Diabetic Ketoacidosis and SGLT-2 Inhibitors

Diabetic ketoacidosis is a condition that is becoming more common in patients with type 1 diabetes who are prescribed an SGLT-2 inhibitor. This is due to patients inappropriately reducing their insulin dose, which causes them to lose glucose into their urine and not have enough insulin to meet their glucose metabolism needs. In a randomized controlled trial, rates of ketoacidosis-related adverse events were as high as 9% in patients prescribed canagliflozin 300 mg. Therefore, insulin dose reduction in patients with type 1 diabetes taking an SGLT-2 inhibitor should only be carried out with specialist advice, and off-label use is not widely recommended.

Hyperosmolar non-ketotic state is an incorrect diagnosis for this condition, as there is evidence of elevated lactate and metabolic acidosis, and the rise in blood glucose is very modest. The acidosis is not related to SGLT-2 inhibition directly, but due to down titration of insulin dosing. The ketosis is not due to starvation, but glycosuria does create a relative calorie deficit. Acidosis is usually seen in the context of tissue hypoxia/hypoperfusion, but usually in the context of a profound hypotensive episode.

Addisonian Crisis and Diagnosis with Synacthen Test

The patient is experiencing an Addisonian crisis, which is a life-threatening condition caused by a severe deficiency of cortisol and aldosterone hormones. To confirm the diagnosis of Addison’s disease, a Synacthen test is performed. This test involves injecting a synthetic hormone called Synacthen, which stimulates the adrenal glands to produce cortisol. Blood samples are taken before and after the injection to measure the levels of cortisol in the blood. If the adrenal glands are functioning properly, the cortisol levels will increase significantly after the injection. However, if the adrenal glands are not producing enough cortisol, the levels will remain low. The Synacthen test is a reliable and accurate way to diagnose Addison’s disease and determine the appropriate treatment plan. It is important to diagnose and treat Addison’s disease promptly to prevent complications and improve the patient’s quality of life.

For pregnant patients who are already taking levothyroxine, it is recommended to check their thyroid function tests at 6-8 weeks, 16-20 weeks, and 28-32 weeks of gestation. During pregnancy, the typical thyroxine requirements may increase by 25-50 mcg. After delivery, the patient should return to their original levothyroxine dose.

During pregnancy, there is an increase in the levels of thyroxine-binding globulin (TBG), which causes an increase in the levels of total thyroxine. However, this does not affect the free thyroxine level. If left untreated, thyrotoxicosis can increase the risk of fetal loss, maternal heart failure, and premature labor. Graves’ disease is the most common cause of thyrotoxicosis during pregnancy, but transient gestational hyperthyroidism can also occur due to the activation of the TSH receptor by HCG. Propylthiouracil has traditionally been the antithyroid drug of choice, but it is associated with an increased risk of severe hepatic injury. Therefore, NICE Clinical Knowledge Summaries recommend using propylthiouracil in the first trimester and switching to carbimazole in the second trimester. Maternal free thyroxine levels should be kept in the upper third of the normal reference range to avoid fetal hypothyroidism. Thyrotrophin receptor stimulating antibodies should be checked at 30-36 weeks gestation to determine the risk of neonatal thyroid problems. Block-and-replace regimes should not be used in pregnancy, and radioiodine therapy is contraindicated.

On the other hand, thyroxine is safe during pregnancy, and serum thyroid-stimulating hormone should be measured in each trimester and 6-8 weeks post-partum. Women require an increased dose of thyroxine during pregnancy, up to 50% as early as 4-6 weeks of pregnancy. Breastfeeding is safe while on thyroxine. It is important to manage thyroid problems during pregnancy to ensure the health of both the mother and the baby.

The patient’s symptoms and blood test results suggest a diagnosis of polyglandular syndrome type 2, which is characterized by adrenal insufficiency, hypothyroidism, and type 1 diabetes. Other conditions such as hypogonadism, coeliac disease, and myasthenia gravis may also be present. Coeliac disease alone cannot explain all of the patient’s symptoms, including hyponatremia, hyperkalemia, and postural drop in blood pressure. Polyglandular syndrome type 1 is characterized by mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency, while type 3 is characterized by autoimmune thyroiditis. HIV infection is unlikely as the blood test results are more consistent with autoimmune polyglandular syndrome.

