Diagnosis and Management of Adrenal Failure: The Short Synacthen® Test

Adrenal failure is a condition characterized by multiple signs and symptoms and abnormal biochemistry. The diagnosis of adrenal failure is established by a failure of the plasma cortisol concentration to increase in response to adrenocorticotropic hormone (ACTH). The short corticotropin test is the gold standard diagnostic tool for this condition. If this test is not possible, an initial screening procedure comprising the measurement of morning plasma ACTH and cortisol levels is recommended. Diagnosis of the underlying cause should include a validated assay of autoantibodies against 21-hydroxylase. Treatment involves once-daily fludrocortisone and hydrocortisone or prednisolone. Follow-up should aim at monitoring appropriate dosing of corticosteroids and associated autoimmune diseases, particularly autoimmune thyroid disease. Serum urea and ESR may not be diagnostic, while serum calcium and thyroid function tests can be abnormal in untreated Addison’s disease. This article discusses the diagnosis and management of adrenal failure, with a focus on the short Synacthen® test.

Congenital adrenal hyperplasia is a genetic disorder that affects cortisol production, leading to an increase in adrenocorticotrophic hormone and enlargement of the adrenal glands. There are different types, with classic/severe presenting at birth with ambiguous genitalia or in an acute salt-losing crisis, and milder forms causing hyperandrogenism. The patient and her cousin are likely to have the milder form. Imperforate hymen, hyperprolactinaemia, and Sheehan syndrome are unlikely causes of the patient’s primary amenorrhoea, while Turner syndrome is ruled out due to the absence of characteristic features.

Explanation of Hypertension and Possible Causes

Hypertension, or high blood pressure, can have various underlying causes. In the case of this patient, their symptoms suggest a rare tumour called phaeochromocytoma, which secretes catecholamines and can lead to malignant hypertension. Hyperaldosteronism and excess cortisol production (Cushing’s syndrome) are other possible causes of hypertension, but they do not explain the patient’s symptoms. Abnormalities in renin, which regulates blood pressure, can also contribute to hypertension. Hyperthyroidism could explain most of the patient’s symptoms, but it is less likely to cause severe hypertension or headaches. Therefore, further investigation is needed to confirm the diagnosis and determine the appropriate treatment.

Medications for Type 2 Diabetes

Metformin: The Initial Drug Treatment of Choice
For adults with type 2 diabetes, standard-release metformin is the recommended initial drug treatment. The dose should be gradually increased to avoid gastrointestinal side effects. If significant GI side effects occur, modified-release metformin can be tried. Metformin reduces hepatic gluconeogenesis and increases insulin sensitivity, leading to an increase in peripheral glucose uptake. However, caution should be exercised when using metformin in patients with renal failure, and it should be stopped if the estimated glomerular filtration rate is less than 30 ml/min per 1.73m2.

Tolbutamide and Chlorpropamide: First-Generation Sulfonylureas
Tolbutamide and chlorpropamide are first-generation sulfonylureas that are no longer routinely used in the treatment of type 2 diabetes due to a higher incidence of side effects compared to newer, second-generation sulfonylureas. Chlorpropamide is not available in the UK.

Insulin: Considered for Dual Therapy
Insulin-based treatment should be considered in type 2 diabetes patients who have not achieved optimal glycated haemoglobin control with dual therapy using metformin and another oral drug. Metformin should continue to be offered to patients without contraindications or intolerance.

Pioglitazone: An Alternative Second-Line Agent
Pioglitazone can be considered as an alternative second-line agent for patients with type 2 diabetes who cannot take metformin or have not tolerated it well. It can also be used in dual therapy for first intensification of treatment.

Treatment Options for Hyperthyroidism in Women Planning a Pregnancy

When it comes to treating hyperthyroidism in women who are planning a pregnancy, there are several options to consider. Definitive treatment, such as thyroidectomy, is the preferred option as it eliminates the risk of thyrotoxicosis during pregnancy and the need for medication that could harm the fetus. However, following thyroidectomy, the patient will need thyroxine replacement and should wait until she is euthyroid before trying to conceive.

Propylthiouracil and thyroxine are not recommended for use during pregnancy due to the risk of fetal goitre or hypothyroidism. Carbimazole is teratogenic and should not be started in women planning a pregnancy. Propylthiouracil can be used in low doses if there is no other suitable alternative.

Radioactive iodine is highly effective but is contraindicated in women planning a pregnancy within six months. This option can be considered if the patient is willing to continue contraception until six months after treatment. Ultimately, the best course of action will depend on the individual patient’s needs and preferences, and should be discussed with a healthcare provider.

