Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

WhatcanIbetestedon? Search for the “UKMLA Content Map” and there is a PDF document on the gmc-uk.org1 Diabetes 4 Addison’s disease 2 Hypoglycaemia 5 Hyperparathyroidism 3 Cushing’s disease 6 Thyroid diseases SBA 1 Rahul, a 6 yearold boyis brought tothe GP becausehe has recentlystartedto wetthe bed again.Hegained continence at age 4, and has A: Islets of Langerhan been fine overnightsince,but has wetthe bed everynight forthe last2 weeks.Also,he is always pesteringhis parentsforwaterand juice. B: Pancreatic alpha cells Otherwise,he isa healthyboy and isgetting on C: Pancreatic beta cells wellat school.On questioning,hisfathernoteshis sonhas lostweightrecently.Hismother has a thyroidconditionand can't eat breador pasta. D: Thyroid follicular cells Onexamination,the boyappears thin.Aurine E: Villous enterocytes dipstickshowsglucose ++. Whichcell typehas been destroyedby theimmune system? SBA 1 Rahul, a 6 yearold boyis brought tothe GP becausehe has recentlystartedto wetthe bed again.Hegained continence overnightat age 4, A: Islets of Langerhan and hasbeen fine overnightsince,but has wet the bed everynight forthe last2 weeks.Also,he is alwayspesteringhis parentsforwaterand B: Pancreatic alpha cells juice.Otherwise,he isa healthy boy and isgetting C: Pancreatic beta cells on wellat school.On questioning,hisfathernotes his sonhas lostweight recently.Hismother has a thyroidconditionand can't eat breador pasta. D: Thyroid follicular cells Onexamination,the boyappears thin.Aurine E: Villous enterocytes dipstickshowsglucose ++. Whichcell typehas been destroyedby theimmune system? Type 1 diabetes Characterised by inability to produce and secrete insulin due to the autoimmune destruction of the pancreatic beta cells Fasting glucose Age of onset Urine dip: >7mmol/L typically <20 Ketouria glucose and Random years common ketones ++ glucose >11.1mmol/L Antibodies to Islet cell More acute, Features of glutamic acid antibodies hours to days DKA decarboxylase (ICA) (anti-GAD) Personal or Insulin Recent weight family history loss is typical of autoimmune autoantibodies disease (IAA)Type 1 diabetes - management Monitored every Target: HbA1c 3-6 months <48mmol/mol or <6.5% Self at least 4x a day Beforemealsand beforebedtime monitoring Blood 5-7 mmol/l on 4-7 mmol/l before waking meals at other times glucose of the day targets Multiple daily INSULIN bolus insulin Twice daily regimen insulin detemir SBA 2 Mohammed presents to the emergency A: Mixed respiratory and department complaining of nausea and metabolic acidosis vomiting over the past day. He complains that before this, he has been excessivelythirstyand passing large amounts of urine. B: Normal anion gap metabolic acidosis On examination, he has dry mucous C: Raised anion gap metabolic membranes, a prolonged capillary refill time acidosis and deep, laboured breathing. His blood results are: D: Reduced anion gap metabolic Serum glucose: 27mmol/L (<11) acidosis Serum ketones: 5mmol/L (<3) What typical finding will be seen on an ABG? E: Respiratory acidosis SBA2 Mohammed presents to the emergency A: Mixed respiratory and department complaining of nausea and metabolic acidosis vomiting over the past day. He complains that before this, he has been excessivelythirstyand passing large amounts of urine. B: Normal anion gap metabolic acidosis On examination, he has dry mucous C: Raised anion gap metabolic membranes, a prolonged capillary refill time acidosis and deep, laboured breathing. His blood results are: D: Reduced anion gap metabolic Serum glucose: 27mmol/L (<11) acidosis Serum ketones: 5mmol/L (<3) What typical finding will be seen on an ABG? E: Respiratory acidosis ANIONGAP The anion gapisa bloodtestthat measures the differenceor the “gap” between the positivelychargedions likesodiumand potassium,and the negatively charges ionslike chlorideand bicarbonate). HCO3 Na+ K+ Cl- - Anion Gap = Na+ – (Cl- + HCO3-) An elevated anion gap suggests the presence of metabolic acidosis. Since the most likely diagnosis is DKA, the accumulation of the ketones is what has caused the raised anion gap. DKA – diagnosis and symptoms DKA is a life-threatening diabetic emergency >6mmol/L N+V Kussmaul’s Ketonaemia breathing >3mmol/L Abdominal pain Altered mental state DKA SYMPTOMS Polyuria pH <7.3 / Hyperglycaemi Fruity breath – acidosis with a “pear drops” HCO3 <15.0mmol/L >11.0mmol/L Polydipsia Hypokalae H <7 or HCO3 <5 mia DKA – pathophysiology DKA is a life-threatening diabetic emergency Lack of insulin= cells Metabolic in starvation mode . Ketone production due to lack of leadsacidosisbolic acidosis absglucose of Highosmolality ofthe Theincreased fluid Osmotic blood resultsin fluid in the intravascular shifting from spaceis excreted Diuresis intravascularspacese via the kidneys.. Alongside fluids, Leads to Electrolyte electrolytes are depletion of also dragged out Na+. Can lead imbalances of the filtrate and to increased K+ excreted SBA 3 A24 year old man attends the Emergency Department after 2 days of vomiting. He has type 1 A: IV 0.9% sodium chloride diabetes. He is drowsy but maintaining his airway. His pulse rate is 100 bpm, BP 90/60 mmHg, respiratory rate 30 breaths per minute and oxygen B: IV 1.26% sodium chloride saturation 96%breathing air. C: IV ABX Investigations: Blood capillary glucose 32 mmol/L D: IV insulin Blood capillary ketones 6.2 mmol/L (<0.6) Venous pH 7.15 (7.35-7.45) E: Subcut insulin Which is the most appropriate initial treatment? SBA 3 A24 year old man attends the Emergency Department after 2 days of vomiting. He has type 1 A: IV 0.9% sodium chloride diabetes. He is drowsy but maintaining his airway. His pulse rate is 100 bpm, BP 90/60 mmHg, respiratory rate 30 breaths per minute and oxygen B: IV 1.26% sodium chloride saturation 96%breathing air. C: IV ABX Investigations: Blood capillary glucose 32 mmol/L D: IV insulin Blood capillary ketones 6.2 mmol/L (<0.6) Venous pH 7.15 (7.35-7.45) E: Subcut insulin Which is the most appropriate initial treatment? DKA – management Follow DKA protocol! Fluids Insulin Potassium IV fluid replacement with Fixed rate insulin Measure serum 0.9% NaCl, large volumes (Actrapid): 50 units in potassium as insulin can relatively quickly, then 50ml of 0.9% NaCl at a cause hypokalaemia. Add over longer durations. rate of 0.1 units/kg/hour. to IV fluids if <5.5 and get senior review if <3.5 DKA –resolution Follow DKA protocol! pH >7.3 Ketonemiaand acidosisshould have settledwithin 24 hours. If not → ENDOCRINOLOGIST HCO3 Ketones Headache? Irritability Visual Focal >15 <0.6 ? disturbance neurology? mmol/L ? mmol/L GLUCOSE If above criteriaare metand the Potential cerebral oedema? patientis eating and drinking, Childrenand youngadults are more vulnerableto movethem to SCInsulin this followingfluidresuscitation(usually4-12 hours after) CTHEADANDSENIORREVIEW! SBA 4 Asiya,a 62 year old female presents to her general practitioner for a diabetic review. She was recently diagnosed with diabetes andhas A: Book another appointment in 6 trialled lifestyle changes.Today, her HbA1c is 58months time mmol/mol. At the time of diagnosis, her HbA1c was 51 mmol/mol. B: Prescribe canagliflozin Herpast medical history comprises chronic C: Prescribe gliclazide ad then kidney disease -with an estimated glomerular canagliflozin filtration rate (eGFR) of 22mL/minute/1.73 m2 - and chronic pancreatitis. Sherecently D: Prescribe metformin underwent a percutaneous coronary intervention. E: Prescribe metformin and then What is the most appropriate management canagliflozin option? SBA 4 Asiya,a 62 year old female presents to her general practitioner for a diabetic review. She was recently diagnosed with diabetes andhas A: Book another appointment in 6 trialled lifestyle changes.Today, her HbA1c is 58 monthsIf metforminis contraindicated + mmol/mol. At the time of diagnosis, her HbA1c patient hasa risk of CVD,established was 51 mmol/mol. B: PCVDo chronic heart failure→ SGLT-2 monotherapy Herpast medical history comprises chronic C: Prescribe gliclazide ad then kidney disease -with an estimated glomerular canagliflozin filtration rate (eGFR) of 22mL/minute/1.73 m2 - and chronic pancreatitis. Sherecently D: Prescribe canagliflozin underwent a percutaneous coronary intervention. E: Prescribe metformin and then What is the most appropriate management canagliflozin option? Type 2 diabetes Repeatedexposureto glucose and insulin makes the cellsresistant to the effects of PRE-DIABETES → Bodystrugglesto insulin. This results in the pancreas get bloodglucosein a normal range becomingfatiguedand produceless even after a prolongedperiod of not insulin → CHRONIC HYPERGLYCAEMIA eating carbohydrates