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Medical Series: Endocrine Part 1 : Adrenals Dr. Acute Medicineman Trust Grade Doctor6PM Curriculum & Endocrinology • Today Part 1: Adrenals • 16/11/21 Electrolyte Abnormalities part 2 • 17/11/21 Acute Medicine 2 • 23/11/21 Part 2: Parathyroid/Thyroid • Stroke Webinar to be given new date during the series • TBD Part 3: Diabetes (Next Med Series) • TBD Part 4: Disorders of the pituitary & sexual development (Next Med Series)Social Medias Case 1 Question A 75-year-old gentleman was admitted with recurrent falls secondary to orthostatic hypotension. The consultant considers starting fludrocortisone for the which layer are mineralocorticoids released from?ure of the adrenal gland. From A. Zona Fasciculata B. Zona Reticularis C. Zona Glomerulosa D. Medulla E. Don’t know Case 1 Answer From which layer are Fasciculata = cortisol mineralocorticoids released from?Reticularis = sex hormones A. Zona Fasciculata Medulla = catecholamines (e.g. adrenaline) B. Zona Reticularis C. Zona Glomerulosa D. Medulla E. Don’t know The zona glomerulosa release mineralocorticoids mainly aldosterone improved in salt regulation. Case 1 Adrenal Cortex • The adRENAL gland is split into the cortex (outer) and the medulla (inner). • The cortex is split in three further layers, each release their own substance. Cortex Medulla adRENALS Cortex (Zona Cortex Functions- Order GFR) you’d spend the evening in.. Glomerulosa Salt- Mineralocorticoids Fasciculata Sugar- Glucocorticoids Reticularis Miray Kirollos, Sex- DHEA/Testosterone The 6PM Series Case 2 Question A 75-year-old gentleman was admitted with recurrent falls secondary to orthostatic hypotension. The consultant considers starting fludrocortisone for the patient. The consultant goes on to ask you, ‘Which catecholamine is the most abundantly produced in the adrenal medulla?’ A. Adrenaline (epinephrine) B. Dopamine C. Noradrenaline (norepinephrine) D. Acetylcholine E. Don’t know Case 2 Answer Which is most produced by the Adrenal medulla releases about 20% adrenals? noradrenaline, about 1% dopamine and A. Adrenaline (epinephrine) acetylcholine is not a catecholamines. B. Dopamine C. Noradrenaline (norepinephrine) D. Acetylcholine E. Don’t know The most abundantly produced catecholamine is adrenaline at about 80%. Remember adrenals = mostly adrenaline. Case 2 Adrenal Medulla Non-essential amino acid Tyrosine Precursor to all catecholamines. Also used by thyroid to produce T3 & T4 Miray Kirollos, The 6PM Series L-DOPA is a replica of this. Medulla = Mostly DOPA Chromaffin Cells Precursor to the catecholamines. Adrenals=Adrenaline Adrenaline Noradrenaline Dopamine Tyrosine unable to produce i80% 20% <1% Phenylketonuria because of lack of Phenylalanine Hydroxylase Case 3 Question A 70-year-old lady presents to you with palpitations and feeling generally unwell. She has a history of hypothyroidism and hypertension. She has abnormality has most likely been caused?tensive agent. What electrolyte A. Hypomagnasaemia B. Hypercalcaemia C. Hypokalaemia D. Hyperkalaemia E. Don’t know Case 3 Answer Which is most produced by the ACEi do not cause the other electrolytes adrenals? abnormalities. A. Hypomagnasaemia However, calcium and magnesium B. Hypercalcaemia derangements can be associated with C. Hypokalaemia D. Hyperkalaemia palpitations but not sodium. E. Don’t know Hypertension Second line medication for >55years = ACEi ACEi indirectly cause inhibition of aldosterone release by inhibiting production of renin. This can lead to a hyperkalaemia.Case 3 Hyptertension Guidance Calcium channel ACEi or ARB blockers <55 years old >55 years old