Understanding Phenylketonuria: An Inborn Error of Metabolism

Phenylketonuria is a genetic disorder that results in a deficiency of the enzyme phenylalanine hydroxylase, which is responsible for converting phenylalanine into tyrosine. This leads to a buildup of phenylalanine and its byproducts in the body, causing symptoms such as mental disability, neurological issues, light pigmentation, and a musty odor.

Phenylketonuria is inherited as an autosomal recessive disorder, meaning that a child must inherit two copies of the mutated gene (one from each parent) to develop the condition. It is caused by a mutation on chromosome 12.

Other conditions, such as Sturge-Weber syndrome, Rett syndrome, and viral encephalitis, can present with similar symptoms but can be ruled out based on the patient’s history and physical exam. Homocystinuria is another inherited disorder that can present at a young age, but the musty odor is more indicative of phenylketonuria.

Early diagnosis and treatment are crucial for managing phenylketonuria. A low-phenylalanine diet, which restricts foods high in protein, can help prevent symptoms and complications. Regular monitoring and follow-up with a healthcare provider are also important for managing this condition.

Insulin therapy can have side-effects that patients should be aware of. One of the most common side-effects is hypoglycaemia, which can cause sweating, anxiety, blurred vision, confusion, and aggression. Patients should be taught to recognize these symptoms and take 10-20g of a short-acting carbohydrate, such as a glass of Lucozade or non-diet drink, three or more glucose tablets, or glucose gel. It is also important for every person treated with insulin to have a glucagon kit for emergencies where the patient is not able to orally ingest a short-acting carbohydrate. Patients who have frequent hypoglycaemic episodes may develop reduced awareness, and beta-blockers can further reduce hypoglycaemic awareness.

Another potential side-effect of insulin therapy is lipodystrophy, which typically presents as atrophy or lumps of subcutaneous fat. This can be prevented by rotating the injection site, as using the same site repeatedly can cause erratic insulin absorption. It is important for patients to be aware of these potential side-effects and to discuss any concerns with their healthcare provider. By monitoring their blood sugar levels and following their treatment plan, patients can manage the risks associated with insulin therapy and maintain good health.

Pregnancy is one of the possible causes of raised alkaline phosphatase, which could be the case based on the patient’s history. To confirm this, a urinary HCG test is recommended. However, the combination of fatigue, absence of menstrual periods, weight gain, and elevated alkaline phosphatase suggests a more probable diagnosis of primary biliary cholangitis, especially considering the patient’s age and gender. This is typically accompanied by severe itching and some degree of dyslipidemia. On the other hand, hypothyroidism usually results in menorrhagia. It is important to consider these potential causes when evaluating a patient with elevated alkaline phosphatase levels.

For black patients with type 2 diabetes and hypertension, the recommended first-line treatment is an angiotensin II receptor blocker, specifically losartan. This is based on evidence that ACE inhibitors, such as ramipril, may be less effective in patients of African or African-Caribbean ethnicity. For non-diabetic patients of this ethnicity, a calcium channel blocker like amlodipine is recommended. If blood pressure remains uncontrolled, a thiazide-like diuretic such as indapamide may be added as a second or third line of treatment. While lifestyle changes are important, this patient’s stage 2 hypertension and diabetes put him at high risk for complications, making prompt and effective treatment essential.

NICE has updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2022 to reflect advances in drug therapy and improved evidence regarding newer therapies such as SGLT-2 inhibitors. For the average patient taking metformin for T2DM, lifestyle changes and titrating up metformin to aim for a HbA1c of 48 mmol/mol (6.5%) is recommended. A second drug should only be added if the HbA1c rises to 58 mmol/mol (7.5%). Dietary advice includes encouraging high fiber, low glycemic index sources of carbohydrates, controlling intake of saturated fats and trans fatty acids, and initial target weight loss of 5-10% in overweight individuals.

Individual HbA1c targets should be agreed upon with patients to encourage motivation, and HbA1c should be checked every 3-6 months until stable, then 6 monthly. Targets should be relaxed on a case-by-case basis, with particular consideration for older or frail adults with type 2 diabetes. Metformin remains the first-line drug of choice, and SGLT-2 inhibitors should be given in addition to metformin if the patient has a high risk of developing cardiovascular disease (CVD), established CVD, or chronic heart failure. If metformin is contraindicated, SGLT-2 monotherapy or a DPP-4 inhibitor, pioglitazone, or sulfonylurea may be used.

Further drug therapy options depend on individual clinical circumstances and patient preference. Dual therapy options include adding a DPP-4 inhibitor, pioglitazone, sulfonylurea, or SGLT-2 inhibitor (if NICE criteria are met). If a patient doesn’t achieve control on dual therapy, triple therapy options include adding a sulfonylurea or GLP-1 mimetic. GLP-1 mimetics should only be added to insulin under specialist care. Blood pressure targets are the same as for patients without type 2 diabetes, and ACE inhibitors or ARBs are first-line for hypertension. Antiplatelets should not be offered unless a patient has existing cardiovascular disease, and only patients with a 10-year cardiovascular risk > 10% should be offered a statin.

If a patient with type 2 diabetes mellitus is taking the maximum dose of metformin and has an HbA1c level of 58 mmol/mol or higher, it is recommended to add a second drug to their treatment regimen. The patient should be closely monitored and have their HbA1c level checked again in 3-6 months to ensure stability on the new therapy. It is important to intensify treatment at this stage, but referral to secondary care is not necessary and primary care should manage the patient’s management. Insulin therapy is not recommended yet, and a further oral agent should be added first. If the second agent fails to reduce HbA1c, triple therapy may be considered. Lifestyle advice and management should also be provided at each review.

NICE has updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2022 to reflect advances in drug therapy and improved evidence regarding newer therapies such as SGLT-2 inhibitors. For the average patient taking metformin for T2DM, lifestyle changes and titrating up metformin to aim for a HbA1c of 48 mmol/mol (6.5%) is recommended. A second drug should only be added if the HbA1c rises to 58 mmol/mol (7.5%). Dietary advice includes encouraging high fiber, low glycemic index sources of carbohydrates, controlling intake of saturated fats and trans fatty acids, and initial target weight loss of 5-10% in overweight individuals.

Individual HbA1c targets should be agreed upon with patients to encourage motivation, and HbA1c should be checked every 3-6 months until stable, then 6 monthly. Targets should be relaxed on a case-by-case basis, with particular consideration for older or frail adults with type 2 diabetes. Metformin remains the first-line drug of choice, and SGLT-2 inhibitors should be given in addition to metformin if the patient has a high risk of developing cardiovascular disease (CVD), established CVD, or chronic heart failure. If metformin is contraindicated, SGLT-2 monotherapy or a DPP-4 inhibitor, pioglitazone, or sulfonylurea may be used.

Further drug therapy options depend on individual clinical circumstances and patient preference. Dual therapy options include adding a DPP-4 inhibitor, pioglitazone, sulfonylurea, or SGLT-2 inhibitor (if NICE criteria are met). If a patient doesn’t achieve control on dual therapy, triple therapy options include adding a sulfonylurea or GLP-1 mimetic. GLP-1 mimetics should only be added to insulin under specialist care. Blood pressure targets are the same as for patients without type 2 diabetes, and ACE inhibitors or ARBs are first-line for hypertension. Antiplatelets should not be offered unless a patient has existing cardiovascular disease, and only patients with a 10-year cardiovascular risk > 10% should be offered a statin.

