Endocrine passmedicine (1)

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DM, poor control, bloating, and vomiting after eating?
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symptoms include erratic blood glucose control, bloating and vomiting
management options include metoclopramide, domperidone or erythromycin (prokinetic

management of neuropathic pain
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
Other associated features include:
***raised uric acid levels
non-alcoholic fatty liver disease
polycystic ovarian syndrome

the most appropriate strategy to reduce the future risk of developing diabetes mellitus is: Treatment with orlistat and diet
The XENDOS study revealed that orlistat, in combination with diet, will reduce the risk of diabetes in these obese patients by 38% more than just diet alone plus placebo.
Image: metabolic syndrome
Weight reduction
the gold-standard treatment for PCOS, and improves ovulation, androgen levels, hirsuitism and metabolic features associated with insulin resistance.
(loss in weight of only 5% reduces hirsuitism by up to 40%.)

Hirsutism and acne
For associated hirsutism Dianette® (cyproterone acetate) combined oral contraceptive pill (COC) is the most effective, along with cosmetic treatments like waxing, shaving, plucking or electrolysis.
Possible options include a third generation COC which has fewer androgenic effects or co-cyprindiol which has an anti-androgen action. Both of these types of COC may carry an increased risk of venous thromboembolism
Co-cyprindrol because it contains cyproterone, an anti-androgen, may be more effective than the COCP in controlling acne and hirsuitism and acne in PCOS.
**if doesn't respond to COC then topical eflornithine may be tried
spironolactone, flutamide and finasteride may be used under specialist supervision
A Cochrane meta-analysis has suggested that metformin is not effective in controlling hirsuitism and acne versus other options such as the COCP or co-cyprindrol

weight loss the most important initial step.
anti-oestrogen therapies such as ***clomifene the most effective treatment (work by occupying hypothalamic oestrogen receptors without activating them.) This interferes with the binding of oestradiol and thus prevents negative feedback inhibition of FSH secretion
***metformin is also used as a second line after clomifene, either combined with clomifene or alone,
gonadotrophins: usually reserved for patients who are resistant to clomifene

Other notes
Surgical intervention with wedge ovarian resection can reduce androgen secretion and symptoms.
= Dapagliflozin is a member of the glofozin anti-diabetic drugs. The medication works by inhibiting the sodium-glucose transport proteins (SGLT2), which reabsorbs glucose in the proximal tubule.

Dapagliflozin can be tried if blood sugars are poorly controlled following commencement of metformin and the patient is unable to take a sulfonylurea.

Common side effects are often secondary to the glycosuria, which include increased predisposition of urinary tract infection and dehydration.
good for erratic lifestyle

increase postprandial insulin release specifically

Meglitinides stimulate insulin release and are particularly useful for post-prandial hyperglycaemia or an erratic eating schedule, as patients take them shortly before meals

***Mechanism of action?
Activates an ATP-dependent K* channel on the cell membrane of pancreatic beta cells

like sulfonylureas they bind to an ATP-dependent K + (K ATP ) channel on the cell membrane of pancreatic beta cells but have a weaker binding affinity and faster dissociation from the SUR1
binding site (acts by closure of the β-cell K+-ATP channel)
Which of the following results establishes a diagnosis of diabetes mellitus?
Asymptomatic patient with fasting glucose 7.9 mmol/L on one occasion
Symptomatic patient with fasting glucose 6.8 mmol/L on two occasions
Glycosuria +++
Asymptomatic patient with random glucose 22.0 mmol/L on one occasion
Symptomatic patient with random glucose 12.0 mmol/L on one occasion
diagnosis towered to Addison's disease.

Although features of
hypothyroidism may co-exist with hypoadrenalism, corticosteroid replacement is the most important first step in therapy because commencing thyroxine may worsen any adrenal crisis.

Fluid restriction is not appropriate given signs of volume depletion and the likelihood of
Addison's being the primary diagnosis. Although fluid replacement with normal saline may be
useful in relieving symptoms of volume depletion, it is unlikely to be effective without
commencing hydrocortisone therapy. Oral fludrocortisone is added to hydrocortisone in patients
who are corticosteroid replete but still suffer from symptoms of hyponatraemia or volume depletion.
Metformin is usually the first line drug treatment when lifestyle changes are ineffective.
Nevertheless, it is contraindicated in this patient as she has end-stage renal disease and so her estimated glomerular filtration rate will be too low. Gliclazide can be used in end-stage renal failure and so would be the treatment of choice.
Having multiple sexual partners is the stronge risk factor for the development of cervical carcinoma,why?This is because having multiple sexual partners greatly increases the chance of being infected with the ***human papilloma virus. ***The 16 and 18 viral strain then triggers the carcinogenesis by inhibiting the tumor suppressor gene p53 and RB.MENMEN type | 3P's -Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia -Pituitary (70% -Pancreas (50%): e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration) 60% of pancreatic endocrine tumours are gastrinomas (most common). -Also: adrenal and thyroid -MEN1 gene - ***Most common presentation = hypercalcaemia (for monitoring) MEN type IIa -Medullary thyroid cancer (70%) 2P's -Parathyroid (60%) -Phaeochromocytoma -***RET oncogene* - young-onset hypertension with feature of hyperparathyroidism (↑Ca &↓P)➡️MEN 2a MEN IIb -Medullary thyroid cancer 1P -Phaeochromocytoma -Marfanoid body habitus -Neuromas -RET oncogene - most characteristic test in (MEN 2B) Elevated metanephrinesMultiple endocrine neoplasia type II is due to mutation in which sort of receptor?Membrane-bound tyrosine kinase receptorpalpitations and heat intolerance. diffuse tender goitre is noted . Thyroid function tests Free T4 = 24 TSH = 0.05 What is the most likely diagnosis? Grave's disease Sick thyroid syndrome De Quervain's thyroiditis Hashimoto's thyroiditis Toxic multinodular goitreThyrotoxicosis with tender goitre = subacute (De Quervain's) thyroiditis Whilst Grave's disease is the most common cause of thyrotoxicosis it would not cause a tender goitre. In the context of thyrotoxicosis this finding is only really seen in De Quervain's thyroiditis. Hashimoto's thyroiditis is an autoimmune disorder of the thyroid gland. It is typically associated with hypothyroidism although there may be a transient thyrotoxicosis in the acute phase. And The goitre is non-tenderWhich one of the following is least characteristic of Addison's disease? Hypoglycaemia Metabolic alkalosis Hyponatraemia Hyperkalaemia Positive short ACTH testAddison's disease is associated with a metabolic acidosisdaily frontal headaches which have not been helped by regular paracetamol. wedding ring no longer fitting, his shoe size apparently increasing and a small amount of milky discharge from both nipples. blood pressure is 168/96 mmHg. What is the most likely diagnosis?AcromegalyEndocervical swabs are taken. A diagnosis of pelvic inflammatory disease is suspected. What is the most appropriate management?Oral ofloxacin + metronidazole Consensus guidelines recommend treatment once a diagnosis of pelvic inflammatory disease is suspected, rather than waiting for the results of swabsHRT after hysterectomy oestrogen only or progestogen oestrogenHRT: adding a progestogen ***increases the risk of breast cancer This is the rationale behind giving women who've had a hysterectomy oestrogen-only treatment. the stroke risk is the same regardless of whether the HRT preparation contains progesterone.recurrent painful oral ulceration (oral Candidal infection) Which one of the following would most suggest type 1 polyglandular syndrome? Hypocalcaemia Rheumatoid arthritis Type Il diabetes mellitus Coeliac disease HypercalcaemiaHypocalcemia