Patients with Addison’s disease should have an IM hydrocortisone injection kit to prevent adrenal crisis, especially when travelling. They can still receive anti-malarial treatment and fly, but should visit a travel clinic for advice on vaccinations and malaria risk.

Addison’s disease is a condition that requires patients to undergo glucocorticoid and mineralocorticoid replacement therapy. This treatment involves taking a combination of hydrocortisone and fludrocortisone. Hydrocortisone is usually given in 2 or 3 divided doses, with patients requiring 20-30 mg per day, mostly in the first half of the day. Fludrocortisone is also included in the treatment regimen. Patient education is crucial in managing Addison’s disease. Patients should be reminded not to miss glucocorticoid doses, and they may consider wearing Medic Alert bracelets and steroid cards. Additionally, patients should be provided with hydrocortisone for injection with needles and syringes to treat an adrenal crisis. It is also important to discuss how to adjust the glucocorticoid dose during an intercurrent illness.

During an intercurrent illness, the glucocorticoid dose should be doubled, while the fludrocortisone dose remains the same. The Addison’s Clinical Advisory Panel has produced guidelines that detail specific scenarios for managing intercurrent illness. These guidelines can be found on the CKS link for more information. Proper management of Addison’s disease is essential to ensure that patients receive the appropriate treatment and care they need to manage their condition effectively.

Gradual Insulin Deficiency and Beta Cell Mass Reduction in Diabetes

Compared to individuals with normal blood sugar levels, those with Impaired Fasting Glucose have a 50% reduction in beta cell mass, while those with Type 2 diabetes have a 65% reduction, and those with Type 1 diabetes have over a 90% reduction. This suggests that insulin deficiency gradually occurs as insulin resistance increases.

To further understand this phenomenon, it is important to investigate the reasons behind the decline in beta cell mass in Type 2 diabetes. Potential mechanisms include beta cell apoptosis, oxidative stress, and inflammation. Research has shown that beta cell apoptosis, or programmed cell death, is a significant contributor to the reduction in beta cell mass in Type 2 diabetes.

Overall, the gradual decline in beta cell mass and insulin deficiency in diabetes highlights the importance of early detection and management of the disease. Further research is needed to better understand the mechanisms behind beta cell mass reduction and develop effective treatments to prevent or slow down the progression of diabetes.

Co-cyprindiol is a medication that contains both cyproterone, an anti-androgen, and ethinylestradiol, a synthetic estrogen. It is commonly used to treat polycystic ovarian syndrome, which is the most probable diagnosis in this case. By combining these two components, co-cyprindiol can effectively alleviate symptoms of hirsutism and acne, which are both associated with excess androgen.

When it comes to inducing ovulation, clomiphene is the preferred option over metformin. However, in obese patients, the two medications may be used together.

Managing Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) is a condition that affects a significant percentage of women of reproductive age. Its management is complex due to the unclear cause of the condition. However, it is known that PCOS is associated with high levels of luteinizing hormone and hyperinsulinemia, and there is some overlap with the metabolic syndrome. General management includes weight reduction if appropriate and the use of combined oral contraceptives (COC) to regulate the menstrual cycle and induce a monthly bleed.

Hirsutism and acne are common symptoms of PCOS, and a COC pill may be used to manage them. Third-generation COCs with fewer androgenic effects or co-cyprindiol with an anti-androgen action are possible options. If these do not work, topical eflornithine may be tried, or spironolactone, flutamide, and finasteride may be used under specialist supervision.

Infertility is another issue that women with PCOS may face. Weight reduction is recommended if appropriate, and the management of infertility should be supervised by a specialist. There is an ongoing debate about whether metformin, clomifene, or a combination should be used to stimulate ovulation. A 2007 trial published in the New England Journal of Medicine suggested that clomifene was the most effective treatment. However, there is a potential risk of multiple pregnancies with anti-oestrogen therapies such as clomifene. The RCOG published an opinion paper in 2008 and concluded that on current evidence, metformin is not a first-line treatment of choice in the management of PCOS. Metformin is also used, either combined with clomiphene or alone, particularly in patients who are obese. Gonadotrophins may also be used.

