Endocrinology Passmedicine 2024 PDF

5/21/24, 12:16 PM PassMedicine PassMedicine Question 1 of 414 A 73-year-old woman is referred to the endocrinology team with hypercalcemia. Her blood results are shown below: Calcium 2.89 mmol/L...

5/21/24, 12:16 PM PassMedicine PassMedicine Question 1 of 414 A 73-year-old woman is referred to the endocrinology team with hypercalcemia. Her blood results are shown below: Calcium 2.89 mmol/L (2.1-2.6) Magnesium 0.9 mmol/L (0.7-1.0) Bilirubin 9 µmol/L (3 - 17) ALP 277 u/L (30 - 100) ALT 15 u/L (3 - 40) γGT 35 u/L (8 - 60) Albumin 42 g/L (35 - 50) PTH 0.4 pmol/L (1.6-6.9) What is the most likely cause of her hypercalcemia? Malignancy 46% Osteomalacia 7% Paget's disease of the bone 22% Primary hypoparathyroidism 12% Secondary hypoparathyroidism 13% In hypercalcaemia secondary to malignancy, PTH is low, although PTHrP may be raised Important for me Less important Malignancy is correct. This patient has hypercalcemia but a low PTH. The calcium is raised due to the presence of PTH-related protein (PTHrP) which is usually due to a malignancy. PTHrP is not detected when testing for PTH levels and requires a separate test. Osteomalacia is incorrect. Osteomalacia is due to vitamin D deficiency in adults. Low vitamin D https://www.passmedicine.com/question/questions.php?q=0 1/4 5/21/24, 12:16 PM PassMedicine causes a decrease in serum calcium and phosphate. To compensate for this, there is a resultant increase in parathyroid hormone, producing secondary hyperparathyroidism. Paget's disease of the bone is incorrect. Paget's disease of the bone is characterized by increased bone turnover resulting in enlarged and brittle bones. Blood tests would usually only show an isolated, raised ALP. The calcium should be normal. Primary hypoparathyroidism is incorrect. This is due to failure of the parathyroid glands, resulting in low PTH and low calcium. Secondary hypoparathyroidism is incorrect. This is a loss of PTH due to irradiation of the parathyroid gland, surgical removal of the gland, or low serum magnesium. This would result in low PTH and low calcium. Discuss (1) Improve Next question Hypercalcaemia: causes Two conditions account for 90% of cases of hypercalcaemia: 1. Primary hyperparathyroidism: commonest cause in non-hospitalised patients 2. Malignancy: the commonest cause in hospitalised patients. This may be due to a number of processes, including; PTHrP from the tumour e.g. squamous cell lung cancer bone metastases myeloma,: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells for this reason, measuring parathyroid hormone levels is the key investigation for patients with hypercalcaemia Other causes include sarcoidosis other causes of granulomas may lead to hypercalcaemia e.g. tuberculosis and histoplasmosis vitamin D intoxication acromegaly thyrotoxicosis Milk-alkali syndrome drugs: https://www.passmedicine.com/question/questions.php?q=0 2/4 5/21/24, 12:16 PM PassMedicine thiazides calcium-containing antacids dehydration Addison's disease Paget's disease of the bone usually normal in this condition but hypercalcaemia may occur with prolonged immobilisation Next question                Textbooks High-yield textbook Extended textbook Links Royal College of Physicians 9 1 Hypercalcaemia – presentation and management Report broken link Media Hypercalcemia in malignancy Armando Hasudungan - YouTube 19 2 https://www.passmedicine.com/question/questions.php?q=0 3/4 5/21/24, 12:17 PM PassMedicine PassMedicine Question 2 of 414 A 72-year-old male is seen in clinic complaining of pain in both feet. He reports the pain is burning in nature and worse at night when sitting watching TV. It can often be severe and he is struggling to manage this with paracetamol alone. He has a past medical history of poorly controlled diabetes, hypertension and high cholesterol. On examination, he has normal power bilaterally but reduced sensation. Pedal pulses are present and there are no vascular related skin changes. What is the most appropriate first line treatment for his pain? Tramadol 3% Topical capsaicin 8% Codeine 2% Duloxetine 83% Naproxen 4% First line treatment in diabetic neuropathy is with amitriptyline, duloxetine, gabapentin or pregabalin Important for me Less important The correct answer is duloxetine. This patient has a history of poorly controlled diabetes and combined with the examination findings of reduced sensation and normal pulses a diagnosis of diabetic neuropathy is most likely. NICE guidelines suggest first-line treatment for diabetic neuropathy is the same as for other causes of neuropathic pain with amitriptyline, duloxetine, gabapentin or pregabalin. Topical capsaicin can be used for localised neuropathic pain such as postherpetic neuralgia but would not be first-line for this patient. Tramadol is also not the first line treatment but can be used as rescue therapy for exacerbations. Neither codeine or naproxen are recommended in neuropathic pain. https://www.passmedicine.com/question/questions.php?q=0 1/3 5/21/24, 12:17 PM PassMedicine Discuss (2) Improve Next question Diabetic neuropathy Peripheral neuropathy Diabetes typically leads to sensory loss and not motor loss. Sensory loss typically results in a 'glove and stocking' distribution, with the lower legs affected first due to the length of the sensory neurons supplying this area. Painful diabetic neuropathy is also a common problem in clinical practice. NICE updated it's guidance on the management of neuropathic pain in 2013. Diabetic neuropathy is now managed in the same way as other forms of neuropathic pain: first-line treatment: amitriptyline, duloxetine, gabapentin or pregabalin if the first-line drug treatment does not work try one of the other 3 drugs tramadol may be used as 'rescue therapy' for exacerbations of neuropathic pain topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia) pain management clinics may be useful in patients with resistant problems Gastrointestinal autonomic neuropathy Gastroparesis occurs secondary to autonomic neuropathy symptoms include erratic blood glucose control, bloating and vomiting management options include metoclopramide, domperidone or erythromycin (prokinetic agents) Chronic diarrhoea often occurs at night Gastro-oesophageal reflux disease caused by decreased lower esophageal sphincter (LES) pressure Next question https://www.passmedicine.com/question/questions.php?q=0 2/3 5/21/24, 12:17 PM PassMedicine                Textbooks High-yield textbook Extended textbook Links NICE 2 0 2013 Neuropathic pain guidelines NICE 0 1 2022 Type 2 diabetes guidelines Report broken link Score: 100% 1 2 All contents of this site are © 2024 Passmedicine Limited Back to top https://www.passmedicine.com/question/questions.php?q=0 3/3 5/21/24, 12:18 PM PassMedicine PassMedicine Question 3 of 414 A 38-year-old woman is reviewed in the Endocrinology clinic, having been referred by her GP for refractory hypertension. Her ambulatory blood pressure readings have consistently been over 170/95 mmHg, in spite of gradual uptitration of amlodipine, enalapril and indapamide. She has no significant past medical history or family history, and examination of the chest and abdomen is normal. Her blood test results are shown below: Na+ 144 mmol/L (135 - 145) K+ 3.1 mmol/L (3.5 - 5.0) Bicarbonate 32 mmol/L (22 - 29) Urea 5.4 mmol/L (2.0 - 7.0) Creatinine 75 µmol/L (55 - 120) Which of the following is the most likely underlying cause of her hypertension? Adrenal carcinoma 1% Adrenal adenoma (Conn's syndrome) 44% Autoimmune adrenalitis 1% Phaeochromocytoma 6% Bilateral adrenal hyperplasia 49% Bilateral idiopathic adrenal hyperplasia is the most common cause of primary hyperaldosteronism Important for me Less important The presence of hypertension with hypokalaemia and mild alkalosis (as evidenced by the raised bicarbonate) should make candidates consider hyperaldosteronism. Hyperaldosteronism can be seen alongside elevated glucocorticoid activity in the context of excessive ACTH secretion (e.g. in Cushing's disease), or in isolation, as is the case in this patient. Hyperaldosteronism can be https://www.passmedicine.com/question/questions.php?q=0 1/5 5/21/24, 12:18 PM PassMedicine primary, or secondary to overzealous renin secretion, e.g. by a tumour, or in response to renal artery stenosis. Amongst the option choices, only causes of primary hyperaldosteronism are given. Of these, the most common epidemiologically is bilateral adrenal hyperplasia, which underlies 60- 70% of cases of primary hyperaldosteronism. Aldosterone-producing adrenal carcinomas account for less than 1% of all cases of primary hyperaldosteronism. Aldosterone-producing adenomas, which produce the clinical entity of Conn's syndrome, account