Endocrine Week 4 Part 2 Study Guide Questions

ENDOCRINE WEEK 4 PART 2 STUDY GUIDE QUESTIONS 1. Adam is a 35-year-old male. He presents to your GP clinic tells you that he has been feeling short of breath more often and his heart seems to be beating lower than usual. When you take his vitals, you find out that his breathing rate, heart rate and blood pressure are all low and his temperature is 38.5 degrees. You perform various physical exams on him, and you could not find a definite diagnosis. However, in the meantime you but him on propanol to improve his heart rate and blood pressure. You send him for a chest X-ray and blood test. You order a full blood test and ask for some CK and troponin serology as well as thyroid peroxide and thyroglobulin antibodies. A week later, he comes back to you with all the investigation results you ordered. He tells you that propanol did not really improve his condition. He tells you that now his muscles fell lot weaker, have been gaining weight and he feels warmer than usual. The investigation results tell you: • • • • Chest X-ray is normal. Blood tests are normal, except that while blood cells are a bit elevated. CK and troponin are normal. Thyroid peroxide and thyroglobulin antibodies are elevated. Based on the given information what is the most likely diagnosis? Justify and explain the pathogenesis. (2 marks). Answer: Hypothyroidism due to Hashimoto’s disease. This is likely to be triggered by an infection that looks like proteins found on thyroid tissue. This is because there is an elevation in white blood cell count and there is a fever. Due to this, when the immune response to the infection happens, after it is done, it will start seeing the thyroid tissue, like the pathogen, because the pathogen looked very similar to it. For this to happen, there needs to a mutation in the HLA-DR3 and HLA-DR5 genes. There will be production of antiTPO and anti-TG antibodies, which will prevent iodination and also destroy thyroid tissue. 2. Name ONE autoimmune disease that make cause hypothyroidism and explain how it causes hypothyroidism. (1 mark) Answer: Riedel’s thyroiditis, this is when there is IgG4 antibodies made against the thyroid follicular cells. These will cause destruction and scarring of the thyroid glands, which will cause hypothyroidism. This is characterised by a hard and a painless thyroid. 3. Name and describe the different types of thyroid cancer. Answer: • Differentiated: - • • - Papillary -> follicular cells have projections that invade into the lymph nodes and lymph vessels. Follicular -> break through the fibrous capsule of the thyroid gland and invade blood vessels, but do not invade lymphatics. Hurtle-> as a compensation to the immune cell attack to the thyroid glands, the thyroid glands respond by making hurtle cells, which have a granular appearance and have a high mitochondria concentration and density. Medullary: Arises from c cells. There is calcitonin deposition between the c cells. However, despite this, there is no hypocalcaemia, as due to the increase in calcitonin, the tissues become resistant to it. This involves a single cell carcinoma. Anaplastic: The thyroid follicular cells become altered and will look nothing like the normal ones. This is the most aggressive thyroid cancer type. 4. Adam is a 7-year-old. He presents to the ED with his mother Caterina. Caterina tells you that she got a phone call from the school, that Adam has fainted. She tells you that this is the first time that this has happened. However, Caterina tells you that for the past month he seems to have less energy and has been getting tired very quickly. She also tells you that before that he has a viral infection. He also has been using the bathroom more often and wetted his bed a few times. Caterina also tells you that despite him drinking a lot more water the usual, he seems dehydrated and always complains that he is thirsty. You take his vitals, and they all are normal. You measure his weight percentile, and he is on 4th percentile. Upon physical examination, you noticed that his breath is sweet smelling. You order a fasting blood glucose for the next day. Three days later, the results return as 7 mmol/L. (9 marks) a. what is the normal weight percentile and where would Adam fall? (1 mark). b. What is the most likely diagnosis? (0.5 marks). c. Based on your answer from part b) explain the pathogenesis and link it to all the features that he is presenting with. (6 marks). d. Explain the differences in the mechanisms of action of GLP-1 and Dipeptidyl Peptidase 4 inhibitors. (2 marks). e. Catherine tells you that in the family they have a history of pancreatitis. Which of the two drugs in part d) would you prefer for Adam? (0.5 marks). Answer: a. Normal weight percentile 5th to 85th. Adam is underweighted according to this. b. Type 1 diabetes. c. The infection would have triggered an immune response. However, it is likely that Adam has a HLA DR3 and HLA DR4 susceptibility genes, which would mean that the immune response has turned into an autoimmune response. This means that the T helper cells will detect the pancreatic beta cells self-antigens as foreign. They will present these antigens on their MHCII plates, and cause the beta cells to make pancreatic islet, anti-insulin and anti-GAD antibodies against various aspects within the beta cells causing their destruction. This means that there will be decreases synthesis and release of insulin. This means that there will be a decrease glucose uptake into the cells, as they require insulin for this to happen. This will cause insulin to build up within the bloodstream, causing hyperglycaemia. Since the cells cannot use glucose for energy, to make ATP, Adam fells fatigue and thus muscle weakness. Since glucose will not be up taken by cells, it will go and get secreted into the urine, as the Na/Glucose exchangers will get saturated, so glucose will not be reabsorbed into the bloodstream and will get spilled into the urine. As glucose is highly osmotically active it will pull water with it, causing increased urination (polyurea) and dehydration. Since, his body will not be able to use glucose for energy, it will refer to burning of fat and breakage of muscles to make ATP for energy, and thus this will cause weight loss. Since fat will be used for energy, there will be lipolysis. This means there will be generation of ketones, which can also be used for energy. Ketones, such as acetone will be made, which is sweat and will cause a fruity/sweet breath. d. GLP-1 receptor agonists, bind to GLP-1 receptors which is Gs coupled. This will activate the AC pathway leading to the formation and activation of PKA. This will increase ATP sensitive K+ channels, thereby increase insulin secretion, decrease glucagon secretion and decrease GIT absorption of glucose. Dipeptidyl Peptidase 4 inhibitors work by inhibiting the Dipeptidyl Peptidase enzyme, which will decrease the breakdown of GIP-1, and will allow it to perform its’ function for longer. The in increase in insulin release, will help with glucose uptake into the cells, and the decrease in glucagon and GIT absorption of glucose, will decrease the concentration go glucose in the blood. e. Dipeptidyl Peptidase 4 inhibitors.