Primary hypoparathyroidism is usually the first endocrine manifestation of type 1 autoimmune polyendocrinopathy syndrome.Which one of the following unwanted effects is most likely to occur in patients taking gliclazide? Peripheral neuropathy Cholestasis Photosensitivity Syndrome of inappropriate ADH secretion Weight gainAll of the above side-effects may be seen in patients taking sulfonylureas but weight gain is the most common.type 1 diabetics, HbA1c target is?In type 1 diabetics, a general HbA1c target of 48 mmol/mol (6.5%) should be usedThe history of prolonged cessation of menses with a normal weight, normal thyroid function tests and a history of coeliac disease is pointed to a diagnosis of?premature ovarian failure Premature ovarian failure is defined as the onset of menopausal symptoms and elevated gonadotrophin levels before the age of 40 years. ↑↑ (FSH), + ↓↓oestradiolA 54-year-old man has a routine medical for work. He is asymptomatic and clinical examination is unremarkable. Which of the following results establishes a diagnosis of impaired fasting glucose? Fasting glucose 7.1 mmol/L on one occasion Fasting glucose 6.8 mmol/L on two occasions Glycosuria ++ 75g oral glucose tolerance test 2 hour value of 8.4 mmol HbA1c of 6.7%A 75g oral glucose tolerance test 2 hour value of 8.4 mmol/L would imply impaired glucose tolerance rather than impaired fasting glucose Fasting glucose 6.8 mmol/L on two occasionsDiabetes Mellitus type 2 diagnosis***Diabetes diagnosis: fasting > 7.0, random > 11.1 - if asymptomatic need two readings If the fasting or random values are not diagnostic, the two hour value should be used. People with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn't have diabetes but does have IGT.' Impaired fasting glucose and ***impaired glucose tolerance. A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG) Impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l What would be the risk of developing type 2 diabetes in patient with (IGT)? 60% over 6 years This increased to 64.5% if individuals had both (IGT) and (IFG).HbA1c testWHO guidance on the use of HbA1c on the diagnosis of diabetes: a HbA1c of greater than or equal to 6.5% (48 mmol/mol) is diagnostic of diabetes mellitus a HbAlc value of less than 6.5% does not exclude diabetes (i.e. it is not as sensitive as fasting samples for detecting diabetes) in patients without symptoms, the test must be repeated to confirm the diagnosis it should be remembered that misleading HbA1c results can be caused by increased red cell turnover Conditions where HbA1c may not be used for diagnosis: haemoglobinopathies haemolytic anaemia untreated iron deficiency anaemia suspected gestational diabetes children HIV chronic kidney disease patients who are acutely ill,Which one of the following is most likely to be found in a patient with Hashimoto's thyroiditis? Raised ESR Anti-TSH receptor stimulating antibodies Anti-thyroid peroxidase antibodies Decreased TSH Co-existing type 2 diabetes mellitusHashimoto's thyroiditis = hypothyroidism + goitre + anti-TPO ***Hashimoto's thyroiditis is associated with thyroid cancer = thyroid lymphoma Hashimoto's thyroiditis is an autoimmune disorder of the thyroid gland. It is typically associated with hypothyroidism although there may be a transient thyrotoxicosis in the acute phase. Early in the course of disease, T4 and TSH levels are normal and there are ***high levels of thyroid peroxidase antibodies and, less commonly, anti-thyroglobulin antibodies. Later in the course of the disease, patients develop hypothyroidism with decreased T4, decreased radioiodine uptake, and increased TSH. It is 10 times more common in women Commonly associated with Turner's syndrome.BMI = 38, HTN 154/92, DM, Lifestyle and a trial of orlistat have failed to reduce his weight, what is the next step? Biliopancreatic diversion with duodenal switch Laparoscopic-adjustable gastric banding Trial of sibutramine Referral for counselling to discuss his excessive eating Sleeve gastrectomyObesity bariatric referral cut-offs -with risk factors (T2DM, BP etc)➡️***BMI > 35 no risk factors: BMI > 40 A trial of sibutramine would not be appropriate given his poorly controlled hypertension. Laparoscopic-adjustable gastric banding is the intervention of choice in patients with a BMI < 40 kg/mA2. Types of bariatric surgery: primarily restrictive: laparoscopic-adjustable gastric banding (LAGB) or sleeve gastrectomy primarily malabsorptive: classic biliopancreatic diversion (BPD) has now largely been replaced by biliopancreatic diversion with duodenal switch mixed: Roux-en-Y gastric bypass surgery Which operation? LAGB produces less weight loss than malabsorptive or mixed procedures but as it has fewer complications it is normally the first-line intervention in patients with a BMI of 30-39 patients with a BMI > 40 kg/m^2 may be considered for a gastric bypass or sleeve gastrectomy. primarily malabsorptive procedures are usually reserved for very obese patients (e.g. BMI > 60 kg/m^2)anti-obesity drugstreatment should be discontinued if weight loss is less than 5% after the first 12 weeks. Combination drug therapy is contraindicated drugs should never be used as the sole element of treatment (should only be prescribed as part of an overall plan for managing obesity). Orlistat Action: pancreatic lipase inhibitor, blocks the breakdown and hence the absorption of dietary fat. used in the management of obesity. Adverse effects faecal urgency/incontinence and flatulence. criteria for the use of orlistat. BMI of 28 kg/m^2 or more with associated risk factors ( (eg: diabetes mellitus, coronary heart disease, hypertension and obstructive sleep apnoea)) BMI of 30 kg/m^2 or more in whom at least three months of managed care involving supervised diet, exercise and behaviour modification fails. continued weight loss e.g. 5% at 3 months orlistat is normally used for < 1 year Sibutramine withdrawn January 2010 by the European Medicines Agency due to an increased risk of cardiovascular events centrally acting appetite suppressant (inhibits uptake of serotonin and noradrenaline at hypothalamic sites that regular food intake) adverse effects include ***hypertension (monitor blood pressure and pulse during treatment), constipation, headache, dry mouth, insomnia and anorexia contraindicated in psychiatric illness, hypertension, IHD, stroke, arrhythmias Rimonabant was withdrawn in October 2008 after the European Medicines Agency warned of serious psychiatric problems including suicide a specific CB1 cannabinoid receptor antagonist,A 30-year-old female is diagnosed with having Grave's disease. What is her chance of developing thyroid eye disease?25-50% In about 10% of patients, the signs will only be unilateral. Ophthalmopathy may occur before the onset of hyperthyroidism, or as late as 20 years afterward. smoking is the most important modifiable risk factor for the development of thyroid eye disease Radioiodine treatment ⬆️thyroid eye disease ➡️ malignant exophthalmos Prednisolone may help reduce the risk For sight-threatening (malignant exophthalmos, diplopia and loss of colour vision) the initial treatment is IV glucocorticoids Block replace with high dose carbimazole and full dose thyroxine replacement is the optimal step. (may be continued for up to 18 months until thyroid eye disease is stable). Stability of thyroid function ↓↓progression of thyroid eye disease. Periods of hypothyroidism worsen peri-orbital oedema ( symptoms related to optic nerve compression.) ***symptoms/signs should indicate the need for urgent review by an ophthalmologist: unexplained deterioration in vision ***awareness of change in intensity or quality of colour vision in one or both eyes (Impaired perception of colour implies acute progressive neuropathy) history of eye suddenly 'popping out' (globe subluxation) obvious corneal opacity cornea still visible when the eyelids are closed disc swellingConstipation, depression Calcium 2.8mmol/| Phosphate 0.7mmol/| Parathyroid hormone 5.0pmol/l (1.2-5.8pmol/I)signs and symptoms of hypercalcaemia. Her parathyroid hormone should be suppressed in the presence of hypercalcaemia. Given that it is normal (inappropriately), this indicates the parathyroid as the cause for the hypercalcaemia. The most common cause of hyperparathyroidism is an parathyroid adenoma.feeling