Polyuria and polydipsia can be caused by various conditions, including cranial diabetes insipidus, chronic cystitis, hypokalaemia-induced polyuria, iatrogenic adrenal insufficiency, and primary polydipsia. Cranial diabetes insipidus is characterized by decreased secretion of antidiuretic hormone, resulting in the passage of large volumes of dilute urine. Chronic cystitis is an ongoing inflammation of the lower urinary tract, while hypokalaemia-induced polyuria occurs when there is a low concentration of potassium in the filtrate. Iatrogenic adrenal insufficiency is a possible cause of polydipsia/polyuria, but less consistent with this scenario. Primary polydipsia is suspected when large volumes of very dilute urine occur with low-normal plasma osmolality. Differentiating between these conditions can be challenging, but a combination of plasma ADH assay and water deprivation testing can lead to greater accuracy.

The most probable diagnosis in this case is primary hyperparathyroidism, which is caused by parathyroid adenoma or hyperplasia. The typical biochemical markers are low phosphate and high serum calcium levels. However, the parathyroid hormone level may be high or inappropriately normal. On the other hand, secondary hyperparathyroidism is caused by chronic hypocalcemia, such as in chronic kidney disease, where serum calcium levels are low or normal, but parathyroid hormone levels are high. Tertiary hyperparathyroidism is a result of autonomous parathyroid production and usually occurs in patients with end-stage renal disease. Sarcoidosis and type 1 renal tubular acidosis are rare causes of hypercalcemia.

Understanding Primary Hyperparathyroidism

Primary hyperparathyroidism is a condition commonly seen in elderly females, characterized by an unquenchable thirst and an inappropriately normal or raised parathyroid hormone level. It is usually caused by a solitary adenoma, with hyperplasia, multiple adenoma, and carcinoma being less common causes. While around 80% of patients are asymptomatic, those who do experience symptoms may have polydipsia, polyuria, depression, anorexia, nausea, constipation, peptic ulceration, pancreatitis, bone pain/fracture, renal stones, and hypertension. Primary hyperparathyroidism is also associated with multiple endocrine neoplasia (MEN I and II).

To diagnose primary hyperparathyroidism, doctors may look for raised calcium levels and low phosphate levels, as well as perform a technetium-MIBI subtraction scan. A characteristic X-ray finding of hyperparathyroidism is the pepperpot skull. Treatment options include total parathyroidectomy, conservative management, and the use of calcimimetics like cinacalcet. Calcimimetics mimic the action of calcium on tissues by allosteric activation of the calcium-sensing receptor.

In summary, primary hyperparathyroidism is a condition that can be asymptomatic or present with a range of symptoms. It is most commonly caused by a solitary adenoma and is associated with multiple endocrine neoplasia. Diagnosis involves blood tests and imaging, while treatment options include surgery and medication.

Individuals with sickle cell anaemia and other haemoglobinopathies may have inaccurate HbA1c readings due to the shortened lifespan of their red blood cells, resulting in lower than actual levels. Conversely, conditions such as splenectomy, iron-deficiency anaemia, B12 deficiency, and alcoholism can lead to falsely elevated HbA1c levels. The accuracy of HbA1c as a measure of average blood glucose concentration is dependent on the lifespan of red blood cells.

Understanding Glycosylated Haemoglobin (HbA1c) in Diabetes Mellitus

Glycosylated haemoglobin (HbA1c) is a commonly used measure of long-term blood sugar control in diabetes mellitus. It is produced when glucose attaches to haemoglobin in the blood at a rate proportional to the glucose concentration. The level of HbA1c is influenced by the lifespan of red blood cells and the average blood glucose concentration. However, certain conditions such as sickle-cell anaemia, GP6D deficiency, and haemodialysis can interfere with accurate interpretation of HbA1c levels.

HbA1c is believed to reflect the blood glucose levels over the past 2-4 weeks, although it is generally thought to represent the previous 3 months. It is recommended that HbA1c be checked every 3-6 months until stable, then every 6 months. The Diabetes Control and Complications Trial (DCCT) has studied the complex relationship between HbA1c and average blood glucose. The International Federation of Clinical Chemistry (IFCC) has developed a new standardised method for reporting HbA1c in mmol per mol of haemoglobin without glucose attached.

Understanding HbA1c is crucial in managing diabetes mellitus and achieving optimal blood sugar control.

If a patient with TD2M is already taking two drugs and their HbA1c is above 58 mmol/mol, they should be offered a third drug or insulin therapy. However, insulin therapy should be avoided if possible for patients who are afraid of needles. In this case, the best option is to add sitagliptin to the patient’s current medication regimen of metformin and gliclazide. SGLT-2 inhibitors should be avoided due to the patient’s history of recurrent urinary tract infections, and pioglitazone is rarely prescribed. Exenatide is not appropriate for this patient as it is a GLP-1 mimetic and should only be added if the patient cannot tolerate triple therapy and has a BMI greater than 35. It is not recommended to stop any current medications and substitute them with sitagliptin, as the drugs should work synergistically together.

