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Question 1
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Whilst an inpatient for a chest infection, a 65-year-old man is seen by the hospital's diabetic specialist nurse. Despite trying various medications, his diabetic control has been generally inadequate. His latest blood test shows his HbA1c to still be above the normal range. The specialist nurse decides to initiate a new medication and advises the GP to review with a repeat blood test in a few months. The patient is cautioned about severe adverse effects, particularly Fournier gangrene.
What is the mechanism of action of the prescribed medication?Your Answer: Activates peroxisome proliferator-activated receptor-gamma
Correct Answer: Inhibits sodium-glucose co-transporter 2
Explanation:SGLT-2 inhibitors work by inhibiting the sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule. This class of drugs includes empagliflozin and dapagliflozin and can lead to weight loss. However, they may also cause urinary/genital infections and normoglycaemic ketoacidosis. Fournier gangrene is a known serious adverse effect of this drug class.
Thiazolidinedione drugs, such as pioglitazone, activate peroxisome proliferator-activated receptor-gamma (PPAR gamma). This receptor complex affects various target genes, ultimately decreasing insulin resistance and causing other effects.
Sulfonylureas, like gliclazide, block ATP-sensitive potassium channels. These drugs may cause weight gain and induce hypoglycaemia.
GLP-1 mimetics, including exenatide, activate glucagon-like peptide 1 receptors. This relatively new class of drug can lead to weight loss but is not widely used in diabetic guidelines.
DPP4 inhibitors, such as sitagliptin and linagliptin, work by inhibiting dipeptidyl peptidase-4 (DPP4). This ultimately leads to increased levels of incretin circulation, similar to GLP-1 mimetics.
Understanding SGLT-2 Inhibitors
SGLT-2 inhibitors are medications that work by blocking the reabsorption of glucose in the kidneys, leading to increased excretion of glucose in the urine. This mechanism of action helps to lower blood sugar levels in patients with type 2 diabetes mellitus. Examples of SGLT-2 inhibitors include canagliflozin, dapagliflozin, and empagliflozin.
However, it is important to note that SGLT-2 inhibitors can also have adverse effects. Patients taking these medications may be at increased risk for urinary and genital infections due to the increased glucose in the urine. Fournier’s gangrene, a rare but serious bacterial infection of the genital area, has also been reported. Additionally, there is a risk of normoglycemic ketoacidosis, a condition where the body produces high levels of ketones even when blood sugar levels are normal. Finally, patients taking SGLT-2 inhibitors may be at increased risk for lower-limb amputations, so it is important to closely monitor the feet.
Despite these potential risks, SGLT-2 inhibitors can also have benefits. Patients taking these medications often experience weight loss, which can be beneficial for those with type 2 diabetes mellitus. Overall, it is important for patients to discuss the potential risks and benefits of SGLT-2 inhibitors with their healthcare provider before starting treatment.
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This question is part of the following fields:
- Endocrine System
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Question 2
Correct
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A 25-year-old woman has a total thyroidectomy to treat papillary carcinoma of the thyroid. During examination of histological sections of the thyroid gland, the pathologist discovers the presence of psammoma bodies. What is the primary composition of these bodies?
Your Answer: Clusters of calcification
Explanation:Clusters of microcalcification, known as psammoma bodies, are frequently observed in papillary carcinomas.
Thyroid cancer rarely causes hyperthyroidism or hypothyroidism as it does not usually secrete thyroid hormones. The most common type of thyroid cancer is papillary carcinoma, which is often found in young females and has an excellent prognosis. Follicular carcinoma is less common, while medullary carcinoma is a cancer of the parafollicular cells that secrete calcitonin and is associated with multiple endocrine neoplasia type 2. Anaplastic carcinoma is rare and not responsive to treatment, causing pressure symptoms. Lymphoma is also rare and associated with Hashimoto’s thyroiditis.
Management of papillary and follicular cancer involves a total thyroidectomy followed by radioiodine to kill residual cells. Yearly thyroglobulin levels are monitored to detect early recurrent disease. Papillary carcinoma usually contains a mixture of papillary and colloidal filled follicles, while follicular adenoma presents as a solitary thyroid nodule and malignancy can only be excluded on formal histological assessment. Follicular carcinoma may appear macroscopically encapsulated, but microscopically capsular invasion is seen. Medullary carcinoma is associated with raised serum calcitonin levels and familial genetic disease in up to 20% of cases. Anaplastic carcinoma is most common in elderly females and is treated by resection where possible, with palliation achieved through isthmusectomy and radiotherapy. Chemotherapy is ineffective.