for approximately one third of cases of primary hyperaldosteronism, making this option epidemiologically less probable. Autoimmune adrenalitis is the most common cause of primary adrenal insufficiency, which gives rise to the clinical entity of Addison's disease. This tends to present with hyperkalaemia rather than hypokalaemia, and in particular, postural hypotension rather than hypotension, due to mineralocorticoid deficiency. A phaeochromocytoma is a rare cause of persistent hypertension. However, the hypertension associated with excessive catecholamine secretion would not explain the hypokalaemia and alkalosis seen in this patient. Discuss (4) Improve Next question Primary hyperaldosteronism Primary hyperaldosteronism was previously thought to be most commonly caused by an adrenal adenoma, termed Conn's syndrome. However, recent studies have shown that bilateral idiopathic adrenal hyperplasia is the most common cause. Differentiating between the two is important as this determines treatment. Causes bilateral idiopathic adrenal hyperplasia: the cause of around 60-70% of cases adrenal adenoma: 20-30% of cases unilateral hyperplasia familial hyperaldosteronism adrenal carcinoma Features https://www.passmedicine.com/question/questions.php?q=0 2/5 5/21/24, 12:18 PM PassMedicine hypertension increasingly recognised but still underdiagnosed cause of hypertension hypokalaemia e.g. muscle weakness this is a classical feature in exams but studies suggest this is seen in only 10-40% of patients, and is more common with adrenal adenomas metabolic alkalosis Investigations guidelines vary but certain patients should be screened for primary hyperaldosteronism, e.g. hypertension with hypokalemia treatment-resistant hypertension the 2016 Endocrine Society recommend that a plasma aldosterone/renin ratio is the first- line investigation in suspected primary hyperaldosteronism should show high aldosterone levels alongside low renin levels (negative feedback due to sodium retention from aldosterone) following this a high-resolution CT abdomen and adrenal vein sampling is used to differentiate between unilateral and bilateral sources of aldosterone excess if the CT is normal adrenal venous sampling (AVS) can be used to distinguish between unilateral adenoma and bilateral hyperplasia Management adrenal adenoma: surgery (laparoscopic adrenalectomy) bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone Next question                https://www.passmedicine.com/question/questions.php?q=0 3/5 5/21/24, 12:18 PM PassMedicine PassMedicine Question 4 of 414 A 57-year-old man with a known history of type-2 diabetes presents to clinic for a review. He currently takes metformin only for his diabetes and reports following the regime as instructed. His HbA1c is 63 mmol/mol (target = 53mmol/mol) and the clinician and patient decide he should start a sulfonylurea in addition to his metformin. Which of the following best describes the new treatment's mechanism of action? Increases stimulation of insulin secretion by pancreatic B-cells and decreases hepatic 80% clearance of insulin Inhibits sodium-glucose co-transporter-2 in the proximal convoluted tubule of the 4% nephron to stop glucose reabsorption, meaning it is excreted in urine Inhibits the principal enzyme that breaks down GLP-1 - an incretin hormone that 3% increases insulin secretion and suppresses glucagon secretion Reduces hepatic gluconeogenesis, increases peripheral glucose uptake and also reduces 8% the absorption of carbohydrate in the gut Upregulation of transcription of insulin responsive genes, leading to an increase in 5% glucose transporters and insulin receptors at the surface of the cell Sulfonyureas increase stimulation of insulin secretion by pancreatic B-cells and decrease hepatic clearance of insulin Important for me Less important The correct answer is option 1 as sulfonylureas are insulin secretagogues - one of the classes of oral hypoglycaemic agents. Option 2 best describes the mechanism of action of SGLT-2 inhibitors (dapagliflozin, canagliflozin). Option 3 best describes the mechanism of action of DPP-4 inhibitors (sitagliptin, vildagliptin). Option 4 best describes the mechanism of action of metformin, an insulin sensitiser. https://www.passmedicine.com/question/questions.php?q=0 1/4 5/21/24, 12:18 PM PassMedicine Option 5 best describes the mechanism of action of thiazolidinediones (pioglitazone), also an insulin sensitiser, According to NICE, metformin should be the first drug treatment of choice for those people who can tolerate it. The second medication, to be given in combination with metformin, can be any one of the four types of oral hypoglycaemic agents listed. 1.) Sola, D., Rossi, L., Schianca, G., Maffioli, P., Bigliocca, M., Mella, R., Corlianò, F., Fra, G., Bartoli, E. and Derosa, G. (2015). State of the art paper Sulfonylureas and their use in clinical practice. Archives of Medical Science, 4, pp.840-848. 2.) Kalra, S. (2014). Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors: A Review of Their Basic and Clinical Pharmacology. Diabetes Therapy, 5(2), pp.355-366. 3.) Vella, A. (2012). Mechanism of Action of DPP-4 Inhibitors'New Insights. The Journal of Clinical Endocrinology & Metabolism, 97(8), pp.2626-2628. 4.) Watkins, P., Amiel, S., Howell, S. and Turner, E. (2008). Diabetes and Its Management. Hoboken: John Wiley & Sons, Ltd., pp.58 60. 5.) Nice.org.uk. (2018). Algorithm for blood glucose lowering therapy in adults with type 2 diabetes. [online] Available at: https://www.nice.org.uk/guidance/ng28/resources/algorithm-for-blood- glucose-lowering-therapy-in-adults-with-type-2-diabetes-pdf-2185604173 [Accessed 4 Oct. 2018]. Discuss (2) Improve Next question Sulfonylureas Sulfonylureas are oral hypoglycaemic drugs used in the management of type 2 diabetes mellitus. They work by increasing pancreatic insulin secretion and hence are only effective if functional B- cells are present. On a molecular level they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells. Common adverse effects hypoglycaemic episodes (more common with long-acting preparations such as chlorpropamide) weight gain Rarer adverse effects https://www.passmedicine.com/question/questions.php?q=0 2/4 5/21/24, 12:18 PM PassMedicine hyponatraemia secondary to syndrome of inappropriate ADH secretion bone marrow suppression hepatotoxicity (typically cholestatic) peripheral neuropathy Sulfonylureas should be avoided in breastfeeding and pregnancy. Next question                Textbooks High-yield textbook Extended textbook Media Type 2 diabetes agents and their mechanism of action Brandl's Basics - YouTube 34 10 Pharmacology of drugs used to treat type 2 diabetes Brandl's Basics - YouTube 12 5 Report broken media https://www.passmedicine.com/question/questions.php?q=0 3/4 5/21/24, 12:18 PM PassMedicine PassMedicine Question 5 of 414 An obese 37-year-old man is referred by his GP to a weight-loss and health class in an attempt to lose a significant amount of weight. The man is currently attending an education session on the glycaemic index of various foods and being advised to avoid those with a high glycaemic index. Which of the following falls into this category? Boiled new potato 9% Brown rice 3% Digestive biscuit 7% Fruit 6% White rice 74% A high glycaemic index food has a greater ability to raise blood glucose compared with glucose in normal glucose-tolerant individuals Important for me Less important From the above options, the correct answer is white rice - this is the only 'high glycaemic index (GI)' food listed, with a value of 87. Other examples of high GI foods include baked potatoes (85) and white bread (70). The boiled new potato is classed as a medium GI food, with a value of 62. Brown rice has a medium GI, with a lower value of 58, compared to white rice's value of 87. Digestive biscuit also has a medium GI. Fruits and vegetables are generally classed as low GI foods. While exact glycemic indices of various foods should not be memorised, it is good to categorise foods into high, medium and low glycemic indices for the exam. https://www.passmedicine.com/question/questions.php?q=0 1/3 5/21/24, 12:18 PM PassMedicine Discuss (6) Improve Next question Glycaemic index The glycaemic index (GI) describes the capacity of a food to raise blood glucose compared with glucose in normal glucose-tolerant individuals. Foods with a high GI may be associated with an increased risk of obesity and the post-prandial hyperglycaemia associated with such foods may also increase the risk of type 2 diabetes mellitus. Classification Examples High GI White rice (87), baked potato (85), white bread (80) Medium GI Couscous (65), boiled new potato (62), digestive biscuit (59), brown rice (58), Porridge (55) Low GI Fruit and vegetables, peanuts The glycaemic index is shown in brackets. Glucose, by definition, would have a glycaemic index of 100 Next question                Textbooks High-yield textbook Extended textbook https://www.passmedicine.com/question/questions.php?q=0 2/3 5/21/24, 12:18 PM PassMedicine PassMedicine Question 6 of 414 A 75-year-old man is admitted to the ward with an infective exacerbation of COPD. He has reached the end of a 5-day course of prednisolone and doxycycline. He reports improvement, with his sputum returned to its normal colour, but he reports an ongoing productive cough and mild breathlessness. Chest auscultation reveals scanty crepitations. He was successfully weaned off oxygen therapy 12 hours ago. His laboratory results are as follows: Hb 165 g/L Male: (135-180) Platelets 220 * 10 9/L (150 - 400) WBC 12.5 * 10 9/L (4.0 - 11.0) Neuts 10.1 * 10 9/L (2.0 - 7.0) CRP 9 mg/L (< 5) What is the most likely cause of his abnormal blood test results? Acute myeloid leukaemia 1% Chronic myeloid leukaemia 2% Medication-induced neutrophilia 76% Hospital-acquired pneumonia 9% Persisting infection 12% Corticosteroids can induce neutrophilia Important for me Less important The most likely cause of this patient's abnormal blood test results is medication-induced neutrophilia. Corticosteroids are known to induce neutrophilia, which in turn causes leukocytosis, by enhancing the survival of neutrophils within the circulation. Persisting infection is less likely given the overall clinical context of the patient. While the patient https://www.passmedicine.com/question/questions.php?q=0 1/4 5/21/24, 12:18 PM PassMedicine has a persistent productive cough, dyspnoea, and some crepitations, this is common after an exacerbation of COPD and may take several weeks to resolve. The patient's general improvement, successful weaning off oxygen therapy, and only mildly elevated C-reactive protein, which is likely on a downward trajectory following treatment, further argue against ongoing infection. Similarly, hospital-acquired pneumonia seems unlikely with the same clinical rationale given above. Leukaemia is much less likely in this patient, given the context of the scenario and lack of mention of constitutional symptoms, organomegaly or pancytopenia. Discuss (1) Improve Next question Corticosteroids Corticosteroids are amongst the most commonly prescribed therapies in clinical practice. They are used both systemically (oral or intravenous) or locally (skin creams, inhalers, eye drops, intra- articular). They augment and in some cases replace the natural glucocorticoid and mineralocorticoid activity of endogenous steroids. The relative glucocorticoid and mineralocorticoid activity of commonly used steroids is shown below: Minimal Predominant Very high glucocorticoid Glucocorticoid glucocorticoid glucocorticoid activity, very high activity, high activity, low activity, minimal mineralocorticoid mineralocorticoid mineralocorticoid mineralocorticoid activity, activity, activity activity Fludrocortisone Hydrocortisone Prednisolone Dexamethasone Betmethasone Side-effects The side effects of corticosteroids are numerous and represent the single greatest limitation on their usage. Side-effects are more common with systemic and prolonged therapy. https://www.passmedicine.com/question/questions.php?q=0 2/4 5/21/24, 12:18 PM PassMedicine Glucocorticoid side-effects endocrine impaired glucose regulation increased appetite/weight gain hirsutism hyperlipidaemia Cushing's syndrome moon face buffalo hump striae musculoskeletal osteoporosis proximal myopathy avascular necrosis of the femoral head immunosuppression increased susceptibility to severe infection reactivation of tuberculosis psychiatric insomnia mania depression psychosis gastrointestinal peptic ulceration acute pancreatitis ophthalmic glaucoma cataracts suppression of growth in children intracranial hypertension neutrophilia Mineralocorticoid side-effects fluid retention hypertension Selected points on the use of corticosteroids: patients on long-term steroids should have their doses doubled during intercurrent illness longer-term systemic corticosteroids suppress the natural production of endogenous steroids. They should therefore not be withdrawn abruptly, as this may precipitate an Addisonian crisis the BNF suggests gradual withdrawal of systemic corticosteroids if patients have: https://www.passmedicine.com/question/questions.php?q=0 3/4 5/21/24, 12:18 PM PassMedicine received more than 40mg prednisolone daily for more than one week received more than 3 weeks of treatment recently received repeated courses Next question                Textbooks High-yield textbook Extended textbook Score: 50% 1 2 3 4 5 6 All contents of this site are © 2024 Passmedicine Limited Back to top https://www.passmedicine.com/question/questions.php?q=0 4/4 5/21/24, 12:19 PM PassMedicine PassMedicine Question 7 of 414 A 32-year-old woman attends the endocrinology clinic with fatigue and constipation. She has a history of menorrhagia, Wolff-Parkinson-White syndrome, and primary hypothyroidism. Her thyroid function tests were satisfactory 6 months ago. Her drug history includes levothyroxine 100 micrograms (once daily at 7am), amiodarone 200mg (once daily at 7am), and ferrous fumarate 210mg (once daily at 7am). Blood results are as follows: Thyroid stimulating hormone (TSH) 24.2 mU/L (0.5-5.5) Free thyroxine (T4) 6.8 pmol/L (9.0 - 18) How will you manage this situation? Advise the patient to take iron tablets at least 2 hours apart from levothyroxine 13% Advise the patient to take iron tablets at least 4 hours apart from levothyroxine 73% Counsel the patient on the consequences of poor compliance 3% Discontinue amiodarone 5% Increase dose of levothyroxine 6% Iron / calcium carbonate tablets can reduce the absorption of levothyroxine - should be given 4 hours apart Important for me Less important Advise the patient to take iron tablets at least 4 hours apart from levothyroxine is correct. The patient has poorly controlled hypothyroidism. The fact that the patient had normal thyroid function tests 6 months ago suggests that she is on the right dose, however, it is important to bear in mind that dose requirements can change. You should note that the patient is taking iron tablets at the same time as the levothyroxine. Iron inhibits levothyroxine absorption and this is the most likely explanation in this situation. The patient should be advised to take iron tablets at least 4 hours apart from levothyroxine, and she should be brought back for repeat thyroid function tests (TFTs) in 6 weeks. https://www.passmedicine.com/question/questions.php?q=0 1/4 5/21/24, 12:19 PM PassMedicine Advise the patient to take iron tablets at least 2 hours apart from levothyroxine is incorrect. A minimum time of 4 hours between iron and levothyroxine is required to prevent poor absorption. Counsel the patient on the consequences of poor compliance is incorrect. It would be important to consider compliance issues. However, in this case, poor absorption due to iron is the more likely cause. Patients with poor compliance will often take a 'loading dose' before attending for blood results resulting in an elevated fT4 and TSH. However, if they have not taken their thyroxine for many days then they may have a normal/low fT4. Discontinue amiodarone is incorrect. Although amiodarone is a well-known cause of hypothyroidism, it is a less likely cause in this scenario since the patient is already on thyroid replacement (which is the treatment for amiodarone-induced hypothyroidism). Furthermore, there is a clear and well-recognised drug interaction between levothyroxine and iron which should be rectified in the first instance. It would also be essential to liaise with the patient's cardiologist before discontinuing the amiodarone. Increase dose of levothyroxine is incorrect. Although the patient may ultimately need an increased dose, it would be essential to exclude drug-drug interactions, drug-food interactions, poor compliance, and malabsorption, before increasing the dose. Discuss Improve Next question Hypothyroidism: levothyroxine therapy Key points initial starting dose of levothyroxine should be lower in elderly patients and those with ischaemic heart disease. The BNF recommends that for patients with cardiac disease, severe hypothyroidism or patients over 50 years the initial starting dose should be 25mcg od with dose slowly titrated. Other patients should be started on a dose of 50-100mcg od following a change in thyroxine dose thyroid function tests should be checked after 8-12 weeks the therapeutic goal is 'normalisation' of the thyroid stimulating hormone (TSH) level. As the majority of