NICE updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2022, reflecting advances in drug therapy and improved evidence regarding newer therapies such as SGLT-2 inhibitors. The first-line drug of choice remains metformin, which should be titrated up slowly to minimize gastrointestinal upset. HbA1c targets should be agreed upon with patients and checked every 3-6 months until stable, with consideration for relaxing targets on a case-by-case basis. Dietary advice includes encouraging high fiber, low glycemic index sources of carbohydrates and controlling intake of foods containing saturated fats and trans fatty acids. Blood pressure targets are the same as for patients without type 2 diabetes, and antiplatelets should not be offered unless a patient has existing cardiovascular disease. Only patients with a 10-year cardiovascular risk > 10% should be offered a statin, with atorvastatin 20mg as the first-line choice.

Abdominal pain can be an initial symptom of DKA, which stands for diabetic ketoacidosis. In this particular case, a young man is showing signs of DKA, such as dehydration, Kussmaul respiration, and a significantly elevated capillary glucose level. DKA patients lose around 5-8 liters of fluids, which require immediate correction. The diagnostic criteria for DKA include a pH level of less than 7.3 and/or bicarbonate level of less than 15mmol/L, blood glucose level of over 11mmol/L or known diabetes mellitus, and ketonaemia level of over 3mmol/L or significant ketonuria ++ on urine dipstick. Alcoholic ketoacidosis is not the correct diagnosis as it usually presents with low or normal glucose levels and occurs due to starvation. Hyperosmolar hyperglycaemic state is also incorrect as it typically presents with marked hyperglycemia without ketoacidosis. Opioid overdose is not the correct diagnosis either as it usually presents with respiratory depression, pinpoint pupils, and a lowered GCS, while this patient has a raised respiratory rate and abnormal respirations consistent with Kussmaul respirations.

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. However, mortality rates have decreased from 8% to under 1% in the past 20 years. DKA is caused by uncontrolled lipolysis, resulting in an excess of free fatty acids that are ultimately 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 acetone-smelling breath. Diagnostic criteria include glucose levels above 13.8 mmol/l, pH below 7.30, serum bicarbonate below 18 mmol/l, anion gap above 10, and ketonaemia.

Management of DKA involves fluid replacement, insulin, and correction of electrolyte disturbance. Most patients with DKA are depleted around 5-8 litres, and 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. DKA resolution is defined as pH above 7.3, blood ketones below 0.6 mmol/L, and bicarbonate above 15.0mmol/L. Complications may occur from DKA itself or the treatment, such as gastric stasis, thromboembolism, arrhythmias, acute respiratory distress syndrome, acute kidney injury, and cerebral oedema. Children and young adults are particularly vulnerable to cerebral oedema following fluid resuscitation in DKA and often need 1:1 nursing to monitor neuro-observations.

If a patient is experiencing metabolic ketoacidosis with normal or low glucose levels, alcohol consumption should be considered as a possible cause. This condition is characterized by partial respiratory compensation. While diabetic ketoacidosis could also be a potential cause, a serum glucose level of 3mmol/L makes it less likely. Therefore, the patient is more likely to be suffering from alcoholic ketoacidosis. It is important to note that a hyperosmolar hyperglycemic state would present with high serum glucose levels and normal ketone levels, while a diabetic hypoglycemic episode would not typically result in elevated ketone levels or metabolic acidosis.

Alcoholic ketoacidosis is a type of ketoacidosis that occurs in individuals who consume large amounts of alcohol regularly. This condition is not related to diabetes and is characterized by normal blood sugar levels. Alcoholics often suffer from malnutrition due to their irregular eating habits and may vomit the food they consume, leading to starvation. When the body becomes malnourished, it starts breaking down body fat, which produces ketones and leads to ketoacidosis.

The typical symptoms of alcoholic ketoacidosis include metabolic acidosis, elevated anion gap, elevated serum ketone levels, and normal or low glucose concentration. The most effective treatment for this condition is an infusion of saline and thiamine. Thiamine is essential to prevent the development of Wernicke encephalopathy or Korsakoff psychosis. Therefore, it is crucial to provide timely and appropriate treatment to individuals suffering from alcoholic ketoacidosis to prevent further complications.

Hypothyroidism can be caused by long-term use of lithium.

The patient’s symptoms suggest hypothyroidism, and the only medication on the list that can lead to this condition is lithium. While the other drugs listed may cause individual side effects that could contribute to the patient’s presentation, none of them would produce all of the symptoms described.

Amlodipine may cause weight gain due to fluid retention, but it is unlikely to cause as much as 5 kg, and it would not cause mood changes or fatigue to the extent described. Bisoprolol can cause significant fatigue, but it would not cause weight gain. Citalopram may cause significant weight gain and mood changes, but it is unlikely to cause the patient to feel cold. Atorvastatin can also cause weight gain, but this is rare.

Understanding the Causes of Hypothyroidism

Hypothyroidism is a condition that affects a small percentage of women in the UK, with females being more susceptible than males. The most common cause of hypothyroidism is Hashimoto’s thyroiditis, an autoimmune disease that may be associated with other conditions such as IDDM, Addison’s or pernicious anaemia. Other causes of hypothyroidism include subacute thyroiditis, Riedel thyroiditis, thyroidectomy or radioiodine treatment, drug therapy, and dietary iodine deficiency. It is important to note that some of these causes may have an initial thyrotoxic phase.

