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ENDOCRINOLOGY CORE CONDITIONS THYROID, PARATHYROID & ELECTROLYTE ABNORMALITIES By Adit Bassi Y6 MBBS University College London Tuesday 28 THNovember 2023 19:00 @BINDIANMEDICS @ BRITISHINDIANMEDICASSOCIATION BRITISH INDIAN MEDICAL @BIMA ASSOCIATION BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL The British Indian Medical Association (BIMA) - The British Indian Medical Association (BIMA) is a national non- profit organisation founded on developing a supportive network amongst students and doctors across the UK - Provides tutorial series, conference events, networking, careers talks, socials and more! - For more information follow us on social media and stay up to date with latest academic events by joining our mailing lists: BIMA Clinical and OSCE series: https://forms.gle/CidGvWAc9YY9WSSs8 BIMA Fundamentals of Medicine & Pathology series: https://forms.gle/KfAgeoX55GPAWqee8 BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Year 6 MBBS University College London 1 class BSc with honours in Paediatrics and Child Health adit.bassi.18@ucl.ac.uk Adit Bassi Y6 MBBS BSc University College London BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Clinical endocrinology: thyroid, parathyroid & electrolyte imbalances BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL The thyroid hormone axis Primary thyroid issue: usually thyroid gland dysfunction Secondary thyroid issue: usually pituitary dysfunction https://www.researchgate.net/figure/The-Hypothalamic-Pituitary-Thyroid-axis-including-the-roles-of-thyrotropin- releasing_fig2_257006752/actions#reference BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Signs & symptoms – hypo vs hyper thyroid – think of ‘opposites’ Hypothyroid Hyperthyroid / thyrotoxicosis • General: Weight gain; lethargy; cold • General: Weight loss; restlessness; intolerance heat intolerance • Cardiac: nil • Cardiac: palpitations +/- arrhythmias • Skin: dry; cold; non-pitting oedema; • Skin: hyperhidrosis; pretibial eyebrowscalp hair; loss of outer third of myxoedema; thyroid acropachy • GI: constipation (clubbing) • Gynae: menorrhagia • GI: diarrhoea • Neuro: Decreased reflexes; carpal tunnel • Gynae: oligomenorrhoea • Neuro: anxiety; tremor BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Most common causes of thyroid dysfunction Hypothyroid Hyperthyroid / thyrotoxicosis • Most common worldwide: iodine • Most common: Grave’s disease deficiency • Other signs including thyroid eye disease, TSH receptor antibodies +’ve • Most common in developed world: Hashimoto’s thyroiditis (autoimmune – F:M 5-10:1) • Anti-TPO +’ve BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Other causes of thyroid dysfunction Hypothyroid Hyperthyroid / thyrotoxicosis • Subacute (de Quervain’s) thyroiditis • Subacute (de Quervain’s) thyroiditis • Painful goitre; raised ESR; initially • Painful goitre; raised ESR; initially hyper, then hypothyroid; self-limiting hyper, then hypothyroid; self-limiting • Postpartum thyroiditis • Toxic multinodular goitre • Drugs: lithium, amiodarone (both) • Autonomously functioning thyroid nodules that secrete excess thyroid hormone • Drugs: amiodarone (both) BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Investigation and diagnosis (TFT interpretation) Diagnosis TSH Free T4 Thyrotoxicosis (e.g. Graves’ disease) ↓ ↑ Primary hypothyroidism ↑ ↓ Secondary hypothyroidism ↓ ↓ Sick euthyroid syndrome ↓/- ↓ Subclinical hypothyroidism ↑ - Poor compliance with thyroxine ↑ - BIMA Clinical and OSCE seriesA 28-year-old woman has felt increasingly irritable over the last few months. She describes herself as ‘hot and bothered’ – she is always trying to cool herself down and is sweating. She has lost 5kg in weight during this time. She smoked 20 cigarettes a day and drinks 30 units of alcohol per week. Which single examination finding is most likely to support the diagnosis? a) Dry skin and hair b) Exophthalmos c) Hyperpigmented skin folds d) Lymphadenopathy e) Malar rashA 28-year-old woman has felt increasingly irritable over the last few months. She describes herself as ‘hot and bothered’ – she is always trying to cool herself down and is sweating. She has lost 5kg in weight during this time. She smoked 20 cigarettes a day and drinks 30 units of alcohol per week. Which single examination finding is most likely to