If intravenous fluid treatment and pamidronate therapy are ineffective in treating refractory hypercalcaemia of malignancy, subcutaneous calcitonin may be considered as the next step. Loop diuretics like furosemide may be used in some cases, but calcitonin is more appropriate for this patient. Trying another bisphosphonate like ibandronic acid would not be recommended after pamidronate has failed. Increasing fluid intake beyond the current 4-6 litres per 24 hours would not be advisable as it may lead to fluid overload.

Managing Hypercalcaemia

Hypercalcaemia can be managed through various methods. The first step is to rehydrate the patient with normal saline, usually at a rate of 3-4 litres per day. Once rehydration is achieved, bisphosphonates can be administered. These drugs take 2-3 days to work, with maximum effect seen at 7 days.

Calcitonin is another option that can be used for quicker effect than bisphosphonates. In cases of sarcoidosis, steroids may also be used. However, loop diuretics such as furosemide should be used with caution as they may worsen electrolyte derangement and volume depletion. They are typically reserved for patients who cannot tolerate aggressive fluid rehydration.

In summary, the management of hypercalcaemia involves rehydration with normal saline followed by the use of bisphosphonates, calcitonin, or steroids in certain cases. Loop diuretics may also be used, but with caution. It is important to monitor electrolyte levels and adjust treatment accordingly.

Denosumab’s Mechanism of Action

Denosumab is a type of medication that inhibits RANK-ligand, a protein that occurs on the surface of osteoclast precursors and osteoclasts. By inhibiting RANK-ligand, denosumab reduces the formation, function, and survival of osteoclasts, which are cells responsible for breaking down bone tissue. This results in a decrease in bone reabsorption in both cortical and trabecular bone. It is important to note that denosumab does not directly affect calcium absorption or excretion, nor does it affect the function of osteoblasts, which are cells responsible for building new bone tissue. Therefore, the only possible outcome of denosumab’s action is a decrease in osteoclast activity.

Diagnosis of Cushing’s Syndrome with Functional Adrenal Adenoma

The patient’s symptoms and test results suggest a diagnosis of Cushing’s syndrome. This is indicated by the elevated levels of urine free cortisol, as well as the presence of obesity and striae. Additionally, the low levels of adrenocorticotropic hormone and the presence of an adrenal mass on CT imaging suggest that this is due to a functional adrenal adenoma. In summary, the patient’s presentation is consistent with Cushing’s syndrome caused by a functional adrenal adenoma.

Insulin Induced Hypoglycaemia

This patient is experiencing hypoglycaemia, which is being caused by insulin. The suppression of 3 beta-hydroxybutyrate, a ketone, and the elevated insulin levels indicate that this is insulin induced hypoglycaemia. Additionally, the suppressed C peptide suggests that the insulin is being administered exogenously.

If sulphonylureas were the cause of the hypoglycaemia, there would be raised insulin and C peptides. In cases where there is suspicion of sulphonylureas being the cause, measuring a sulphonylurea concentration can be helpful.

Insulinoma, on the other hand, would be associated with proportionately elevated insulin and C peptide levels.

Overall, the combination of suppressed 3 beta-hydroxybutyrate, elevated insulin, and suppressed C peptide points towards insulin induced hypoglycaemia in this patient.

Congenital adrenal hyperplasia is a genetic condition that affects the adrenal glands and can result in various symptoms depending on the specific enzyme deficiency. One common form is 21-hydroxylase deficiency, which can cause virilization of female genitalia, precocious puberty in males, and a salt-losing crisis in 60-70% of patients during the first few weeks of life. Another form is 11-beta hydroxylase deficiency, which can also cause virilization and precocious puberty, as well as hypertension and hypokalemia. A third form is 17-hydroxylase deficiency, which typically does not cause virilization in females but can result in intersex characteristics in boys and hypertension.

Overall, congenital adrenal hyperplasia can have significant impacts on a person’s physical development and health, and early diagnosis and treatment are important for managing symptoms and preventing complications.

During pregnancy, prolactin levels increase rapidly, leading to symptoms such as amenorrhoea (absence of menstrual periods), breast fullness and tenderness, and weight gain. Therefore, a urine pregnancy test is the most appropriate initial investigation for a woman presenting with these features and high prolactin levels.