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This question is part of the following fields:
- Endocrine System
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Question 3
Correct
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A 12-year-old girl, previously healthy, presents to the emergency department with symptoms of nausea, vomiting, and confusion. The patient's father reports his child appearing fatigued, and having increased thirst and urinary frequency over the past few days. Upon laboratory analysis, the patient's serum glucose is found to be 25 mmol/L and urinalysis is positive for ketones. The medical team initiates fluid resuscitation and insulin therapy.
What electrolyte changes are anticipated following the treatment of this patient?Your Answer: Decrease in potassium levels
Explanation:The Na+/K+ ATPase pump is stimulated by insulin, leading to a decrease in serum potassium levels. This effect is particularly relevant in patients with diabetic ketoacidosis, who experience insulin deficiency and hyperkalemia. It is important to monitor serum potassium levels closely during the management of diabetic ketoacidosis to avoid the potential complications of hypokalemia. Insulin does not cause a decrease in sodium levels, and its effects on calcium and phosphate homeostasis are minimal. The resolution of ketoacidosis with insulin and fluids will result in an increase in serum bicarbonate levels back to normal range.
Insulin is a hormone produced by the pancreas that plays a crucial role in regulating the metabolism of carbohydrates and fats in the body. It works by causing cells in the liver, muscles, and fat tissue to absorb glucose from the bloodstream, which is then stored as glycogen in the liver and muscles or as triglycerides in fat cells. The human insulin protein is made up of 51 amino acids and is a dimer of an A-chain and a B-chain linked together by disulfide bonds. Pro-insulin is first formed in the rough endoplasmic reticulum of pancreatic beta cells and then cleaved to form insulin and C-peptide. Insulin is stored in secretory granules and released in response to high levels of glucose in the blood. In addition to its role in glucose metabolism, insulin also inhibits lipolysis, reduces muscle protein loss, and increases cellular uptake of potassium through stimulation of the Na+/K+ ATPase pump.
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This question is part of the following fields:
- Endocrine System
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Question 4
Incorrect
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A 38-year-old woman is diagnosed with hyperthyroidism and started on carbimazole. What is the mechanism of action of this medication?
Your Answer: Prevents thyroxine (T4) conversion to triiodothyronine (T3)
Correct Answer: Prevents iodination of the tyrosine residue on thyroglobulin
Explanation:Carbimazole is a medication used to treat thyrotoxicosis, a condition where the thyroid gland produces too much thyroid hormone. It is usually given in high doses for six weeks until the patient’s thyroid hormone levels become normal, after which the dosage is reduced. The drug works by blocking thyroid peroxidase, an enzyme that is responsible for coupling and iodinating the tyrosine residues on thyroglobulin, which ultimately leads to a reduction in thyroid hormone production. In contrast, propylthiouracil has a dual mechanism of action, inhibiting both thyroid peroxidase and 5′-deiodinase, which reduces the peripheral conversion of T4 to T3.
However, carbimazole is not without its adverse effects. One of the most serious side effects is agranulocytosis, a condition where the body’s white blood cell count drops significantly, making the patient more susceptible to infections. Additionally, carbimazole can cross the placenta and affect the developing fetus, although it may be used in low doses during pregnancy under close medical supervision. Overall, carbimazole is an effective medication for managing thyrotoxicosis, but its potential side effects should be carefully monitored.
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This question is part of the following fields:
- Endocrine System
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Question 5
Correct
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A 55-year-old woman comes to her doctor complaining of fatigue, difficulty passing stool, and muscle weakness. Her lab results show:
Free T4 6 pmol/l (9-18 pmol/l)
TSH 7.2 mu/l (0.5-5.5 mu/l)
Based on the probable diagnosis, which of the following tests is most likely to be positive in this patient?Your Answer: Anti-thyroid peroxidase (anti-TPO) antibodies
Explanation:Rheumatoid factor is not the most suitable answer for a patient with hypothyroidism, despite its presence in various rheumatological conditions and healthy individuals.
Understanding Thyroid Autoantibodies
Thyroid autoantibodies are antibodies that attack the thyroid gland, causing various thyroid disorders. There are three main types of anti-thyroid autoantibodies: anti-thyroid peroxidase (anti-TPO) antibodies, TSH receptor antibodies, and thyroglobulin antibodies. Anti-TPO antibodies are present in 90% of Hashimoto’s thyroiditis cases and 75% of Graves’ disease cases. TSH receptor antibodies are found in 90-100% of Graves’ disease cases. Thyroglobulin antibodies are present in 70% of Hashimoto’s thyroiditis cases, 30% of Graves’ disease cases, and a small proportion of thyroid cancer cases.