In rare cases, hypothyroidism may also be caused by pituitary failure, which is known as secondary hypothyroidism. Additionally, there are certain conditions that may be associated with hypothyroidism, such as Down’s syndrome, Turner’s syndrome, and coeliac disease.

An HbA1c level ranging from 42-47 mmol/mol suggests the presence of prediabetes. Individuals with this condition should be motivated to enhance their physical activity, shed excess weight, and adopt a healthier diet by consuming more dietary fiber and reducing fat intake. Metformin may be an option for those with prediabetes, but the initial dose should be 500mg once daily. Regular HbA1c monitoring is necessary for individuals diagnosed with prediabetes as they are at a heightened risk of developing diabetes.

Type 2 diabetes mellitus can be diagnosed through a plasma glucose or HbA1c sample. The diagnostic criteria vary depending on whether the patient is experiencing symptoms or not. If the patient is symptomatic, a fasting glucose level of 7.0 mmol/l or higher or a random glucose level of 11.1 mmol/l or higher (or after a 75g oral glucose tolerance test) indicates diabetes. If the patient is asymptomatic, the same criteria apply but must be demonstrated on two separate occasions.

In 2011, the World Health Organization released supplementary guidance on the use of HbA1c for diagnosing diabetes. A HbA1c level of 48 mmol/mol (6.5%) or higher is diagnostic of diabetes mellitus. However, a HbA1c value of less than 48 mmol/mol (6.5%) does not exclude diabetes and may not be as sensitive as fasting samples for detecting diabetes. For patients without symptoms, the test must be repeated to confirm the diagnosis. It is important to note that increased red cell turnover can cause misleading HbA1c results.

There are certain conditions where HbA1c cannot be used for diagnosis, such as haemoglobinopathies, haemolytic anaemia, untreated iron deficiency anaemia, suspected gestational diabetes, children, HIV, chronic kidney disease, and people taking medication that may cause hyperglycaemia (such as corticosteroids).

Impaired fasting glucose (IFG) is defined as a fasting glucose level of 6.1 mmol/l or higher but less than 7.0 mmol/l. Impaired glucose tolerance (IGT) is defined as a fasting plasma glucose level less than 7.0 mmol/l and an OGTT 2-hour value of 7.8 mmol/l or higher but less than 11.1 mmol/l. People with IFG should be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person does not have diabetes but does have IGT.

Differential Diagnosis: Addisonian Crisis and Other Conditions

Addisonian Crisis: A Brief Overview

Addison’s disease, or adrenal insufficiency, is a condition that results from the destruction of the adrenal cortex, leading to a deficiency in glucocorticoid and mineralocorticoid hormones. The majority of cases in the UK are due to autoimmune disease, while tuberculosis is the most common cause worldwide. Patients with Addison’s disease may present with vague symptoms such as anorexia, weight loss, and gastrointestinal upset, as well as hyperpigmentation of the skin. Basic investigations may reveal hyponatremia, hyperkalemia, and hypoglycemia. A short ACTH stimulation test is used to confirm the diagnosis. Emergency treatment involves IV or IM hydrocortisone and fluids, while long-term treatment is based on oral cortisol and mineralocorticoid replacement.

Differential Diagnosis

Insulin Overdose: While hypoglycemia is a common feature of insulin overdose, the clinical information provided suggests that the low glucose level is due to the loss of the anti-insulin effect of cortisol, which is a hallmark of Addison’s disease.

Meningococcal Septicaemia: Although hypotension and tachycardia may be present in meningococcal septicaemia, the other features described do not support this diagnosis.

Paracetamol Overdose: Paracetamol overdose can cause liver toxicity, but the clinical features described are not typical of this condition and are more suggestive of an Addisonian crisis.

Salicylate Overdose: Salicylate overdose can cause a range of symptoms, including nausea, vomiting, and abdominal pain, but the clinical features described do not support this diagnosis.

Conclusion

Based on the information provided, an Addisonian crisis is the most likely diagnosis. However, further investigations may be necessary to rule out other conditions. Prompt recognition and treatment of an Addisonian crisis are essential to prevent life-threatening complications.

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 exhibits 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.

Autoantibodies are also present in Graves’ disease, including TSH receptor stimulating antibodies in 90% of patients and anti-thyroid peroxidase antibodies in 75% of patients. Thyroid scintigraphy can also aid in the diagnosis of Graves’ disease, as it shows diffuse, homogenous, and increased uptake of radioactive iodine.

Overall, Graves’ disease presents with both typical and unique features that distinguish it from other causes of thyrotoxicosis. Early diagnosis and treatment are crucial to prevent complications and improve outcomes for patients.