support the diagnosis? a) Dry skin and hair b) Exophthalmos c) Hyperpigmented skin folds d) Lymphadenopathy e) Malar rashA 49-year old woman has felt tired over the last few months, and her thyroid function tests are returned as follows: TSH: 6.8 mU/L T4: 19 pmol/L She has no detectable goitre. Which is the single most likely explantion for the blood results? a) Hashimoto’s thyroiditis b) Iodine deficiency c) Sick euthyroidism d) Subclinical hypothyroidism e) Unknown use of levothyroxineA 49-year old woman has felt tired over the last few months, and her thyroid function tests are returned as follows: TSH: 6.8 mU/L T4: 19 pmol/L She has no detectable goitre. Which is the single most likely explantion for the blood results? a) Hashimoto’s thyroiditis b) Iodine deficiency c) Sick euthyroidism d) Subclinical hypothyroidism e) Unknown use of levothyroxine Adit Bassi Y6 MBBS UCL A 27 year old presents to A&E following a seizure and is found to be profoundly hyponatraemic. He is euvolaemic and has a low plasma osmolality (<270 mOSm/kg). Which metabolic condition is most in keeping with these results and presentation? a) SIADH b) Conn's syndrome c) Hyperosmolar hyperglycaemic syndrome d) Diabetes insipidus e) Cushing's disease BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL A 27 year old presents to A&E following a seizure and is found to be profoundly hyponatraemic. He is euvolaemic and has a low plasma osmolality (<270 mOSm/kg). Which metabolic condition is most in keeping with these results and presentation? a) SIADH b) Conn's syndrome c) Hyperosmolar hyperglycaemic syndrome d) Diabetes insipidus e) Cushing's disease BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Sodium abnormalities 135 – 145 mmol/L BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Pseudohyponatraemia - Serum osmolality for pseudo-hyponatraemia is normal (280- 300 mOsm/kg) or raised i.e. an iso-osmolar hyponatraemia Potential causes: - Hypercholesterolaemia, hyperlipidaemia; abnormally high protein levels e.g. chronic infection, malignancy; hyperglycaemia; iatrogenic (e.g. bloods taken from arm with IV fluids); alcohol intake; mannitol; glycine washout during TURP BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Investigations To assess hyponatraemia: Bloods: - Fluid status !! - Paired serum / urine osmolality - FBC, U&E, LFT, TFT, CRP - Urinary sodium - Short synacthen test * >20mmol – hypovolaemia due to renal causes * Diuretics, salt-losing nephropathy, Addison’s * <20mmol – hypovolaemia due to non-renal losses * Diarrhoea, vomiting, fistula, burns, SBO, hyperthermia BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Fluid status Hypovolaemia Hypervolaemia • Tachycardia • Raised JVP • Postural hypotension • Bibasal crackles (on chest • Dry mucous membranes auscultation) • Peripheral oedema • Reduced skin turgor • Confusion / drowsiness • Reduced urine output BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hyponatraemia causes From pulsenotes: https://app.pulsenotes.com/specialities/biochemistry/notes/hyponatraemia BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Classification Clinical severity Biochemical classification • Mild hyponatraemia: serum • Mild: Asymptomatic or mild Na 130-135 mmol/L features of nausea, lethargy, irritability • Mo+erate hyponatraemia: serum • Moderate: nausea, confusion, Na 125-129 mmol/L • Severe hyponatraemia: serum headache Na < 125 mmol/L • Severe: vomiting, cardioresp distress, drowsiness, seizures, coma BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Management Mainstay of treatment is to treat the underlying cause that you have identified • A-E approach • Senior input (in particular HDU or ITU) if severe / neurological symptoms present • Use of 0.9% Sodium Chloride to correct hyponatraemia • Aim for slow correction if stable to avoid osmotic demyelination syndrome (maximum correction 8-10 mmol/L per 24 hours unless severe) • Euvolemia / hypervolaemia – consider fluid restriction BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hypernatraemia (very quickly) Causes: • Mainly dehydration • Iatrogenic: excess IV saline (0.9% Sodium Chloride) • Diabetes insipidus Correct with CAUTION - Risk of cerebral oedema BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL A 52-year-old man with a past medical history of renal failure, diabetes mellitus and hypertension is