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Thyroid Disorders Xavier MachadoTILOs 1 Function of thyroid glands: Summarise the function of the thyroid glands, including the synthesis, regulation and physiological effects of their hormones. 2 Endocrine disorders: Describe the clinical features and treatment options of thyroid disorders. 3 Refresher on the regulation of calcium 3 Causes of hypo- and hyper- calcaemiaLecture Timeline Pathophysiology Features Management Anatomy Function DisorderAnatomyFunction Thyroid hormones Simple is best T3 Active form T4 Inactive T3 sensitises beta- adrenoreceptors This lowers activation threshold of the sympathetic nervous system Fight or flightDisorders Hypothyroidism Hyperthyroidism Less T3 More T3 Hashimoto’s thyroiditis Grave’s, toxic multinodular goitre (Plummer’s disease), thyroiditisostpartumVSAQ A 42-year-old woman presents with progressively worsening weight loss, anxiety, heat intolerance, and dry skin and eyes. What two further signs/symptoms would you expect for a diagnosis of Grave’s Disease.VSAQ A 42-year-old woman presents with progressively worsening weight loss, anxiety, heat intolerance, and dry skin and eyes. What two further signs/symptoms would you expect for a diagnosis of Grave’s Disease. Exophthalmos Pretibial Myoxoedema (Thyroid acropachy)SBA I What labs would you expect for a patient with Grave’s? T3 TSH a. b. c. d. e.SBA I What labs would you expect for a patient with Grave’s? T3 TSH a. Follow-up questions: b. 1. Why? 2. What might the others signify? c. d. e.Thyrotoxicosis Definition Symptoms caused by the excessive circulation of thyroid hormones Overactive thyroid gland Primary TSH Problem with the thyroid gland; if TSH is low, the thyroid gland is not stimulated yet still produces excess thyroid hormones Secondary TSH Extra-thyroid problem; if TSH is high, and so is T3/4, then the negative feedback mechanism has been lost in some manner Thyroid Storm Acute exacerbation of thyrotoxicosis that results in a life- threatening hyper-metabolic statePathophysiology Grave’s Disease Autoimmune T4 T3 Thyroxine released Symptoms T3 Signs Thyroid gland stimulated (not TSH) Thyroid gland Auto-antibody presence swells (all over) Auto-antibodies also attack muscles behind the eye leading to exophthalmos Auto-antibodies also cause pretibial myxoedema - growth of soft tissue causing non-pitting swelling in lower legsPathophysiology Toxic Nodular Goitre T4 Symptoms T3 Releases thyroxine T3 Signs Thyroid gland Benign Adenoma swells in one place muscles behind the eye leading to exophthalmos Auto-antibodies also cause pretibial myxoedema - growth of soft tissue causing non-pitting swelling in lower legs Pathophysiology Viral Thryoiditis T4 T3 Throws up thyroxine store Symptoms T3 Signs Thyroid stops making thyroxine and No iodine makes virus uptake 4 weeks later Virus attacks thyroid gland Thyroxine stores are depleted and Viral Infection patient becomes hypothyroid Auto-antibodies also attack Postpartum Thryoiditis muscles behind the eye leading 4 more to exophthalmos weeks Similar disease course to viral No pain (as no infection) Patient recovers Auto-antibodies also cause pretibial from virus and Only occurs after pregnancy myxoedema - growth of soft tissue causing becomes euthyroid non-pitting swelling in lower legsFeatures Hyperthyroidism Symptoms and Signs Thyroxine sensitises beta adrenoreceptors to ambient levels of adrenaline This means beta adrenoreceptors are stimulated more easily Thus, there is sympathetic nervous system activation This causes symptoms in many body systems General Skin Increased sweating Weight loss (despite increased appetite) Restlessness Itching Heat intolerance Other Cardiac/Respiratory Diarrhoea Oligo-/a-menorrhoea Palpitations Breathlessness Tachycardia Anxiety Lid lag Tremor Disease Specific Features Symptoms and Signs Grave’s Disease Toxic Nodular Goitre Thyroid Storm Medical Emergency ! 50% mortality if untreated Hyperpyrexia (>41℃) Accelerated tachycardia Arrhythmia Diffuse smooth goitre Asymmetrical swelling Jaundice Antibodies lead to No exophthalmos or exophthalmos and pre-tibial myxoedema Hepatocellular pretibial dysfunction (LFTs) myxoedema Delirium / Psychosis Viral Thryoiditis Dysphagia Needs aggressive Tender goitre treatment Pyrexia Exophthalmos No uptake on myxoedemal iodine scanManagement 1 Drugs 2 Radioiodine 3 Surgery1 Drugs A Thionamides Reduce hormone synthesis B Potassium Iodide C β-blockers Symptomatic relief 2 Radioiodine 3 Surgery1 Drugs A Thionamides Drug names Propylthiouracil (PTU)Carbimazole Drug use Daily treatment of hyperthyroid Drug action of Carbimazole Thyroid perioxidase inhibitors Biochemical effect in hours Clinical effect in weeks