tired and cold all the time. On examination a firm, non-tender goitre is noted. Blood tests TSH 24.2 mu/l Free T4 5.4 pmol/l What is the most likely diagnosis?Hashimoto's thyroiditis = hypothyroidism + goitre + anti-TPO The combination of a goitre with hypothyroidism points to a diagnosis of Hashimoto's. De Quervain's thyroiditis typically causes a painful goitre.A 68-year-old woman presents with lethargy and generalised aches. Calcium 2.83 mmol/l Albumin 42 g/l ESR 26 mm/hr What is the most likely cause of these blood results? Multiple myeloma Sarcoidosis Normal Breast cancer metastases Primary hyperparathyroidismMalignancy and primary hyperparathyroidism account for 90% of hypercalcaemia cases All of the above may cause hypercalcaemia but cancer and primary hyperparathyroidism are the most common causes in this age group. A normal ESR (given her age) points towards a diagnosis of primary hyperparathyroidism.The fasting glucose for a patient is 6.3 mmol/l What is the most likely underlying pathophysiological change? Beta-cell hyperplasia Beta-cell atrophy Muscle insulin resistance Hepatic insulin resistance Adipose tissue insulin resistanceImpaired fasting glucose and impaired glucose tolerance there are two main types of IGR: impaired fasting glucose (IFG) - due to hepatic insulin resistance impaired glucose tolerance (IGT) - due to muscle insulin resistance patients with IGT are more likely to develop T2DM and cardiovascular disease than patients with IFG The risk of progression from (IGT) to frank diabetes is 20- 30% within 5 years. As well as demonstrating a reduction in risk of new onset type 2 diabetes of 25%, acarbose was associated in the STOP-NIDDM study with a 49% reduction in cardiovascular events. Metformin and pioglitazone have not been shown to reduce cardiovascular disease in impaired glucose tolerance.confusion and fever. She has a past history of thyrotoxicosis previously treated with radioiodine therapy. Pulse 120/min regular, blood pressure 150/90 mmHg, temperature of 39.1°C and a respiratory rate of 18/min. Free T4 84 pmol/I Free T3 29 pmol/l TSH < 0.01 mU/I Which one of the following does not have a role in the subsequent management? Lugol's iodine Propranolol Propylthiouracil Bicarbonate DexamethasoneManagement of thyroid storm? Transfer the patient to the Intensive Therapy Unit symptomatic treatment e.g. Paracetamol Chlorpromazine can be used to treat agitation and, because of its effect in inhibiting central thermoregulation, it can be useful in treating the hyperpyrexia. propranolol anti-thyroid drugs: e.g. methimazole or propylthiouracil Lugol's iodine used in conjunction with Carbimazole (more rapid resolution.) Iodine: Blocks uptake of iodine into the thyroid gland and blocks the release of hormone. dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to T3 Plasmapheresis and peritoneal dialysis can be effective in cases resistant to pharmacological measures. Precipitating factors Any acute stressful condition such as surgery acute infectionsfeeling 'hot all the time' and is consequently worried she is going through an early menopause. fullness' of her neck which has become apparent over the past few weeks. pulse is 90/minute and she has a small, non-tender goitre. TSH 0.05 mu/l Free T4 24 Anti-thyroid peroxidase antibodies 102 IU/mL (35 IU/m ESR 23 What is the most likely diagnosis? Hashimoto's thyroiditis Toxic multinodular goitre Thyroid cancer De Quervain's thyroiditis Graves' diseaseThe thyrotoxic symptoms and blood tests, goitre and anti-thyroid peroxidase antibodies suggest a diagnosis of Graves' disease. Whilst anti-thyroid peroxidase antibodies are seen in 90% of Hashimoto's disease they are also seen in 75% of patients with Graves' disease. Hashimoto's thyroiditis is also generally associated with hypothyroidism, which is not in keeping with this presentation.Which one of the following drugs is least likely to cause gynaecomastia? Spironolactone Sodium valproate Digoxin Cimetidine Anabolic steroidsWhilst sodium valproate rarely causes gynaecomastia Gynaecomastia is an abnormal amount of breast tissue in males caused by an increased oestrogen: androgen ratio. Causes physiological: normal in puberty syndromes with androgen deficiency: Kallman's, Klinefelter's (***47, XXY karyotype) testicular failure: e.g. mumps liver disease testicular cancer e.g. **seminoma secreting hCG ectopic tumour secretion ***hyperthyroidism haemodialysis starvation/refeeding drugs: Common causes *spironolactone (most common drug cause) cimetidine *digoxin cannabis diamorphine cyproterone finasteride gonadorelin analogues e.g. ***Goserelin, Very rare drug causes of gynaecomastia tricyclics isoniazid calcium channel blockers heroin busulfan methyldopaA 27-year-old man in a fertility clinic. Semen analysis has revealed azoospermia. 1.83 metres tall with a body mass index of 25 kg / m"2. A degree of gynaecomastia is noted, testicular volume is around 10ml . Which investigation is likely to be diagnostic?Klinefelter's? - do a karyotypeHbA1c to Average blood glucose?HbA1c 10 =~ 15A 36-year-old woman who presented with a goitre is diagnosed with autoimmune thyroiditis. Which one of the following types of thyroid cancer is she predisposed to developing? Anaplastic Lymphoma Medullary Follicular PapillanyHashimoto's thyroiditis is associated with thyroid lymphomaA 43-year-old man is admitted to hospital with pneumonia. His past medical history includes Addison's disease for which he takes hydrocortisone (20mg in the mornings and 10mg in the afternoon). What is the most appropriate action with respect to his steroid dose?Patients on long-term steroids should have their doses doubled during intercurrent illness 40 at mornings, 20 at eveningoral steroid has the least amount of mineralocorticoid activity?Dexamethsone This is clinically relevant as there are some situations where it is important to combine high glucocorticoid (anti-inflammatory) activity with minimal mineralocorticoid (fluid-retention) effects. A good example is the use of dexamethsone for patients with raised intracranial pressure secondary to brain tumours.18y male have delayed pubertal development, despite being 1.77m tall. On examination he has scant pubic hair and reduced testicular volume. Testosterone 6.7 nmol/i (9- 30) LH 3.1 (3-10) FSH 5.7 (3 -10) What is the most likely diagnosis? Klinefelter's syndrome Acute lymphoblastic leukaemia Testicular feminisation syndrome Primary testicular failure Kallman's syndromeKlinefelter's - LH & FSH raised Kallman's - LH & FSH low-normal The LH and FSH levels are inappropriately low-normal given the low testosterone concentration, which points towards a diagnosis of hypogonadotrophic hypogonadism. In Klinefelter's syndrome the LH and FSH levels are raisedWhich one of the following features is least associated with primary hyperparathyroidism? Depression Polydipsia Sensory loss Peptic ulceration HypertensionFeatures - 'bones, stones, abdominal groans and psychic moans' (The PTH level in primary hyperparathyroidism may be normal) polydipsia, polyuria (Chronic hypercalcaemia can compromise the renal concentrating ability leading to polydipsia and polyuria from nephrogenic diabetes insipidus). peptic ulceration /constipation/*pancreatitis* bone pain/fracture ( kyphosis due to osteoporosis) renal stones calculi-induced hydronephrosis Renal impairment *depression* , Confusion hypertension, Short QT syndrome on the ECG Associations ***hypertension* multiple endocrine neoplasia: MEN I and II The association of primary hyperparathyroidism and a gastrinoma would suggest a diagnosis of multiple endocrine neoplasia type 1.A 33-year female with thyrotoxicosis. Following a discussion of management options she elects to have radioiodine therapy. Which one of the following is the most likely adverse effect? Hypothyroidism Thyroid malignancy Agranulocytosis Oesophagitis Precipitation of thyroid eye diseaseIt is well documented that radioiodine therapy can precipitate thyroid eye disease but a majority of patients will eventually require thyroxine replacementH/O gained 10 kg in weight in the past 3 months + early morning sweating & double vision What is the most likely diagnosis?