Fatigue Polydipsiaand Polyuria Impaired fasting glucose – 6.1- 6.9 mmol/L Impaired glucose tolerance– RF’s( Ethnicity, familyplasma glucosmmol/L hrs 7.8-11.1 history,obesity, high on an OGTT Blurryvision carbohydrate diet, HbA1c– 42-47 mmol/mol sedentary lifestyle) Fasting glucose > 7mmol/L Random glucose > 11.1 mmol/L HbA1c >48 mmol/mol Type 2 diabetes MANAGEMENTOFT2D Measure 1) Lifestyle measures HbA1c levels at 3-6 month 2) Lifestyle + metformin intervals When HbA1c is >58 → add more drugs Insulin orhigh 3) Lifestyle + hypoglycaemia causing drug hypoglycaemia risk? → self (sulfonylurea, pioglitazone, SGLT2 inhibitor) monitoring of glucoseat 4) Add another drug from the list or move to home insulin-based treatment Type 2 diabetes METFORMIN SULFYNOLUREAS gliclazide, glimepiride, glipizide, tolbutamide DDP-4INHIBITORS alogliptin, linagliptin, sitagliptin SGLT2INHIBITORS canagliflozin, dapagliflozin, empagliflozin GLP-1 INHIBITORS Dulaglutide, exenatide, liraglutide SBA 5 An 83 year old woman has recurring dizzy spells.The episodes are associated with transient shaking of her A: Increase gliclazide dose hands that is most noticeable before her lunch and evening meals.She has hypertension and type 2 diabetes mellitus.She takes metformin (1g twice B: Increase metformin dose daily), gliclazide (80 mg twice daily) and ramipril (10 mg daily). Her BP is 138/82 mmHg lying and 130/78 C: Reduce gliclazide dose mmHg standing. Her blood capillary glucose is 6 mmol/L. Investigations: Sodium 136mmol/L (135- 146) Potassium 5.0 mmol/L (3.5-5.3)Urea 3.9 mmol/L D: Reduce metformin dose (2.5-7.8)Creatinine 77 μmol/L (60-120)Glycated E: Reduce ramipril dose haemoglobin 50 mmol/mol (20-42). Which is the most appropriate therapeutic change? SBA 5 An 83 year old woman has recurring dizzy spells.The episodes are associated with transient shaking of her A: Increase gliclazide dose hands that is most noticeable before her lunch and evening meals.She has hypertension and type 2 diabetes mellitus.She takes metformin (1g twice B: Increase metformin dose daily), gliclazide (80 mg twice daily) and ramipril (10 mg daily). Her BP is 138/82 mmHg lying and 130/78 C: Reduce gliclazide dose mmHg standing. Her blood capillary glucose is 6 mmol/L. Investigations: Sodium 136mmol/L (135- 146) Potassium 5.0 mmol/L (3.5-5.3)Urea 3.9 mmol/L D: Reduce metformin dose (2.5-7.8)Creatinine 77 μmol/L (60-120)Glycated E: Reduce ramipril dose haemoglobin 50 mmol/mol (20-42). Which is the most appropriate therapeutic change? Type 2 diabetes - medication METFORMIN Weight neutral SGLT2 e.g. DAPAGLIFLOZIN DPP-4 e.g. SITAGLIPTIN Doesn’t cause hypos Weight loss Weight neutral SEs: Diarrhoea/abdo pain (can Doesn’t cause hypos Doesn’t cause hypos give modified release), lactic SEs: SEs: acidosis • Urinary and genital infections • GI tract upset CONTRAINDICATIONS: • Euglycaemic ketoacidosis • URTI • Lactic acidosis (stop 48hrs before surgery) • Pancreatitis • Caution in renal impairment • Acute metabolic acidosis Sulfonylureas e.g. GLICLAZIDE GLP-1 e.g. EXENATIDE PIOGLITAZONE Weight gain Given as an injection (A thiazolidinedione) Weight loss Doesn’t cause hypos Cause hypos Doesn’t cause hypos SEs: think ELBOW SEs: Hyponatraemia, GI upset SEs: GI upset, weight loss, dizziness • Edema-fluid retention CIs: Consider if triple therapy is • Severe renal or hepatic • Liver impairment impairment ineffective: • Bladder cancer • Ketoacidosis BMI>35 + high weight • Osteoporosis • Avoid in pregnancy (risk of BMI <35 + insulin unacceptable/ • Weight gain neonatal hypoglycaemia) weight loss would help CIs: heart failure, active bladder cancer SBA 6 Priya,a 63 yearolddiabeticwoman is admitted to hospital inorderto have intravenous antibioticsfor community A: IV glucagon acquiredpneumonia. Onday3 of admission shebecomes confusedanddrowsyafter B: Oral glucose tablets which shehas ashortseizurewhich C: IM glucagon spontaneously resolves.Her capillaryglucose isnoted at3.1mmol/L andsheis D: IV lorazepam unconscious. What is the mostappropriate immediate E: Stop all diabetic medication management of this patient? SBA 6 Priya,a 63 yearolddiabeticwoman is admitted to hospital inorderto have intravenous antibioticsfor community A: IV glucagon acquiredpneumonia. Onday3 of admission shebecomes confusedanddrowsyafter B: Oral glucose tablets which shehas ashortseizurewhich C: IM glucagon spontaneously resolves.Her capillaryglucose isnoted at3.1mmol/L andsheis D: IV lorazepam unconscious. What is the mostappropriate immediate E: Stop all diabetic medication management of this patient? Hypoglycaemia Glucose <4mmol/L CONSCIOUSANDCANSWALLOW Blood symptoms due SShaking 15-30mg fast acting carbohydrate, to the release of Hunger glucosetablets and drink (Lucozade) glucose glucagon and Anxiety <3.3mmol/L adrenaline. Nausea CONSCIOUSANDCAN’T Blood Neuroglycopenic Weakness SWALLOW syinadequate to Visualchanges Glucosegelaround the teeth (e.g glucose glucose supply to Confusion glucogelor dextrogel) the brain. Dizziness <2.8mmol/L UNCONSCIOUS Severe and Seizures IVaccessand giveIV glucoseload uncommon (glucagon).IMglucagonifdifficult Coma IV. features SBA 7 A 35-year-oldwoman presentswith weight gain,purplestriae onher abdomen, and A: High-dose dexamethasone proximalmuscleweakness. Laboratory suppression test investigationsreveal elevated 24-hour urinary free cortisoland lackof suppressionof serum B: Morning serum ACTH cortisolafter a low-dose dexamethasone measurement suppressiontest. C: Abdominal CT scan to look at adrenal glands Which additional investigationismost appropriateto determine the cause of her Cushing’ssyndrome? D: Pituitary MRI E: Salivary cortisol measurement SBA 7 A 35-year-oldwoman presentswith weight gain,striaeon her abdomen, and proximal A: High-dose dexamethasone suppression test muscleweakness. Laboratory investigations reveal elevated 24-hour urinary free cortisolB: Morning serum ACTH and lackofsuppressionofserum cortisolafter a measurement low-dose dexamethasone suppressiontest. C: Abdominal CT scan to look at Which additional investigationismost adrenal glands appropriateto determine the cause of her Cushing’ssyndrome? D: Pituitary MRI E: Salivary cortisol measurement Cushing’s Cushing’s syndrome is a disorder caused by prolonged exposure to a excess of glucocorticoids. This can be endogenous or exogenous. Cushing’s disease is a specific type of Cushing’s syndrome and it’s the most common endogenous cause, where the high cortisol is a result of an ACTH-producing pituitary tumour. That ACTH then acts on the adrenal glands to produce more cortisol. Abdominal ‘Lemonon sticks’ Centralobesity striae or ‘roundin the Amenorrhoea middle with think limbs’ PRESENTATION Hirsutism Round‘moonface’ Proximal myopathy Easy bruisingCushing’s ACTHDependent ACTHIndependent Cushings disease : Most Prolonged exposure to common → Pituitary exogenous steroids is the adenoma usually most common cause of Cushings syndrome EctopicACTHproduction: Adrenal tumours eg paraneoplastic syndromes adenomas, carcinomas and eglung cancers hyperplasias result in cortisol excess EctopicCRHproduction : CRHproducedbymalignant tissue INVESTIGATIONS: 24Hoururinarycortisol Lowandhighdosedexamethasone suppressiontestCushing’s – investigations NORMALRESPONSE=DexamethasonesuppressingACTHdue to negative feedback on the hypothalamusand pituitarygland, leading to lowerlevelsof cortisol LOWDOSEDEXAMETHASONESUPPRESSIONTEST=Using1mg of dexamethasone. No suppressionof cortisol, sofurther investigationrequired HIGHDOSEDEXAMETHASONESUPPRESSIONTEST=Using8mg of dexamethasone. Ectopic Adrenal Pituitary adenoma ACTH Cortisol production is tumour adenoma separate from Neither ACTHor 8mg is enough to pituitary, asit is Cortisol suppressed suppress both coming fromthe here.ThisACTH cortisol and ACTH adrenal glands. production comes via negative Suppression of ACTH from outside of the feedback is seenthrough axisandis negative feedback, unaffected bythe but cortisol levels stay dexamethasone. high. ACTH=LOW ACTH=LOW ACTH=HIGH CORTISOL=LOW CORTISOL=HIGH CORTISOL=HIGHCushing’s – interpretation of results Dexamethasone Low High dose dose High cortiso Low High Low cortisol cortisol LOW HIGH cortisol ACTH ACTH Adrenal Ectopic NORMAL Cushings Cushings adenoma syndrome disease ACTH secretion Cushing’s - management EXOGENOU Withdrawal of Not stop abruptly S the corticosteroid → Adcrisisan CUSHING’S CUSHING’S resection of the Doa DRUGS DISEASE pituitary pituitaryMRI Metyrapone Ketoconazol ECTOPIC Surgical removal CT Tap e of the source + ACTH CAUSE chemo Mifeproston e Pasireotide ADRENAL Adrenalectomy CT Tap orthe tumour of LESIONS SBA 8 Anna,a39 yearoldwoman isreferredto an A: Adrenal antibody test endocrinologyclinic. Forthe