Understanding the different types of thyroid autoantibodies is important in diagnosing and treating thyroid disorders. Hashimoto’s thyroiditis and Graves’ disease are the most common autoimmune thyroid disorders, and the presence of specific autoantibodies can help differentiate between the two. Additionally, monitoring the levels of these antibodies can help track the progression of the disease and the effectiveness of treatment. Overall, understanding thyroid autoantibodies is crucial in managing thyroid health.
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This question is part of the following fields:
- Endocrine System
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Question 6
Incorrect
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As a medical student in community care, while shadowing a health visitor, I observed her measuring the height and weight of children to monitor their growth. What factors drive growth during the developmental stage of 4 to 10 years old?
Your Answer: Nutrition and growth hormones
Correct Answer: Growth and thyroid hormones
Explanation:Understanding Growth and Factors Affecting It
Growth is a significant difference between children and adults, and it occurs in three stages: infancy, childhood, and puberty. Several factors affect fetal growth, including environmental, placental, hormonal, and genetic factors. Maternal nutrition and uterine capacity are the most crucial environmental factors that affect fetal growth.
In infancy, nutrition and insulin are the primary drivers of growth. High fetal insulin levels result from poorly controlled diabetes in the mother, leading to hypoglycemia and macrosomia in the baby. Growth hormone is not a significant factor in infancy, as babies have low amounts of receptors. Hypopituitarism and thyroid have no effect on growth in infancy.
In childhood, growth is driven by growth hormone and thyroxine, while in puberty, growth is driven by growth hormone and sex steroids. Genetic factors are the most important determinant of final adult height.
It is essential to monitor growth in children regularly. Infants aged 0-1 years should have at least five weight recordings, while children aged 1-2 years should have at least three weight recordings. Children older than two years should have annual weight recordings. Children below the 2nd centile for height should be reviewed by their GP, while those below the 0.4th centile for height should be reviewed by a paediatrician.
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This question is part of the following fields:
- Endocrine System
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Question 7
Incorrect
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A 42-year-old woman complains of fatigue after experiencing flu-like symptoms two weeks ago. Upon examination, she has a smooth, small goiter and a pulse rate of 68 bpm. Her lab results show a Free T4 level of 9.3 pmol/L (normal range: 9.8-23.1) and a TSH level of 49.3 mU/L (normal range: 0.35-5.50). What additional test would you perform to confirm the diagnosis?
Your Answer: TSH receptor antibodies
Correct Answer: Thyroid peroxidase (TPO) antibodies
Explanation:Diagnosis and Management of Primary Hypothyroidism
The patient’s test results indicate a case of primary hypothyroidism, characterized by low levels of thyroxine (T4) and elevated thyroid-stimulating hormone (TSH). The most likely cause of this condition is Hashimoto’s thyroiditis, which is often accompanied by the presence of thyroid peroxidase antibodies. While the patient has a goitre, it appears to be smooth and non-threatening, so a thyroid ultrasound is not necessary. Additionally, a radio-iodine uptake scan is unlikely to show significant uptake and is therefore not recommended. Positive TSH receptor antibodies are typically associated with Graves’ disease, which is not the likely diagnosis in this case. For further information on Hashimoto’s thyroiditis, patients can refer to Patient.info.
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This question is part of the following fields:
- Endocrine System
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Question 8
Incorrect
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Which one of the following does not trigger insulin secretion?
Your Answer: Gastrin
Correct Answer: Atenolol
Explanation:The release of insulin is prevented by beta blockers.
Factors that trigger insulin release include glucose, amino acids, vagal cholinergic stimulation, secretin/gastrin/CCK, fatty acids, and beta adrenergic drugs.
Insulin is a hormone produced by the pancreas that plays a crucial role in regulating the metabolism of carbohydrates and fats in the body. It works by causing cells in the liver, muscles, and fat tissue to absorb glucose from the bloodstream, which is then stored as glycogen in the liver and muscles or as triglycerides in fat cells. The human insulin protein is made up of 51 amino acids and is a dimer of an A-chain and a B-chain linked together by disulfide bonds. Pro-insulin is first formed in the rough endoplasmic reticulum of pancreatic beta cells and then cleaved to form insulin and C-peptide. Insulin is stored in secretory granules and released in response to high levels of glucose in the blood. In addition to its role in glucose metabolism, insulin also inhibits lipolysis, reduces muscle protein loss, and increases cellular uptake of potassium through stimulation of the Na+/K+ ATPase pump.