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. rapid weight gain may be seen Patients eat in an attempt to avoid hypoglycaemia and may avoid physical activity because this is also recognised as a trigger. Diagnosis supervised, prolonged fasting (up to 72 hours) If the patient develops symptoms, then a plasma glucose is measured and if low, insulin and C-peptide is then collected and the fast terminated. After a 15 h fast, the cut-off normal limits for glucose are 2.5 mmol/l and 5 mU/l for insulin. By 24 h, fasting leads to a detection rate of 78% for insulinoma. If the fast is extended to 72 h, this detection rate increases to 98%. CT pancreas To exclude possible drug administration, a sulphonylurea screen should be undertaken.What is the mechanism of action of thiazolidinediones?PPAR-gamma receptor agonistWhich one of the following increases the risk of developing peripheral oedema in a patient taking pioglitazone? Concomitant use with gliclazide Serum sodium 140 mmol/ Concomitant use with insulin Concomitant use with metformin Serum potassium < 4.0 mmollConcomitant use with insulin Adverse effects of Thiazolidinediones Weight gain (caused by a combination of fat accumulation and fluid retention). liver impairment: monitor LFTs Fluid retention: therefore contraindicated in heart failure. in 10% of patients, mechanism: by means of an action on the collecting ducts of the kidney so promoting sodium and water retention. The risk of fluid retention is increased if the patient also ***takes insulin , or other drugs that cause fluid retention (for example, NSAIDs, calcium antagonists) increased risk of osteoporotic fractures due to reduced bone mineral density. The underlying mechanism is thought to be due to bone cell precursors differentiating into adipocytes rather than osteoblasts. bladder cancer: recent studies have showed an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64)Each one of the following is associated with pseudohypoparathyroidism, except: Low calcium levels Low PTH levels Shortened 4th and 5th metacarpals Low IQ Short staturePseudohypoparathyroidism is caused by target cell insensitivity to parathyroid hormone (PTH) due to a mutation in alpha subunit of the G-protein. The G-protein-coupled receptor for parathyroid hormone (PTH) becomes unresponsive to the hormone, hence patients become ***hypocalcaemic in the face of normal or elevated PTH levels. Management **Calcium and vitamin D supplementationWhich one of the following conditions is most likely to contradict the prescription of varenicline? Previous or current central nervous system tumour Past history of deliberate self-harm Hypertension Myasthenia gravis ObesityVarenicline Nicotinic receptor partial agonist « Should be started 1 week before the patient target date to stop « The recommended course is 12 weeks (but patients should be monitored regularly and treatment only continued if not smoking) « more effective than bupropion Adverse effect: « the most common SE is Nausea. « Other SE: headache, insomnia, abnormal dreams used with caution in «*** patients with a history of depression or self-harm > risk of suicidal behaviour Contraindicated in « pregnancy and breast feedingA 79-year-old lower back pain and right hip pain. Calcium 2.20 mmol/l Phosphate 0.8 mmol/I ALP 890 u/L What is the most likely diagnosis?Paget's disease - old man, bone pain, raised ALP The normal calcium and phosphate combined with a raised alkaline phosphate points to a diagnosis of Paget's Paget's disease is a disease of increased but uncontrolled bone turnover. It is thought to be primarily a disorder of osteoclasts, with excessive osteoclastic resorption followed by increased osteoblastic activity. Paget's disease is common (UK prevalence 5%) but symptomatic in only 1 in 20 patientstender neck swelling. TSH <0.1 mu/t T4 188 nmol/l ESR 65 mm/hr Technetium thyroid scan shows decreased uptake globally What is the most likely diagnosis? Sick thyroid syndrome Acute bacterial thyroiditis Hashimoto's thyroiditis Subacute thyroiditis Toxic multinodular goitreSubacute thyroiditis is suggested by the tender goitre, hyperthyroidism and raised ESR. The globally reduced uptake on technetium thyroid scan is also typicalSGLT2 inhibitors (gliflozin) SGLT2 inhibitors reversibly inhibit sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion. Examples include canagliflozin, dapagliflozin and empagliflozin Advantages promotes greater weight loss (modest calorie spillage into the urine) there for it is better than gliptins in obese patient who not achieve control by metformin has positive effects on blood pressure control. Sodium loss the most likely cause of the fall in blood pressure some four weeks after therapy initiation. associated with positive cardiovascular outcomes. reduce uric acid, which may over the longer term reduce nephropathy progression Important adverse effects include genital infection (secondary to glycosuria) Due to an increased amount of glucose being secreted in the urine, these medications are ***contra-indicated in patients with recurrent thrush. The increased amount of glucose in the urine is thought to predispose to bacterial growth. diabetic ketoacidosis increased risk of bone fracture SGLT-2 inhibitors ⬆️PTH ⬆️bone turnover ⬆️risk of bone fracture. SGLT-2 inhibitors ⬆️ fibroblast growth factor (FGF-23) ⬇️vitamin D ⬇️ bone mineralisationYou are wanting to assess for diabetic neuropathy affecting the feet. What is the most appropriate screening test to use?Test sensation using a 10 g monofilament Factors associated with an increased risk of plantar ulceration, neuropathy disability score, loss of 10-g monofilament sensation foot deformity However, the *strongest predictive factor with respect to future risk of ulceration is either active ulceration or a history of a previous ulcer. Callus formation at pressure areas is an important predictor of ulceration Plantar ulceration is usually a consequence of neuropathy and minor skin trauma is probably the most common initiating event.Which one of the following statements regarding impaired glucose regulation is correct? All patient should have a repeat oral glucose tolerance test every 2 years Patients with impaired glucose tolerance are more likely to develop diabetes than patients with impaired fasting glycaemia Impaired glucose tolerance (IGT) is defined as a fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l Around 1 in 20 adults in the UK have impaired glucose regulation Patients should be offered pioglitazone if lifestyle changes fail to improve their glucose profilePatients with impaired glucose tolerance are more likely to develop diabetes than patients with impaired fasting glycaemiaA 49-year-old woman with type 2 diabetes mellitus is being considered for exenatide therapy. Which one of the following is not part of the NICE criteria for starting or continuing this drug? BMI > 35 kg/m^2 0% , Greater than 1.0 percentage point HbA1c reduction after 6 months 14% Has failed with insulin therapy 55% Has type 2 diabetes mellitus 7% Weight loss > 3% at 6 months ,Patients do not need to have been on insulin prior to using exenatide Criteria to consider exenatide : if triple therapy is not effective, not tolerated or contraindicated then we consider combination therapy with metformin, a sulfonylurea and a glucagonlike peptide1 (GLP1) mimetic if: BMI >= 35 kg/m² and specific psychological or other medical problems associated with obesity or BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or Weight loss would benefit other significant obesity related comorbidities only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 monthsDiabetes type 2 managementThe best way to reduce the incidence of type 2 diabetes in individuals with IGT is Intensive lifestyle change Tolerates metformin: metformin is still first-line and should be offered if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions if the HbA1c has risen to 58 mmol/mol (7.5%) then a second drug should be added from the following list: sulfonylurea gliptin pioglitazone SGLT-2 inhibitor if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then triple therapy with one of the following combinations should be offered: metformin + gliptin + sulfonylurea metformin + pioglitazone + sulfonylurea metformin + sulfonylurea + SGLT-2 inhibitor metformin + pioglitazone + SGLT-2 inhibitor OR insulin therapy should be considered if triple therapy is not effective, not tolerated or