unaffected people have a TSH value 0.5-2.5 mU/l it is now thought preferable to aim for a TSH in this range women with established hypothyroidism who become pregnant should have their dose increased 'by at least 25-50 micrograms levothyroxine'* due to the increased demands of pregnancy. The TSH should be monitored carefully, aiming for a low-normal value https://www.passmedicine.com/question/questions.php?q=0 2/4 5/21/24, 12:19 PM PassMedicine there is no evidence to support combination therapy with levothyroxine and liothyronine Side-effects of thyroxine therapy hyperthyroidism: due to over treatment reduced bone mineral density worsening of angina atrial fibrillation Interactions iron, calcium carbonate absorption of levothyroxine reduced, give at least 4 hours apart *source: NICE Clinical Knowledge Summaries Next question                Textbooks High-yield textbook Extended textbook Links Clinical Knowledge Summaries 7 6 Management of hypothyroidism Report broken link Media https://www.passmedicine.com/question/questions.php?q=0 3/4 5/21/24, 12:19 PM PassMedicine PassMedicine Question 8 of 414 A 38-year-old, with a raised BMI and confirmed type II diabetes is seen in the clinic for a review of his glucose control. Despite already being initiated on treatment several months previously his home blood glucose readings and latest Hb1Ac remain high. It is decided that the patient is to be commenced on a gliclazide. The patient is warned that this new medication may induce hypoglycaemia as an adverse effect due to an increase in the production and release of insulin. What pancreatic cell membrane channels does this new medication bind to? ATP-dependent potassium 75% Dipeptidyl peptidase-4 (DDP) 9% Ligand-gated chloride 5% Tyrosine kinase 7% Voltage-gated calcium 4% Sulfonylureas - bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells Important for me Less important Gliclazide is a sulfonylurea antidiabetic drug whose mechanism of action is via the increased release of insulin from the pancreatic beta cells. Sulfonylureas bind to and close ATP-dependent potassium channels on these beta cells, depolarising them. This results in an increase in intracellular calcium, due to the opening of calcium channels, which in turn increases the secretion of insulin. Dipeptidyl peptidase-4 (DDP) is a type of enzyme, not a membrane channel, that affects glucose metabolism. DDP inhibitors, used in the management of diabetes, increase levels of incretin such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), which in turn result in an increase in insulin secretion, decrease in gastric emptying and therefore a decrease in blood glucose levels. https://www.passmedicine.com/question/questions.php?q=0 1/4 5/21/24, 12:19 PM PassMedicine Chloride channels are involved in several regulatory functions within the body including the transport of epithelial fluid in the lung, pancreas and other organs. These channels are not affected by sulfonylureas. Insulin binds to tyrosine kinase, a type of enzyme receptor in the cell membrane, resulting in a signal transduction cascade, activating enzymes and transcription factors within the cell that mediates the intracellular effects of insulin. Again, sulfonylureas do not affect these receptors. Voltage-gated calcium channels are opened within pancreatic beta cells resulting in the release of insulin however they are not directly bound to by sulfonylureas. Instead, it is the depolarising effect of sulfonylureas binding to ATP-dependent potassium channels which opens these calcium channels. Discuss (2) Improve Next question Sulfonylureas Sulfonylureas are oral hypoglycaemic drugs used in the management of type 2 diabetes mellitus. They work by increasing pancreatic insulin secretion and hence are only effective if functional B- cells are present. On a molecular level they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells. Common adverse effects hypoglycaemic episodes (more common with long-acting preparations such as chlorpropamide) weight gain Rarer adverse effects hyponatraemia secondary to syndrome of inappropriate ADH secretion bone marrow suppression hepatotoxicity (typically cholestatic) peripheral neuropathy Sulfonylureas should be avoided in breastfeeding and pregnancy. Next question https://www.passmedicine.com/question/questions.php?q=0 2/4 5/21/24, 12:19 PM PassMedicine PassMedicine Question 9 of 414 A 27-year-old man presents to his general practitioner with his wife due to an inability to conceive after 1 year of regular unprotected sexual intercourse. The patient's medical history is unremarkable. Examination of the external genitalia reveals bilaterally low-volume testes and sparse pubic and axillary hair. Moderate gynecomastia is present bilaterally. Semen analysis is significant for azoospermia. The results of an endocrine panel are shown below: Luteinising Hormone 22.3 IU/L (1.2-8.6) Follicle Stimulating Hormone 30 IU/L (1.3-19.3) Testosterone 3 nmol/L (6 -27) What is the most likely diagnosis? Congenital androgen insensitivity syndrome 12% Kallmann syndrome 14% Klinefelter's syndrome 72% Leydig cell tumour 1% Pituitary adenoma 2% Klinefelter's syndrome causes high LH and low testosterone Important for me Less important Klinefelter's syndrome is the correct answer. Klinefelter's syndrome, with karyotype 47XXY, is associated with primary hypogonadism in patients with male external genitalia. Patients with Klinefelter's syndrome may be unaware of their condition until they wish to start a family. General examination of patients with Klinefelter's syndrome may reveal tall stature, low-volume testes, sparse pubic hair, and gynecomastia. The condition is associated with hypergonadotrophic https://www.passmedicine.com/question/questions.php?q=0 1/4 5/21/24, 12:19 PM PassMedicine hypogonadism, in which FSH and LH concentrations are elevated and serum testosterone concentrations are low. Gonadal dysgenesis secondary to Klinefelter's syndrome impairs spermatogenesis, with semen analysis commonly showing azoospermia. Congenital androgen insensitivity syndrome is incorrect. Patients with this condition are genetically male (46XY), yet are phenotypically female with female external genitalia due to a defect in the androgen receptor. The patient in this vignette has male external genitalia, excluding the diagnosis of congenital androgen insensitivity syndrome. Kallmann syndrome is incorrect. Kallman syndrome is a pituitary disorder associated with an impaired sense of smell (anosmia) hypogonadotrophic hypogonadism. The condition is characterised by low concentrations of LH and FSH, in contrast to Klinefelter's syndrome, which is associated with increased concentrations of LH and FSH. Leydig cell tumour is incorrect. Leydig cell tumours are sex-chord tumours of the testes or ovaries that secrete testosterone. Male patients commonly present with testicular swelling, which is not present in this patient. Pituitary adenoma is incorrect. Pituitary tumours may rarely cause hypogonadotrophic hypogonadism, in which low concentrations of LH and FSH result in low testosterone, but the high concentrations of LH and FSH in this patient make this diagnosis unlikely. Discuss (1) Improve Next question Klinefelter's syndrome Klinefelter's syndrome is associated with karyotype 47, XXY. Features often taller than average lack of secondary sexual characteristics small, firm testes infertile gynaecomastia - increased incidence of breast cancer elevated gonadotrophin levels but low testosterone Diagnosis is by karyotype (chromosomal analysis). https://www.passmedicine.com/question/questions.php?q=0 2/4 5/21/24, 12:19 PM PassMedicine PassMedicine Question 10 of 414 A 35-year-old man presents to his GP with a six-week history of weight gain, cold intolerance, low mood, and headaches. He has a past medical history of primary hyperparathyroidism and underwent parathyroidectomy one year ago. The following blood tests have been arranged: Thyroid-stimulating hormone (TSH) 2.3 mU/L (0.5-5.5) Free thyroxine (T4) 5.6 pmol/L (9.0 - 18) Prolactin 34 ng/mL (< 20) What is the most likely cause of the patient's symptoms? Hashimoto's thyroiditis 14% Hypothalamic dysfunction 13% Microprolactinoma 27% Non-functioning pituitary adenoma 34% Subacute thyroiditis 13% The presence of an elevated prolactin level along with secondary hypothyroidism and hypogonadism is indicative of stalk compression is consistent with a non-functioning pituitary adenoma Important for me Less important In this scenario, the patient presents with clinical features of hypothyroidism, including weight gain, cold intolerance, and low mood. Thyroid function tests reveal a decreased T4 level alongside an inappropriately normal TSH level, suggesting