Understanding Insulin Regimens for Type I Diabetes

When a patient is diagnosed with type I diabetes, it is crucial to refer them to a diabetes specialist team for immediate care. One of the recommended treatment regimens is the basal-bolus insulin regimen, which involves taking a longer-acting insulin to stabilize blood glucose levels during fasting periods (basal regimen) and separate injections of shorter-acting insulin to prevent post-meal blood sugar spikes (bolus regimen). This is the preferred treatment according to NICE guidelines.

A bolus insulin regimen involves monitoring blood sugar levels multiple times a day and administering insulin in response to rises in blood sugar. However, this is not recommended for newly diagnosed type I diabetes. A basal insulin regimen involves taking a long-acting basal insulin injection at regular intervals, but with no additional insulin to compensate for postprandial blood sugar spikes. This may be appropriate for severe insulin resistance in poorly managed type II diabetes, but not for type I diabetes.

Oral hypoglycemic agents are used in the management of type II diabetes, but not for type I diabetes, which requires insulin. A twice-daily mixed insulin regimen may be suitable for those with a regular daily routine that includes three main meals at similar times each day. However, NICE guidance recommends against non-basal-bolus insulin regimens for adults with newly diagnosed type I diabetes. This patient, a student with an irregular daily routine, would not be suitable for a twice-daily mixed insulin regimen.

Managing Diabetes Mellitus During Ramadan

Type 2 diabetes mellitus is more prevalent in people of Asian ethnicity, including a significant number of Muslim patients in the UK. With Ramadan falling in the long days of summer, it is crucial to provide appropriate advice to Muslim patients to ensure they can safely observe their fast. While it is a personal decision whether to fast, it is worth noting that people with chronic conditions are exempt from fasting or may delay it to shorter days in winter. However, many Muslim patients with diabetes do not consider themselves exempt from fasting. Around 79% of Muslim patients with type 2 diabetes mellitus fast during Ramadan.

To help patients with type 2 diabetes mellitus fast safely, they should consume a meal containing long-acting carbohydrates before sunrise (Suhoor). Patients should also be given a blood glucose monitor to check their glucose levels, especially if they feel unwell. For patients taking metformin, the dose should be split one-third before sunrise (Suhoor) and two-thirds after sunset (Iftar). For those taking sulfonylureas, the expert consensus is to switch to once-daily preparations after sunset. For patients taking twice-daily preparations such as gliclazide, a larger proportion of the dose should be taken after sunset. No adjustment is necessary for patients taking pioglitazone. Diabetes UK and the Muslim Council of Britain have an excellent patient information leaflet that explores these options in more detail.

Managing diabetes mellitus during Ramadan is crucial to ensure Muslim patients with type 2 diabetes mellitus can safely observe their fast. It is important to provide appropriate advice to patients, including consuming a meal containing long-acting carbohydrates before sunrise, checking glucose levels regularly, and adjusting medication doses accordingly.

Ratios and Activities of Corticosteroids

The ratios of prednisolone to hydrocortisone and dexamethasone to hydrocortisone are approximately 1:4 and 1:24, respectively. While prednisolone mainly exhibits glucocorticoid activity, hydrocortisone has some mineralocorticoid activity, making it suitable for adrenal replacement therapy on its own. However, fludrocortisone is often required for its mineralocorticoid activity. The split dose of hydrocortisone is intended to mimic normal diurnal variation.

Distinguishing Hyperthyroidism from Other Conditions

Hyperthyroidism is a common condition that presents with a variety of symptoms, including weight loss, heat intolerance, and muscle weakness. It is typically caused by Graves’ disease or multinodular goitre. In contrast, carcinoid syndrome is a rare condition associated with carcinoid tumours that primarily affect the midgut. Symptoms of carcinoid syndrome include flushing, diarrhoea, and abdominal pain. Hypothyroidism, on the other hand, results in weight gain, dry skin, and a slow resting pulse. New-onset type 1 diabetes mellitus typically presents with polyuria, polydipsia, and weight loss, while polycystic ovarian syndrome is characterized by obesity, oligomenorrhoea, and signs of hyperandrogenism. By understanding the unique symptoms of each condition, healthcare providers can accurately diagnose and treat patients with hyperthyroidism.

Distinguishing Hyperthyroidism from Other Conditions

Guidelines for Monitoring Blood Glucose Levels in Diabetes

Monitoring blood glucose levels is crucial for individuals with diabetes to manage their condition effectively. Here are some guidelines to follow:

Frequency of Monitoring: Monitoring should be more frequent during a febrile illness, and the frequency should be increased if HBA1c targets are not achieved, hypoglycaemic episodes increase, or if it is a Driver and Vehicle Driving Agency (DVLA) requirement. Monitoring should also be increased before, during, and after sport, during pregnancy and while breastfeeding, and if the patient needs to know the glucose level more than 4 times a day.

Morning and Evening Testing: Blood glucose should be measured in the morning and evening. Self-monitoring of blood glucose is recommended for all adults with Type 1 Diabetes Mellitus, with testing at least 4 times a day, including before each meal and before bedtime.

Excessive Physical Activity: Monitoring should be more frequent during excessive physical activity as it can cause precipitous drops in blood sugar that should be swiftly remedied.

Hypoglycaemic Attacks: Self-monitoring is not only effective, but should also be increased if hypoglycaemic episodes become more common.

Blood Glucose Targets: The target plasma glucose on waking is 7-9 mmol/l. Blood glucose targets are as follows: Fasting plasma glucose level of 5–7 mmol/l on waking, plasma glucose level of 4–7 mmol/l before meals at other times of the day, and plasma glucose level of 5–9 mmol/l at least 90 minutes after eating (timing may be different in pregnancy). Bedtime targets may be different and take into account the time of the last meal and the waking target.

By following these guidelines, individuals with diabetes can effectively manage their condition and prevent complications.

Diabetic Amyotrophy: A Painful Proximal Motor Neuropathy

This patient exhibits several symptoms of diabetic amyotrophy, a painful asymmetrical proximal motor neuropathy that primarily affects the lower limbs. While it can occur bilaterally, it typically presents with pain in the thigh that progresses to proximal muscle wasting, loss of knee reflexes, and tender proximal muscles. While the plantars can become extensor, this is not a common occurrence.

The condition is believed to be caused by the occlusion of the vasa nervorum of the proximal lumbar plexus and/or femoral nerve. It is often associated with poor diabetic control, but it may improve with good control or resolve on its own over time.

Other conditions, such as osteomalacia, hyperthyroidism, and Cushing’s, are unlikely to cause a proximal myopathy involving the quadriceps and hamstrings, with preserved knee reflexes and pain not being a predominant feature. Vitamin B12 deficiency, on the other hand, initially causes peripheral neuropathy, with loss of vibration sense and position, followed by areflexia and weakness. If left untreated, it can lead to spasticity, Babinski plantars, and ataxia.

Autonomic Neuropathy and Gastric Emptying

She has a lengthy medical history of diabetes and has been experiencing nausea after eating, along with a feeling of fullness and a reduced appetite. These symptoms suggest that she may be experiencing reduced gastric emptying, which is a common symptom of autonomic neuropathy. Other symptoms that may be present include postural hypotension, gustatory sweating, diarrhea, or changes in bowel habits. To confirm the diagnosis, a barium swallow and meal may be necessary.