Side-effect Agranulocytosis Rashes Follow-up Aim to stop anti-thyroid drug after 18 months // review patient often B Potassium Iodide C β-blockers1 Drugs A Thionamides B Potassium Iodide Aim is to increase Iodine, usually through potassium iodide (KI) Used in preparation for thyroidectomy, or severe thyroid storm Aim is to increase Iodine, usually through potassium iodide (KI) This inhibits thyroid hormone synthesis & secretion through WOLFF- CHAIKOFF effect This is a presumed auto-regulatory effect Symptomatic relief within 2 days Vascularity and gland size reduced within 2 weeks C β-blockers1 Drugs A Thionamides B Potassium Iodide C β-blockers This is a non-thyroid reduction drug Symptomatic relief, quicker than thionamides Reduced tremor, slower heart rate, less anxiety Non-selective β-blocker e.g. propranolol 2 Radioiodine 3 Surgery1 Drugs 2 Radioiodine Swallow a capsule of radioactive iodine This radioactive iodine gets absorbed by the thyroid, as it is iodine The radioactivity kills the thyroid cells, thereby killing the thyroid Patient however also becomes radioactive, so is contraindicated in pregnant patients and patients undergoing this treatment must stay away from other pregnant mothers and children. Remember that when we stop production of thyroxine permanently, the body still requires thyroxine, so we must replace this thyroxine (levothyroxine) 3 Surgery1 Drugs 2 Radioiodine 3 Surgery Thyroidectomy Here, the surgeon just removes the whole thyroid gland Again, similar to radioiodine, the thyroid gland is forever lost, so endogenous thyroxine production is also lost We must replace this thyroxine with exogenous thyroxine - levothyroxine Complications: general surgical concerns, risk of voice change (why?), risk of losing parathyroid glands (will mention this in next half of lecture) Recurrent laryngeal nerve - controls movement of vocal chordsManagement 1 Drugs Thyroid suppressing 2 Radioiodine Thyroid killing 3 SurgeryHypothyroidism Hashimoto’s Thyroiditis Myxoedemic Coma Autoimmune Potentially fatal complication of hypothyroidism Symptoms: confusion, psychosis, apathy, Damaged thyroid bradycardia, hypotension, hypothermia + Produces less thyroxine long-standing hypothyroid symptoms Treat with levothyroxine Treat with levothyroxine Hypothyroid symptoms Weight gain, lethargy, cold intolerance, dry skin and scalp, constitution, menorrhagia, decreased deep tendon reflexesSBA II A 28-year-old female has been diagnosed with hyperthyroidism. She complains of heat intolerance and palpitations, the latter is proving to be very frightening to her. The GP starts her on Carbimazole and a second medication to manage the palpitations. What receptors are being over stimulated by the enhanced catecholamine effects in this patient to cause her palpitations? a. ⍺1 receptors b. ⍺2 receptors c. β1 receptors d. TSH receptors e. β2 receptorsSBA II A 28-year-old female has been diagnosed with hyperthyroidism. She complains of heat intolerance and palpitations, the latter is proving to be very frightening to her. The GP starts her on Carbimazole and a second medication to manage the palpitations. What receptors are being over stimulated by the enhanced catecholamine effects in this patient to cause her palpitations? a. ⍺1 receptors b. ⍺2 receptors Follow-up questions: What is the medication? c. β1 receptors What do the other receptors do? d. TSH receptors e. β2 receptorsSBA III A 42-year-old woman presents with progressively worsening weight loss, anxiety, heat intolerance, and dry skin and eyes. Hyperthyroidism is confirmed on thyroid-function tests and the patient is commenced on carbimazole. A set hormone testing is scheduled in 4 to 6 weeks.ate up the drug until the patient becomes euthyroid. Further thyroid What is the mechanism of action of this medication? Blocks thyroxine-binding globulin a. b. Enhances thyroid peroxidase c. Inhibiting 5'-deiodinase d. Prevents iodination of the tyrosine residue on thyroglobulin e. Prevents thyroxine (T4) conversion to T3SBA III A 42-year-old woman presents with progressively worsening weight loss, anxiety, heat intolerance, and dry skin and eyes. Hyperthyroidism is confirmed on thyroid-function tests and the patient is commenced on carbimazole. A set hormone testing is scheduled in 4 to 6 weeks.ate up the drug until the patient becomes euthyroid. Further thyroid What is the mechanism of action of this medication? Blocks thyroxine-binding globulin a. b. Enhances thyroid peroxidase c. Inhibiting 5'-deiodinase d. Prevents iodination of the tyrosine residue on thyroglobulin e. Prevents thyroxine (T4) conversion to T3ExtraCalcium Dysregulation Xavier MachadoSBA IV A 72-year-old woman with back pain and chronic renal failure has the following