a secondary aetiology for his symptoms. The most likely diagnosis is a pituitary adenoma, which is corroborated by the patient's headache complaints—a symptom attributable to dural irritation from an enlarging tumour. The patient's mildly elevated prolactin level suggests a non-functioning pituitary adenoma compressing the pituitary stalk rather than a prolactinoma, which would cause a greater rise. Non-functioning adenomas characteristically present with signs and symptoms resulting from mass effects, such as https://www.passmedicine.com/question/questions.php?q=0 1/5 5/21/24, 12:19 PM PassMedicine hypopituitarism due to compression of the intact pituitary gland tissue and bitemporal hemianopia caused by impingement of the optic chiasm. Hypothalamic dysfunction typically manifests with hypopituitarism, presenting with some of the symptoms seen here, such as weight gain and cold intolerance due to hypothyroidism. However, it would not cause a raised prolactin. Hashimoto's thyroiditis, as a primary cause of hypothyroidism, would be expected to elevate TSH levels—in contrast to what is observed in this patient. Hashimoto's thyroiditis is an autoimmune condition associated with anti-TPO antibodies. It would be unusual for a microprolactinoma to induce hypopituitarism via compression exerted by the tumour on healthy pituitary tissue as they typically do not grow to a sufficient size. Furthermore, one would expect to observe an increased prolactin level (above 100 ng/mL). The modest elevation in prolactin noted here aligns more closely with stalk compression secondary to a non-functioning pituitary adenoma. Subacute thyroiditis (also known as De Quervain's thyroiditis), presents after a viral infection with hyperthyroidism, both of which are absent in this case. As the condition progresses the patient develops hypothyroidism before returning to a euthyroid state. However, without a history of hyperthyroidism, this answer is very unlikely. Discuss (1) Improve Next question Pituitary adenoma A pituitary adenoma is a benign tumour of the pituitary gland. They are common (10% of all people) but in most cases will never be found (asymptomatic) or are found as an incidental findings. They account for around 10% of adult brain tumours. Pituitary adenomas can be classified according to: size (a microadenoma is = 35 kg/m² in people of European descent and there are problems associated with high weight, or BMI < 35 kg/m² and insulin is unacceptable because of occupational implications or weight loss would benefit other comorbidities. NICE like patients to have achieved a > 11 mmol/mol (1%) reduction in HbA1c and 3% weight loss after 6 months to justify the ongoing prescription of GLP-1 mimetics. The major adverse effect of GLP-1 mimetics is nausea and vomiting. The Medicines and Healthcare products Regulatory Agency has issued specific warnings on the use of exenatide, reporting that is has been linked to severe pancreatitis in some patients. Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin) Key points dipeptidyl peptidase-4, DPP-4 inhibitors increase levels of incretins (GLP-1 and GIP) by decreasing their peripheral breakdown oral preparation trials to date show that the drugs are relatively well tolerated with no increased incidence of hypoglycaemia do not cause weight gain NICE guidelines on DPP-4 inhibitors NICE suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight gain would cause significant problems, a thiazolidinedione is contraindicated or the person has had a poor response to a thiazolidinedione Next question                https://www.passmedicine.com/question/questions.php?q=0 3/5 5/21/24, 12:21 PM PassMedicine Textbooks High-yield textbook Extended textbook Links NICE 12 7 2022 Type 2 diabetes guidelines Report broken link Media How does sitagliptin work? DPP-4 inhibitors and GLP-1 mimetics Zero to Finals - YouTube 45 2 Glucagon-like Peptide (GLP-1) and the treatment of diabetes Medicosis Perfectionalis - YouTube 41 7 Type 2 diabetes agents and their mechanism of action Brandl's Basics - YouTube https://www.passmedicine.com/question/questions.php?q=0 4/5 5/21/24, 12:21 PM PassMedicine PassMedicine Question 16 of 414 A 37-year-old woman presents to her GP with a six-week history of increasing fatigue, headaches, and cold intolerance. She also reports vomiting and abdominal pain. Her blood pressure is measured at 95/57 mmHg. Blood tests are conducted with the following results: Na+ 129 mmol/L (135 - 145) K+ 4.8 mmol/L (3.5 - 5.0) Bicarbonate 28 mmol/L (22 - 29) Urea 6.0 mmol/L (2.0 - 7.0) Creatinine 89 µmol/L (55 - 120) Thyroid-stimulating hormone (TSH) 2.1 mU/L (0.5-5.5) Free thyroxine (T4) 5.8 pmol/L (9.0 - 18) Prolactin 41 ng/mL (< 20 ng/mL) What is the definitive treatment for this patient's condition? Cabergoline 9% Hydrocortisone and fludrocortisone 17% Levothyroxine 5% Phenoxybenzamine 1% Transsphenoidal surgery 68% Non-functioning adenomas are generally diagnosed due to their compressive symptoms (e.g. visual problems) or hormone deficiencies - transsphenoidal surgery is therefore the first-line treatment https://www.passmedicine.com/question/questions.php?q=0 1/5 5/21/24, 12:21 PM PassMedicine Important for me Less important Non-functional adenomas may manifest with pan-hypopituitarism due to the compression of the normally functioning pituitary tissue. The patient in this case has exhibited symptoms indicative of hypothyroidism, such as fatigue and cold intolerance, as well as symptoms consistent with adrenal insufficiency, including hypotension, vomiting and abdominal pain. Additionally, she reports headaches, which could be attributable to dural irritation caused by the growing adenoma. Examination of the blood test results reveals that the patient is experiencing secondary hypothyroidism; this is evidenced by low T4 levels and an inappropriately normal TSH level, indicating a likely pituitary origin of pathology. Furthermore, hyponatraemia is present, supporting the diagnosis of adrenal insufficiency due to diminished ACTH secretion from the pituitary. Hyponatraemia is seen in adrenal insufficiency due to reduced mineralocorticoid production. Non- functioning adenomas can also lead to elevated prolactin levels through stalk effect compression, as observed in this case. The definitive treatment for a non-functioning pituitary adenoma is transsphenoidal surgery. Cabergoline is utilised in the management of prolactinomas. Prolactinomas can induce hypopituitarism through compression of healthy pituitary tissue when they grow to a significant size. However, in this case, the prolactin level is only mildly raised, which is more in keeping with stalk compression. Typically, a prolactinoma would cause a prolactin level > 100ng/mL and a level of 41 ng/mL is more in keeping with a non-functioning adenoma. Hydrocortisone and fludrocortisone are administered to address adrenal insufficiency conditions such as Addison's disease. These medications might be used as interim measures while awaiting definitive transsphenoidal surgery. Levothyroxine serves as a therapeutic agent for hypothyroidism arising from conditions such as Hashimoto's disease. In this instance, the laboratory findings point to a secondary cause for her hypothyroidism. When coupled with adrenal insufficiency, it strongly indicates the presence of a non-functioning pituitary adenoma, warranting surgical intervention. Phenoxybenzamine, an alpha-adrenergic receptor antagonist, is employed preoperatively to manage hypertension associated with pheochromocytomas. While such tumours often cause headaches similar to those reported by our patient, they are typically accompanied by palpitations and sweating—symptoms absent in this case—and are not linked with secondary hypothyroidism or adrenal insufficiency. Discuss (1) Improve Next question https://www.passmedicine.com/question/questions.php?q=0 2/5 5/21/24, 12:21 PM PassMedicine Pituitary adenoma A pituitary adenoma is a benign tumour of the pituitary gland. They are common (10% of all people) but in most cases will never be found (asymptomatic) or are found as an incidental findings. They account for around 10% of adult brain tumours. Pituitary adenomas can be classified according to: size (a microadenoma is 30 5% Doesn't respond to glimepiride 4% Autosomal recessive inheritance 10% Frequent episodes of diabetic ketoacidosis are typical 6% The correct answer is There is usually a strong family history. Maturity-onset diabetes of the young (MODY) is a group of monogenic forms of diabetes that typically presents in adolescence or early adulthood. It is characterised by autosomal dominant inheritance, hence a strong family history is often present. This means that an affected individual