Microprolactinoma, a benign pituitary tumor that secretes prolactin, may also cause elevated prolactin levels, but usually to a slightly higher degree than in this case. Hypothyroidism, a condition in which the thyroid gland does not produce enough hormones, can cause weight gain, but typically presents with menorrhagia (heavy menstrual bleeding), which is not reported by this patient. Macroprolactinoma, a larger pituitary tumor that produces excessive prolactin, can cause more severe symptoms, such as compression of the optic chiasm (the crossing point of the optic nerves). Polycystic ovarian syndrome (PCOS), a common endocrine disorder in women of reproductive age, is associated with weight gain, irregular and heavy periods, and signs of hyperandrogenism (e.g. acne, hirsutism, male-pattern baldness), but usually does not cause high prolactin levels.

Diagnosis of Hypoadrenalism in a Young Woman with Type 1 Diabetes

The young woman with type 1 diabetes presents with weight loss, lethargy, and an increase in hypoglycemic events despite reduced insulin requirements. These symptoms suggest an increase in insulin sensitivity, which may be caused by hypoadrenalism due to her history of autoimmune disease. A short Synacthen test is the most appropriate diagnostic test to confirm this suspicion.

Other potential causes of her symptoms were ruled out. Hypothyroidism would cause weight gain, while hyperthyroidism would increase insulin requirements and have typical signs such as tachycardia and fine tremors. There were no symptoms to suggest inflammatory bowel disease, and the rash on her shins was indicative of necrobiosis rather than pyoderma. Coeliac disease would not have such a significant impact on insulin requirements, and anemia would be expected with this diagnosis.

In conclusion, the young woman’s symptoms and medical history suggest hypoadrenalism as the most likely cause of her increased insulin sensitivity. A short Synacthen test will confirm this diagnosis and allow for appropriate treatment.

Managing Sore Throat in a Patient with Graves’ Disease on Carbimazole

Graves’ disease is confirmed in a patient with positive TSH receptor antibodies, but they have developed a sore throat while on carbimazole. Carbimazole can cause neutropenia, which is a decrease in neutrophil count, and therefore an urgent FBC was requested. The patient’s WBC and neutrophil count are slightly below normal, but not related to the sore throat, and there is no need to discontinue carbimazole. In fact, a mild decrease in WBC can occur with hyperthyroidism.

The best course of action is to continue carbimazole until the neutrophil count drops to less than 1.5 x 10/L, after which the drug should be stopped and blood counts monitored. This is because the drug will continue to work for a period of time even after it is stopped until it is eliminated from the system. By closely monitoring the patient’s blood counts, healthcare providers can ensure that the patient receives the appropriate treatment for their Graves’ disease while managing any potential side effects of carbimazole.

Craniopharyngioma is a type of slow-growing brain tumor that arises from the remnants of the craniopharyngeal duct. It is more common in males and accounts for 4.2% of all childhood tumors. Symptoms develop slowly and typically appear once the tumor has reached a diameter of 3 cm. Growth failure and delayed puberty are common in young patients. The tumor is characterized by a suprasellar calcified cyst, with calcification being more common in children than in adults. CT is useful in demonstrating the calcifications, while MRI is essential for defining the local anatomy before surgery. Surgery is the preferred treatment and may involve complete resection or reducing the size followed by postoperative radiotherapy.

Treatment and Hormonal Imbalances in Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is a condition that affects women and is characterized by hirsutism, or excessive hair growth. The most appropriate treatment for this condition is the oral contraceptive pill (OCP), specifically the preparation Dianette, which contains ethinyloestradiol and cyproterone acetate. Hyperprolactinaemia, or high levels of prolactin in the blood, may also be present in women with PCOS, but it is most likely due to functional hyperprolactinaemia associated with the condition rather than a prolactin-secreting pituitary disorder. Additionally, women with PCOS have lower levels of sex hormone binding globulin, which is a protein that transports hormones in the blood. This is due to androgens reducing globulin production while estrogen promotes it. these hormonal imbalances is important in managing PCOS.

Overall, the treatment for PCOS with hirsutism is the OCP, specifically Dianette. Hyperprolactinaemia may also be present, but it is likely due to functional hyperprolactinaemia associated with PCOS. Additionally, women with PCOS have lower levels of sex hormone binding globulin, which is important to consider in managing the condition.