past sixmonths, B: CT abdo shehascomplainedoffatigue,weightloss and dizzinessonstanding.Shehas arange of bloodtestsandthe followingresultis C: Dexamethasone suppression found to besignificant. test 9am cortisol: 312 nmol/L (>500 nmol/L) D: Glucocorticoid replacement E: Short synacthen test Whatis the next beststepin management? SBA 8 Anna,a39 yearoldwoman isreferredto an A: Adrenal antibody test endocrinologyclinic. Forthe past sixmonths, B: CT abdo shehascomplainedoffatigue,weightloss and dizzinessonstanding.Shehas arange of bloodtestsandthe followingresultis C: Dexamethasone suppression found to besignificant. test 9am cortisol: 312 nmol/L (>500 nmol/L) D: Glucocorticoid replacement E: Short synacthen test Whatis the next beststepin management? Adrenal insufficiency Causedby destructionor dysfunctionof the adrenal cortex CAUSEIN THEUK :Autoimmune adrenalitis CAUSEWORLDWIDE:TB PRIMARYADRENAL SECONDARYADRENAL TERTIARYADRENAL INSUFFICIENCY INSUFFICIENCY INSUFFICIENCY • Addisons • ReductioninACTH • ReductioninCRH • Affectingthepituitarygland • Destruction/ • Seen aspartof • Affectingthe dysfunctionof adrenal panhypopituitarism,isolated hypothalamus cortex deficiency,afterbraininjury, • Seen followingchronic orduetodrugs glucocorticoiduse • CORTISOL:LOW • CORTISOL:LOW • CORTISOL:LOW • ACTH:LOW • ACTH:LOW • ACTH:HIGH Addison’s disease - diagnosis Saltcraving SHORTSYNACTHENTEST: Non-specific symptoms,e.g. HYPOnatraemia SyntheticACTHgivenin the lethargy,weakness, morning andserumcortisolis anorexia,vitiligo HYPERkalaemia measured 0, 30 and 60 minutes after administration. Hyperpigmentatio Normal individuals→ cortisol ninthepalmer SIGNS AND creasesinprimary SYMPTOMS level doublesin responseto adrenal synacthen ADDISONS=Failure insufficiency of cortisol to rise (lessthan • 9am serumcortisol doublethe • U&Esne) ADDISONIANCRISIS • VBG/ABG Hypotensionand Shock,abdominalpain, hypoglycaemia severeelectrolyte • Adrenal antibodies-21 hydroxylase deficiency abnormalities • Chest X-ray • CT scan of adrenal glands • MRI of the brain Addison’s disease - management Acutemanagement of Addisonian crisis • Fluidresuscitation • IVhydrocortisone STAT • Forpatientsalreadydiagnosed with Addisons, the glucocorticoiddose shouldbe doubledand the fludrocortisonedose remainthesame ChronicAddisonsdisease • Hydrocortisone in2 or 3 divideddoses→ 20- 30mg per daywiththe majoritygiveninthe first halfof theday • Fludrocortisone • PATIENT EDUCATION: Not missing doses, hydrocortisone injection in case of crisis, doubling their steroids on sick days, carrying a steroid card and wearing a medical alert bracelet, regular screening for adrenal crisis, osteoporosis and others complications SBA 9 A45year oldman hashadweightloss, fatigue andpolyuriafor 3months.Hetakesa numberof A: Bony metastases multivitaminpreparations.Clinical examination is unremarkable. B: Excess calcium intake Investigations: Serumcorrectedcalcium 2.9mmol/L(2.2–2.6) C: Primary hyperparathyroidism Phosphate0.82mmol/L(0.8–1.5) Serumalkalinephosphatase154IU/L(25–115) D: Sarcoidosis Parathyroidhormone7.9pmol/L(1.6–8.5) Serumelectrolytesandureaare normal. E: Vitamin D excess Whichisthemostlikely diagnosis? SBA 9 A45year oldman hashadweightloss, fatigue andpolyuriafor 3months.Hetakesa numberof A: Bony metastases multivitaminpreparations.Clinical examination is unremarkable. B: Excess calcium intake Investigations: Serumcorrectedcalcium 2.9mmol/L (2.2–2.6) C: Primary hyperparathyroidism Phosphate0.82mmol/L(0.8–1.5) Serumalkalinephosphatase154IU/L(25–115) D: Sarcoidosis Parathyroidhormone7.9pmol/L(1.6–8.5) Serumelectrolytesandureaare normal. E: Vitamin D excess Whichisthemostlikely diagnosis? SBA 10 Priyaisa 74yrold femalewithend-stage renal failurewhopresentstotheEDwithsevere A: Remove the parathyroid abdominalpain, constipation, frequencyand adenoma dysuriafor thepastweek. B: Fluid resuscitation with isotonic Blood testsshow: saline Correctedcalcium level= 3.54mmol/L(2.1- 2.6mmol/L) C: Intravenous bisphosphonates Phosphate=2.8mmol/L(0.8-1.4mmol/L) PTH level =24.7pmol/L(1.6-6.9pmol/L) D: Parathyroidectomy Given themostlikelydiagnosis, whatis the definitivetreatmentfor thispatient’s E: Oral furosemide 40mg once presentation? daily SBA 10 Priyaisa 74yrold femalewithend-stage renal failurewhopresentstotheEDwithsevere A: Remove the parathyroid