has a 50% chance of passing the condition on to each offspring. The statement Body mass index is typically > 30 is incorrect. MODY patients are typically non- obese and have normal or low body mass index (BMI). This distinguishes MODY from type 2 diabetes, where BMI is often greater than 25-30 due to insulin resistance. Doesn't respond to glimepiride is also incorrect. Glimepiride, a sulfonylurea, stimulates insulin secretion from pancreatic beta cells and can be effective in some types of MODY, particularly MODY 2 and MODY 3 where there's functional impairment of these cells. However, response to glimepiride may vary depending on the specific genetic mutation present in different subtypes of MODY. Regarding the statement Autosomal recessive inheritance, this too is incorrect as it contradicts the actual inheritance pattern for MODY which is autosomal dominant. Autosomal recessive diseases require both parents to carry and pass on the faulty gene for the disease to manifest in their offspring. Lastly, Frequent episodes of diabetic ketoacidosis are typical does not accurately describe clinical features associated with MODY. Diabetic ketoacidosis (DKA) tends to occur more frequently in patients with type 1 diabetes due to absolute insulin deficiency. In contrast, https://www.passmedicine.com/question/questions.php?q=0 1/4 5/21/24, 12:23 PM PassMedicine individuals with MODY generally have some endogenous insulin production preventing DKA under most circumstances. Discuss (2) Improve Next question MODY Maturity-Onset Diabetes of the Young (MODY) is a form of monogenic diabetes, typically characterized by an autosomal dominant inheritance pattern, onset usually before 25 years of age, and impairment in insulin secretion with minimal or no defects in insulin action. Unlike more common forms of diabetes, such as Type 1 and Type 2, MODY is not primarily driven by lifestyle factors. It is thought that around 1-2% of patients with diabetes mellitus have MODY, and around 90% are misclassified as having either type 1 or type 2 diabetes mellitus. Classification and Genetics MODY is a heterogenous group, with over 14 types identified as of the latest revision, each corresponding to mutations in different genes. The most common types are MODY2 (GCK mutation) and MODY3 (HNF1A mutation), but others include MODY1 (HNF4A), MODY4 (PDX1), MODY5 (HNF1B), and so on. MODY 3 accounts for around 60% of cases with MODY 2 causing 20% of cases. Each subtype varies in its clinical presentation, management, and prognosis, emphasizing the importance of precise genetic diagnosis in order to guide treatment strategy and genetic counselling. Clinical Features Patients with MODY often present with mild non-ketotic hyperglycemia that is often detected incidentally or during routine screening. It may also be discovered during pregnancy. Unlike Type 1 diabetes, patients with MODY usually do not present with diabetic ketoacidosis except under severe stress conditions, and unlike Type 2 diabetes, they are often of normal weight and do not exhibit signs of insulin resistance. https://www.passmedicine.com/question/questions.php?q=0 2/4 5/21/24, 12:23 PM PassMedicine The specific clinical manifestations and complications can vary depending on the subtype of MODY. For example, individuals with MODY2 generally have mild, stable fasting hyperglycemia and rarely develop severe complications, whereas those with MODY3 or MODY1 may have progressive hyperglycemia and are at higher risk for complications typically associated with diabetes, such as retinopathy, nephropathy, and cardiovascular disease. Diagnosis MODY should be suspected in individuals with persistent, asymptomatic hyperglycemia detected before the age of 25, without the typical features of Type 1 or Type 2 diabetes. The diagnosis is confirmed by genetic testing, which is crucial for identifying the specific type of MODY, as this has direct implications for management. It's important to remember, however, that genetic testing can be expensive and may not be available in all settings. Treatment The treatment for MODY depends on the specific genetic subtype. For example, MODY2 often does not require specific treatment, as the hyperglycemia is mild and usually does not lead to complications. In contrast, MODY associated with HNF1A often respond well to treatment with low-dose sulfonylureas. Insulin therapy may be necessary in some cases, especially during pregnancy or if sulfonylureas are contraindicated or ineffective. Next question                Textbooks High-yield textbook Extended textbook https://www.passmedicine.com/question/questions.php?q=0 3/4 5/21/24, 12:24 PM PassMedicine PassMedicine Question 25 of 414 A 55-year-old woman presents to the emergency department with complaints of persistent fatigue, headache, and occasional blurred vision that have developed over several months. She has normal vital signs but reports experiencing weight gain and cold intolerance. On examination of her visual fields, she is found to have peripheral vision loss. Her blood test results are as follows: TSH 15.0 mIU/L 0.4-4.0 FT4 0.05 pmol/L 12 – 21.9 FSH 30 IU/L 40-250 LH 20 IU/L 30-200 Prolactin 500 ng/ml < 25 What is the first-line treatment for the most likely diagnosis? Bromocriptine 15% Cabergoline 5% Octreotide 3% Radiotherapy 5% Surgery 72% Non-functioning adenomas are generally diagnosed due to their compressive symptoms (e.g. visual problems) or hormone deficiencies - transsphenoidal surgery is therefore the first-line treatment Important for me Less important The correct choice in this scenario is surgical resection, which represents the first-line management for this patient. The clinical presentation and laboratory findings are indicative of a non-functioning pituitary macroadenoma. Symptoms such as fatigue, weight gain, and cold intolerance may be attributed to secondary hypothyroidism, characterised by an elevated TSH and https://www.passmedicine.com/question/questions.php?q=0 1/5 5/21/24, 12:24 PM PassMedicine low FT4 levels, resulting from tumour compression on the normal pituitary gland. Additionally, headache and visual field defects—specifically bitemporal hemianopia—are frequently associated with a pituitary macroadenoma due to the expansive effect of the lesion on the optic chiasm. Bromocriptine is not an appropriate selection because it acts as a dopamine agonist primarily indicated for prolactin-secreting adenomas (prolactinomas). Given that the patient exhibits signs of secondary hypothyroidism alongside headache and bitemporal hemianopia, these symptoms do not align with those typically observed in prolactinoma but rather suggest a non-functioning pituitary macroadenoma. Similarly, cabergoline is another dopamine agonist utilised predominantly for treating prolactinomas; hence it is not suited for cases of non-functioning pituitary macroadenoma. The patient's clinical manifestation and laboratory evidence of secondary hypothyroidism combined with visual field impairment support the diagnosis of non-functioning pituitary macroadenoma. Octreotide has its use in managing growth hormone-secreting adenomas. As such, given that the clinical picture and laboratory results do not correspond to this type of tumour, octreotide would be an incorrect choice for treatment in this context as it holds no therapeutic benefit for non- functioning pituitary macroadenomas. Finally, while radiotherapy might be considered if surgical intervention is contraindicated or if there is residual disease following surgery, it is generally not employed as a primary therapy. Radiotherapy may also be indicated in cases where tumour recurrence occurs after surgery. However, given that the question specifies seeking first-line treatment options, radiotherapy does not represent the correct choice under these circumstances. Discuss Improve Next question Pituitary adenoma A pituitary adenoma is a benign tumour of the pituitary gland. They are common (10% of all people) but in most cases will never be found (asymptomatic) or are found as an incidental findings. They account for around 10% of adult brain tumours. Pituitary adenomas can be classified according to: size (a microadenoma is normal range (inappropriately normal given the low thyroxine and T3). Changes are reversible upon recovery from the systemic illness and hence no treatment is usually needed. Next question                Textbooks High-yield textbook Extended textbook Score: 34.1% 1 2 3 4 5 6 https://www.passmedicine.com/question/questions.php?q=0 2/4 5/21/24, 12:28 PM PassMedicine PassMedicine Question 42 of 414 A 71-year-old woman with a history of type 2 diabetes mellitus presents with lethargy and polyuria. A diagnosis of hyperosmolar hyperglycaemic