Due to his youth and increased risk of cardiovascular disease over his lifetime, the patient is an ideal candidate for PCSK9 inhibition. While cholestyramine was previously utilized for hypercholesterolemia treatment as a cholesterol binding resin, it is not as effective as statins in reducing cholesterol levels. Fenofibrate and nicotinic acid are most effective in lowering triglycerides, and switching from atorvastatin to rosuvastatin is unlikely to significantly decrease LDL levels.

Familial Hypercholesterolaemia: Causes, Diagnosis, and Management

Familial hypercholesterolaemia (FH) is a genetic condition that affects approximately 1 in 500 people. It is an autosomal dominant disorder that results in high levels of LDL-cholesterol, which can lead to early cardiovascular disease if left untreated. FH is caused by mutations in the gene that encodes the LDL-receptor protein.

To diagnose FH, NICE recommends suspecting it as a possible diagnosis in adults with a total cholesterol level greater than 7.5 mmol/l and/or a personal or family history of premature coronary heart disease. For children of affected parents, testing should be arranged by age 10 if one parent is affected and by age 5 if both parents are affected.

The Simon Broome criteria are used for clinical diagnosis, which includes a total cholesterol level greater than 7.5 mmol/l and LDL-C greater than 4.9 mmol/l in adults or a total cholesterol level greater than 6.7 mmol/l and LDL-C greater than 4.0 mmol/l in children. Definite FH is diagnosed if there is tendon xanthoma in patients or first or second-degree relatives or DNA-based evidence of FH. Possible FH is diagnosed if there is a family history of myocardial infarction below age 50 years in second-degree relatives, below age 60 in first-degree relatives, or a family history of raised cholesterol levels.

Management of FH involves referral to a specialist lipid clinic and the use of high-dose statins as first-line treatment. CVD risk estimation using standard tables is not appropriate in FH as they do not accurately reflect the risk of CVD. First-degree relatives have a 50% chance of having the disorder and should be offered screening, including children who should be screened by the age of 10 years if there is one affected parent. Statins should be discontinued in women 3 months before conception due to the risk of congenital defects.

Legionnaire’s Disease and Hyponatraemia Treatment

This patient is exhibiting symptoms of high temperature, dyspnoea, and mild hyponatraemia after returning from a trip to Spain. The most likely diagnosis is Legionnaire’s disease, which is treated with antimicrobials that can achieve high concentrations intracellularly, such as macrolides, quinolones, rifampicin, and tetracycline.

In addition to the Legionnaire’s disease, the patient also has moderate hyponatraemia, which is likely caused by multiple factors. Due to the high fever, low blood pressure, tachycardia, elevated BUN, and urine Na <30, the recommended treatment is IV normal saline. It is important to note that demeclocycline should only be used for chronic Syndrome of Inappropriate Antidiuretic Hormone (SIADH) and is not an appropriate therapy for Legionnaire’s disease. Therefore, it is crucial to properly diagnose and treat the underlying cause of hyponatraemia to ensure the best possible outcome for the patient.

To diagnose PCOS according to the Rotterdam criteria, at least two of the following must be present: clinical or biochemical evidence of hyperandrogenism, evidence of oligo- or anovulation, and the presence of polycystic ovaries on ultrasound.

Numerous clinical trials have been conducted to determine the most effective drug for aiding fertility in PCOS patients. A study published in the New England Journal of Medicine found that Clomiphene is superior to metformin in achieving live birth in infertile women with PCOS, although multiple births can be a complication. Another article published in Trends in Endocrinology and Metabolism reported that both Clomiphene and metformin are better than placebo for increasing ovulation and pregnancy rates in PCOS patients, but Clomiphene is more effective than metformin for ovulation, pregnancy, and live-birth rates in patients with a BMI over 30.

In PCOS, serum prolactin levels may be slightly elevated, but they rarely exceed 1500 mU/l. Reverse circadian rhythm steroids are used to treat congenital adrenal hyperplasia, while cabergoline is used to manage hyperprolactinemia. Spironolactone can improve hirsutism in PCOS due to its antiandrogenic activity, but it does not affect fertility.

Managing Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) is a condition that affects a significant percentage of women of reproductive age. Its management is complex due to the unclear cause of the condition. However, it is known that PCOS is associated with high levels of luteinizing hormone and hyperinsulinemia, and there is some overlap with the metabolic syndrome. General management includes weight reduction if appropriate and the use of combined oral contraceptives (COC) to regulate the menstrual cycle and induce a monthly bleed.