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, Monitoring, and Side-Effects

Hypothyroidism is a condition where the thyroid gland does not produce enough thyroid hormone. The main treatment for hypothyroidism is levothyroxine, a synthetic form of thyroid hormone. When managing hypothyroidism, it is important to consider the patient’s age, cardiac history, and initial starting dose. Elderly patients and those with ischaemic heart disease should start with a lower dose of 25mcg od, while other patients can start with 50-100mcg od. After a change in dosage, thyroid function tests should be checked after 8-12 weeks to ensure the therapeutic goal of normalising the thyroid stimulating hormone (TSH) level is achieved. The target TSH range is 0.5-2.5 mU/l.

Women with 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. It is important to note that there is no evidence to support combination therapy with levothyroxine and liothyronine.

While levothyroxine is generally well-tolerated, there are some potential side-effects to be aware of. Over-treatment can lead to hyperthyroidism, while long-term use can reduce bone mineral density. In patients with cardiac disease, levothyroxine can worsen angina and lead to atrial fibrillation. It is also important to be aware of drug interactions, particularly with iron and calcium carbonate, which can reduce the absorption of levothyroxine. These medications should be given at least 4 hours apart.

In summary, managing hypothyroidism involves careful consideration of dosage, monitoring of TSH levels, and awareness of potential side-effects and drug interactions. With appropriate management, patients with hypothyroidism can achieve normal thyroid function and improve their overall health.

Endocrine Disorders and Their Clinical Presentations

Acromegaly, Cushing’s syndrome, hyperprolactinaemia, hyperthyroidism, and multiple sclerosis are all endocrine disorders that can present with various clinical features. Acromegaly is caused by excess growth hormone secretion and can lead to enlarged hands, coarse facial features, and bitemporal hemianopia. Cushing’s syndrome may present with central obesity, muscle atrophy, and osteoporosis, but visual dysfunction is not typical. Hyperprolactinaemia can cause amenorrhoea or oligomenorrhoea, infertility, and galactorrhoea, but this presentation more closely fits with acromegaly. Hyperthyroidism may present with weight loss, tremor, and heat intolerance, but bitemporal hemianopia is not typical. Multiple sclerosis is a chronic inflammatory demyelination of the central nervous system and can present with various symptoms, but this patient’s presentation does not fit with features of multiple sclerosis.

Based on the presence of thyrotoxic symptoms, goitre, and anti-thyroid peroxidase antibodies, the likely diagnosis is

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 exhibits 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.

Autoantibodies are also present in Graves’ disease, including TSH receptor stimulating antibodies in 90% of patients and anti-thyroid peroxidase antibodies in 75% of patients. Thyroid scintigraphy can also aid in the diagnosis of Graves’ disease, as it shows diffuse, homogenous, and increased uptake of radioactive iodine.

Overall, Graves’ disease presents with both typical and unique features that distinguish it from other causes of thyrotoxicosis. Early diagnosis and treatment are crucial to prevent complications and improve outcomes for patients.

Choosing the Right Treatment for Hypoglycaemic Episodes in Type 2 Diabetes

When metformin alone is not enough to control HbA1c in type 2 diabetes, NICE recommends adding a sulfonylurea, pioglitazone, or a DPP-4 inhibitor. However, if the patient experiences hypoglycaemic episodes, it is important to reassess the treatment plan.

Stopping gliclazide, a sulfonylurea, is necessary as it is likely causing the hypoglycaemic episodes. Pioglitazone is contraindicated in patients with heart failure, so a DPP-4 inhibitor like sitagliptin is the appropriate next step.

Initiating insulin is not recommended as it can be dangerous, and should only be considered after other options have failed. Reducing metformin is unlikely to prevent hypoglycaemic episodes as it does not typically cause them on its own.

In summary, choosing the right treatment for hypoglycaemic episodes in type 2 diabetes involves careful consideration of the patient’s medical history and NICE guidelines.

Subacute thyroiditis can be differentiated from Hashimoto’s thyroiditis as a cause of hypothyroidism by the presence of tenderness in the thyroid gland. The symptoms are indicative of hypothyroidism, which is confirmed by elevated TSH levels and low T4 levels in the thyroid function tests. The occurrence of a painful goitre points towards subacute thyroiditis as the most probable diagnosis. Graves’ disease, on the other hand, leads to hyperthyroidism and not hypothyroidism. Although Hashimoto’s thyroiditis can also cause hypothyroidism, it is typically painless. Riedel thyroiditis can cause hypothyroidism and may be painful, but it is less likely than subacute thyroiditis.

Understanding the Causes of Hypothyroidism

Hypothyroidism is a condition that affects a small percentage of women in the UK, with females being more susceptible than males. The most common cause of hypothyroidism is Hashimoto’s thyroiditis, an autoimmune disease that may be associated with other conditions such as IDDM, Addison’s or pernicious anaemia. Other causes of hypothyroidism include subacute thyroiditis, Riedel thyroiditis, thyroidectomy or radioiodine treatment, drug therapy, and dietary iodine deficiency. It is important to note that some of these causes may have an initial thyrotoxic phase.