state is considered. Which one of the following findings would be least consistent with this diagnosis? pH of 7.38 10% Ketones 1+ in urine 29% Serum osmolality of 310 mosmol/kg 30% Serum bicarbonate of 19 mmol/l 21% Glucose of 45 mmol/l 10% A trace of ketones may be found in hyperosmolar hyperglycaemic state. Serum osmolality is typically > 320 mosmol/kg Discuss (10) Improve Next question Hyperosmolar hyperglycaemic state Hyperosmolar hyperglycaemic state (HHS) is a medical emergency that can be difficult to manage and has a significant associated mortality (up to 20%). Hyperglycaemia results in osmotic diuresis, severe dehydration, and electrolyte deficiencies. HHS typically presents in the elderly with type 2 diabetes mellitus (T2DM). Pathophysiology hyperglycaemia → ↑ serum osmolality → osmotic diuresis → severe volume depletion Precipitating factors intercurrent illness dementia https://www.passmedicine.com/question/questions.php?q=0 1/5 5/21/24, 12:28 PM PassMedicine sedative drugs Clinical features whilst DKA presents within hours of onset, HHS comes on over many days, and consequently, the dehydration and metabolic disturbances may be more extreme consequences of volume loss clinical signs of dehydration polyuria polydipsia systemic lethargy nausea and vomiting neurological altered level of consciousness focal neurological deficits haematological hyperviscosity (may result in myocardial infarctions, stroke and peripheral arterial thrombosis) There are no precise diagnostic criteria but the following are typically seen hypovolaemia marked hyperglycaemia (>30 mmol/L) significantly raised serum osmolarity (> 320 mosmol/kg) can be calculated by: 2 * Na+ + glucose + urea no significant hyperketonaemia ( 15 mmol/l or pH > 7.3 - acidosis can occur due to lactic acidosis or renal impairment) Management fluid replacement fluid losses in HHS are estimated to be between 100 - 220 ml/kg IV 0.9% sodium chloride solution typically given at 0.5 - 1 L/hour depending on clinical assessment potassium levels should be monitored and added to fluids depending on the level insulin should not be given unless blood glucose stops falling while giving IV fluids venous thromboembolism prophylaxis patients are at risk of thrombosis due to hyperviscosity Complications https://www.passmedicine.com/question/questions.php?q=0 2/5 5/21/24, 12:28 PM PassMedicine vascular complications may occur due to hyperviscosity: such as myocardial infarction stroke Next question                Textbooks High-yield textbook Extended textbook Links Joint British Diabetes Societies 1 0 The management of the hyperosmolar hyperglycaemic state (HHS) Report broken link Score: 33.3% 1 2 3 4 5 6 7 https://www.passmedicine.com/question/questions.php?q=0 3/5 5/21/24, 12:29 PM PassMedicine PassMedicine Question 43 of 414 A 5-year-old boy presents to the emergency department with polyuria and polydipsia. He appears fatigued and has experienced vomiting twice in the past 24 hours. On examination, he is found to have reduced skin turgor and dry mucous membranes, with a blood pressure of 121/67 mmHg. The results of his blood tests are as follows: Na+ 138 mmol/L (135 - 145) K+ 2.7 mmol/L (3.5 - 5.0) Mg+ 0.85 mmol/L (0.8-1) Bicarbonate 34 mmol/L (22 - 29) Urea 12.3 mmol/L (2.0 - 7.0) Creatinine 65 µmol/L (55 - 120) pH 7.51 (7.35-7.45) A rare inherited renal condition is suspected. What is the cause of the most likely diagnosis? A defective NKCC2 channel in the ascending loop of Henle 68% A defective epithelial sodium channel 5% A defective thiazide-sensitive sodium-chloride co-transporter 12% Failure of acid excretion in the distal convoluted tubule 6% Primary hyperaldosteronism caused by an adrenal adenoma 8% Bartter's syndrome results from a defective NKCC2 channel in the ascending loop of Henle Important for me Less important Bartter's syndrome is attributable to a defective NKCC2 channel in the ascending loop of Henle. It is a genetic condition that arises from a defect in chloride reabsorption at the Na+ K+ https://www.passmedicine.com/question/questions.php?q=0 1/5 5/21/24, 12:29 PM PassMedicine 2Cl- cotransporter (NKCC2) within the ascending limb of the loop of Henle. This abnormality leads to marked hypokalaemia, as demonstrated in this patient. The compromised chloride reabsorption interferes with the proper exchange of bicarbonate for chloride, leading to increased levels of bicarbonate in the blood and consequent metabolic alkalosis. Additionally, Bartter's syndrome results in elevated renin and aldosterone levels, which promote hydrogen ion excretion and further aggravate the alkalosis. A characteristic feature of Bartter's syndrome is normotension, which concurs with our case presentation. Liddle's syndrome stems from a defective epithelial sodium channel. This disorder presents with hypokalaemic metabolic alkalosis along with hypertension. Considering that our patient has normal blood pressure readings, Liddle's syndrome can be confidently excluded. Gitelman's syndrome involves a defect in the thiazide-sensitive sodium-chloride cotransporter and shares many features with Bartter's syndrome. Clinical manifestations include dehydration, hypokalaemia, hypomagnesaemia, hypocalciuria, metabolic alkalosis and normotension. Typically manifesting during adolescence or early adulthood, Gitelman's syndrome could be considered. Nonetheless, since our patient has normal magnesium levels, Bartter's syndrome remains more likely. Failure of acid excretion in the distal convoluted tubule underpins type 1 renal tubular acidosis. While this condition also presents with hypokalaemia, it is typically associated with metabolic acidosis rather than alkalosis as observed in our patient. Conn's syndrome constitutes a form of primary hyperaldosteronism due to an adrenal adenoma, leading to hypokalaemia and hypertension - features not seen in our normotensive patient. Conn's syndrome is less frequently encountered as a cause of primary hyperaldosteronism than bilateral adrenal hyperplasia. Differentiation between these two entities can be facilitated by adrenal venous sampling. Discuss (1) Improve Next question Bartter's syndrome Bartter's syndrome is an inherited cause (usually autosomal recessive) of severe hypokalaemia due to defective chloride absorption at the Na+ K+ 2Cl- cotransporter (NKCC2) in the ascending loop of Henle. It should be noted that it is associated with normotension (unlike other endocrine causes of hypokalaemia such as Conn's, Cushing's and Liddle's syndrome which are associated with hypertension). https://www.passmedicine.com/question/questions.php?q=0 2/5 5/21/24, 12:29 PM PassMedicine Loop diuretics work by inhibiting NKCC2 - think of Bartter's syndrome as like taking large doses of furosemide Features usually presents in childhood, e.g. Failure to thrive polyuria, polydipsia hypokalaemia normotension weakness Next question                Textbooks High-yield textbook Extended textbook Links Royal College of Physicians 9 3 2012 Renal tubular disorders review Report broken link Score: 32.6% 1 https://www.passmedicine.com/question/questions.php?q=0 3/5 5/21/24, 12:29 PM PassMedicine PassMedicine Question 44 of 414 Liddle's syndrome is associated with each one of the following, except: Alkalosis 13% Response to treatment with amiloride 20% Hypertension 15% Autosomal recessive inheritance 39% Hypokalaemia 11% Discuss (6) Improve Next question Liddle's syndrome Liddle's syndrome is a rare autosomal dominant condition that causes hypertension and hypokalaemic alkalosis. It is thought to be caused by disordered sodium channels in the distal tubules leading to increased reabsorption of sodium. Treatment is with either amiloride or triamterene Next question                https://www.passmedicine.com/question/questions.php?q=0 1/3 5/21/24, 12:29 PM PassMedicine PassMedicine Question 45 of 414 A man presents to his GP with a tender mass in his neck. He reports it has only recently become apparent, but it seems to be growing rapidly. On questioning, he reports he has noticed some weight loss and sometimes wakes at night very sweaty and has to change his pillow-case. He denies any recent illnesses and reports no symptoms of palpitations, anxiety, or trembling. Thyroid function tests are normal and an ultrasound scan of the neck is performed, which shows an enlarged thyroid gland. He goes on to have a fine-needle aspiration biopsy and finally a surgical biopsy of the gland which reveals a thyroid lymphoma. Which of these is an associated risk factor for this condition? Being male 2% Exposure to radiation 11% Past medical history of Hashimoto's thyroiditis 79% Smoking 8% Young age 1% Hashimoto's thyroiditis is associated with thyroid lymphoma Important for me