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Y2: Endocrine Qs LAULWA AL SALLOUM, YEAR 4 2367445A@STUDENT.GLA.AC.UKThe adrenal gland is divided into 3 distinct zones. Which of the following correctly pairs the adrenal gland zone and the main hormone(s) it produces? A. Zona reticularis – cortisol B. Zona glomerulosa - aldosterone C. Zona glomerulosa – cortisol D. Zona fasciculata – DHEA E. Zona reticularis - aldosteroneThe adrenal gland is divided into 3 distinct zones. Which of the following correctly pairs the adrenal gland zone and the main hormone(s) it produces? A. Zona reticularis – cortisol B. Zona glomerulosa - aldosterone C. Zona glomerulosa – cortisol D. Zona fasciculata – DHEA E. Zona reticularis - aldosteroneAdrenal cortex: Zona Glomerulosa: • Secretes mineralocorticoids (aldosterone) • Cells arranged in ovoid clusters Zona Fasciculata: • Secretes glucocorticoids (cortisol, corticosterone) • Cells arranged in narrow columns and cords Zona Reticularis: • Secretes adrenal androgens (DHEA; Androstenedione) • Cells arranged irregularly Adrenal medulla: • Composed of chromaffin cells • Secretes catecholamines (Epinephrine; Norepinephrine)A 20-year-old woman has just been diagnosed with Type 1 Diabetes Mellitus and is curious about the genetics behind the disease. What gene(s) is thought to be linked to T1DM? A. HLA DR3/4 B. HLA B27 C. HLA B51 D. HLA DQ2/8 E. HLA D3Question 40: the genetics behind the disease.n diagnosed with Type 1 Diabetes Mellitus and is curious about What gene(s) is thought to be linked to T1DM? A. HLA DR3/4 B. HLA B27 Ankylosing spondylitis; Reactive arthritis; Acute anterior uveitis C. HLA B51 Behcet’s disease D. HLA DQ2/8 Coeliac’s disease E. HLA D3Question 41: A 44-year-old woman is admitted with cellulitis after having a cut on her leg. She is found to be hypertensive and have Type 2 On examination, she has central obesity with red ‘stretch marks’, bruising on her arms and a plethoric round face. Which of the following is the most appropriate next investigation to identify the likely cause? A. 24-hour urinary free cortisol B. High dose dexamethasone suppression test C. Late night salivary cortisol D. Low dose dexamethasone suppression test E. Short synacthen testQuestion 41: A 44-year-old woman is admitted with cellulitis after having a cut on her leg. She is found to be hypertensive and have Type 2 On examination, she has central obesity with red ‘stretch marks’, bruising on her arms and a plethoric round face. Which of the following is the most appropriate next investigation to identify the likely cause? A. 24-hour urinary free cortisol B. High dose dexamethasone suppression test C. Late night salivary cortisol D. Low dose dexamethasone suppression test E. Short synacthen testHigh dose: Other investigations: Tells you if the excess cortisol is Step 1: due to excess ACTH from 24hr urinary free cortisol Establish cortisol excess • Elevated in Cushing’s pituitary or other reason • Doesn’t indicate underlying cause A) Low dose dexamethasone B) High dose dexamethasone suppression test suppression test Late night salivary cortisol • Elevated in Cushing’s Normal response: Suppress cortisol • Doesn’t indicate underlying cause release by affecting negative feedback Performed after abnormal result on low on hypothalamus and pituitary. dose test • Hypothalamus responds ▯ • In Cushing’s disease (pituitary adenoma): reduces CRH output • 8mg enough to suppress cortisol • Pituitary ▯ reduces ACTH output • Shows some response to –ve • feeddback Reduces cortisol • In Adrenal adenoma • Cortisol not suppressed When cortisol not suppressed ▯ • ACTH not suppressed due to –ve feedback Cushing’s • Cortisol production separate from pituitary • In ectopic ACTH (e.g. SCLC) • ACTH + Cortisol