Sick Day Rules for Addison’s Disease

The sick day rules for Addison’s disease are important to know and follow. In the case of a major injury, it is crucial to take 20 mg of Hydrocortisone immediately to prevent shock. If a patient has a fever of more than 37.5 C or an infection/sepsis requiring antibiotics, they should double their normal dose of hydrocortisone. For severe nausea with a headache, taking 20 mg of hydrocortisone orally and sipping rehydration/electrolyte fluids (e.g. Dioralyte) is recommended. In the event of vomiting, the emergency injection of 100 mg hydrocortisone should be used immediately, followed by calling a doctor and stating Addison’s emergency. It is also important to inform any medical professionals, such as anaesthetists, surgical teams, dentists, or endoscopists, of the need for extra oral medication and to check the ACAP surgical guidelines for the correct level of steroid cover. By following these guidelines, patients with Addison’s disease can manage their condition and prevent potentially life-threatening situations.

The TFTs indicate a diagnosis of hypothyroidism, which can be treated with levothyroxine. Carbimazole is not suitable for this condition as it is used to treat hyperthyroidism. To ensure proper absorption, levothyroxine should be taken 30 minutes before consuming food, caffeine, or other medications.

Managing Hypothyroidism: Dosage, Goals, and Side-Effects

Hypothyroidism is a condition where the thyroid gland doesn’t produce enough thyroid hormone. The management of hypothyroidism involves the use of levothyroxine, a synthetic form of thyroid hormone. The initial starting dose of levothyroxine should be lower in elderly patients and those with ischaemic heart disease. For patients with cardiac disease, severe hypothyroidism, or patients over 50 years, the initial starting dose should be 25mcg od with dose slowly titrated. Other patients should be started on a dose of 50-100 mcg od. After a change in thyroxine dose, thyroid function tests should be checked after 8-12 weeks. The therapeutic goal is to achieve a ‘normalisation’ of the thyroid stimulating hormone (TSH) level, with a TSH value of 0.5-2.5 mU/l being the preferred range.

Women with established hypothyroidism who become pregnant should have their dose increased ‘by at least 25-50 micrograms levothyroxine’* due to the increased demands of pregnancy. The TSH should be monitored carefully, aiming for a low-normal value. There is no evidence to support combination therapy with levothyroxine and liothyronine.

Levothyroxine therapy may cause side-effects such as hyperthyroidism due to over-treatment, reduced bone mineral density, worsening of angina, and atrial fibrillation. Interactions with iron and calcium carbonate may reduce the absorption of levothyroxine, so they should be given at least 4 hours apart.

In summary, the management of hypothyroidism involves careful dosage adjustment, regular monitoring of thyroid function tests, and aiming for a TSH value in the normal range. Women who become pregnant should have their dose increased, and combination therapy with levothyroxine and liothyronine is not recommended. Patients should also be aware of potential side-effects and interactions with other medications.

*source: NICE Clinical Knowledge Summaries

Thyrotoxicosis is primarily caused by Graves’ disease in the UK, while the other conditions that can lead to thyrotoxicosis are relatively rare.

Understanding Thyrotoxicosis: Causes and Investigations

Thyrotoxicosis is a condition characterized by an overactive thyroid gland, resulting in an excess of thyroid hormones in the body. Graves’ disease is the most common cause, accounting for 50-60% of cases. Other causes include toxic nodular goitre, subacute thyroiditis, postpartum thyroiditis, Hashimoto’s thyroiditis, amiodarone therapy, and contrast administration. Elderly patients with pre-existing thyroid disease are also at risk.

To diagnose thyrotoxicosis, doctors typically look for a decrease in thyroid-stimulating hormone (TSH) levels and an increase in T4 and T3 levels. Thyroid autoantibodies may also be present. Isotope scanning may be used to investigate further. It is important to note that many causes of hypothyroidism may have an initial thyrotoxic phase, highlighting the complexity of thyroid dysfunction. Patients with existing thyrotoxicosis should avoid iodinated contrast medium, as it can result in hyperthyroidism developing over several weeks.

Exercise Recommendations for Different Diabetic Complications

Untreated diabetic proliferative retinopathy can lead to haemorrhage, which is why patients with this condition should avoid strenuous exercise until they have received photocoagulation therapy. On the other hand, exercise is actually encouraged for patients with peripheral vascular disease and ischaemic heart disease. It is important to understand the different exercise recommendations for various diabetic complications in order to promote optimal health and prevent further complications. By following these guidelines, patients can improve their overall well-being and reduce their risk of developing additional health issues.

Understanding Cushing Syndrome and its Differential Diagnosis

Cushing syndrome is a condition characterized by excessive levels of cortisol in the body. It can be caused by prolonged use of oral corticosteroids or, in rare cases, by a tumor in the adrenal gland. Patients with Cushing syndrome may present with symptoms such as weight gain, moon face, buffalo hump, easy bruising, and thinning of the skin.

It is important to differentiate Cushing syndrome from other conditions with similar symptoms. Addison’s disease, for example, is caused by adrenal failure and presents with weakness, fatigue, and hyperpigmentation of the skin. Conn syndrome, on the other hand, is characterized by hypertension and hypokalemia due to excess aldosterone secretion from an adrenal adenoma.

Diabetes mellitus is a common complication of Cushing syndrome, as it can impair glucose metabolism. Hypothyroidism, while also causing fatigue and weight gain, doesn’t typically present with striae or glycosuria.

In summary, a thorough evaluation is necessary to accurately diagnose Cushing syndrome and differentiate it from other conditions with similar symptoms.

Managing Statin Intolerance in Patients with Ischaemic Heart Disease and Type 2 Diabetes Mellitus

This patient has both ischaemic heart disease and type 2 diabetes mellitus, making him a candidate for statin therapy due to his elevated cholesterol levels. However, he has experienced myalgia and raised liver function tests while taking atorvastatin at its maximum dose, indicating statin intolerance. NICE guidance recommends reducing the dose or trying an alternative statin in such cases. Fibrate and ezetimibe are not recommended for patients with type 2 diabetes. Referral to a specialist may be necessary if statins are not tolerated at all.

To minimize the risk of side effects, starting at a low dose and gradually titrating up can be helpful. Rosuvastatin and pravastatin may have a lower incidence of myalgia compared to other statins. If another statin is prescribed, cautious monitoring of liver function tests is necessary. Patients with a history of statin-related hepatitis or rhabdomyolysis should generally avoid statins in the future if possible.

Pharmacological Management of Neuropathic Pain in Diabetic Patients

According to the NICE guidelines on the pharmacological management of neuropathic pain (CG173), patients with painful diabetic neuropathy should be offered duloxetine, amitriptyline, pregabalin, or gabapentin as first-line treatment. If these medications are contraindicated or not tolerated, capsaicin cream topically may be used for very localized neuropathic pain. Patients should be reviewed early for their symptoms, and treatment should be continued or gradually reduced if symptoms allow. If all the above fail, referral to secondary care is recommended, and adding tramadol while the patient is waiting is worth a try.