Hirsutism and acne are common symptoms of PCOS, and a COC pill may be used to manage them. Third-generation COCs with fewer androgenic effects or co-cyprindiol with an anti-androgen action are possible options. If these do not work, topical eflornithine may be tried, or spironolactone, flutamide, and finasteride may be used under specialist supervision.

Infertility is another issue that women with PCOS may face. Weight reduction is recommended if appropriate, and the management of infertility should be supervised by a specialist. There is an ongoing debate about whether metformin, clomifene, or a combination should be used to stimulate ovulation. A 2007 trial published in the New England Journal of Medicine suggested that clomifene was the most effective treatment. However, there is a potential risk of multiple pregnancies with anti-oestrogen therapies such as clomifene. The RCOG published an opinion paper in 2008 and concluded that on current evidence, metformin is not a first-line treatment of choice in the management of PCOS. Metformin is also used, either combined with clomiphene or alone, particularly in patients who are obese. Gonadotrophins may also be used.

Chronic Kidney Disease and Hyporeninaemic Hypoaldosteronism in Diabetic Patients

Chronic kidney disease in diabetic patients is often related to diabetic nephropathy and hypertension. Electrolyte abnormalities, such as low sodium and high potassium levels, suggest a diagnosis of hyporeninaemic hypoaldosteronism, also known as type IV renal tubular acidosis. This condition is common in elderly diabetic patients and is associated with nephropathy. Hyperkalaemia, although usually mild, can be worsened by medications like beta blockers and ACE inhibitors.

Diabetic nephropathy primarily affects the glomeruli and decreases renin production. Patients with diabetes may also have impaired potassium homeostasis due to insulin deficiency and autonomic neuropathy, which impairs beta2-mediated potassium influx into cells.

Conservative measures like avoiding provocative agents and following a low potassium diet are usually effective in treating hyporeninaemic hypoaldosteronism. In refractory cases, small doses of fludrocortisone may be considered.

Even if a patient with well-controlled type 1 diabetes denies any lifestyle changes and has a normal HbA1c, diabetic ketoacidosis (DKA) can still occur without a clear precipitant. It is important to rule out myocardial infarction as a potential trigger. While blood glucose monitors are highly accurate, they should not be solely relied upon to determine the cause of DKA.

Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes mellitus, accounting for around 6% of cases. It can also occur in rare cases of extreme stress in patients with type 2 diabetes mellitus. DKA is caused by uncontrolled lipolysis, resulting in an excess of free fatty acids that are converted to ketone bodies. The most common precipitating factors of DKA are infection, missed insulin doses, and myocardial infarction. Symptoms include abdominal pain, polyuria, polydipsia, dehydration, Kussmaul respiration, and breath that smells like acetone. Diagnostic criteria include glucose levels above 11 mmol/l or known diabetes mellitus, pH below 7.3, bicarbonate below 15 mmol/l, and ketones above 3 mmol/l or urine ketones ++ on dipstick.

Management of DKA involves fluid replacement, insulin, and correction of electrolyte disturbance. Fluid replacement is necessary as most patients with DKA are deplete around 5-8 litres. Isotonic saline is used initially, even if the patient is severely acidotic. Insulin is administered through an intravenous infusion, and correction of electrolyte disturbance is necessary. Long-acting insulin should be continued, while short-acting insulin should be stopped. Complications may occur from DKA itself or the treatment, such as gastric stasis, thromboembolism, arrhythmias, acute respiratory distress syndrome, acute kidney injury, and cerebral edema. Children and young adults are particularly vulnerable to cerebral edema following fluid resuscitation in DKA and often need 1:1 nursing to monitor neuro-observations, headache, irritability, visual disturbance, focal neurology, etc.

Diabetes Insipidus

Diabetes insipidus (DI) is a condition where the body fails to produce, secrete, or respond to antidiuretic hormone (ADH), resulting in inadequate aquaporin channels and the inability to concentrate urine. As a result, large volumes of dilute urine are excreted to clear the body’s daily solute and toxin excretion requirements. In the water deprivation test, limiting water intake can cause dangerously high serum osmolality, and the urine will remain dilute even with prolonged water deprivation.