contraindicated then we consider combination therapy with metformin, a sulfonylurea and a glucagonlike peptide1 (GLP1) Cannot tolerate metformin or contraindicated if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions, consider one of the following: sulfonylurea gliptin pioglitazone if the HbA1c has risen to 58 mmol/mol (7.5%) then a one of the following combinations should be used: gliptin + pioglitazone gliptin + sulfonylurea pioglitazone + sulfonylurea if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then consider insulin therapy ***meglitinides (insulin secretagogues) should be considered for patients with an erratic lifestyle **However, you can consider using sitagliptin or a thiazolidinedione instead of insulin if there would be employment (eg: truck driver), social, recreational or personal issues. Exenatide should be used only when insulin would otherwise be started, obesity is a problem (BMI > 35 kg/m^2) and the need for high dose insulin is likely. Continue only if beneficial response occurs and is maintained (> 1.0 percentage point HbA1c reduction and weight loss > 3% at 6 months) In patients with diabetes starting thyroxine, doses of antidiabetic drugs including insulin may need to be increased.H/O (T2DM) & bladder cancer on gliclazide and atorvastatin. A recent trial of metformin was unsuccessful due to gastrointestinal side-effects. He works as an accountant, is a non-smoker his BMI is 31 kg/m². HisHbA1c = 62 mmol/mol (7.8%) What is the most appropriate next step in management?Add sitagliptin (Pioglitazone is contraindicated in bladder cancer and may contribute to his obesity. he does not meet the NICE body mass index criteria of 35 kg/m².)A taxi driver with type 2 DM , on metformin and the dose was titrated up. His HbA1c one year ago was 75 mmol/mol (9%) and is now 69 mmol/mol (8.5%). His BMI 33 kg/m². What is the most appropriate next step in management?Add sitagliptin ( because DPP-4 inhibitors are weight neutral & no risk of hypoglycaemia)Which laboratory test results would be most significantly associated with an increased incidence of cardiovascular disease in type 2 diabetics?Raised proinsulin levelsphaeochromocytoma, Which anti-hypertensive medication should be started first?PHaeochromocytoma - give PHenoxybenzamine before beta-blockers Phenoxybenzamine is a non-selective alpha-adrenoceptor antagonist and should be started before a beta-blocker is introduced There is ongoing debate about the optimal medical management of phaeochromocytoma, with the suggestion that antihypertensive treatment regimes other than non specific alpha-blockade are just as effective and safe. There are however no trials to provide an answer to this question yetA 23-yea-old woman is diagnosed with Graves' disease. Which one of the following statements regarding treatment is correct? Block-and-replace regimes are usually of a shorter duration than carbimazole titration therapy Concurrent administration of propranolol and carbimazole should be avoided Patients on block-and-replace regimes have fewer side-effects than those using titration therapy Carbimazole should be started at no higher than 10mg/day for patients commencing a titration regime In the block-and-replace regime levothyroxine should be started at the same time as carbimazoleBlock-and-replace regimes are usually of a shorter duration than carbimazole titration therapy *TSH is used to assess the response of patient to carbimazole for treating Grave's Treatment options include titration of anti-thyroid drugs (ATDs, for example carbimazole), block-and-replace regimes, radioiodine treatment and surgery. Propranolol is often given initially to block adrenergic effects Propranolol, a nonselective beta blocker, may help to lower the heart rate, control tremor, reduce excessive sweating, and alleviate anxiety. Propranolol is also known to reduce the conversion of T4 to T3. In patients with underlying asthma, beta-1 selective antagonists, such as atenolol or metoprolol, would be safer options. In patients with contraindications to beta blockers (eg, moderate to severe asthma), calcium channel antagonists (eg, diltiazem) may be used to help control the heart rate. ATD titration carbimazole is started at 40mg and reduced gradually to maintain euthyroidism typically continued for 12-18 months Long-term remission following antithyroid drugs is of the order of 15%, with the vast majority relapsing. Thus, frequently, radio-iodine is advocated as a primary treatment -particularly for multi-nodular or toxic solitary nodules. Radioiodine iodine (RAI) treatment contraindications include pregnancy (should be avoided for 4-6 months following treatment) and age < 16 years. Thyroid eye disease is a relative contraindication, as it may worsen the condition Hypothyroidism is the most common adverse effect. the proportion of patients who become hypothyroid depends on the dose given, but as a rule the majority of patient will require thyroxine supplementation after 5 years **approximately 80% will have long-term hypothyroidism following radio-iodine. Goitre shrinkage may occur in up to 30% following RAI. _____________________________________octreotide. What is the mechanism of action of this drug?***Somatostatin analogue Acromegaly is caused by excessive growth hormone. Somatostatin directly inhibits the release of growth hormone, and hence somatostatin analogues are used to treat acromegaly This question is two-fold. First, one has to recognise the symptoms of acromegaly. Carpal tunnel syndrome and sleep apnoea are classic complications of acromegaly. The changing nature of his face over time is another clue. The second part of the question was to acknowledge that octreotide, a useful treatment for acromegaly is a somatostatin analogue. Dopamine agonists were initially used to treat acromegaly but have fallen out of favour due to superior treatments. Dopamine antagonists have never been a treatment for acromegaly. An example of a growth hormone antagonist is pegvisomant. Growth hormone stimulates insulin growth factor-1 release from the liver, but antagonists have not been developed yet.Which one of the following may be associated with galactorrhoea? Primary hypothyroidism Addison's disease Cushing's syndrome Grave's disease BromocriptinePrimary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release) Levels of prolactin < 1000 drug-induced prolactinaemia 1000 -- 3000 mU/l microprolactinoma. > 3000 macroprolactinoma. Levels less than 1000 are most likely to be drug related metoclopramide (most common) Physiological causes (via oestrogen stimulation): Pregnancy Sleep Coitus Stress. ExerciseA T2DM around 10 years ago and currently only takes gliclazide and atorvastatin. Three years ago he was successfully treated for bladder cancer. A recent trial of metformin was unsuccessful due to gastrointestinal side-effects. his BMI is 31 kg/m2. HbAlc 62 mmol/mol (7.8%) What is the most appropriate next step in management? Add pioglitazone Add exenatide Add acarbose Add repaglinide Add sitagliptinAdd sitagliptin Pioglitazone is contraindicated by his history of bladder cancer and may contribute to his obesity. A DPP-4 inhibitor such as sitagliptin is therefore the best option. Exenatide generally causes weight loss and is therefore useful in obese diabetics but he does not meet the NICE body mass index criteria of 35 kg/m2.Where is its main site of action of empagliflozin,?Early proximal convoluted tubule in the normal kidney up to 180 g virtually all of it is reabsorbed in the proximal convoluted tubule. This reabsorption is carried out by two sodium-dependent glucose co-transporter (SGLT) proteins, SGLT1, which reabsorbs 10%, and SGLT2, which reabsorbs the remaining 90%. While SGLT1 is expressed elsewhere in the body, SGLT2 is expressed solely in the kidney, making it an attractive target for novel diabetic treatments. To date a number of SGLT2 inhibitors have been developed. These agents have been shown to enhance renal glucose excretion by inhibiting renal glucose reabsorption with consequent improvements in HbA1C and insulin resistance. Furthermore, they have been shown to have protective effects in the progression of chronic kidney disease, blood pressure lowering effects and reduce cardiovascular events in high risk type ll diabetic patients. To date they are they only oral