not supressed • ACTH production is independent of hypothalamys and pituitary Step 2: Measure ACTHQuestion 42: What step is essential for the formation of all steroid hormones? A. Conversion of cholesterol to pregnenolone B. Conversion of cholesterol to progesterone C. Conversion of progesterone to pregnenolone D. Conversion of cholesterol to prednisolone E. Conversion of pregnenolone to progesteroneQuestion 42: What step is essential for the formation of all steroid hormones? A. Conversion of cholesterol to pregnenolone B. Conversion of cholesterol to progesterone C. Conversion of progesterone to pregnenolone D. Conversion of cholesterol to prednisolone E. Conversion of pregnenolone to progesteroneQuestion 43: Which of the following cells in the anterior pituitary secrete growth hormone? A. Somatotrophs B. Lactotrophs C. Thyrotrophs D. Gonadotrophs E. CorticotrophsQuestion 43: Which of the following cells in the anterior pituitary secrete growth hormone? A. Somatotrophs B. Lactotrophs C. Thyrotrophs D. Gonadotrophs E. Corticotrophs ANTERIOR PITUITARY CELLS Anterior pituitary cellsPituitary hormone released Target Somatotrophs Growth hormone Liver, bone, muscles Lactotrophs Prolactin Mammary glands Thyrotrophs Thyroid stimulating hormone Thyroid gland Gonadotrophs LH and FSH Reproductive system Corticotrophs ACTH Adrenal glandsQuestion 44: to run a few tests and find that her urine osmolality does not increase with fluid deprivation testing but does increase after administering DDAVP. What is the most likely diagnosis? A. SIADH B. Nephrogenic diabetes insipidus C. Psychogenic polydipsia D. Type 2 diabetes mellitus E. Cranial diabetes insipidusQuestion 44: to run a few tests and find that her urine osmolality does not increase with fluid deprivation testing but DOES INCREASE after administering DDAVP. What is the most likely diagnosis? A. SIADH B. Nephrogenic diabetes insipidus DDAVP = SYNTHETIC ADH C. Psychogenic polydipsia D. Type 2 diabetes mellitus E. Cranial diabetes insipidus Cranial diabetes insipidus Nephrogenic diabetes insipidus Clinical features Polyuria; Polydipsia; Nocturia Characterized by passing large volumes (>3L/day) of dilute urine Must exclude: hyperglycaemia + hypercalcaemia Due to: Deficiency of ADH Resistance to ADH Causes • Head trauma • Drugs e.g. lithium • Inflammatory conditions (Sarcoidosis) • Metabolic disturbances (↑Ca, ↑glucose, ↓K ) • Cranial infections (Meningitis) • Renal disease • Vascular conditions (Sickle cell disease) • Genetics (AVPR2 mutation) Diagnosis Starting plasma osmolality High High Final urine osmolality (after 8h) <300 <300 mOsmo/L Normal = >600 After ddAVP mOsmo/L >600 <300 Treatment Desmopressin Correct metabolic abnormalities Monitor Na for risk of hyponatraemia Stop offending drugs High dose desmopressin (variable results)A 62-year-old man presented with palpitations. He also complained of increased weight loss, heat intolerance, increased sweating and a tremor. symptoms?firmed to have primary hyperthyroidism. What would you prescribe for management of his thyrotoxic A. Propranolol B. Levothyroxine C. Carbimazole D. Propylthiouracil E. ThyroidectomyA 62-year-old man presented with palpitations. He also complained of increased weight loss, heat intolerance, increased sweating and a tremor. symptoms?firmed to have primary hyperthyroidism. What would you prescribe for management of his thyrotoxic A. Propranolol B. Levothyroxine C. Carbimazole D. Propylthiouracil E. Thyroidectomy HYPERTHYROIDISM MANAGEMENT Medical management: st 1 line: Carbimazole • Blocks thyroid peroxidase from coupling and iodinating tyrosine residues on thyroglobulin • Leading to reduced thyroid production • Important adverse effect: Agranulocytosis Symptomatic management: 2nd line: Propylthiouracil Beta blockers: Propranolol • Non-selectively blocks adrenergic activity Radio-iodine therapy • Selective BBs only work on the heart • Indications: Multinodular goitre, adenomas • Particularly useful in thyroid storm • Contraindications: Grave’s eye disease Surgery: Thyroidectomy • Risks: Hypoparathyroidism; Hypocalcaemia; Laryngeal nerve palsy; HaemorrhageMr. Ahmed is a 50-year-old man who has just been diagnosed with Type 2 Diabetes Mellitus. You want to start him on diabetic medication that increases sensitivity to insulin. Which of the following is the most appropriate to prescribe? A. Gliclazide B. Inulin C. Liraglutide D. Metformin E. ExenatideQuestion 46: Mr. Ahmed is a 50-year-old man who has just been diagnosed with Type 2 Diabetes Mellitus. You want to start him on diabetic medication that increases sensitivity to insulin. Which of the following is the most appropriate to prescribe? Gliclazide: increases insulin secretion A. Gliclazide Inulin: prebiotic polysaccharide produced by plants B. Inulin Liraglutide: increases insulin secretion C. Liraglutide D. Metformin Exenatide: increases insulin secretion E. Exenatide Drug name Class MoA Side effects: Metformin Biguanide 1 line in T2DM (+lifestyle_ GI upset (abdominal pain, diarrhoea) Lactic acidosis Increase peripheral insulin sensitivity and hepatic glucose uptake. Doesn’t cause: • Hypoglycaemia • Weight change Gliclazide Sulphonylureas Depolarise islet cells in the pancreas Hypoglycaemia increasing insulin release. Increased appetite and weight gain Syndrome of inappropriate ADH secretion Liver dysfunction (cholestatic) Pioglitazone Thiazolidinediones Depolarise islet cells in the pancreas Weight gain (Glitazones) increasing insulin release. Fluid retention Liver dysfunction Fractures Sitagliptin DPP4-inhibitors Inhibit GLP1 breakdown. Hypoglycaemia (Gliptins) Increased risk of pancreatitis when used with GLP1 analogues Exenatide GLP1 analogues Increase insulin secretion and sensitivity. Hypoglycaemia GI upset Increased risk of pancreatitis when used with DPP4- inhibitors Acarbose Intestinal Alpha- Delay intestinal carbohydrate GI disturbance Glucosidase Inhibitors absorption FlatulenceQuestion 47: Calcium and phosphate homeostasis is tightly regulated through various hormones, including PTH and vitamin D. Which of the following is true about the role of PTH in this homeostasis? A. PTH works to increase the levels of calcium and phosphate B. PTH is crucial in the stimulation of reabsorption of calcium in the kidney C. PTH works directly on bone and kidney to regulate calcium and phosphate homeostasis D. PTH is the only hormone that works to decrease phosphate levels in the plasma E. PTH is crucial for the increased efficient absorption of calcium from the intestineQuestion 47: Calcium and phosphate homeostasis is tightly regulated through various hormones, including PTH and vitamin D. Which of the following is true about the role of PTH in this homeostasis? A. PTH works to increase the levels of calcium and phosphate B. PTH is crucial in the stimulation of reabsorption of calcium in the kidney C. PTH works directly on bone and kidney to regulate calcium and phosphate homeostasis D. PTH is the only hormone that works to decrease phosphate levels in the plasma E. PTH is crucial for the increased efficient absorption of calcium from the intestine In the kidney: Activates vitamin D3 ▯ works in intestine to increase calcium levels PARATHYROID HORMONE • Released from chief cells of parathyroid gland • Binds to PTH receptors to induce activate of cAMP and IP3 signaling cascade • Results in increase of serum Ca In bone: • Recruits + increases proliferation of osteoclasts • Promoting bone resorption + release of Ca from bone In kidney: 