abdominalpain, constipation, frequencyand adenoma dysuriafor thepastweek. B: Fluid resuscitation with isotonic Blood testsshow: saline Correctedcalcium level= 3.54mmol/L(2.1- 2.6mmol/L) C: Intravenous bisphosphonates Phosphate=2.8mmol/L(0.8-1.4mmol/L) PTH level =24.7pmol/L(1.6-6.9pmol/L) D: Parathyroidectomy Given themostlikelydiagnosis, whatis the definitivetreatmentfor thispatient’s E: Oral furosemide 40mg once presentation? daily Parathyroid Disorders Parathyroidhormoneissecretedbythechiefcellsinthethyroidglandbyrespondingtohypocalcaemiato increaseserumcalcium.ItfunctionsbyenhancingvitaminDactivity,increasingreabsorptionofcalciumin thekidneys,increaseactivationofosteoclasts. PRIMARY SECONDARY HYPERPARATHYROIDISM HYPERPARATHYROIDISM Vitamin D deficiency orCKD reduces Uncontrolled PTH production by parathyroid gland (tumour). PTH calciumabsorption. This leads tohypercalcaemia This leads tohypocalcaemia • ‘Bones’–excessive bone resorption Kidney 𝑪𝒂 • NM irritability –Chvostek sign, rebsorption Trousseau sign • ‘Stones’–renalcalculi,polyuria • ECG –QT prolongation • ‘Groans’– N&V, constipation,pain • ‘Moans’–lethargy/disorientation 𝟐+ The parathyroid glands reactto the Treatment: remove tumour absorption 𝑪𝒂 low calciumbysecreting more PTH. surgically Osteoclast 𝑪𝒂 resorption from boneTreatment:correctVitD deficiency, CKD (e.g.renaltransplant). ↑ serum 𝑪𝒂 𝟐+ Metabolic Bone Disorders Calcium Phosphate ALP PTH Primary ↑ Increased ↓ Decreased ↑ Increased ↑ Increased hyperparathyroidism Secondary ↓ Decreased ↑ Increased ↑ Increased ↑ Increased hyperparathyroidism Tertiary ↑ Increased ↑ Increased/ normal ↑ Increased ↑↑ Very increased hyperparathyroidism Osteoporosis Normal Normal Normal Normal ↓ Decreased ↓ Decreased ↑ Increased ↑ Increased *Osteomalacia *Paget’s disease Normal Normal ↑ Increased Normal *Renal Osteodystrophy ↓ Decreased ↑ Increased ↑ Increased ↑ Increased *OtherMSKconditionstolookover:ostemalacia(incompletemineralisationofbone),Paget’sdisease(abnormalbone remodellingduetoincreasedosteoclastactivity),renalosteodystrophy(chronickidneydisease-mineralandbonedisorder) SBA 11 A35-year-old woman presents to the Emergency Department worsening symptoms. She complains of palpitations, fever, A: IV propranolol sweating, and restlessness.On examination, she appears anxious and agitated, with a B: IV carbimazole heart rate of 150 bpm, blood pressure of 155/90mmHg,and atemperature of 39.2°C. C: Emergency thyroidectomy Blood tests reveal: • FreeT4: 45 pmol/L (normal: 10-22 pmol/L) D: High-dose prednisolone • TSH: <0.01 mIU/L (normal: 0.4-4.0 mIU/L) E: Radioactive-iodine therapy Which of the following is the most appropriate initial step in managing this patient? SBA 11 A35-year-old woman presents to the Emergency Department worsening symptoms. She complains of palpitations, fever, A: IV propranolol sweating, and restlessness.On examination, she appears anxious and agitated, with a B: IV carbimazole heart rate of 150 bpm, blood pressure of 155/90mmHg,and atemperature of 39.2°C. C: Emergency thyroidectomy Blood tests reveal: • FreeT4: 45 pmol/L (normal: 10-22 pmol/L) D: High-dose prednisolone • TSH: <0.01 mIU/L (normal: 0.4-4.0 mIU/L) E: Radioactive-iodine therapy Which of the following is the most appropriate initial step in managing this patient? Thyroid Disorders - Hyperthyroidism Hypothalamus PRIMARY SECONDARY HYPERTHYROIDISM HYPERTHYROIDISM TRH HighT4 and highTSH HighT4 and lowTSH Anterior pituitary Pathology is in the thyroid Pathology is in the gland TSH hypothalamus or pituitary ❑ Grave’s disease - ❑ TSH-secreting pituitary autoimmune,TSH-R Thyroid adenoma antibodiesmimic TSH ❑ TRH-secreting tumour ❑ Toxicmultinodular goitre– nodules develop in thyroidgland and act independently by producing excessive T3 & T4 T4 T3 SignsandSymptoms:weightloss,fatigue,loosestools,sweating, anxietyandirritability,sexualdysfunction,heatintolerance, Hyperthyroidism- management Acute management of thyroid storm A severe presentation of hyperthyroidism with pyrexia, tachycardia and delirium. • Supportive care with fluid resuscitation • Symptom control: IV propranolol (IV digoxin if asthmatic), • Reduce thyroid activity: propylthiouracil or methimazole , Lugol’s iodine 4 hrs later • IV hydrocortisone to reduce thyroid inflammation • Dexamethasone (e.g. 4mg IV qds) - blocks the conversion of T4 to T3. Long-term management of