Exenatide and its Metabolic Effects

Exenatide is a medication that imitates the effects of GLP-1, a hormone produced in the gut. It has been found to have beneficial effects on the metabolism of individuals with diabetes mellitus. This medication has several metabolic effects, including the suppression of appetite, inhibition of glucose production in the liver, slowing of gastric emptying, and stimulation of insulin release. However, it doesn’t increase insulin sensitivity, which is achieved by other drugs such as metformin and the glitazones. Overall, exenatide has been shown to have a positive impact on the management of diabetes by regulating various metabolic processes.

The correct answer is the FP92A form, which is a medical exemption certificate that can be claimed to entitle a patient to free prescriptions. This form can be claimed if a patient has certain conditions, such as a permanent fistula or diabetes mellitus.

The FP57 form is an NHS receipt for payment of a prescription, which can be used to claim money back later. The GMS1 form is completed by new patients when registering with a GP surgery. The DS1500 form is completed by a doctor for patients with a terminal illness, allowing them to apply for certain benefits.

Prescription Charges in England: Who is Eligible for Free Prescriptions?

In England, prescription charges apply to most medications, but certain groups of people are entitled to free prescriptions. These include children under 16, those aged 16-18 in full-time education, the elderly (aged 60 or over), and individuals who receive income support or jobseeker’s allowance. Additionally, patients with a prescription exemption certificate are exempt from prescription charges.

Certain medications are also exempt from prescription charges, such as contraceptives, STI treatments, hospital prescriptions, and medications administered by a GP.

Women who are pregnant or have had a child in the past year, as well as individuals with certain chronic medical conditions, are eligible for a prescription exemption certificate. These conditions include hypoparathyroidism, hypoadrenalism, diabetes insipidus, diabetes mellitus, myasthenia gravis, hypothyroidism, epilepsy, and certain types of cancer.

For patients who are not eligible for free prescriptions but receive frequent prescriptions, a pre-payment certificate (PPC) may be a cost-effective option. PPCs are cheaper if the patient pays for more than 14 prescriptions per year.

To avoid reducing the absorption of levothyroxine, iron/calcium carbonate tablets should be given four hours apart. The patient’s blood results indicate that her iron levels have been replenished and her blood count is now normal, but her thyroid-stimulating hormone level remains elevated. According to NICE guidelines, iron treatment should be continued for three more months after normalizing haemoglobin concentrations and blood counts before being discontinued. Since the patient’s iron levels are now normal, continuing ferrous sulphate is unnecessary and may hinder the absorption of levothyroxine. Therefore, it is advisable to discontinue iron and observe if her thyroid hormone levels normalize before adjusting her levothyroxine dosage.

If a patient with hypothyroidism has a structural change in the thyroid gland or is suspected of having an underlying endocrine disease such as Addison’s disease, they should be referred to endocrinology. However, this patient doesn’t appear to have any of these conditions, but it is essential to conduct a neck examination to ensure that there are no palpable masses.

Managing Hypothyroidism: Dosage, Goals, and Side-Effects

Hypothyroidism is a condition where the thyroid gland doesn’t produce enough thyroid hormone. The management of hypothyroidism involves the use of levothyroxine, a synthetic form of thyroid hormone. The initial starting dose of levothyroxine should be lower in elderly patients and those with ischaemic heart disease. For patients with cardiac disease, severe hypothyroidism, or patients over 50 years, the initial starting dose should be 25mcg od with dose slowly titrated. Other patients should be started on a dose of 50-100 mcg od. After a change in thyroxine dose, thyroid function tests should be checked after 8-12 weeks. The therapeutic goal is to achieve a ‘normalisation’ of the thyroid stimulating hormone (TSH) level, with a TSH value of 0.5-2.5 mU/l being the preferred range.

Women with established hypothyroidism who become pregnant should have their dose increased ‘by at least 25-50 micrograms levothyroxine’* due to the increased demands of pregnancy. The TSH should be monitored carefully, aiming for a low-normal value. There is no evidence to support combination therapy with levothyroxine and liothyronine.

Levothyroxine therapy may cause side-effects such as hyperthyroidism due to over-treatment, reduced bone mineral density, worsening of angina, and atrial fibrillation. Interactions with iron and calcium carbonate may reduce the absorption of levothyroxine, so they should be given at least 4 hours apart.

In summary, the management of hypothyroidism involves careful dosage adjustment, regular monitoring of thyroid function tests, and aiming for a TSH value in the normal range. Women who become pregnant should have their dose increased, and combination therapy with levothyroxine and liothyronine is not recommended. Patients should also be aware of potential side-effects and interactions with other medications.

*source: NICE Clinical Knowledge Summaries

Understanding Hypogonadism: Interpreting Testosterone Results and Treatment Considerations

Hypogonadism, or low testosterone, can present with a variety of symptoms including low libido, erectile dysfunction, and loss of early morning erections. When low testosterone is detected, further testing with follicle-stimulating hormone (FSH), luteinising hormone (LH), and prolactin measurements can help distinguish primary from secondary hypogonadism.

There are several factors that can contribute to reversible hypogonadism, including concurrent illness, certain medications, and lifestyle factors such as excessive alcohol consumption and stress. However, it is important to note that hypogonadism should be treated with testosterone replacement therapy, regardless of age, but only after confirming the diagnosis with repeat testing.

It is also important to consider age-related declines in testosterone levels, which typically occur after the age of 30. However, this decline may be a result of deteriorating general health rather than the cause. Therefore, it is crucial to interpret testosterone results in the context of the patient’s symptoms and overall health status.

In cases where hypogonadism is suspected, referral to an endocrinologist may be necessary if there are suggestive clinical symptoms and chronic androgen deficiency. However, it is important to note that testosterone replacement therapy should not be initiated solely based on age or a single low testosterone result.

Patients with type 2 diabetes mellitus should aim for the same blood pressure targets as those without diabetes, as long as they are under 80 years old. This means keeping clinic readings below 140/90 and ABPM/HBPM readings below 135/85. It is important to note that these targets apply regardless of whether the patient has any end-organ damage.

NICE has updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2022 to reflect advances in drug therapy and improved evidence regarding newer therapies such as SGLT-2 inhibitors. For the average patient taking metformin for T2DM, lifestyle changes and titrating up metformin to aim for a HbA1c of 48 mmol/mol (6.5%) is recommended. A second drug should only be added if the HbA1c rises to 58 mmol/mol (7.5%). Dietary advice includes encouraging high fiber, low glycemic index sources of carbohydrates, controlling intake of saturated fats and trans fatty acids, and initial target weight loss of 5-10% in overweight individuals.

Individual HbA1c targets should be agreed upon with patients to encourage motivation, and HbA1c should be checked every 3-6 months until stable, then 6 monthly. Targets should be relaxed on a case-by-case basis, with particular consideration for older or frail adults with type 2 diabetes. Metformin remains the first-line drug of choice, and SGLT-2 inhibitors should be given in addition to metformin if the patient has a high risk of developing cardiovascular disease (CVD), established CVD, or chronic heart failure. If metformin is contraindicated, SGLT-2 monotherapy or a DPP-4 inhibitor, pioglitazone, or sulfonylurea may be used.

Further drug therapy options depend on individual clinical circumstances and patient preference. Dual therapy options include adding a DPP-4 inhibitor, pioglitazone, sulfonylurea, or SGLT-2 inhibitor (if NICE criteria are met). If a patient doesn’t achieve control on dual therapy, triple therapy options include adding a sulfonylurea or GLP-1 mimetic. GLP-1 mimetics should only be added to insulin under specialist care. Blood pressure targets are the same as for patients without type 2 diabetes, and ACE inhibitors or ARBs are first-line for hypertension. Antiplatelets should not be offered unless a patient has existing cardiovascular disease, and only patients with a 10-year cardiovascular risk > 10% should be offered a statin.