hypoglycaemic agent to demonstrate any benefit on macrovascular outcomes in type II diabetic patients. Important side effects to be aware of with this class of drug are genital tract infections and euglycaemic diabetic ketoacidosis.Each one of the following is associated with autoimmune polyendocrinopathy syndrome type 1 except: Chronic mucocutaneous candidiasis Addison's disease Primary hyperparathyroidism Autosomal recessive inheritance A mutation of the AIRE1 gene on chromosome 21Primary hyperparathyroidism Autoimmune polyendocrinopathy syndrome (Polyglandular syndrome) Primary HYPOparathyroidism is usually the first endocrine manifestation of type 1 autoimmune POLYendocrinopathy syndrome. While (MEN) hyperparathyroidism is a common finding Autoimmune polyendocrine syndrome is associated with: Hypothyroidism Type 1 diabetes, Addison's disease. APS type 2 Also called (Schmidt's disease) Patients have Addison's disease plus either: 1. type 1 diabetes mellitus 2. autoimmune thyroid disease more common has a polygenic inheritance linked to HLA DR3/DR4. APS type 1 occasionally referred to as Multiple Endocrine Deficiency Autoimmune Candidiasis (MEDAC). It is a very rare autosomal recessive disorder caused by mutation of AIRE1 gene on chromosome 21 usually begins in childhood.Which one of the following medications would increase insulin sensitivity? Repaglinide Tolbutamide Pioglitazone Acarbose GliclazidePioglitazoneA male type 2 diabetes mellitus . 12 months ago he was started on metformin and the dose was titrated up. His IFCC-HbA1c one year ago HbA1c 9.96) and is now (8.596). His body mass index is 33 kg/m2. What is the most appropriate next step in management? Add exenatide Add sitagliptin Add glipizide Make no changes to his medication Add insulinHis HbA1c is still significantly above target so some change to the medication is indicated. The NICE type 2 diabetes mellitus guidelines would generally advocate the use of a sulfonylurea in this situation. However. the patient is a taxi driver and overweight. A DPP-4 inhibitor such as sitagliptin would be ideal in this situation. There is no risk of hypoglycaemia and they DPP-4 inhibitors are weight neutral.A 56-year-old Muslim man with a history of type 2 diabetes asks for advice. He is due to start fasting for Ramadan soon and is unsure what he should do with regards to his diabetes medications. He currently takes metformin 500mg tds. What is the most appropriate advice? Switch to subcutaneous biphasic insulin for the duration of Ramadarn 500 mg at the predawn meal1000 mg at the sunset meal No change to the metformin dose 1000 mg at the predawn meal 500 mg at the sunset meal Stop metformin for the duration of Ramadan500 mg at the predawn meal + 1000 mg at the sunset meal During Ramadan, one-third of the normal metformin dose should be taken before sunrise and two-thirds should be taken after sunset If a patient with type 2 diabetes mellitus does decide to fast: they should try and and eat a meal containing long-acting carbohydrates prior to sunrise (Suhoor) patients should be given a blood glucose monitor to allow them to check their glucose levels, particularly if they feel unwell for patients taking metformin the expert consensus is that the dose should be split onethird before sunrise (Suhoor) and two-thirds after sunset (Iftar) expert consensus also recommends switching once-daily sulfonylureas to after sunset. For patients taking twice-daily preparations such as gliclazide it is recommended that a larger proportion of the dose is taken after after sunset no adjustment is needed for patients taking pioglitazoneA 29-year-old pregnant for the second time . Her first pregnancy was complicated by gestational diabetes. Following her first pregnancy she was told she was no longer diabetic. What is the most appropriate management? Check HbA1c immediately Start metformin and ask the woman to self-monitor glucose Do oral glucose tolerance test as soon as possible after booking Do oral glucose tolerance test at 16-18 weeks Do oral glucose tolerance test at 24-28 weeksNICE have recently updated their guidelines. Women who are at risk of gestational diabetes should have an oral glucose tolerance test as soon as possible after booking, rather than waiting to 16-18 weeks as was previously advocatedWhich one of the following statements regarding glucagon-like peptide-1 (GLP-1) is incorrect? Secreted in response to an oral glucose load Increased levels are seen in type 2 diabetes mellitus Slows gastric emptying Secreted by the small intestine Responsible for the incretin effectDecreased levels of GLP-1 are seen in type 2 diabetes mellitus Glucagon-like peptide-1 (GLP-1) mimetics (e.g. exenatide) - causes vomiting GLP analogs such as exenatide, liraglutide, slow gastric emptying, promote weight loss and lower glucose Metabolic effect of exenatide increase insulin secretion inhibit glucagon secretion. inhibits glucose production in the liver, slows gastric emptying Suppresses appetite When to choose exenatide as an alternative to insulin or sulphonylurea as first choice add-in options to metformin? morbid obesity or risk of hypoglycaemia, (eg : HGV drivers) Both sitagliptin and exenatide are not recommended in patients sever renal impairment, and metformin is contraindicated. Liraglutide is the other GLP-1 mimetic currently available. One the main advantages of liraglutide over exenatide is that it only needs to be given once a day. It is a particularly useful medication as it can be used in renal impairment with an estimated glomerular filtration rate [eGFR] as low as 30 mL/min/1.73 m2. weight loss of approximately 6% at 6 months can be achieved with liraglutide 1.8 mg. Liraglutide is associated with an approximately 7 beats per minute increase in heart rate versus control in diabetes Dapagliflozin, tolbutamide, gliclazide and metformin are all contraindicated in renal impairment. Both exenatide and liraglutide may be combined with metformin and a sulfonylurea. Standard release exenatide is also licensed to be used with basal insulin alone or with metformin. Combination of GLP-1 and DPP- 4 inhibitors trials of DPP- 4 inhibitor and GLP-1 together suggest no added efficacy versus GLP-1 alone. Adding a GLP-1 analogue has the advantage of improving glycaemic control, with modest weight loss, without increasing the risk of hypoglycaemia compared with uptitration of insulin. Current NICE guidance suggests the use of GLP-1 mimetics only if BMI is above 35 and there are specific medical or psychological problems associated with high body weight.Which of the following statements is true regarding the pathophysiology of diabetes mellitus? Concordance between identical twins is higher in type 2 diabetes mellitus than type 1 Patients with type 1 diabetes mellitus are rarely HLA-DR4 positive Type 2 diabetes mellitus is associated with HLA-DR3 Haemochromatosis is an example of primary diabetes Type 1 diabetes mellitus is thought to be inherited in an autosomal dominant fashionType 1 diabetes mellitus is caused by autoimmune destruction of the Beta-cells of the pancreas. Identical twins show a genetic concordance of 40%. It is associated with HLA-DR3 and DR4. It is inherited in a polygenic fashion Type 2 diabetes mellitus is thought to be caused by a relative deficiency of insulin and the phenomenon of insulin resistance. Age, obesity and ethnicity are important aetiological factors. There is almost 100% concordance in identical twins and no HLA associations. Haemochromatosis is an example of secondary diabetesWhich one of the following features would most suggest a diagnosis of Grave's disease? Atrial fibrillation Lid lag Family history of radioiodine treatment Pretibial myxoedema Multinodular goitrePretibial myxoedema is not seen in other causes of thyrotoxicosis and points towards a diagnosis of Graves'gained 10 kg in weight in the past 3 months but her main problem is episodic sweating associated with double vision and typically occur early in the morning. What is the most likely diagnosis? Bronchial carcinoid Hashimoto's thyroiditis Menopause Cushing's syndrome InsulinomaThis is a typical presentation of insulinomaWhich one of the following statements regarding the management of diabetes mellitus during pregnancy is incorrect? A previous macrosombb riak factorfstatonal diabates Diabetes