Grave’s disease • Carbimazole is thefirst lineanti-thyroid drug. Itis usuallysuccessfulin treating patients with Grave’s Disease, leaving them with normal thyroid functionafter 4-8 weeks. • Propylthiouracil is thesecond lineanti-thyroid drug. Itis usedin asimilar way to carbimazole. There is a small risk of severe hepatic reactions, includingdeath, whichis whycarbimazole is preferred. Thyroid Disorders – Hypothyroidism Hypothalamus SECONDARY PRIMARY HYPOTHYROIDISM HYPOTHYROIDISM TRH LowT4 and highTSH LowT4 and lowTSH Anterior pituitary ❑ Hashimoto’s thyroiditis – Pituitarygland fails to produce autoimmuneinflammation of enoughTSH. the thyroidgland,associated TSH withTPOantibodies. Causedbytumours,infection, ❑ Iodine deficiency vascular(e.g.Sheehan Thyroid Syndrome), radiation. T4 T3 ❖ SignsandSymptoms:weightgain,fatigue,dryskin,hairloss, fluidretention,heavyorirregularperiods,coldintolerance, SBA 12 Hannah is 35yr old lady under the care of the neurosurgeons for treatmentof a pituitary adenoma. Following endocrine A: CT adrenals testingthis is found to be non-functional. However, prior to surgery she is found to B: CT chest have a hinmol/l. A diagnosis of of 3.8 hyperparathyroidism is then made. It is C: CT pancreas suspectedthat she may have an endocrine syndrome affecting multiple D: Upper GI endoscopy parts of her body. What investigation should you undertake E: Thyroid ultrasound next? SBA 12 Hannah is 35yr old lady under the care of the neurosurgeons for treatmentof a pituitary adenoma. Following endocrine A: CT adrenals testingthis is found to be non-functional. However, prior to surgery she is found to B: CT chest have a hinmol/l. A diagnosis of of 3.8 hyperparathyroidism is then made. It is C: CT pancreas suspectedthat she may have an endocrine syndrome affecting multiple D: Upper GI endoscopy parts of her body. What investigation should you undertake E: Thyroid ultrasound next? Multiple Endocrine Neoplasia (MEN) MEN are a group of conditions where there is formation of hormone producing tumours in different organs around the body. MEN Subtype Features Multiple endocrine neoplasia - 1 Mutation in the MEN-1 gene Affects the following: • Parathyroid = hyperplasia/adenomas • Pancreas = gastronoma, insulinoma • Pituitary = prolactinoma Multiple endocrine neoplasia – 2a Mutation in the RET gene Affects the following: • Thyroid = medullary thyroid cancer • Adrenal = phaeochromocytoma • Parathyroid = hyperplasia/adenomas Multiple endocrine neoplasia – 2b Same as 2b but usually causes mucosal neuromas and can cause marfanoid body habitus. SBA 13 70-year-old man is brought to the mergency Department with confusion A: Diabetic ketoacidosis nd lethargy. His family reports several eeks of increased thirst and urination. B: Hyperosmolar hyperglycaemic state n examination, he is dehydrated with a eart rate of 110 bpm and blood C: Hypoglycaemia ressure of 90/60 mmHg. nd urinalysis shows glucose but noL, etones. Serum osmolality is 330 mOsm/kg. D: Central diabetes insipidus hat is the most likely diagnosis? E: Acute kidney injury SBA 13 70-year-old man is brought to the mergency Department with confusion A: Diabetic ketoacidosis nd lethargy. His family reports several eeks of increased thirst and urination. B: Hyperosmolar hyperglycaemic state n examination, he is dehydrated with a eart rate of 110 bpm and blood C: Hypoglycaemia ressure of 90/60 mmHg. nd urinalysis shows glucose but noL, etones. Serum osmolality is 330 mOsm/kg. D: Central diabetes insipidus hat is the most likely diagnosis? E: Acute kidney injury Hyperosmolar Hyperglycaemic State COMPLICATION OF T2DM LEADING TO Fatigue, lethargy, UNCONTROLLED HYPERGLYCAEMIA nausea, vomiting, General Thelack of insulinis coupled with a rise in POLYURIA AND counter-regulatory hormones (cortisol, growth POLYDIPSIA hormoneandglucagon) →profoundrise in glucagon Altered consciousness, Acertain amount of insulin Is headaches, retained which prevents the Neurological development of ketosis that papilloedema, defines DKA weakness OSMOTIC DIURESIS →leadingto loss Hyperviscosity of electrolytes (kidneysonlyhavea Haematological of the blood → certain capacityfor glucose Potential stroke, reabsorption) PAD, infarctions Dehydration, Cardiovascular hypotension, If they fail to tachycardia Dehydration and reduced Compensatory renal water loss, circulating volume