Oxford Handbook of Clinical Medicine) Why are symptoms of thyroid disease so various, and so subtle? Almost all cell nuclei have high affinity T 3 receptors: – TRα-1 is abundant in muscle and fat – TRα-2 is abundant in brain – TR β-1 is abundant in brain, liver, and kidney. These receptors, influence transcription of various enzymes, affecting: – The metabolism of substrates, vitamins, and minerals. – Modulation of all other hormones and their target-tissue responses. – Stimulation of O 2 consumption and generation of metabolic heat. – Regulation of protein synthesis, and carbohydrate and lipid metabolism. – Stimulation of demand for co-enzymes and related vitamins.

4. Embryology

5. Congenital defects – cysts and accessory tissue

9. Hormone

12. AP anterior pituitary C thyroid colloid F thyroid follicle H Herring body PP posterior pituitary S fibrous septum

13. Examination - Look (Adapted from McGee S, Evidence-based physical diagnosis, 2nd edition, St Louis, Saunders, 2007.)

14. Examination - Look Swelling Swallowing Scars Skin Veins

15. Examination - Feel Back, front, swallow Size Shape Consistency Tenderness Mobility Thrill Cervical nodes

16. Examination – Percuss, Ausculate, Special Percuss across manubrium Listen for bruit – Distinguish from carotid bruit and venous hum Listen for stridor (compress lateral lobes) Pemberton’s sign (thoracic inlet obstruction)

17. Examination Other organs / systemic signs Pulse Heart murmurs Lungs Legs Reflexes Neuropathy Eyes Skin Hair Hands Sweating Tremor

18. T3, T4, Transport Mostly T4 released from thyroid (20:1) T3 has short life. Plasma T4:T3 about 50:1 Mainly protein bound in plasma – Mainly thyroxine binding globulin (TBG) T4 converted to T3 in target cells (deiodinase enzymes, eg TPO)

21. DNA binding

22. DNA activation/repression

23. T3 effect in nucleus Increases – Transcription of Na + -K + -ATPase – Transcription of uncoupling proteins, leading to increased fatty acid oxidation and heat generation without production of ATP – Protein synthesis and degradation, contributing to growth and differentiation – Adrenaline-induced glycogenolysis and gluconeogenesis, affecting insulin-induced glycogen synthesis and glucose utilisation – Cholesterol synthesis and LDL receptor regulation Net result is increased BMR

24. Organ specific effects Bone - Activation of osteoclast and osteoblast activities, stimulating bone growth and development Heart and vessels - Increases cardiac output and blood volume; decreases systemic vascular resistance Fat - Stimulates proliferation and differentiation; stimulates lipolysis Liver - Regulates triglyceride and cholesterol metabolism and lipoprotein homeostasis; modulates cell proliferation and mitochondrial respiration Pituitary - Regulates synthesis of pituitary hormones, stimulates GH production, decreases TSH Brain - Stimulates axonal growth and development - critical during foetal and neonatal development

25. Thyroid signs and symptoms ThyrotoxicHypothyroid General Fatigue Heat intolerance Irritability Fine tremor Generalised fatigue Listlessness Cold intolerance Weight gain Distinctive facies CVS Tachycardia AF Palpitations Bradycardia Decreased cardiac output Non-pitting edema Cool, pale skin (decreased blood flow) GI Weight loss  Appetite Thirst  Bowel movements Decreased appetite/anorexia Constipation Neuro Proximal muscle weakness Hypokalemic periodic paralysis Apathy Mental sluggishness/poor memory Slow speech GU Scant menses  Fertility Menstrual abnormalities Dermatology Fine hair Skin moist & warm Vitiligo Soft nails with onycholysis Dry skin (decreased sweating) Thickened skin Hair loss Brittle nails and hair

26. Hyperthyroid Hyperthyroidism – excess production of thyroid hormone Thyrotoxicosis – response to elevated thyroid hormone Graves disease – Activating antibodies to TSH receptors – Also affects other tissues Toxic multinodular goitre Exogenous thyroxin Adenoma

27. Thyroid storm Acute onset of severe hyperthyroidism – Usually occurs in patients with underlying Graves disease, probably due to acute elevation in catecholamines, e.g. surgery, trauma, infection, stress – Present with fever, tachycardia (out of proportion to fever) and extreme restlessness – Is a medical emergency - patients can die of arrhythmias Requires immediate propranolol with potassium iodide, antithyroid drugs, corticosteroids and full supportive treatments

28. Hypothyroid Autoimmune – Hashimoto thyroiditis Congenital – Inborn errors (often with thyroid peroxidase) Iodine deficiency Iatrogenic – Surgery – Drugs – Radioablation

29. Myxoedema coma Presentation with confusion or coma in severe hypothyroidism  Most commonly occurs in elderly Patients will often have:  Hypothermia  Severe heart failure  Hypoventilation  Hypoglycaemia  Hyponatraemia Treatment:  Oxygen  Monitor cardiac output and pressures  Gradual rewarming  Hydrocortisone  Glucose infusion

30. Investigations T3, T4 levels TSH levels Thyroid antibodies (Hashimoto’s) TSH receptor antibodies (Grave’s) Iodine kinetics Scintillation imaging (hot vs cold nodules)

31. Treatment Thyroxine (exogenous thyroid hormone) Iodine – correct deficiency, – or blocks hormone release? PTU (anti thyroid peroxidase) Carbimazole (anti thyroid hormone) β blockers – ↓ adrenergic tone, ↓ T4→T3 conversion) Surgery