1) Increases Ca reabsorption in DCT 2) Increases phosphate excretion in PCT 3) Upregulates expression of 1a-hydroxylase to PTH and phosphate: catalyse conversion of 25- • Decreases phosphate reabsorption at PCT hydroxycholecalciferol into calcitriol • Phosphate ions in serum form insoluble salts w/ Ca • Leads to decreased serum Ca • Decreased phosphate ▯ more ionized Ca in bloodYou attend PBL early and find yourself alone with the tutor. They start quizzing you on physiology and ask you which cells secrete Calcitonin. What do you tell them? A. Chief cells B. Somatotrophs C. Juxtaglomerular cells D. Parafollicular C cells E. Follicular cellsQuestion 48: You attend PBL early and find yourself alone with the tutor. They start quizzing you on physiology and ask you which cells secrete Calcitonin. What do you tell them? In the parathyroid. Release PTH in response to low calcium levels A. Chief cells In anterior pituitary. Secrete growth hormone B. Somatotrophs C. Juxtaglomerular cells In the kidneys. Secrete renin to reduce tubular flow D. Parafollicular C cells Produced in response to high calcium levels E. Follicular cells In the thyroid. Secrete thyroid hormones T3 and T4Question 49: weight gain, fatigue, constipation, low mood and menorrhagia.recently despite having her heating on constantly. She is also complaining of You decide to check her thyroid function and her results are as follows: High TSH, Low T4. Which of the following is the correct diagnosis? A. Primary hyperthyroidism B. Secondary hyperthyroidism C. Primary hypothyroidism D. Secondary hypothyroidism E. Sick euthyroidQuestion 49: Mrs. X has just presented to your practice feeling more cold recently despite having her heating on constantly. She is also complaining of weight gain, fatigue, constipation, low mood and menorrhagia. You decide to check her thyroid function and her results are as follows: High TSH, Low T4. Which of the following is the correct diagnosis? Mrs. X’s symptoms are related A. Primary hyperthyroidism to hypothyroidism The typical picture of primary B. Secondary hyperthyroidism hypothyroidism leads to high TSH and low T4 C. Primary hypothyroidism If the TSH were low also, it D. Secondary hypothyroidism would be secondary E. Sick euthyroid hypothyroidism HYPOTHYROIDISM Causes: Investigations: • Primary • Serum TSH – elevated  • Hashimotos • Subacute thyroiditis • Free serum T4 – low  • Thyroidectomy  • • Autoantibodies – positive if Radioactive iodine therapy  Hashimoto's  • Radiotherapy  • Thyroglobulin antibody  • Drugs: lithium, amiodarone  • Iodine deficiency  • Thyroid peroxidase antibody  • Secondary • Hypopituitarism Management: • LevothyroxineA 55-year-old patient presents with polydipsia, polyuria and polyphagia. You check their BMs and find that they are hyperglycaemic. They also begin complaining of visual disturbances. You perform a fundoscopy and see this. What is it? A. Hard exudates B. Vitreous haemorrhage C. Soft exudates D. Dot haemorrhages E. Cotton wool spotsA 55-year-old patient presents with polydipsia, polyuria and polyphagia. You check their BMs and find that they are hyperglycaemic. They also begin complaining of visual disturbances. You perform a fundoscopy and see this. What is it? A. Hard exudates B. Vitreous haemorrhage C. Soft exudates D. Dot haemorrhages E. Cotton wool spots VITREOUS HAEMORRHAGE? • Late stage of diabetic retinopathy • Extravasation of blood into vitreous • Due to retinal ischaemia promoting neovascularization via angiogenic factors such as VEGF , basic fibroblast growth factor and insulin-like growth factors • Treated with: Laser therapy; VEGF inhibitors; Vitrectomy • Treatment of retinopathy: • Lifestyle – Good glycaemia control; Stop smoking; Good BP controlThank you! ANY QUESTIONS?