DI can be classified as cranial or nephrogenic, depending on the cause of the ADH dysfunction. Cranial DI is caused by a failure in the production or secretion of ADH, while nephrogenic DI is caused by a failure in the action of ADH. To diagnose cranial DI, synthetic ADH can be administered during the water deprivation test to allow the urine to become concentrated.

DI is crucial in managing the condition and preventing complications. Patients with DI should be monitored closely and treated accordingly to prevent dehydration and electrolyte imbalances.

Continuing Metformin Therapy in Patients with Myocardial Ischaemia

Experimental evidence suggests that metformin has a positive effect on cardiac function, making it safe to continue metformin therapy in patients with myocardial ischaemia unless there is evidence of significant circulatory compromise. In cases where HbA1c is at target, there is no need to increase blood glucose lowering therapy. Transitioning to insulin may not be beneficial as it is associated with weight gain, increased risk of hypoglycaemia and hypertension, and may increase sympathetic drive, leading to an increased risk of myocardial ischaemia. Therefore, unless there is evidence of circulatory compromise, there is no need to temporarily discontinue metformin.

The administration of intravenous dextrose infusion can lead to the onset of Wernicke’s encephalopathy. Furthermore, patients often have low levels of sodium, necessitating the use of 0.9% sodium chloride.

Hyperemesis gravidarum is a severe form of nausea and vomiting that affects around 1% of pregnancies. It is usually experienced between 8 and 12 weeks of pregnancy but can persist up to 20 weeks. The condition is thought to be related to raised beta hCG levels and is more common in women who are obese, nulliparous, or have multiple pregnancies, trophoblastic disease, or hyperthyroidism. Smoking is associated with a decreased incidence of hyperemesis.

The Royal College of Obstetricians and Gynaecologists recommend that a woman must have a 5% pre-pregnancy weight loss, dehydration, and electrolyte imbalance before a diagnosis of hyperemesis gravidarum can be made. Validated scoring systems such as the Pregnancy-Unique Quantification of Emesis (PUQE) score can be used to classify the severity of NVP.

Management of hyperemesis gravidarum involves using antihistamines as a first-line treatment, with oral cyclizine or oral promethazine being recommended by Clinical Knowledge Summaries. Oral prochlorperazine is an alternative, while ondansetron and metoclopramide may be used as second-line treatments. Ginger and P6 (wrist) acupressure can be tried, but there is little evidence of benefit. Admission may be needed for IV hydration.

Complications of hyperemesis gravidarum can include Wernicke’s encephalopathy, Mallory-Weiss tear, central pontine myelinolysis, acute tubular necrosis, and fetal growth restriction, preterm birth, and cleft lip/palate (if ondansetron is used during the first trimester). The NICE Clinical Knowledge Summaries recommend considering admission if a woman is unable to keep down liquids or oral antiemetics, has ketonuria and/or weight loss (greater than 5% of body weight), or has a confirmed or suspected comorbidity that may be adversely affected by nausea and vomiting.

De Quervain’s thyroiditis is characterized by initial hyperthyroidism, a painful goitre, and globally reduced uptake of iodine-131. This condition is believed to occur after a viral infection. The preferred diagnostic test is thyroid scintigraphy, which shows a decrease in iodine-131 uptake throughout the thyroid gland. Most cases of subacute thyroiditis resolve on their own and do not require treatment. The other options provided are not typical findings for De Quervain’s thyroiditis. A normal thyroid gland is usually associated with globally normal uptake and uniform iodine-131 uptake. Grave’s disease is typically associated with globally increased uptake. A cold thyroid nodule is characterized by a well-defined area of decreased uptake, while a hot thyroid nodule is characterized by a well-defined area of increased uptake. These findings are not consistent with the symptoms and laboratory results of De Quervain’s thyroiditis.

Understanding Subacute (De Quervain’s) Thyroiditis

Subacute thyroiditis, also known as De Quervain’s thyroiditis and subacute granulomatous thyroiditis, is a condition that is believed to occur after a viral infection. It is characterized by hyperthyroidism, a painful goitre, and raised ESR during the first phase, which lasts for 3-6 weeks. The second phase, which lasts for 1-3 weeks, is characterized by euthyroidism, while the third phase, which lasts for weeks to months, is characterized by hypothyroidism. The fourth phase is when the thyroid structure and function return to normal.