Less important This man has been diagnosed with thyroid lymphoma, this is a rare disease that is linked with Hashimoto's thyroiditis, therefore that is the correct answer. Being male is incorrect as thyroid lymphoma is more common in women. Radiation is incorrect as this is a risk factor for other forms of thyroid cancer, but not for thyroid lymphoma. Smoking and thyroid cancer remains a heavily researched topic. However, there is currently no correlation between smoking and increased risk of thyroid cancer. In fact, some studies show an inverse relationship between smoking and thyroid cancer, while other studies found no association. https://www.passmedicine.com/question/questions.php?q=0 1/6 5/21/24, 12:29 PM PassMedicine Young age is incorrect as thyroid lymphoma most commonly occurs between the ages of 65 to 75 years. Discuss Improve Next question Thyroid cancer Features of hyperthyroidism or hypothyroidism are not commonly seen in patients with thyroid malignancies as they rarely secrete thyroid hormones Main points Type Percentage Papillary 70% Often young females - excellent prognosis Follicular 20% Medullary 5% Cancer of parafollicular (C) cells, secrete calcitonin, part of MEN-2 Anaplastic 1% Not responsive to treatment, can cause pressure symptoms Lymphoma Rare Associated with Hashimoto's thyroiditis Management of papillary and follicular cancer total thyroidectomy followed by radioiodine (I-131) to kill residual cells yearly thyroglobulin levels to detect early recurrent disease Further information Type Notes Papillary Usually contain a mixture of papillary and colloidal filled follicles carcinoma Histologically tumour has papillary projections and pale empty nuclei Seldom encapsulated https://www.passmedicine.com/question/questions.php?q=0 2/6 5/21/24, 12:29 PM PassMedicine Type Notes Lymph node metastasis predominate Haematogenous metastasis rare Follicular Usually present as a solitary thyroid nodule adenoma Malignancy can only be excluded on formal histological assessment Follicular May appear macroscopically encapsulated, microscopically capsular carcinoma invasion is seen. Without this finding the lesion is a follicular adenoma. Vascular invasion predominates Multifocal disease raree Medullary C cells derived from neural crest and not thyroid tissue carcinoma Serum calcitonin levels often raised Familial genetic disease accounts for up to 20% cases Both lymphatic and haematogenous metastasis are recognised, nodal disease is associated with a very poor prognosis. Anaplastic Most common in elderly females carcinoma Local invasion is a common feature Treatment is by resection where possible, palliation may be achieved through isthmusectomy and radiotherapy. Chemotherapy is ineffective. Next question                Textbooks High-yield textbook Extended textbook https://www.passmedicine.com/question/questions.php?q=0 3/6 5/21/24, 12:29 PM PassMedicine Links British Thyroid Association 3 3 2014 Guidelines for the Management of Thyroid Cancer Report broken link Media Thyroid cancer Osmosis - YouTube 20 1 Thyroid Nodule Armando Hasudungan - YouTube 12 4 Report broken media Score: 31.1% 1 2 3 4 5 6 7 8 9 https://www.passmedicine.com/question/questions.php?q=0 4/6 5/21/24, 12:29 PM PassMedicine PassMedicine Question 46 of 414 A 45-year-old woman presents with weight gain and recurrent 'dizzy' episodes. Over the past four months she has gained 20 kg. The episodes occur on an almost daily basis and are characterised by blurred vision, sweating, headaches and palpitations. Her GP checked a blood sugar during one of these episodes which was record as being 1.4 mmol/l. What is the single most useful test? Glucagon stimulation test 6% Oral glucose tolerance test with growth hormone measurements 12% Insulin + C-peptide levels during a hypoglycaemic episode 62% Short ACTH test 12% Insulin tolerance test 8% This patient has symptoms typical of an insulinoma. Whilst supervised fasting is normally the investigation of choice if this option is not given then insulin + C-peptide levels during an acute hypoglycaemic episode are useful. Discuss (7) Improve Next question Insulinoma An insulinoma is a neuroendocrine tumour deriving mainly from pancreatic Islets of Langerhans cells Basics most common pancreatic endocrine tumour 10% malignant, 10% multiple of patients with multiple tumours, 50% have MEN-1 Features f https://www.passmedicine.com/question/questions.php?q=0 f 1/4 5/21/24, 12:29 PM PassMedicine of hypoglycaemia: rapid typically weight gain may early in morning or just before meal, e.g. diplopia, weakness etc be seen high insulin, raised proinsulin:insulin ratio high C-peptide Diagnosis supervised, prolonged fasting (up to 72 hours) CT pancreas Management surgery diazoxide and somatostatin if patients are not candidates for surgery Next question                Textbooks High-yield textbook Extended textbook Media Pancreatic neuroendocrine neoplasms Osmosis - YouTube 19 0 Report broken media https://www.passmedicine.com/question/questions.php?q=0 2/4 5/21/24, 12:30 PM PassMedicine PassMedicine Question 47 of 414 A 32-year-old woman who is 24 weeks pregnant with her third child comes to the clinic for review. She has been diagnosed with gestational diabetes mellitus, and a fasting plasma glucose following 2 weeks of adherence to lifestyle changes is still elevated at 6.8 mmol/l. Her blood pressure is 122/82 mmHg, and her body mass index is 25 kg/m². She is reluctant to start insulin initially because her sister has Type 1 diabetes and suffers from frequent hypoglycaemia. Which of the following is the most appropriate next intervention? Metformin 76% Glibenclamide 7% Insulin glargine 10% Dapagliflozin 2% Insulin pump therapy 5% Metformin is the first line therapy of choice for diabetes in pregnancy Important for me Less important Metformin has been evaluated in a large Australasian trial for the treatment of gestational diabetes mellitus. Versus insulin initiation at the point of diagnosis, those patients treated with metformin gained less weight during pregnancy and suffered slightly fewer episodes of hypoglycaemia. There was no difference in the primary endpoint of adverse foetal outcomes, and women treated with metformin first preferred this option, even though most eventually progressed to insulin in addition to oral therapy. This has precipitated NICE to recommend metformin as a first line option where fasting glucose is less than 7.0 mmol/l despite dietary modification. https://www.nejm.org/doi/full/10.1056/NEJMoa0707193 https://www.nice.org.uk/guidance/ng3 Although glibenclamide is safe in pregnancy it does not limit weight gain and control is inferior to insulin therapy. It's therefore only an option in patients who refuse metformin and insulin. Out of the insulin options listed, insulin pump therapy is preferred, although many women find it more https://www.passmedicine.com/question/questions.php?q=0 1/6 5/21/24, 12:30 PM PassMedicine difficult to comply with pump therapy and are therefore treated with a basal bolus regimen. There is no evidence to support the use of SGLT-2 inhibitors such as dapagliflozin in pregnancy. One problem which leads to diabetes is relative insulin resistance, which SGLT-2 inhibitors will not significantly impact upon. Discuss (2) Improve Next question Gestational diabetes Diabetes mellitus may be a pre-existing problem or develop during pregnancy, gestational diabetes. It complicates up to 1 in 20 pregnancies. NICE estimates the following breakdown: 87.5% have gestational diabetes 7.5% have type 1 diabetes 5% have type 2 diabetes Gestational diabetes Gestational diabetes is the second most common medical disorder complicating pregnancy (after hypertension), affecting around 4% of pregnancies. Risk factors for gestational diabetes BMI of > 30 kg/m² previous macrosomic baby weighing 4.5 kg or above previous gestational diabetes first-degree relative with diabetes family origin with a high prevalence of diabetes (South Asian, black Caribbean and Middle Eastern) Screening for gestational diabetes the oral glucose tolerance test (OGTT) is the test of choice women who've previously had gestational diabetes: OGTT should be performed as soon as possible after booking and at 24-28 weeks if the first test is normal. NICE also recommend that early self-monitoring of blood glucose is an alternative to the OGTTs women with any of the other risk factors should be offered an OGTT at 24-28 weeks Diagnostic thresholds for gestational diabetes https://www.passmedicine.com/question/questions.php?q=0 2/6 5/21/24, 12:30 PM PassMedicine these have recently been updated by NICE, gestational diabetes is diagnosed if either: fasting glucose is >= 5.6 mmol/L 2-hour glucose is >= 7.8 mmol/L Manage