In rare cases, hypothyroidism may also be caused by pituitary failure, which is known as secondary hypothyroidism. Additionally, there are certain conditions that may be associated with hypothyroidism, such as Down’s syndrome, Turner’s syndrome, and coeliac disease.

On the day of surgery, sulfonylureas should be omitted, except for patients who take them twice a day. In this case, the morning dose should be withheld, and the afternoon dose given after the surgery. This is because there is a risk of hypoglycemia in the fasted state before surgery. Withholding both doses or withholding for 24 or 48 hours is incorrect. The BNF website provides a comprehensive guide for managing diabetic patients on insulin and anti-diabetic drugs during surgery, including information on when to introduce variable rate insulin infusions and withholding anti-diabetic medications.

Preparation for surgery varies depending on whether the patient is undergoing an elective or emergency procedure. For elective cases, it is important to address any medical issues beforehand through a pre-admission clinic. Blood tests, urine analysis, and other diagnostic tests may be necessary depending on the proposed procedure and patient fitness. Risk factors for deep vein thrombosis should also be assessed, and a plan for thromboprophylaxis formulated. Patients are advised to fast from non-clear liquids and food for at least 6 hours before surgery, and those with diabetes require special management to avoid potential complications. Emergency cases require stabilization and resuscitation as needed, and antibiotics may be necessary. Special preparation may also be required for certain procedures, such as vocal cord checks for thyroid surgery or bowel preparation for colorectal cases.

Due to his history of bladder cancer and obesity, pioglitazone is not recommended and contraindicated. Instead, sitagliptin, a DPP-4 inhibitor, is the most suitable option. Exenatide, which typically leads to weight loss, is beneficial for obese individuals with diabetes, but it does not meet the NICE criteria for body mass index of 35 kg/m².

NICE updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2022, reflecting advances in drug therapy and improved evidence regarding newer therapies such as SGLT-2 inhibitors. The first-line drug of choice remains metformin, which should be titrated up slowly to minimize gastrointestinal upset. HbA1c targets should be agreed upon with patients and checked every 3-6 months until stable, with consideration for relaxing targets on a case-by-case basis. Dietary advice includes encouraging high fiber, low glycemic index sources of carbohydrates and controlling intake of foods containing saturated fats and trans fatty acids. Blood pressure targets are the same as for patients without type 2 diabetes, and antiplatelets should not be offered unless a patient has existing cardiovascular disease. Only patients with a 10-year cardiovascular risk > 10% should be offered a statin, with atorvastatin 20mg as the first-line choice.

Patients with T1DM typically have low C-peptide levels.

The patient in question is exhibiting classic symptoms of diabetes, including polyuria and tiredness, and their fasting glucose level is 8.2 mmol/L, which meets the diagnostic criteria for diabetes according to the World Health Organization. Given their age and risk factors, NICE guidelines recommend testing for C-peptide levels. C-peptide is a byproduct of proinsulin cleavage into insulin, and low levels indicate a lack of insulin production, which is characteristic of T1DM.

Impaired fasting glucose is an incorrect answer because the patient’s fasting glucose level is above the diagnostic threshold for diabetes. Maturity-onset diabetes of the young is also incorrect because it is an autosomal-dominant condition that typically presents as T2DM in patients under 25, and C-peptide levels remain normal. Suggests diabetes mellitus but further testing is needed is also incorrect because the patient’s symptoms and fasting glucose level meet the diagnostic criteria for diabetes.

Diagnosis of Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) is typically diagnosed through symptoms and signs that are similar to those seen in diabetic ketoacidosis (DKA), although the diagnosis may take longer. Symptoms of DKA include abdominal pain, polyuria, polydipsia, dehydration, Kussmaul respiration, and an acetone-smelling breath. To confirm a diagnosis, urine should be dipped for glucose and ketones, and fasting glucose and random glucose levels should be measured. C-peptide levels are typically low in patients with T1DM, and diabetes-specific autoantibodies can be useful in distinguishing between type 1 and type 2 diabetes. Antibodies to glutamic acid decarboxylase (anti-GAD), islet cell antibodies (ICA), insulin autoantibodies (IAA), and insulinoma-associated-2 autoantibodies (IA-2A) are commonly used.

The diagnostic criteria for T1DM include a fasting glucose level greater than or equal to 7.0 mmol/l or a random glucose level greater than or equal to 11.1 mmol/l if the patient is symptomatic. If the patient is asymptomatic, the criteria must be demonstrated on two separate occasions. To distinguish between type 1 and type 2 diabetes, age of onset, speed of onset, weight of the patient, and symptoms should be considered. NICE recommends further investigation for adults suspected of having T1DM if the clinical presentation includes atypical features. Conversely, for patients suspected of having type 2 diabetes, if they respond well to oral hypoglycaemic agents and are over the age of 40 years, further testing for T1DM may not be necessary.