To diagnose subacute thyroiditis, a thyroid scintigraphy is usually performed, which shows a globally reduced uptake of iodine-131. Treatment for subacute thyroiditis is usually not required, as the condition is self-limiting. However, if thyroid pain is present, it may respond to aspirin or other NSAIDs. In more severe cases, steroids may be used, particularly if hypothyroidism develops.

It is important to note that many causes of hypothyroidism may have an initial thyrotoxic phase, as shown in the Venn diagram. Therefore, it is crucial to seek medical attention if any symptoms of thyroid dysfunction are present.

The recommended treatment for RTA involves correcting the acidaemia through the use of oral sodium bicarbonate, sodium citrate, or potassium citrate. In cases where a patient has a low bicarbonate level, it is important to determine the anion gap to aid in diagnosis. A normal anion gap metabolic acidosis (NAGMA) is typically caused by Addison’s disease, bicarbonate loss via the GI or renal tract, chloride excess, or drugs such as acetazolamide. On the other hand, a high anion gap metabolic acidosis (HAGMA) is usually caused by ketoacidosis, uraemia, lactic acidosis, or toxins like salicylates, ethylene glycol, or methanol. In this particular case, the presence of NAGMA, hypokalaemia, and renal stones suggests the possibility of renal tubular acidosis (RTA), with type 1 (distal) being the most likely diagnosis due to the patient’s medical history of Sjögren’s syndrome and rheumatoid arthritis.

Renal tubular acidosis (RTA) is a condition that results in hyperchloraemic metabolic acidosis, which is characterized by a normal anion gap. There are three types of RTA, each with its own unique set of causes and complications. Type 1 RTA, also known as distal RTA, is caused by an inability to generate acid urine in the distal tubule, leading to hypokalaemia. This type of RTA can be caused by a variety of factors, including rheumatoid arthritis, SLE, and amphotericin B toxicity. Complications may include nephrocalcinosis and renal stones.

Type 2 RTA, or proximal RTA, is characterized by a decreased reabsorption of HCO3- in the proximal tubule, which also leads to hypokalaemia. This type of RTA can be caused by a variety of factors, including Wilson’s disease and outdated tetracyclines. Complications may include osteomalacia.

Type 3 RTA, or mixed RTA, is an extremely rare form of the condition that is caused by carbonic anhydrase II deficiency. This results in hypokalaemia.

Type 4 RTA, or hyperkalaemic RTA, is caused by a reduction in aldosterone, which leads to a reduction in proximal tubular ammonium excretion. This type of RTA can be caused by hypoaldosteronism and diabetes, and it results in hyperkalaemia.

Overall, RTA is a complex condition that can have a variety of causes and complications. It is important to work with a healthcare provider to determine the underlying cause of the condition and develop an appropriate treatment plan.

Calcitonin is utilized for screening, prognosis, and monitoring of medullary thyroid cancer.

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 colloid 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.

Patients who have undergone surgery and radioiodine therapy for papillary thyroid cancer, and have no lymph node or organ involvement with a tumor size less than 4 cm, have a positive prognosis. The recommended method for monitoring cancer recurrence is through annual thyroglobulin testing. Imaging is not effective in detecting early recurrence, and therefore not recommended. Frequent measurement of TSH and free T4 levels is necessary for thyroxine replacement, but not for detecting malignancy recurrence.

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.

Postpartum Thyroid Dysfunction: Likelihood of Recovery and Treatment Options

Postpartum thyroid dysfunction affects 5-10% of women in the first year after childbirth. Hyperthyroidism may occur within the first 4 months of pregnancy, while hypothyroidism occurs later, at the 3-7-month stage. Symptoms are often mild and non-specific, with spontaneous recovery occurring in the majority of patients within 6-12 months of delivery. However, around 40% of patients eventually develop permanent hypothyroidism. The anti-TPO titre at the end of pregnancy is not closely related to the risk of permanent hypothyroidism, as titres progressively fall during pregnancy.

Low-dose thyroxine (e.g. 50 μg) may be used to allow for spontaneous recovery in patients with postpartum hypothyroidism, with re-checking of thyroid function off therapy after 6 months of treatment. Corticosteroids have no role in treatment. Long-term thyroxine replacement is only necessary in patients who develop permanent hypothyroidism. Overall, the likelihood of becoming euthyroid is higher than remaining hypothyroid, but rapid progression to thyrotoxicosis may occur in some cases.