complicates around 1 in 40 pregnancies A higher dose of folic acid (5 mg/day) should be used Metformin is contraindicated Tight glycaemic control reduces complication ratesThere is increasing evidence that metformin is safe during pregnancyThe first-line treatment in remnant hyperlipidaemia (dysbetalipoproteinaemia) is: Ursodeoxycholic acid Vitamin A Statins Fish oil FibratesFibrates Remnant hyperlipidaemia (type III) rare cause of mixed hyperlipidaemia (raised cholesterol and triglyceride levels) A significantly elevated TG, despite normal VLDL and chylomicron concentrations, simply implies increased concentrations of IDL and chylomicron remnants. This can be due to apoE deficiency which results in the accumulation of IDL and chylomicron remnants in the plasma. Normally, these particles have apoE on the surface through which they are taken up by the liver. yellow palmar creases (palmar xanthoma is diagnostic ) Diagnosis Definitive diagnosis can be made by lipoprotein electrophoresis or genotyping of apoprotein Management fibrates are first line treatmentAn insulin stress test is most useful in the investigation of: Glucagonoma Insulinoma Addison's disease Hypopituitarism Diabetes mellitusHypopituitarism Insulin stress tests are also occasionally used to differentiate Cushing's from pseudo-Cushing'snine month history of weight gain. Prior to this he was of a normal weight and cannot identify any obvious lifestyle changes that would account for his obesity. On examination he is noted to have abdominal striae and a degree of proximal myopathy. Blood pressure is 130/80 mmHg. K : 3.3 What is the most appropriate next test? High-dose dexamethasone suppression test Plasma ACTH Short ACTH test 24 hour urinary free cortisol Renin:aldosterone ratio24 hour urinary free cortisol The overnight dexamethasone suppression test is the best test to diagnosis Cushing's syndrome There is some debate as to whether a 24 hour urinary free cortisol or an overnight dexamethasone suppression test should be used to screen patients for Cushing's. The overnight (not high-dose) dexamethasone suppression test has however been shown to be more sensitive and is now much more commonly used in clinical practice. As this is not offered then 24 hour urinary free cortisol is the next best answer The high-dose dexamethasone suppression test is used to help differentiate the cause of Cushing's syndromeWhich of the following can interfere with testing for primary hyperaldosteronism? Digoxin Amlodipine Ivabradine Bisoprolol RamiprilThe answer here is ramipril. The reason behind this is due to its interference with the renin-angiotensin-aldosterone system, for which the other medications do not. Medications that can cause false negative renin:aldosterone ratio results are the following: « Angiotensin-converting enzyme inhibitors (e.g. ramipril or lisinopril). * Angiotensin receptor blockers (e.g. losartan). « Direct renin inhibitors (e.g aliskiren). « Aldosterone antagonists (e.g. spironolactone or eplerenone).woman facial hirsutism. suspected (PCOS). Which one of the following features would suggest the need for further investigations before confidently making a diagnosis of PCOS? Clitoromegaly Acanthosis nigricans Obesity Amenorrhoea AcneClitoromegaly is seen occasionally in PCOS but is normally associated with very high androgen levels. If clitoromegaly is found then further investigations to exclude an ovarian or adrenal androgen secreting tumour are required.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 Ketones 1+ in urine Serum osmolality of 310 mosmol/kg Serum bicarbonate of 19 mmol/ Glucose of 45 mmol/lA trace of ketones may be found in hyperosmolar hyperglycaemic state. Serum osmolality is typically > 320 mosmol/kg Hyperosmolar hyperglycaemic state (HHS) is confirmed by: « Dehydration * Osmolality>320 * Hyperglycaemia >30 mmol/L with pH >7.3, bicarbonate >15mmolL and no significant ketonenaemia <3mmol/LA 56-year-old female is admitted to ITU with a severe pneumonia. Thyroid function tests are most likely to show:TSH normal / low; thyroxine low; T3 low In sick euthyroid syndrome (now referred to as non-thyroidal illness) it is often said that everything (TSH, thyroxine and T3) is low. In the majority of cases however the TSH level is within the normal range (inappropriately normal given the low thyroxine and T3). Changes are reversible upon recovery from the systemic illness.right-sided hearing loss and left-sided bony hip pain. Blood results show ALP 440 Calcium2.20 mmol/ Phosphate 1.05 mmol/l Total Protein 65 g/ What is the most appropriate initial management step in the treatment of this condition? Risedronate Teriparatide Prednisolone Vitamin D CalcitoninThe constellation of bony pain, unilateral hearing loss, and an isolated raised ALP should point you in the direction of Paget's disease of the bone. In symptomatic Paget's disease, treatment is with a nitrogen-containing bisphosphonate such as alendronate, risedronate, or zoledronic acid. In patients who cannot tolerate these, calcitonin is second-line therapy Unless contraindicated, all patients on bisphosphonates should be given calcium and Vitamin D to avoid symptomatic hypocalcaemia of There is no role for prednisolone in the treatment of Paget's disease of the bone. Teriparatide is a recombinant form of human parathyroid hormone (PTH) that may be used in the treatment of osteoporosisA 34-year-old female with Addison's disease complains of a decrease in her libido. On examination there is a slight loss of pubic hair. What is the most likely cause?Dehydroepiandrosterone (DHEA) is the most abundant circulating adrenal steroid. Adrenal glands are the main source of dehydroepiandrosterone in females - loss of functioning adrenal tissue as in Addison's disease may result in symptoms secondary to androgen deficiency, such as loss of libido. Research is ongoing as to whether routine replacement of DHEA is beneficialAt which point in the menstrual cycle do progesterone levels peak?Luteal phase Progesterone is secreted by the corpus luteum following ovulation.-woman with known ovarian cancer |What is the most likely cause of her elevated calcium? Osteolytic hypercalcaemia Calcitriol-mediated hypercalcaemia Ectopic PTH secretion Parathyroid-hormone-related peptide release Primary hyperparathyroidismThe correct answer is parathyroid-hormone-related peptide release. Whilst this is classically described as secondary to squamous cell lung cancer, it can occur in many malignancies.The two most common causes of hypercalcaemia are malignancy and primary hyperparathyroidism. In malignancy, roughly 80% of cases are due to parathyroid-hormone-related peptide release. The vast majority of remaining cases are due to osteolysis, and some due to calcitriol-mediated hypercalcaemia and ectopic PTH secretion. Primary hyperparathyroidism is another common cause but is not as likely as malignant hypercalcaemia given the known diagnosis of ovarian cancer.A 67-year-old man who has a history of type 2 diabetes mellitus and benign prostatic hypertrophy presents with burning pain in his feet. He has tried taking duloxetine but unfortunately has received no benefit. What is the most suitable initial management? Carbamazepine Amitriptyline Pregabalin Fluoxetine Sodium valproatePregabalin Amitriptyline would normally be first choice but given his history of benign prostatic hyperplasia it is better to avoid amitriptyline due to the risk of urinary retention. Diabetic neuropathy is now managed in the same way as other forms of neuropathic pain: first-line treatment: amitriptyline, duloxetine, gabapentin or pregabalin **Duloxetine is preferred to amitryptiline because it is associated with a lower risk of urinary retention. Duloxetine is first line therapy for neuropathy except where it is contraindicated due to a history of glaucoma or previous hypersensitivity. Amitriptyline is recommended by NICE as an option for second line therapy in patients for whom home duloxetine is unsuitable. Doses of 10-75 mg amitriptyline are usually appropriate, but again is contraindicated here due to history of glaucoma. *** Pregabalin or gabapentin can be considered as second or third line monotherapy or in combination. However where there is renal impairment, pregabalin is preferable over gabapentin. if the first-line drug treatment