Lipophilic statins such as simvastatin and atorvastatin are more likely to cause myopathy compared to relatively hydrophilic statins like rosuvastatin, pravastatin, and fluvastatin.

Statins are drugs that inhibit the action of HMG-CoA reductase, which is the enzyme responsible for cholesterol synthesis in the liver. However, they can cause adverse effects such as myopathy, liver impairment, and an increased risk of intracerebral hemorrhage in patients with a history of stroke. Statins should not be taken during pregnancy or in combination with macrolides. NICE recommends statins for patients with established cardiovascular disease, a 10-year cardiovascular risk of 10% or higher, type 2 diabetes mellitus, or type 1 diabetes mellitus with certain criteria. It is recommended to take statins at night, especially simvastatin, which has a shorter half-life than other statins. NICE recommends atorvastatin 20 mg for primary prevention and atorvastatin 80 mg for secondary prevention.

If a patient over the age of 60 presents with new-onset diabetes and weight loss, it is recommended to refer them for an urgent CT abdomen to rule out pancreatic cancer. In this case, the patient has been diagnosed with type 2 diabetes mellitus based on symptoms and blood tests. While metformin can be initiated in primary care, it is important to prioritize ruling out pancreatic cancer as a potential cause for the diabetes. Medication options should be considered based on the patient’s history and blood tests, with gliclazide not being the best choice for this patient’s body mass index. Blood sugar monitoring devices are not typically necessary for type 2 diabetes mellitus patients, unless they are started on a medication that can cause hypoglycemia. Hba1c monitoring is usually sufficient. This information is based on guidelines from NICE CKS.

The diagnosis of type 2 diabetes mellitus can be made through a plasma glucose or HbA1c sample. Diagnostic criteria vary depending on whether the patient is symptomatic or not. WHO released guidance on the use of HbA1c for diagnosis, with a value of 48 mmol/mol or higher being diagnostic of diabetes. Impaired fasting glucose and impaired glucose tolerance are also defined. People with IFG should be offered an oral glucose tolerance test to rule out a diagnosis of diabetes.

To evaluate diabetic neuropathy in the feet, it is recommended to utilize a monofilament weighing 10 grams.

Diabetic foot disease is a significant complication of diabetes mellitus that requires regular screening. In 2015, NICE published guidelines on diabetic foot disease. The disease is caused by two main factors: neuropathy, which results in a loss of protective sensation, and peripheral arterial disease, which can cause macro and microvascular ischaemia. Symptoms of diabetic foot disease include loss of sensation, absent foot pulses, reduced ankle-brachial pressure index (ABPI), intermittent claudication, calluses, ulceration, Charcot’s arthropathy, cellulitis, osteomyelitis, and gangrene.

All patients with diabetes should be screened for diabetic foot disease at least once a year. Screening for ischaemia involves palpating for both the dorsalis pedis pulse and posterial tibial artery pulse, while screening for neuropathy involves using a 10 g monofilament on various parts of the sole of the foot. NICE recommends that patients be risk-stratified into low, moderate, and high-risk categories based on factors such as deformity, previous ulceration or amputation, renal replacement therapy, and the presence of calluses or neuropathy. Patients who are moderate or high-risk should be regularly followed up by their local diabetic foot centre.

Understanding Diabetic Nephropathy: Myths and Facts

Diabetic nephropathy is a serious complication of diabetes that can lead to renal failure. However, there are several myths and misconceptions surrounding this condition. Here are some important facts to help you better understand diabetic nephropathy:

Myth: Only patients with proteinuria are at risk of developing diabetic nephropathy.
Fact: Microalbuminuria, a small increase in albumin excretion in the urine, is an early sign of diabetic nephropathy. Approximately 40% of patients with type 1 diabetes of 30 years’ disease duration have microalbuminuria. Optimal control of blood pressure, blood glucose, and lipids can help prevent the progression of microalbuminuria to proteinuria.

Myth: Aggressive antihypertensive therapy can stop the decline in glomerular filtration rate in patients with proteinuria.
Fact: Even with aggressive antihypertensive therapy, patients with proteinuria still lose glomerular filtration rate at a rate of approximately 4 ml/min/year.

Myth: ACE inhibitors are only indicated for patients with proteinuria, not microalbuminuria.
Fact: ACE inhibitors should be started and increased up to the full dose in all adults with diabetic nephropathy, including those with microalbuminuria. ACE inhibitors significantly reduce the risk of all-cause mortality for patients with diabetic kidney disease.

Myth: Microalbuminuria, once developed, doesn’t regress.
Fact: In about one-third of cases, microalbuminuria can return to normal.

Myth: The combination of proteinuria and hypertension only slightly increases the risk of mortality.
Fact: When proteinuria and hypertension are present, the standardised mortality ratio is increased by 11 times in men and 18 times in women. Many of the deaths are due to cardiovascular disease.

Debunking Myths About Diabetic Nephropathy

NICE Guidelines on Lipid Modification

According to the NICE guidelines on lipid modification (CG181), it is important to consider the possibility of familial hypercholesterolaemia in patients with a total cholesterol concentration of more than 7.5 mmol/L and a family history of premature coronary heart disease. In such cases, investigation is necessary to determine the presence of the condition.

For patients with a total cholesterol concentration of more than 9.0 mmol/L or a non-HDL cholesterol concentration of more than 7.5 mmol/L, specialist assessment is recommended even in the absence of a first-degree family history of premature coronary heart disease. This is important to ensure appropriate management and treatment of high cholesterol levels, which can significantly increase the risk of cardiovascular disease.

Overall, following these guidelines can help healthcare professionals identify and manage patients with high cholesterol levels, reducing the risk of serious health complications.

When a patient has consistently high prolactin levels without a clear cause, it may be due to a prolactinoma, a type of pituitary tumor. In the case of a microprolactinoma, the prolactin levels may be between 1000-5000 mIU/l, but the patient’s hormone profile and visual fields are normal. Hyperprolactinemia can inhibit the release of gonadotropin-releasing hormone, leading to symptoms such as infertility and decreased libido. Treatment options include surgery or medication with dopamine agonists. Macroprolactinoma, acromegaly, and hypothyroidism are unlikely causes in this case. Psychogenic impotence doesn’t explain the elevated prolactin levels.

To ensure safe use of metformin, it is important to regularly monitor renal function in patients. Prior to prescribing metformin, renal function should be assessed and then monitored periodically thereafter. Patients with normal renal function should have their renal function checked at least once a year, while those with additional risk factors for renal impairment should have it checked at least twice a year. If the estimated glomerular filtration rate (eGFR) falls below 30, metformin should not be initiated. If the eGFR drops below 45, the metformin dosage should be reevaluated.