or Afro-carribean ACEi/ARB + CCB A + C + Thiazide diuretic A + C + T + other (e.g. Alpha blocker)ARB ACEi/ARBs & Aldosterone ACEi ENaC Indirect Na+ + Aldosterone K } Case 4 Question A 70-year-old gentleman presents with a new presentation of acute CCF likely secondary to ischaemic heart disease. On discharge he has been Eplerenone, Aspirin, Ticagrelor and Atorvastatin. How does Epleneronesemide, work? A. inhibitionC synthesis B. Competitive mineralocorticoid receptor binding C. Reduces cortisol production D. NKCC inhibitor E. Don’t know Case 4 Answer How does Eplerenone work? Direct inhibition of ENaC = Amiloride A. Direct ENaC synthesis inhibitioReduce cortisol production = e.g. B. Competitive mineralocorticoid ketoconazole receptor binding NKCC inhibition = loop directs e.g. C. Reduces cortisol production D. NKCC inhibitor furosemide & bumetanide E. Don’t know Potassium Sparing Diuretics Eplerenone and Spironolactone sound like aldosterone – they therefore compete to bind to the same receptor they are aldosteroneanatagonists. K+ Diuretics Mechanism of action ENaC Na+ Aldosterone K+ } Eplerenone Amiloride Competitive mineralocorticoid receptor binding Inhibition of ENAC synthesis Case 5 Question and nauseous. Prior to this she had worsening symptoms of headache, necknwell stiffness and photophobia. O/E A-patent, B- clear air entry, RR 21, Sats 94% OA, C- BP 70/30, HR 110 sinus tachy. D- GCS 13, BM 3.4, E- Abdo SNT. You also note hyperpigmentation around the hands. What is the most likely cause? A. Steroid Withdrawal B. Waterhouse-Friederichsen Syndrome C. TB D. Autoimmune E. Don’t know Case 5 Answer What is the most likely cause? • Steroid Withdrawal- No history of taking A. Steroid Withdrawal steroids. B. Waterhouse-Friederichsen • TB- Most common cause of Addison’s Syndrome worldwide but no history to indicate it. C. TB • Autoimmune- Most common cause in the D. Autoimmune UK, but history of meningitis make this E. Don’t know cause less likely. Waterhouse-Friederichsen Syndrome Likely meningococcal septicaemia (rash not yet developed) causing B/L adrenal haemorrhage. Case 5 Adrenal Insufficiency • Waterhouse-Friederichsen - Rarer cause of adrenal insufficiency. • Usually B/L haemorrhage of the adrenal glands secondary to severe sepsis. • Commonly associated with Neisseria meningitidis (gram -VE diplococci), but other causes. • further adrenal shock on top of septic shock.able to ischaemia, eventual insufficiency causes Primary (Addison’s Disease) Secondary Decreased ACTH = 1. Autoimmune (UK) Most commonly due to steroids, withdrawal is followed by insufficiency. 2. Infection (TB worldwide) Rarely due to hypothalamic/pituitary axis issues. 3. B/L Haemorrhage 4. Infiltrative process 5. Drugs (Ketoconazole) Ketoconazole inhibits steroid forming CYP450 enzymes Case 5 Insufficiency Features ↓ Glucocorticoids ↓ Mineralocorticoids ↑ ACTH Non-specific symptoms Hyponatraemia Hyperpigmentation Hypotension Hyperkalaemia Hypoglycaemia Case 5 Investigations & Management • If suspicion of index is high enough take bloods and treat, do not wait to do further investigations such as a short synacthen test. • Long synacthen test is rarely used, but lasts 48 hours and is used to differentiate between primary and secondary causes of adrenal insufficiency. Investigations Management Maintenance Oral Steroids + Fludrocorticone 1. Random Vs 9am Cortisol 2. Short Synacthen Test 3. Anti-21-hydroxylase ABs 4. CT Adrenals 6. MRI Head Case 5 Question a lightheaded, unwell and nauseous. Prior to this she had worsening symptoms of headache, neck stiffness and photophobia. O/E A-patent, B- clear air entry, RR 21, Sats 