does not work try one of the other 3 drugsA 45-year-old co lethargy and reduced libido. Have also reduced sexual drive. Testosterone 5.4 nmol/L (>9.0) Subsequent blood tests show : Prolactin 450 (< 400) Cortisol 120 (130-690)(, FSH 0.8 (1-8) What is the most likely diagnosis?Non-functioning pituitary adenoma Non-functioning pituitary tumours present with hypopituitarism and pressure effects Whilst the prolactin level is slightly raised this can be caused by the pressure effects of the tumour preventing dopamine (which inhibits prolactin release) from reaching the normal prolactin-producing cells. Much higher levels would be expected with a prolactinoma.Which one of the following hormones is under continuous inhibition? Growth hormone Prolactin Gonadotropin releasing hormone Thyroid releasing hormone Adrenocorticotrophic hormoneProlactin - under continuous inhibition Prolactin is unique amongst the pituitary hormones in being tonically inhibited by the hypothalamusEach one of the following is seen in Klinefelter's syndrome, except: Small, firm testes Lack of secondary sexual characteristics Infertility Increased incidence of breast cancer Reduced gonadotrophin levelsReduced gonadotrophin levelsA 15-year-old girl have primary amenorrhoea, developed secondary sexual characteristics at 11 years of age. On examination she has well developed breasts with scanty pubic hair and small bilateral groin swellings. What is the most likely diagnosis?Androgen insensitivity syndrome (new term for testicular feminisation syndrome) The presence of breast development in the absence of secondary sexual hair, with a history of hernias as a child is suggestive of a diagnosis of androgen insensitivity syndrome. It is likely that the hernias were related to undescended testes. The vagina is blind ended, and there are no ovaries. X-linked recessive due to end-organ resistance to testosterone causing genotypically male children (46XY) to have a female phenotype. Features primary amennorhoea ***undescended testes causing groin swellings, Cryptorchidism (absence of one or both testes from the scrotum) External genitalia ranges from normal female, to female with cliteromegaly, to under-developed male (hypospadias). ***Associated with abdominal hernias. ***breast development may occur as a result of conversion of testosterone to oestradiol The feminisation is a consequence of: increased testicular secretion of oestradiol peripheral conversion of androgens to oestradiol. Elevated LH levels. Diagnosis buccal smear or chromosomal analysis to reveal 46XY genotype Management counselling - raise child as female bilateral orchidectomy (increased risk of testicular cancer due to undescended testes) oestrogen therapyAn 81-year female history dysphagia to both solids and liquids. She describes odynophagia, weight loss and night sweats. On examination firm irregular mass in the right side of the anterior triangle of the neck. It was fixed, cold and painless. The mass moved with swallowing and you note a faint stridor like sound on inspiration. There was a further 3 irregular lymph nodes of note on palpation. An ultrasound-guided biopsy is likely to reveal which histological tumour?Anaplastic Anaplastic thyroid cancer is a highly aggressive, locally invasive tumour. It typically presents in older patients with a rapidly increasing mass or lymph node.. Anaplastic tumours invades local surrounding tissues causing compression symptoms including: pain, shortness of breath and dysphagia. The aggression of the tumour often leads to lymphovascular invasion and subsequent bone and lung metastasis. The cancer originates from follicular cells, which are poorly differentiated and have a high mitotic rate. The prognosis is poor with a 5-year survival rate quoted between 7% and 14%. Treatment is usually palliative, with a combination of radiotherapy and chemotherapy.Plasma glucose and calcium are normal. A water deprivation test is performed with the following results: Starting plasma osm. 319 (275-295 mOsmol/l) Final urine osm. 142 Urine osm. post-DDAVP 885 What is the most likely diagnosis?Water deprivation test (A dramatic improvement in the ability of the kidneys to concentrate urine following the administration of DDAVP points towards a diagnosis of cranial diabetes insipidus) Method prevent patient drinking water patients are deprived of fluids for a period of 8 h or until 5% of body weight is lost. ask patient to empty bladder Patients should be weighed hourly. hourly urine and plasma osmolalities Plasma osmolality is measured 4-hourly, with urine volume and osmolality measurements occurring every 2 h. The patient is then given 2 μg intramuscular (i/m) desmopressin with urine volume and urine and serum osmolality measured over the next 4 h. If serum osmolality rises above 305 , then the patient is said to have diabetes insipidus and the test is stopped. Urine osmolality less than 300 after fluid deprivation, rising to above 800 mOsmol/kg after desmopressin indicates cranial diabetes insipidus (DI). Urine osmolality less than 300, remaining at less than 300 mOsmol/kg after desmopressin indicates nephrogenic DI. Where urine osmolality reaches levels above 800 without desmopressin, then the diagnosis is primary polydipsia. Where urine osmolality is intermediate (300-800), and fails to rise above 800 after demopressin, the diagnosis may be partial DI or polydipsia. Psychogenic polydipsia Patients with this disorder ingest and excrete up to 6L of fluid/day and are often emotionally disturbed. they do not have nocturia, nor does increased thirst wake them at night.DKA Pt 'weighs 80 kg What rate should insulin be initially given?8 unit / hr starting the insulin infusion at a rate of 0.1 unit/kg/hour.What is the most significant risk of prescribing an oestrogen-only preparation rather than a combined oestrogen-progestogen preparation?Increased risk of endometrial cancer HRT: unopposed oestrogen increases risk of endometrial cancerWhich one of the following statements regarding the normal menstrual cycle is incorrect? A number of follicles develop in the follicular phase under the influence of FSH The luteal phase is also known as the secretory phase The follicular phase follows menstruation and occurs around day 5-13 A surge of FSH causes ovulation Progesterone levels are low in the follicular phaseLH surge causes ovulationEach one of the following is a feature of pseudohypoparathyroidism, except: Short fourth and fifth metacarpals Round face Normal calcium and phosphate levels Cognitive impairment Short statureNormal calcium and phosphate levelsA 27-year-old female develops eye pain and reduced visual acuity following the initiation of treatment for her recently diagnosed Grave's disease.Radioiodine treatment may lead to the development / worsening of thyroid eye disease in up to 15% of patients with Grave's diseaseLiddle's syndrome is associated with each one of the following, except: Alkalosis Response to treatment with amiloride Hypertension Hypokalaemia Autosomal recessive inheritanceLiddle'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.Young pt have HTN Serum potassium 1.9 mmol/L (3.5-5.0) Plasma aldosterone (after 30 minutes supine) 700 pmol/L (135-400) Plasma renin activity (after 30 minutes supine) 0.4 pmol/mL/hr (1.1-2.7) What is the most likely cause of his hypertension? Addison disease Bilateral renal artery stenosis Coarctation of the aorta Phaeochromocytoma Primary hyperaldosteronismPrimary hyperaldosteronism is typically caused by an aldosterone producing adenoma (Conn's syndrome), other causes include: bilateral adrenocortical hyperplasia and adrenal carcinoma. Primary hyperaldosteronism and bilateral renal artery stenosis are associated with hypokalaemia due raised serum aldosterone, which causes increased sodium reabsorption and potassium excretion. Aldosterone is elevated in bilateral renal artery stenosis due to reduced renal perfusion. Adosterone is high in primary hyperaldosteronism, however, serum renin is usuaily low primary hyperaldosteronism due to the resulting hypertension causing excessive renal perfusion, which results in decreased renin production (negative feedback mechanism). High renin levels are seen in renal artery stenosis as renal perfusion is permanently reduced, despite hypertension, due to the stenotic renal arteries.