Metformin is a medication commonly used to treat type 2 diabetes mellitus, as well as polycystic ovarian syndrome and non-alcoholic fatty liver disease. Unlike other medications, such as sulphonylureas, metformin doesn’t cause hypoglycaemia or weight gain, making it a first-line treatment option, especially for overweight patients. Its mechanism of action involves activating the AMP-activated protein kinase, increasing insulin sensitivity, decreasing hepatic gluconeogenesis, and potentially reducing gastrointestinal absorption of carbohydrates. However, metformin can cause gastrointestinal upsets, reduced vitamin B12 absorption, and in rare cases, lactic acidosis, particularly in patients with severe liver disease or renal failure. It is contraindicated in patients with chronic kidney disease, recent myocardial infarction, sepsis, acute kidney injury, severe dehydration, and those undergoing iodine-containing x-ray contrast media procedures. When starting metformin, it should be titrated up slowly to reduce the incidence of gastrointestinal side-effects, and modified-release metformin can be considered for patients who experience unacceptable side-effects.

Carbimazole and Infection Risk

Carbimazole is a medication used to treat thyrotoxicosis by blocking the iodination of thyroid hormone. However, patients taking carbimazole should be aware of the potential risk of infection, particularly sore throat, and report any symptoms or signs of infection to their healthcare provider. This is because carbimazole can cause bone marrow suppression, which can lead to agranulocytosis, a rare but serious adverse effect.

If a patient on carbimazole presents with an acute illness consisting of fever, malaise, and sore throat, a full blood count should be performed to assess the white blood cell count and differential. If neutropenia is found, carbimazole should be stopped immediately. It is important for healthcare providers to monitor patients taking carbimazole for signs of infection and to take appropriate action if necessary to prevent serious complications.

Understanding the Association of Metabolic Syndrome with Various Health Conditions

Metabolic syndrome is a condition that is characterized by multiple cardiovascular risk factors and is associated with insulin resistance. It is prevalent worldwide, affecting approximately 1 in every 4 or 5 adults, and is caused by a combination of genetics and lifestyle. The syndrome is typically defined by raised fasting plasma glucose, high blood pressure, low HDL, central obesity, and hypertriglyceridemia. Treatment involves exercise, weight loss, management of dyslipidemia and hypertension, and correction of glucose levels. However, the usefulness of the metabolic syndrome concept in predicting cardiovascular risk has been questioned.

Thyrotoxicosis, type I diabetes, and hypothyroidism are not associated with metabolic syndrome. Endocrine conditions associated with thyrotoxicosis include insulin resistance, type II diabetes, and polycystic ovarian syndrome. Alcoholic liver disease is not associated with metabolic syndrome, but non-alcoholic fatty liver disease is. Other conditions that are linked to metabolic syndrome include obesity, sleep apnea, and gallstones. Understanding the association of metabolic syndrome with various health conditions is crucial in managing and preventing the syndrome’s complications.

If a patient with T2DM cannot take metformin due to contraindications and has a risk of CVD, established CVD, or chronic heart failure, the recommended initial therapy is SGLT-2 monotherapy.

NICE has updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2022 to reflect advances in drug therapy and improved evidence regarding newer therapies such as SGLT-2 inhibitors. For the average patient taking metformin for T2DM, lifestyle changes and titrating up metformin to aim for a HbA1c of 48 mmol/mol (6.5%) is recommended. A second drug should only be added if the HbA1c rises to 58 mmol/mol (7.5%). Dietary advice includes encouraging high fiber, low glycemic index sources of carbohydrates, controlling intake of saturated fats and trans fatty acids, and initial target weight loss of 5-10% in overweight individuals.

Individual HbA1c targets should be agreed upon with patients to encourage motivation, and HbA1c should be checked every 3-6 months until stable, then 6 monthly. Targets should be relaxed on a case-by-case basis, with particular consideration for older or frail adults with type 2 diabetes. Metformin remains the first-line drug of choice, and SGLT-2 inhibitors should be given in addition to metformin if the patient has a high risk of developing cardiovascular disease (CVD), established CVD, or chronic heart failure. If metformin is contraindicated, SGLT-2 monotherapy or a DPP-4 inhibitor, pioglitazone, or sulfonylurea may be used.

Further drug therapy options depend on individual clinical circumstances and patient preference. Dual therapy options include adding a DPP-4 inhibitor, pioglitazone, sulfonylurea, or SGLT-2 inhibitor (if NICE criteria are met). If a patient doesn’t achieve control on dual therapy, triple therapy options include adding a sulfonylurea or GLP-1 mimetic. GLP-1 mimetics should only be added to insulin under specialist care. Blood pressure targets are the same as for patients without type 2 diabetes, and ACE inhibitors or ARBs are first-line for hypertension. Antiplatelets should not be offered unless a patient has existing cardiovascular disease, and only patients with a 10-year cardiovascular risk > 10% should be offered a statin.

Diagnosing Chest Tightness and Palpitations in Primary Care

Symptoms of chest tightness and palpitations are common in primary care, but diagnosing the underlying cause can be challenging. Episodic symptoms often require catching the symptoms during an attack to make an accurate diagnosis. Patients may describe a previous attack, but positive examination findings are often lacking when they are asymptomatic. Therefore, history is crucial, and patients should seek review when experiencing symptoms.

In this case, the patient presented with high blood pressure, tachycardia, and glycosuria during an attack. The episodic nature of the symptoms suggested panic attacks, phaeochromocytoma, or a paroxysmal tachyarrhythmia such as Wolff-Parkinson-White (WPW) syndrome. However, WPW typically causes paroxysmal supraventricular tachycardia and would not cause glycosuria. Panic attacks would not cause glycosuria, and the severity of the hypertension would go against this diagnosis. Phaeochromocytoma unifies the history and clinical features and is the underlying disorder.

Phaeochromocytoma is a rare tumour that produces catecholamines and causes episodes of hypertension, chest tightness, sweating, tremor, and flushing. Glycosuria occurs in approximately 30% of patients during an attack. Diagnosis is made by a 24-hour urine collection for metanephrines, and surgical removal is the treatment of choice.

The HbA1c target for individuals with type 2 diabetes mellitus who are taking a single drug not linked to hypoglycemia, such as metformin, is 48 mmol/mol. However, if they are taking multiple medications or a single medication that is associated with hypoglycemia, the target may differ.

NICE has updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2022 to reflect advances in drug therapy and improved evidence regarding newer therapies such as SGLT-2 inhibitors. For the average patient taking metformin for T2DM, lifestyle changes and titrating up metformin to aim for a HbA1c of 48 mmol/mol (6.5%) is recommended. A second drug should only be added if the HbA1c rises to 58 mmol/mol (7.5%). Dietary advice includes encouraging high fiber, low glycemic index sources of carbohydrates, controlling intake of saturated fats and trans fatty acids, and initial target weight loss of 5-10% in overweight individuals.

Individual HbA1c targets should be agreed upon with patients to encourage motivation, and HbA1c should be checked every 3-6 months until stable, then 6 monthly. Targets should be relaxed on a case-by-case basis, with particular consideration for older or frail adults with type 2 diabetes. Metformin remains the first-line drug of choice, and SGLT-2 inhibitors should be given in addition to metformin if the patient has a high risk of developing cardiovascular disease (CVD), established CVD, or chronic heart failure. If metformin is contraindicated, SGLT-2 monotherapy or a DPP-4 inhibitor, pioglitazone, or sulfonylurea may be used.