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This question is part of the following fields:
- Endocrine System
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Question 9
Incorrect
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A 44-year-old man has been diagnosed with type II diabetes mellitus but cannot tolerate metformin therapy. What is the mechanism of action of alogliptin, which has been prescribed as an alternative?
Your Answer: Directly stimulates the release of insulin from pancreatic beta cells
Correct Answer: Reduce the peripheral breakdown of incretins
Explanation:Gliptins (DPP-4 inhibitors) work by inhibiting the enzyme DPP-4, which reduces the breakdown of incretin hormones such as GLP-1. This leads to a glucose-dependent increase in insulin secretion and a reduction in glucagon secretion, ultimately regulating glucose homeostasis. However, gliptins do not increase the production of GLP-1, directly stimulate the release of insulin from pancreatic beta cells, inhibit the SGLT2 receptor, or reduce insulin resistance.
Diabetes mellitus is a condition that has seen the development of several drugs in recent years. One hormone that has been the focus of much research is glucagon-like peptide-1 (GLP-1), which is released by the small intestine in response to an oral glucose load. In type 2 diabetes mellitus (T2DM), insulin resistance and insufficient B-cell compensation occur, and the incretin effect, which is largely mediated by GLP-1, is decreased. GLP-1 mimetics, such as exenatide and liraglutide, increase insulin secretion and inhibit glucagon secretion, resulting in weight loss, unlike other medications. They are sometimes used in combination with insulin in T2DM to minimize weight gain. Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as vildagliptin and sitagliptin, increase levels of incretins by decreasing their peripheral breakdown, are taken orally, and do not cause weight gain. Nausea and vomiting are the major adverse effects of GLP-1 mimetics, and the Medicines and Healthcare products Regulatory Agency has issued specific warnings on the use of exenatide, reporting that it has been linked to severe pancreatitis in some patients. NICE guidelines 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.
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This question is part of the following fields:
- Endocrine System
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Question 10
Incorrect
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A 26-year-old woman with a history of type 1 diabetes mellitus and borderline personality disorder is brought to the emergency department by ambulance due to a decreased level of consciousness. She is currently on regular insulin. Upon examination, her Glasgow coma scale is 3/15. The venous blood gas results show a pH of 7.36 (7.35-7.45), K+ of 3.8 mmol/L (3.5-4.5), Na+ of 136 mmol/L (135-145), glucose of 1.2 mmol/L (4.0-7.0), HCO3- of 23 mmol/L (22-26), and Hb of 145 g/dL (12.1-15.1). What is the first hormone to be secreted in response to the likely diagnosis?
Your Answer: Cortisol
Correct Answer: Glucagon
Explanation:The correct answer is Glucagon, as it is the first hormone to be secreted in response to hypoglycaemia. The patient’s reduced level of consciousness is likely due to profound hypoglycaemia caused by exogenous insulin administration. Borderline personality disorder patients have a higher incidence of self harm and suicidality than the general population. Insulin is not the correct answer as its secretion decreases in response to hypoglycaemia, and this patient has T1DM resulting in an absolute deficiency. Cortisol is also not the correct answer as it takes longer to be secreted, although it is another counter-regulatory hormone that seeks to raise blood glucose levels in response to hypoglycaemia.
Understanding Hypoglycaemia: Causes, Features, and Management
Hypoglycaemia is a condition characterized by low blood sugar levels, which can lead to a range of symptoms and complications. There are several possible causes of hypoglycaemia, including insulinoma, liver failure, Addison’s disease, and alcohol consumption. The physiological response to hypoglycaemia involves hormonal and sympathoadrenal responses, which can result in autonomic and neuroglycopenic symptoms. While blood glucose levels and symptom severity are not always correlated, common symptoms of hypoglycaemia include sweating, shaking, hunger, anxiety, nausea, weakness, vision changes, confusion, and dizziness. In severe cases, hypoglycaemia can lead to convulsions or coma.
Managing hypoglycaemia depends on the severity of the symptoms and the setting in which it occurs. In the community, individuals with diabetes who inject insulin may be advised to consume oral glucose or a quick-acting carbohydrate such as GlucoGel or Dextrogel. A ‘HypoKit’ containing glucagon may also be prescribed for home use. In a hospital setting, treatment may involve administering a quick-acting carbohydrate or subcutaneous/intramuscular injection of glucagon for unconscious or unable to swallow patients. Alternatively, intravenous glucose solution may be given through a large vein.
Overall, understanding the causes, features, and management of hypoglycaemia is crucial for individuals with diabetes or other conditions that increase the risk of low blood sugar levels. Prompt and appropriate treatment can help prevent complications and improve outcomes.
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This question is part of the following fields:
- Endocrine System
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