94% OA, C- BP 70/30, HR 110 sinus tachy. D- GCS 13, BM 3.4, E- the hyperpigmentation?e hyperpigmentation around the hands. What caused A. Decreased Cortisol B. Increased ACTH C. Increased ADH D. Increased GH E. Don’t know Case 5 a Answer What is the most likely cause? Decreased cortisol leads to decreased A. Decreased Cortisol inhibition of ADH B. Increased ACTH ADH related to fluid and sodium regulation C. Increased ADH GH is implicated in acromegaly and D. Increased GH gigantism E. Don’t know Hyperpigmentation In Addison’s increased ACTH release promotes increased MSH production, which leads to hyperpigmentation. It is therefore only seen in PRIMARY and NOT SECONDARY. Case 5 a Insufficiency Features ↓ Glucocorticoids ↓ Mineralocorticoids ↑ ACTH (Primary) Non-specific symptoms Hyponatraemia Hyperpigmentation Hypotension Hyperkalaemia HypoglycaemiaHPA Axis CRH ACTH -VE Feedback Cortisol Miray Kirollos, The 6PM Series Anterior Pituitary Posterior Pituitary ACTH ADH (Vasopressin) MSH Oxytocin LH/FSH Prolactin GH TSH ACTH increase stimulates MSH production =Increased melanocytes = hyperpigmentation Commonly affects sun exposed areas Case 5 Question b Which of these steroids has the highest mineralocorticoid activity? A. Dexamethasone B. Methylprednisolone C. Prednisolone D. Hydrocortisone E. Don’t know Case 5 Answer b Most MC acitivity? Steroid Mineralocorticoid Duration Oral A. Dexamethasone activity Bioavailability Prednisone 5 mg Medium 12-36 N/A B. Methylprednisolone (prodrug- hepatic) hours C. Prednisolone Hydrocortisone High 8-12 1:1 D. Hydrocortisone 20 mg hours E. Don’t know Methylprednisolone Very Low 12-36 1:1 4 mg hours All equal to 5mg Prednisolone Dexamethasone Very low 36-72 1:1 750 micrograms hours SC 3.3 = IV 3.8 = 4 oral Fludrocortisone Very High 24-48 https://bnf.nice.org.uk/treatment-(No glucocorticoid hours activity) summary/glucocorticoid-therapy.html Case 6 Question A 40-year-old gentleman presented with recent 5kg weight gain, tiredness and feels a swelling building between his shoulder blades. O/E he his hypertensive, has an interscapular fat pad and moon facies. He is well in himself otherwise. What initial investigation would you like to carry out? A. Random plasma cortisol B. 1mg Overnight Dexamethasone Suppression Test C. Long synacthen test D. 24 hour urinary cortisol E. Don’t know Case 6 Answer Which initial test? 24 hour urinary cortisol is the best A. Random plasma cortisol investigation but least practical and most B. 1mg Overnight Dexamethasone difficult to do but it is another option, may Suppression Test be better to do as an inpatient, but the C. Long synacthen test D. 24 hour urinary cortisol patient is well so would not need to be kept E. Don’t know in necessarily. Dexamethasone suppression test In a normal patient will cause negative feedback and therefore suppresses ACTH release and should decrease cortisol levels to less than 50nmol/L. If not consider Cushing's Syndrome. Case 6 Cushing’s Syndrome Exogenous Endogenous Steroid Use Primary Secondary ACTH Independent ACTH Dependent ↓ ACTH Adrenal adenoma Cushing’s disease - pituitary Malignancy Ectopic (e.g. SCLC) ↑ cortisol → ↓ ACTH ↑ ACTH → ↑ cortisol Cushing Syndrome = Glucocorticoid Excess Exogenous most common Cushing’s disease > Primary endogenous Causes Case 6 Features, Investigations & Mx Clinical Features • Investigations • 1st- 24 urinary cortisol (best but Central obesity, Cataracts impractical) or 1mg dexamethasone suppression test or late night Ulcers & (m)Uscle loss salivary cortisol (multiple to add to Skin thinning & Striae index of suspicion) HTN, Hyperglycaemia • 2nd 48 hour dexamethasone