Example scenarios include a 15-year-old with weight loss and lethargy, a 38-year-old obese man with polyuria, a 52-year-old woman with polyuria and polydipsia, and a 59-year-old obese man with polyuria. The appropriate diagnostic tests should be conducted based on the patient’s symptoms and risk factors.

Diagnostic Tests for Various Medical Conditions

Multiple Endocrine Neoplasia (MEN) 1 Syndrome: A genetic study to detect MEN 1 gene mutation on chromosome 11 is the best diagnostic test for patients with new-onset diabetes, diarrhea, and a past episode of deep vein thrombosis (DVT) who have a family history of renal calculi at a young age. This autosomal dominant disease is characterized by endocrine hyperfunction in various glands, with the parathyroid gland being the most common gland affected. Enteropancreatic tumors are the second most common, with gastrinoma and insulinoma being the two most common tumors. Glucagonoma can also occur, but rarely. Plasma glucagon and ghrelin levels are elevated in these cases.

Giardiasis: A blood test for Giardia antigen is recommended for patients with watery, sometimes foul-smelling, diarrhea that may alternate with soft, greasy stools, fatigue or malaise, abdominal cramps and bloating, gas or flatulence, nausea, and weight loss. Tinidazole should have eliminated Giardia, but if symptoms persist, a blood test for Giardia antigen can confirm the diagnosis.

Diabetes: A C-peptide assay can help distinguish type I diabetes from type II diabetes or maturity-onset diabetes of the young (MODY) by measuring how much of their own natural insulin a person is producing. This is useful if a patient receives insulin injections. The C-peptide assay will help clarify the cause of diabetes, but it will not help in detecting the underlying disease.

Colonoscopy: Colonoscopy is not needed for the occasional diarrhea at present.

Deep Vein Thrombosis (DVT): Protein C measurement will not help in the diagnosis of DVT. DVT occurs as a rare complication of glucagonoma, and treatment for glucagonoma includes octreotide, surgery, and streptozotocin (rarely).

Distinguishing between type 1 and type 2 diabetes can be achieved through the measurement of C-peptide levels and diabetes-specific autoantibodies.

Diagnosis of Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) is typically diagnosed through symptoms and signs that are similar to those seen in diabetic ketoacidosis (DKA), although the diagnosis may take longer. Symptoms of DKA include abdominal pain, polyuria, polydipsia, dehydration, Kussmaul respiration, and an acetone-smelling breath. To confirm a diagnosis, urine should be dipped for glucose and ketones, and fasting glucose and random glucose levels should be measured. C-peptide levels are typically low in patients with T1DM, and diabetes-specific autoantibodies can be useful in distinguishing between type 1 and type 2 diabetes. Antibodies to glutamic acid decarboxylase (anti-GAD), islet cell antibodies (ICA), insulin autoantibodies (IAA), and insulinoma-associated-2 autoantibodies (IA-2A) are commonly used.

The diagnostic criteria for T1DM include a fasting glucose level greater than or equal to 7.0 mmol/l or a random glucose level greater than or equal to 11.1 mmol/l if the patient is symptomatic. If the patient is asymptomatic, the criteria must be demonstrated on two separate occasions. To distinguish between type 1 and type 2 diabetes, age of onset, speed of onset, weight of the patient, and symptoms should be considered. NICE recommends further investigation for adults suspected of having T1DM if the clinical presentation includes atypical features. Conversely, for patients suspected of having type 2 diabetes, if they respond well to oral hypoglycaemic agents and are over the age of 40 years, further testing for T1DM may not be necessary.

Example scenarios include a 15-year-old with weight loss and lethargy, a 38-year-old obese man with polyuria, a 52-year-old woman with polyuria and polydipsia, and a 59-year-old obese man with polyuria. The appropriate diagnostic tests should be conducted based on the patient’s symptoms and risk factors.

Thyroid Cancer Types and their Association with Multiple Endocrine Neoplasia Type 2 (MEN2)

Thyroid cancer can be classified into different types based on their histology and clinical features. Among these types, medullary thyroid cancer is associated with multiple endocrine neoplasia type 2 (MEN2), a genetic disorder that predisposes individuals to develop tumors in various endocrine glands. MEN2 has three subtypes, and medullary thyroid cancer is a hallmark feature of MEN2a and MEN2b. Other associated neoplasms include phaeochromocytoma and parathyroid tumors in MEN2a, and marfanoid habitus/mucosal neuromas in MEN2b.

Anaplastic thyroid cancer, on the other hand, is not associated with MEN2 and has a poor prognosis. It is more common in older women and is characterized by rapid growth and aggressiveness. Follicular thyroid cancer is also not associated with MEN2 and is more prevalent in women over 50 years old. Lymphoma and papillary thyroid cancer are also not associated with MEN2, with the latter having an excellent prognosis and primarily affecting young women.

Medical Conditions and Differential Diagnosis

Addisonian Crisis: A condition caused by adrenal insufficiency, often due to autoimmune disease, TB, metastases, or adrenal haemorrhage. Symptoms include vague complaints such as depression, anorexia, and GI upset, as well as tanned skin and pigmented palmar creases. Diagnosis is confirmed through a short ACTH stimulation test. Emergency treatment involves IV hydrocortisone and fluids, while long-term treatment involves oral cortisol and mineralocorticoid.