Further drug therapy options depend on individual clinical circumstances and patient preference. Dual therapy options include adding a DPP-4 inhibitor, pioglitazone, sulfonylurea, or SGLT-2 inhibitor (if NICE criteria are met). If a patient doesn’t achieve control on dual therapy, triple therapy options include adding a sulfonylurea or GLP-1 mimetic. GLP-1 mimetics should only be added to insulin under specialist care. Blood pressure targets are the same as for patients without type 2 diabetes, and ACE inhibitors or ARBs are first-line for hypertension. Antiplatelets should not be offered unless a patient has existing cardiovascular disease, and only patients with a 10-year cardiovascular risk > 10% should be offered a statin.

The Pros and Cons of Self-Monitoring Blood Glucose Levels in Type 2 Diabetes

Self-monitoring of blood glucose levels is a common practice among individuals with type 2 diabetes. While it has its benefits, there are also some drawbacks to consider.

Association with Increased Levels of Depression:
The ESMON trial found that participants in the self-monitoring group were more depressed compared to the control group. This suggests that self-monitoring may have a negative impact on mental health.

No Significant Difference in Episodes of Hypoglycemia:
Contrary to popular belief, self-monitoring did not lead to fewer episodes of hypoglycemia compared to the control group in the ESMON study.

Not More Effective in Reducing Long-Term Complications:
While good diabetic control can reduce long-term complications, self-monitoring has not been shown to be more effective than monitoring HbA1c levels.

Not Cost-Effective:
The DiGEM trial found that self-monitoring was more expensive and resulted in lower quality of life compared to the control group.

No Significant Difference in HbA1c Levels:
In the ESMON study, there was no significant difference in HbA1c levels between the self-monitoring group and the control group.

In conclusion, self-monitoring blood glucose levels may have some benefits, but it is important to consider the potential drawbacks before making it a regular practice. It is recommended to discuss with a healthcare provider to determine if self-monitoring is appropriate for individual needs.

Understanding Hashimoto’s Thyroiditis

Hashimoto’s thyroiditis is a chronic autoimmune disorder that affects the thyroid gland. It is more common in women and is typically associated with hypothyroidism, although there may be a temporary period of thyrotoxicosis during the acute phase. The condition is characterized by a firm, non-tender goitre and the presence of anti-thyroid peroxidase (TPO) and anti-thyroglobulin (Tg) antibodies.

Hashimoto’s thyroiditis is often associated with other autoimmune conditions such as coeliac disease, type 1 diabetes mellitus, and vitiligo. Additionally, there is an increased risk of developing MALT lymphoma with this condition. It is important to note that many causes of hypothyroidism may have an initial thyrotoxic phase, as shown in the Venn diagram. Understanding the features and associations of Hashimoto’s thyroiditis can aid in its diagnosis and management.

Understanding Glycaemic Index: Comparing the Effect of Different Foods on Blood Glucose Levels

The glycaemic index is a measure of how quickly a carbohydrate-containing food raises blood glucose levels. It compares the digestion rate of a food to that of glucose, which has a glycaemic index of 100. Choosing foods with a lower glycaemic index can help regulate blood glucose levels in people with diabetes.

In this list, cornflakes have the highest glycaemic index (80), while bananas (58), carrots (41), yoghurt (33), and peanuts (14) have lower glycaemic indices. However, other factors such as cooking methods, ripeness of fruits and vegetables, and the fat or protein content of a meal can also affect the glycaemic index of a food. For example, chocolate has a low glycaemic index due to its fat content, which slows down carbohydrate absorption.

Understanding the glycaemic index can help individuals make informed choices about their diet and manage their blood glucose levels effectively.

Metformin: The Preferred Drug for Overweight Patients with Diabetes

Metformin is the preferred drug for overweight patients with diabetes due to its ability to suppress appetite, decrease gluconeogenesis, and increase peripheral glucose utilization. Unlike other diabetes medications, metformin doesn’t cause hypoglycemia. However, caution should be exercised when using metformin in patients with renal impairment as it may increase the risk of lactic acidosis. According to the National Institute of Health and Care Excellence guidance, the dose of metformin should be reviewed if the estimated glomerular filtration rate (eGFR) is less than 45 ml/minute/1.73 m2 and avoided if the eGFR is less than 30 ml/minute/1.73 m2. Treatment should be discontinued in patients at risk of tissue hypoxia or sudden deterioration in renal function, such as those with dehydration, severe infection, shock, sepsis, acute heart failure, respiratory failure, hepatic impairment, or those who have recently had a myocardial infarction.

Symptoms of Hypoadrenalism and Hypopituitarism

Hypoadrenalism, also known as Addison’s disease, can be caused by autoimmune destruction of the adrenal cortex, granulomatous disorders, tuberculosis, tumours, or infections. Glucocorticoid deficiency, commonly seen in Addison’s disease, can cause pigmentation of the palms due to elevated levels of melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH).

Hypopituitarism can cause a variety of symptoms, including pallor due to normochromic, normocytic anaemia, postural hypotension related to glucocorticoid deficiency, and visual-field defects from pressure on the optic nerve caused by a pituitary tumour. Lack of body hair and amenorrhoea are also features of hypogonadism in hypopituitarism.

Graves’ Disease: Common Features and Unique Signs

Graves’ disease is the most frequent cause of thyrotoxicosis, which is commonly observed in women aged 30-50 years. The condition presents typical features of thyrotoxicosis, such as weight loss, palpitations, and heat intolerance. However, Graves’ disease also displays specific signs that are not present in other causes of thyrotoxicosis. These include eye signs, such as exophthalmos and ophthalmoplegia, as well as pretibial myxoedema and thyroid acropachy. The latter is a triad of digital clubbing, soft tissue swelling of the hands and feet, and periosteal new bone formation.

Graves’ disease is characterized by the presence of autoantibodies, including TSH receptor stimulating antibodies in 90% of patients and anti-thyroid peroxidase antibodies in 75% of patients. Thyroid scintigraphy reveals a diffuse, homogenous, and increased uptake of radioactive iodine. These features help distinguish Graves’ disease from other causes of thyrotoxicosis and aid in its diagnosis.

Hypothyroidism as a Possible Cause of Weight Gain, Menorrhagia, and Carpal Tunnel Syndrome

The combination of weight gain, menorrhagia, and carpal tunnel syndrome in a patient is highly suggestive of hypothyroidism. While the patient may also be at risk of type 2 diabetes due to her obesity, it is not the primary cause of her symptoms. The most common cause of hypothyroidism in the UK population is autoimmune lymphocytic thyroiditis. Treatment for this condition typically involves thyroid hormone replacement.

According to NICE, women who experience menopause before the age of 45 should contemplate using hormone replacement therapy to decrease the likelihood of developing osteoporosis and to manage menopausal symptoms. It is recommended that the therapy be evaluated at the age of 50. Additionally, patients should receive guidance on lifestyle choices that promote bone health, such as engaging in weight-bearing exercise, quitting smoking, avoiding excessive alcohol consumption, and ensuring sufficient intake of calcium and vitamin D.

Hormone Replacement Therapy: Uses and Varieties

Hormone replacement therapy (HRT) is a treatment that involves administering a small amount of estrogen, combined with a progestogen (in women with a uterus), to alleviate menopausal symptoms. The indications for HRT have changed significantly over the past decade due to the long-term risks that have become apparent, primarily as a result of the Women’s Health Initiative (WHI) study.