blood test results: Blood test Patient resultsReference Range Ca2+ 2.03 2.15 - 2.55 Phormoneoid 10.4 1 - 6.5 Phosphate 0.80 0.60 - 1.25 What is the most likely diagnosis? a. Hypoparathyroidism b. Primary hyperparathyroidism c. Secondary hyperparathyroidism d. Tertiary hyperparathyroidism e. PseudohypoparathyroidismSBA IV A 72-year-old woman with back pain and chronic renal failure has the following blood test results: Blood test Patient resultsReference Range Ca2+ 2.03 2.15 - 2.55 Phormoneoid 10.4 1 - 6.5 Phosphate 0.80 0.60 - 1.25 What is the most likely diagnosis? a. Hypoparathyroidism b. Primary hyperparathyroidism c. Secondary hyperparathyroidism d. Tertiary hyperparathyroidism e. PseudohypoparathyroidismCalcium Regulation D2 from diet Pre-D3 Parathyroid hormone Calcitonin D3 (cholecalciferol) Secreted by parathyroid gland Secreted by thyroid parafollicular cells 1⍺- and 25- hydroxylases Active D3 (calcitriol)Calcium Regulation Effects Active D3 (calcitriol) Parathyroid hormone Calcitonin Osteoclasts Osteoclasts Osteoblasts Ca 2+PO 4-absorption Ca2+ absorption Ca2+ PO43-absorption 2+ Ca absorption Ca 2+PO 4-reabsorption PO 43excretion Ca 2+PO 43reabsorption 1⍺-hydroxylase Calcium Calcium Calcium serum Phosphate Phosphate PhosphateFeatures Frame in the context of calcium Hypocalcaemia Hypercalcaemia CATs go numb Stones, moans and psychic groans Convulsions Renal stones Arrhythmias Tetany GI: anorexia, dyspepsia, constipation, pancreatitis Paraesthesia (numb) CNS: fatigue, depression, impaired concentration, , altered mentation, coma Chvosteks’ sign Facial twitch Trousseau’s sign Carpopedal spasmAetiology I Frame in the context of calcium Hypocalcaemia Hypercalcaemia PTH PTH Hypoparathyroidism Secondary Malignancy Primary hyperparathyroidism hyperparathyroidism Tertiary hyperparathyroidismAetiology II Hypocalcaemia Hypercalcaemia Primary Hypoparathyroidism hyperparathyroidism Low calcium as not enough PTH to increase it Will explain pathophysiology later Surgical - neck Too much PTH Autoimmune Parathyroid gland adenoma Magnesium deficiency No negative feedback Congenital (very rare) Malignancy Bony mets produce local factors to activate osteoclasts Secondary Certain cancers secrete PTH (squamous cell carcinoma) hyperparathyroidism Will explain pathophysiology later Is a normal physiological response Tertiary But basically vitamin D deficiency hyperparathyroidism From: poor diet, poor absorption, lack of UV light, Will explain pathophysiology later impaired productionParathyroid hormone activity PT H PT H PT H Ca+ Ca2+ Hyperparathyroidism Primary Secondary Tertiary uncontrolled parathyroid hormone Normal physiological response when secondary hyperparathyroidism continues production by a tumour of the insufficient vitamin D or chronic kidney for an extended period parathyroid glands (hyperplasia or disease reduces calcium absorption from the Hyadapt to producing a higher baseline level of parathyroidey adenoma) intestines, kidneys and bones. hormone. Then, when the underlying cause of the secondary This leads to a raised blood calcium (hypercalcaemia) result in low blood calcium (hypocalcaemia). hyperparathyroidism is treated, the baseline parathyroid There is a bit of failure of negative feedback of The parathyroid glands react to the low serum hormone production remains inappropriately high calcium on PTH, although it doesn’t really calcium by excreting more parathyroid hormone. In the absence of the previous pathology, this high parathyroid matter as tumour will continue to secrete PTH hormone level leads to the inappropriately high absorption of calcium in the intestines, kidneys and bones, causing hypercalcaemia. PTH PTH Cause treated PTH Ca 2+ PO 4 3- PTH Ca 2+ PTH Ca 2+ PO 4 3- Underlying cause (Vit D/CKD) Parathyroidectomy ParathyroidectomySBA V A 43-year-old male has come in to discuss the management of primary hyperparathyroidism. He was diagnosed 2 weeks ago after presenting with bone pain and gastrointestinal discomfort. His blood results from today show an electrolyte abnormality. blood results?he following electrolyte abnormalities is most likely to be seen on the a. Hyperkalaemia b. Hypokalaemia c. Hyperphosphataemia d. Hypophosphataemia e. HypocalcaemiaSBA V A 43-year-old male has come in to discuss the management of primary hyperparathyroidism. He was diagnosed 2 weeks ago after presenting with bone pain and gastrointestinal discomfort. His blood results from today show an electrolyte abnormality. blood results?he following electrolyte abnormalities is most likely to be seen on the a. Hyperkalaemia b. Hypokalaemia c. Hyperphosphataemia d. Hypophosphataemia e. HypocalcaemiaPlease fill this out, really helps MedEd and meQuestions? Xavier Machado