Other Differential Diagnoses: Meningococcal septicaemia, insulin overdose, paracetamol overdose, and salicylate overdose. However, the clinical features described in the scenario are not suggestive of these conditions.

The patient is displaying symptoms of type 2 diabetes, with a random blood glucose level exceeding 11.1 and experiencing related symptoms. As per protocol, the first line of treatment for type 2 diabetes is metformin, which should be prescribed to the patient. It is important to note that insulin is the primary treatment for type 1 diabetes, while gliclazide, pioglitazone, and glibenclamide are secondary medications used in the management of type 2 diabetes, but are not typically prescribed as first line treatments.

Type 2 diabetes mellitus can be diagnosed through a plasma glucose or HbA1c sample. The diagnostic criteria vary depending on whether the patient is experiencing symptoms or not. If the patient is symptomatic, a fasting glucose level of 7.0 mmol/l or higher or a random glucose level of 11.1 mmol/l or higher (or after a 75g oral glucose tolerance test) indicates diabetes. If the patient is asymptomatic, the same criteria apply but must be demonstrated on two separate occasions.

In 2011, the World Health Organization released supplementary guidance on the use of HbA1c for diagnosing diabetes. A HbA1c level of 48 mmol/mol (6.5%) or higher is diagnostic of diabetes mellitus. However, a HbA1c value of less than 48 mmol/mol (6.5%) does not exclude diabetes and may not be as sensitive as fasting samples for detecting diabetes. For patients without symptoms, the test must be repeated to confirm the diagnosis. It is important to note that increased red cell turnover can cause misleading HbA1c results.

There are certain conditions where HbA1c cannot be used for diagnosis, such as haemoglobinopathies, haemolytic anaemia, untreated iron deficiency anaemia, suspected gestational diabetes, children, HIV, chronic kidney disease, and people taking medication that may cause hyperglycaemia (such as corticosteroids).

Impaired fasting glucose (IFG) is defined as a fasting glucose level of 6.1 mmol/l or higher but less than 7.0 mmol/l. Impaired glucose tolerance (IGT) is defined as a fasting plasma glucose level less than 7.0 mmol/l and an OGTT 2-hour value of 7.8 mmol/l or higher but less than 11.1 mmol/l. People with IFG should be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person does not have diabetes but does have IGT.

If a person with Addison’s disease experiences vomiting and is unable to take their regular oral hydrocortisone, they should be administered IM hydrocortisone until the vomiting subsides. This is crucial to prevent an Addisonian crisis. It is recommended that all patients with Addison’s disease have access to IM hydrocortisone in case of such situations. In case of systemic involvement, hospitalization for IV fluids and IV hydrocortisone may be necessary.

Addison’s disease is a condition that requires patients to undergo both glucocorticoid and mineralocorticoid replacement therapy. This treatment usually involves taking a combination of hydrocortisone and fludrocortisone. Hydrocortisone is typically given in 2 or 3 divided doses, with patients requiring 20-30 mg per day, mostly in the first half of the day. Patient education is crucial, and it is essential to emphasize the importance of not missing glucocorticoid doses. Additionally, patients should consider wearing MedicAlert bracelets and steroid cards, and they should be provided with hydrocortisone for injection with needles and syringes to treat an adrenal crisis.

During an intercurrent illness, it is crucial to manage the glucocorticoid dose properly. In simple terms, the glucocorticoid dose should be doubled, while the fludrocortisone dose should remain the same. The Addison’s Clinical Advisory Panel has produced guidelines that detail specific scenarios, and patients should refer to these guidelines for more information. It is essential to discuss how to adjust the glucocorticoid dose during an intercurrent illness with a healthcare professional. Proper management of Addison’s disease is crucial to ensure that patients can lead healthy and fulfilling lives.

On the day of surgery, it is recommended to omit the morning dose of gliclazide for patients taking sulfonylureas. However, if the patient takes BD, they can have the afternoon dose. Metformin should be taken as usual on the day before and on the day of elective surgery, except for lunchtime dose if taken three times a day.

Preparation for surgery varies depending on whether the patient is undergoing an elective or emergency procedure. For elective cases, it is important to address any medical issues beforehand through a pre-admission clinic. Blood tests, urine analysis, and other diagnostic tests may be necessary depending on the proposed procedure and patient fitness. Risk factors for deep vein thrombosis should also be assessed, and a plan for thromboprophylaxis formulated. Patients are advised to fast from non-clear liquids and food for at least 6 hours before surgery, and those with diabetes require special management to avoid potential complications. Emergency cases require stabilization and resuscitation as needed, and antibiotics may be necessary. Special preparation may also be required for certain procedures, such as vocal cord checks for thyroid surgery or bowel preparation for colorectal cases.