The most common indication for HRT is vasomotor symptoms such as flushing, insomnia, and headaches. Other indications, such as reversal of vaginal atrophy, should be treated with other agents as first-line therapies. HRT is also recommended for women who experience premature menopause, which should be continued until the age of 50 years. The most important reason for giving HRT to younger women is to prevent the development of osteoporosis. Additionally, HRT has been shown to reduce the incidence of colorectal cancer.

HRT generally consists of an oestrogenic compound, which replaces the diminished levels that occur in the perimenopausal period. This is normally combined with a progestogen if a woman has a uterus to reduce the risk of endometrial cancer. The choice of hormone includes natural oestrogens such as estradiol, estrone, and conjugated oestrogen, which are generally used rather than synthetic oestrogens such as ethinylestradiol (which is used in the combined oral contraceptive pill). Synthetic progestogens such as medroxyprogesterone, norethisterone, levonorgestrel, and drospirenone are usually used. A levonorgestrel-releasing intrauterine system (e.g. Mirena) may be used as the progestogen component of HRT, i.e. a woman could take an oral oestrogen and have endometrial protection using a Mirena coil. Tibolone, a synthetic compound with both oestrogenic, progestogenic, and androgenic activity, is another option.

HRT can be taken orally or transdermally (via a patch or gel). Transdermal is preferred if the woman is at risk of venous thromboembolism (VTE), as the rates of VTE do not appear to rise with transdermal preparations.

In the case of a child weighing 25kg or less experiencing hypoglycaemia, glucagon 500 mcg should be given via IM if oral treatment is not possible or ineffective. Hypoglycaemia is clinically defined as a blood glucose level below 3.5 mmol/L, which is the case for this child. Despite the mother’s attempts at oral treatment, the child has not improved, making it necessary to administer glucagon to prevent further deterioration. Once the child is stable, it is advisable to contact the paediatric team for further evaluation and management.

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.

Effects of Cholesterol-Lowering Medications on Glucose Control

The mechanism by which nicotinic acid affects glucose levels is not fully understood, but it may increase blood glucose in some patients by stimulating hepatic glucose output or blocking glucose uptake by skeletal muscle. However, for most patients with diabetes, nicotinic acid has minimal effect. A meta-analysis in 2011 suggested an increased risk of inducing diabetes in patients treated with intensive statin therapy, but this did not examine whether statins worsened glucose control in established diabetics. Cholestyramine may interact with oral hypoglycemics, but it doesn’t typically worsen diabetic control and may even improve it. Fenofibrate and ezetimibe have not been shown to worsen diabetic control. Overall, the effects of cholesterol-lowering medications on glucose control vary and should be monitored closely in patients with diabetes.

Diagnosis of Diabetes: Interpreting Plasma Glucose Concentrations

The diagnosis of diabetes is based on interpreting plasma glucose concentrations. To diagnose diabetes mellitus, a fasting plasma glucose above 7 mmol/L or a random glucose above 11.1 mmol/L is required. However, it is important to note that two plasma glucose readings are needed according to these parameters in an asymptomatic patient to make the diagnosis. In a symptomatic patient, only one reading is needed.

It is crucial to pay attention to the details of the question and not misinterpret any of the options. For instance, candidates may misread or misinterpret the threshold of 7.0 mmol/L and argue that 7.1 mmol/L cannot be the correct answer. Therefore, using good examination technique, it is recommended to go over the options again to ensure that the question has been read correctly.

If a woman has hypothyroidism, it is recommended to promptly raise the dosage of levothyroxine and closely observe her TSH levels.

Managing Hypothyroidism: Dosage, Goals, and Side-Effects

Hypothyroidism is a condition where the thyroid gland doesn’t produce enough thyroid hormone. The management of hypothyroidism involves the use of levothyroxine, a synthetic form of thyroid hormone. The initial starting dose of levothyroxine should be lower in elderly patients and those with ischaemic heart disease. For patients with cardiac disease, severe hypothyroidism, or patients over 50 years, the initial starting dose should be 25mcg od with dose slowly titrated. Other patients should be started on a dose of 50-100 mcg od. After a change in thyroxine dose, thyroid function tests should be checked after 8-12 weeks. The therapeutic goal is to achieve a ‘normalisation’ of the thyroid stimulating hormone (TSH) level, with a TSH value of 0.5-2.5 mU/l being the preferred range.

Women with established hypothyroidism who become pregnant should have their dose increased ‘by at least 25-50 micrograms levothyroxine’* due to the increased demands of pregnancy. The TSH should be monitored carefully, aiming for a low-normal value. There is no evidence to support combination therapy with levothyroxine and liothyronine.

Levothyroxine therapy may cause side-effects such as hyperthyroidism due to over-treatment, reduced bone mineral density, worsening of angina, and atrial fibrillation. Interactions with iron and calcium carbonate may reduce the absorption of levothyroxine, so they should be given at least 4 hours apart.

In summary, the management of hypothyroidism involves careful dosage adjustment, regular monitoring of thyroid function tests, and aiming for a TSH value in the normal range. Women who become pregnant should have their dose increased, and combination therapy with levothyroxine and liothyronine is not recommended. Patients should also be aware of potential side-effects and interactions with other medications.

*source: NICE Clinical Knowledge Summaries

Endocrine Conditions and Associated Symptoms

Endocrine conditions can lead to various symptoms depending on the hormones involved. Diabetes secondary to other endocrine conditions is caused by excess hormones that have antagonistic actions to insulin. Growth hormone and cortisol are two such hormones that can cause diabetes. Maculopathy is a common symptom of diabetes of long duration and is related to poor glycaemic control. It can also be present in patients with secondary diabetes if they have gone undiagnosed for some time. However, maculopathy is not related to any of the hormone excesses seen in these conditions.

Hypertension can be a feature of both acromegaly and Cushing syndrome. A bitemporal visual-field defect can also be a feature of both conditions due to the pressure effect of a pituitary adenoma. Long-lasting stimulation of the follicular epithelium by growth hormone and insulin-like growth factor 1 can cause disorders in thyroid function, an increase in its mass and the development of goitre. Patients with acromegaly most frequently present with non-toxic multinodular goitre.

Cushing syndrome can cause multiple striae and bruises due to deficient collagen synthesis, resulting in thin and fragile skin. It is important to recognize these symptoms and seek medical attention for proper diagnosis and treatment.

Postpartum Thyroiditis

The likely diagnosis for the patient is postpartum thyroiditis, which typically occurs within three months of delivery and is followed by a hypothyroid phase at three to six months. In one third of cases, there is spontaneous recovery, while the remaining two-thirds may experience a single-phase pattern or the reverse. Management of this condition involves symptomatic treatment using beta blockers to alleviate tremors or anxiety, and observation for the development of persistent hypo- or hyperthyroidism.

Graves’ disease is a less likely diagnosis due to the proximity to delivery and the absence of other signs such as Graves’ ophthalmopathy, goitre, and bruit. Hashitoxicosis is a possibility but less likely than Graves’. While carbimazole and propylthiouracil (PTU) are thyroid peroxidase inhibitors used in thyrotoxicosis, postpartum thyroiditis is usually transient, and symptomatic treatment with beta blockers is typically sufficient. Radioactive iodine is used in cases of thyrotoxicosis that have not responded to PTU or carbimazole. Lugol’s iodine is part of the treatment for a thyrotoxic storm, which is not the diagnosis in this case.