Immunosuppressed suppression test (suppresses cortisol in Cushing’s disease) Avascular Necrosis (Fem) • ACTH with serum cortisol levels for Gynae problems primary vs secondary. Sleep Apnoea • Mx- depends on cause Dexamethasone is the preferred glucocorticoid for does not interfere with the measurement of cortisol or its urinary metabolites. Case 7 Question despite dual antihypertensive therapy. She also states she has been getting headaches and palpitations occasionally. Her blood sugars, FBC and RFTs are unremarkable. Her blood pressure during this clinic is 160/140. What is the most likely diagnosis? A. Hyperaldosteronism B. Renovascular HTN C. Phaeochromocytoma D. Cushing’s disease E. Don’t know Case 7 Answer Which initial test? • Hyperaldosteronism Another common cause, but A. Hyperaldosteronism nothing in the vignette to suggest it. • Renovascular HTN Most common cause of B. Renovascular HTN secondary hypertension, but patient very young C. Phaeochromocytoma • Cushing’s disease other signs and symptoms and D. Cushing’s disease not episodic and patient has normal blood sugars. E. Don’t know Phaeochromacytoma Disease of the renal medulla (majority) Young patients with episode headaches and uncontrolled hypertension Case 7 Features, Investigations & Mx • Neoplasm of the chromaffin cells of Clinical Features the adrenal medulla. Episodic • Aetiology: Majority sporadic and 10% rule. Headaches • 10% B/L, 10% Familial (E.g. MEN), 10% Palpitations no associated HTN.agangliomas), 10% Sweating • Investigations: 1. Urinary & serum Hypertension metanephrines(inactive catecholamines) 2. Abdo CT/MRI • Mx: Surgery with prior adrenergic blockade. • Alpha blockade then beta blockade within a week of surgery If beta blockade takes place first this can precipitate a hypertensive crisis through increased vasoconstriction. Case 8 Question A 40-year-old gentleman presents to the acute medical unit with hypertension (160/120) confirmed with ambulatory monitoring. He is normally fit and well. His plasma renin concentration (PRC) is low. What is the most likely diagnosis? Value Range pH 7.49 7.35-7.45 A. Gitelman’s Syndrome pCO 2 5 4-6 B. Renal artery stenosis HCO 3- 30 22-26 C. Liddle’s Syndrome Na 149 135-145 D. Primary Hyperaldosteronism K 2.6 3.5-5 E. Don’t know - Cl 110 2+ iCa 1.2 1.2-1.5 Case 8 Answer Which initial test? • Gitelman’s does not cause hypertension and is A. Gitelman’s Syndrome salt wasting with high renin and aldosterone • Renal artery stenosis is common but again high B. Renal artery stenosis renin and aldosterone levels. C. Liddle’s Syndome • Liddle’s ENaC mutation = increased channels and D. Primary Hyperaldosteronism increased sodium reabsorption causing E. Don’t know levels (congenital and rarer)d aldosterone Hyperaldosteronism Hypertension with a metabolic alkalosis, abnormally high plasma aldosterone levels suppressing renin levels, causing low renin. Case 8 Features, Investigations & Mx • Primary (commonly adrenal hyperplasia) Clinical Features or secondary e.g. renovascular disease. • ↑ENaC = ↑Na+ & ↓K+ via the kidneys. Hypertension • Intercalated cell = attempts to preserve K+ Hypokalaemia in exchange for H+ excretion. • ↓K+ = H+ intracellular shifting. Metabolic Alkalosis • This can lead to a metabolic alkalosis. • Primary = ↓PRC &↑PAC • Secondary= ↑PRC &↑PAC • Hypokalaemia is not always present, especially when caught early. • Mx: Unilateral = complete adrenalectomy and bilateral = spironolactone OR eplerenone O O F Feedback & Instagram + 3C N O Please complete feedback to receive slides and cheat sheet!Follow our In3tagram pa e for MCQs! NH O Cl CH 3 CH3 OH CH 3 CH OH 3 3HC CH3 3HC O