mechanisms hypovolemia HYPEROSMOLARITY egADH release occur→ AKI, & HYPERGLYCAEMIA and thirst Hypotension, coma Hyperosmolar Hyperglycaemic State Fluidand Switchto0.45%NaClif Hypovolemia electrolyte IV0.9%NaCl declining(moret hypotonicsolution) replacement Rapidchangesin Therateoffallofplasma Increasedserum Monitor Cardiovascular sodiumshouldnot osmolality management collapseandCentral exceed10mmol/Lin24 Hyperglycaemia >320mosmol/kg pontinemyelinosis hours. >30mmol/l (withno ketosisoracidosis) KETONEMIA PRESENT Checkketonestosee (MIXED DKA/HHS) → Insulin if insulinneeded. fixed rate insulin started attime 0 KETOENMIA ABSENT = NO INSULIN Primary Hyperaldosteronism PRIMARY= High 1) Aldosterone:Renin aldosterone, lowrenin ↑ ALDOSTERONE ratio SECONDARY=High aldosterone, highrenin 2) HighresolutionCT ↑Na+ ↑H+secretion scanof the adrenal reabsorption ↑K+secretion from the gland from distaltubule from distaltubule collectingducts ADRENAL ADENOMA: Surgery 3)Adrenal Venous Sampling–invasive BILATERALADRENAL HypertensionandHypokalemiaandAlkalosis HYPERPLASIA(most common): Aldosteroneantagonist eg spironoloactone Hyperkalaemia Potassium levels <5.5mmol/L Causes Management Impaired excretion from cells 10mls over 10mins AKI, CKD, ACEi, NSAIDs, Addison’s Calcium as this stabilises the cardiac membrane, gluconate remember ECGs! Increased release from cells Lactic acidosis, rhabdomyolysis, Insulin causes K+ to insulin deficiency, tumour lysis IV insulin in shift intracellularly. Glucose is required to sOther causes 25g glucose hypoglycaemiaoping Haemolysis, delayed analysis of blood, contamination with K+ Nebulised K+ intracellular shift ECGchanges:tall tented T-waves, flat P-waves salbutamol and prolonged PR interval Hypercalcaemia Calcium levels <2.65mmol/L Causes Management • Corrects dehydration Primary Malignancy • Protects kidneys IV fluids • Increases Ca2+ hyperparathyroid excretion ism E.g. zolendronate Medication e.g. Reduce bone lithium,thiazides Bisphosphonates resorption → Osteolyticbone decrease Ca2+ lesions • Radiotheraoy for Prevent tumours Thyrotoxicosis • Chemotherapy recurrence • sarcoidosisr Myxoedema coma – hypothyroid state (symptoms = bradycardia + confusion) SIADH Conn’s Other conditions to look over: Congenital adrenal Prolactinoma hyperplasia Quick conditions! Carcinoid syndrome Insulinoma Acromegaly symptoms: ❑ Whipple's triad symptoms -Diarrhoea, flushing, wheeze - signsand symptomsof - Bitemporal hemianopia -Abdominalpain hypoglycaemia -Prominent forehead,largehandsand - serumglucose < 2.2 feet etc. Test = 24hrurinary5HIAA - symptomreversal Test = IGF-1 is initial,thenOGTT uponglucose Management= Octreotide or administration Definitive Treatment = surgical resection ❑ Investigation= 72hr fasting glucose transsphenoidal surgery (high C-peptideand insulin) Pheochromocytoma Diagnostic Pathophysiology Symptoms Criteria ❑ Adrenaline = produced by Anxiety chromaffin cells in adrenalmedulla Sweating o 24hr urine catecholamines ❑ Phaeochromocytoma = tumour of Headaches o Plasma free metanephrines – the chromaffin cells leading to Hypertension better as tells you how much increased Palpitations,tachycardia and adrenaline is secretionof adrenaline paroxysmal AF secreted during the 24hr period ❑ Adrenaline is secreted in bursts – pointsmsare worse at certain Management Alpha blockers e.g., phenoxybenzamine Once on alpha blockers, add beta blockers Definitive management = adrenalectomy to remove tumour Diabetes insipidus Management Pathophysiology Symptoms o Treating underlyingcause ❑ Lack of ADHor lack of responseto ADH Polyuria Polydipsia o Desmopressin can be given ❑ Can be nephrogenicor cranial Hypernatremia in cranial ❑ Nephrogenic=when the CDs of Dehydration o Low salt/protein diet, the kidneysdo not respondto Postural ADH hypotension thiazides can be given in ❑ Cranial= when hypothalamusdoes nephrogenic not produce ADH Investigations & Diagnosis Investigations – low urineosmolality and high serum osmolality Diagnosis = water deprivation test –pt does not drink fluids for 8hrs, then synthetic ADH (desmopressin) is given, and urineosmolality is measured 8hrs later - Cranial diabetes: initially= urineosmolalityis low -------→nthetic ADH administration= urineosmolalityhigh - Nephrogenicdiabetes: initially= urine osmolalitylowaftersynthetic ADHadministration= urine osmolalitystill low