referred to the emergency department by his GP with complaints of palpitations, oedema and increased fatigue. On examination, the patient is obese and has a blood pressure of 174/92 mmHg, alongside a heart rate of 52 bpm. His heart sounds are regular but slow, and lung auscultation is clear, with no added sounds. His ECG shows: BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL The medical team are awaiting his blood results. What condition most likely explains the above ECG changes? a) ST-elevation myocardial infarction (STEMI) b) Hypercalcaemia c) Hypokalaemia d) Hyperkalaemia e) Atrial fibrillation BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL The medical team are awaiting his blood results. What condition most likely explains the above ECG changes? a) ST-elevation myocardial infarction (STEMI) b) Hypercalcaemia c) Hypokalaemia d) Hyperkalaemia e) Atrial fibrillation BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Potassium abnormalities 135 – 145 mmol/L BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hyperkalaemia causes https://app.pulsenotes.com/specialities/biocheBIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Pseudohyperkalaemia!! • Prolonged tourniquet time • Haemolysed sample (if it’s been left for too long without running) • Sample from a limb receiving K+ intravenously • Traumatic sample (cellular damage releasing K+ into blood bottle) • Marked leukocytosis or thrombocytosis BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Clinical features Symptoms Signs • Fatigue • Arrythmias • Generalised weakness • Reduced power • Chest pain • Reduced reflexes • Palpitations • Signs of underlying cause (e.g. trauma leading to rhabdo) BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL ECG changes in ↑K+ (in order of appearance) 1. Tall, tented T waves 2. PR prolongation 3. Small / absent p-waves 4. Broadening QRS 5. Sine waves (sinusoidal pattern) 6. Asystole BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Investigations Bedside: urinalysis, ECG Bloods: FBC, U&Es, Bone profile, CRP , blood cultures (if febrile), CK (if rhabdomyolysis suspected), VBG/ABG These are not extensive, and you can justify a lot more based on the clinical picture, but this is a good starting point / baseline BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Initial management (key points) • A to E approach! Stabilise the patient as best you can • Make sure the sample is re-run (to confirm true hyperkalaemia) • ECG +/- cardiac monitoring as soon as possible • Stop any offending drugs or potassium-containing fluids • If K+ ≥6.5 mmol/L OR ECG changes suggestive, it’s important to stabilise the cardiac membrane first BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Management in stages Stabilise the myocardium: 10ml of 10% calcium gluconate over 10 minutes Drive K+ intracellularly: Insulin (+ glucose) infusion or nebulised salbutamol Potassium elimination: Loop diuretics or other agents such as calcium resonium (enema more effective than oral as K+ is secreted by the rectum) Refractory hyperkalaemia: Haemodialysis BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hypokalaemia Acidotic-related causes Alkalotic-related causes • Diarrhoea • Vomiting • Renal tubular acidosis • Thiazide and loop diuretics • Acetazolamide • Cushing’s syndrome • Partially treated DKA • Conn’s syndrome (primary hyperaldosteronism) BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Features of ↓K+ ECG changes Other features • U waves • Muscle weakness • Hypotonia • Small or absent T waves • Prolonged PR interval • May predispose to digoxin • ST depression toxicity • Prolonged QT BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Calcium abnormalities 2.2 – 2.6 mmol/L BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hypocalcaemia features • Tetany: muscle twitching, cramping and spasm • Perioral paraesthesia • Voice changes (laryngospasm) • Palpitations (arrhythmias) • ECG changes: prolonged QT BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hypocalcaemia signs Trousseau’s sign Chvostek’s sign https://www.ncbi.nlm.nih.gov/books/NBK557832/figure/article-30639.image.f3/ BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Investigations • ECG (super important because can cause prolonged QT and other arrhythmias) • Bloods: • Bone profile • U&Es • Vitamin D • Parathyroid hormone • Magnesium BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hypocalcaemia management • Mild ↓Ca2+ (≥1.9mmol/L cCa2+) & asymptomatic • Oral calcium supplements • Ensure correction of hypomagnesaemia • Treat underlying cause e.g. Vit D replacement • Severe ↓Ca2+ (<1.9mmol/L cCa2+) OR symptomatic • Cardiac monitoring • IV calcium gluconate (10ml of 10% in 100mls 0.9% NaCl) • Consider repeat dose & slow infusion if necessary • Treat co-existent pathology if identified BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hypercalcaemia (↑Ca2+) causes BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hypercalcaemia causes Malignancy related causes Other causes (most common in hospitalised patients) • Sarcoidosis • PTHrP from the tumour (e.g. squamous cell lung cancer) • Vit D intoxication • Bony metastases causing • Acromegaly destruction • Thyrotoxicosis • Milk alkali syndrome (yes, • Myeloma (↑ osteoclastic drinking too much milk) bone resorption) • Drugs • Dehydration • Addison’s disease BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hypercalcaemia features _of_hypercalcaemia.jpg.cloudfront.net/uploads/ckeditor/picBIMA Clinical and OSCE seriesnt/features Adit Bassi Y6 MBBS UCL Hypercalcaemia features Symptoms Signs • Fatigue • Dehydration (skin turgor) • Myalgia • Hypertension • Mood changes • Cardiac arrhythmia (severe) • Depression • Confusion (severe) • Insomnia • Corneal calcification • Polydipsia • Shortened QT interval on • Polyuria ECG • Constipation BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hypercalcaemia investigations • Confirm hypercalcaemia with a bone profile (remember to look at corrected calcium) • Parathyroid hormone most important • Routine bloods: FBC, U&E, LFT, CRP/ESR, TFT • Vitamin D levels • ACE (if sarcoid suspected) • Malignancy screen (e.g. protein electrophoresis, tumour markers) • Imaging: routine CXR, ?CTCAP (if malignancy suspected), parathyroid imaging (if 1 hyperparathyroidism suspected) BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hypercalcaemia initial management • A-E: stabilise patient • Mainstay of initial treatment involves (aggressive) fluid resuscitation • Mild/asymptomatic (<3mmol/L): increase oral fluids & avoid ↑Ca2+ precipitants • Moderate (3-3.5 mmol/L) and an acute rise: inpatient admission for IV fluids • Severe (>3.5mmol/L): urgent admission, aggressive IV fluids and consideration of bisphosphonates BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hypercalcaemia other treatment options • Corticosteroids (can be used if ↑↑ Vit D) • Surgery: largely curative in 1 hyperparathyroidism. Also a potential option in 3 hyperparathyroidism • Cinacalcet: calcimimetic that replicates the action of calcium on the calcium-sensing receptors • Dialysis: reserved for severe, refractory hypercalcaemia BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Parathyroid axis (simplified) https://zerotofinals.com/wp-content/uploads/Parathyroid-Action-1024x515.jpg BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL Hyperparathyroidism causes (simplified) https://youtu.be/j_LPQT5t_88?si=K6JznzDtU5kUrWcI&t=365 BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL A 42-year-old woman is referred by her general practitioner with constipation, low mood and a history of renal stones. Her GP organised some blood tests after she was found to have a fracture of her lumbar spine, Corrected calcium 2.82 mmol/L, PTH 12.7 pmol/L, vitamin D 73 nmol/L, creatinine 43 micromoles/L. Which is the single best explanation for the pathological process behind her symptoms? a) Primary hyperparathyroidism b) Sarcoidosis c) Malignancy d) Hyperthyroidism e) Tertiary hyperparathyroidism BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL A 42-year-old woman is referred by her general practitioner with constipation, low mood and a history of renal stones. Her GP organised some blood tests after she was found to have a fracture of her lumbar spine. Corrected calcium 2.82 mmol/L, PTH 12.7 pmol/L, vitamin D 73 nmol/L, creatinine 43 micromoles/L. Which is the single best explanation for the pathological process behind her symptoms? a) Primary hyperparathyroidism b) Sarcoidosis c) Malignancy d) Hyperthyroidism e) Tertiary hyperparathyroidism BIMA Clinical and OSCE series Adit Bassi Y6 MBBS UCL THANK YOU FOR LISTENING ANY QUESTIONS adit.bassi.18@ucl.ac.uk BIMA Clinical and OSCE series