For a patient with T2DM who is on metformin and has an HbA1c level of 58 mmol/mol, the most appropriate choice for a second antidiabetic agent is gliclazide, according to NICE guidelines and the patient’s clinical factors. Pioglitazone is not recommended due to the patient’s history of bladder cancer, and SGLT-2 inhibitors and GLP-1 receptor agonists are not appropriate in this case. Modified-release metformin is not recommended for improving HbA1c control. Dual therapy with a sulfonylurea, DPP-4 inhibitor, or pioglitazone is recommended by NICE once HbA1c is 58 mmol/mol or over on metformin, but the choice of agent depends on the individual clinical scenario.

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.

In the management of DKA, it is important to continue the patient’s regular long-acting insulin while stopping their short-acting insulin. Fixed-rate insulin and fluids should also be administered. Continuing short-acting insulin may lead to hypoglycaemia, so it should be stopped until the patient is stable. Increasing the dose of both long-acting and short-acting insulin is not recommended.

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.

The guidelines of NICE have been revised, stating that women who are at risk of gestational diabetes should undergo an oral glucose tolerance test immediately after booking, instead of waiting until 16-18 weeks as previously recommended.

Gestational diabetes is a common medical disorder affecting around 4% of pregnancies. Risk factors include a high BMI, previous gestational diabetes, and family history of diabetes. Screening is done through an oral glucose tolerance test, and diagnostic thresholds have recently been updated. Management includes self-monitoring of blood glucose, diet and exercise advice, and medication if necessary. For pre-existing diabetes, weight loss and insulin are recommended, and tight glycemic control is important. Targets for self-monitoring include fasting glucose of 5.3 mmol/l and 1-2 hour post-meal glucose levels.

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.

Medication Recommendations for a Patient with Diabetes and High Blood Pressure

Based on the patient’s HbA1c level, it is recommended to start first-line treatment with metformin. If the patient experiences poor tolerance or side-effects from metformin, gliclazide may be considered as a second-line option. Pioglitazone may also be used in conjunction with metformin if HbA1c is poorly controlled on monotherapy. However, the patient’s blood pressure is adequately controlled, so an additional antihypertensive is not necessary. Lastly, the patient’s LDL cholesterol level suggests adequate control, and therefore, there is no need to increase the dosage of atorvastatin.

Insulin-dependent diabetes patients rely on insulin to regulate their blood glucose levels. Without insulin, several physiological changes occur. However, these changes do not happen immediately. Here are some effects of insulin absence in insulin-dependent diabetes patients:

Unchanged HbA1c levels – Correct: HbA1c levels do not change significantly over two to three days without insulin. Changes in HbA1c levels are observed over weeks and months.

Below normal fatty acid levels – Incorrect: In the absence of insulin, triglyceride hydrolysis and increased release from adipose tissue occur, giving raised fatty acid levels. Fatty acids are utilised to synthesise ketones.

Below normal glucagon levels – Incorrect: The body responds to the absence of insulin by increasing glucagon levels. In a healthy individual, this raised glucagon would raise glucose levels in the bloodstream, providing target organs with utilisable glucose. However, in a diabetic patient, the absence of insulin means target organs are still not able to utilise this resource.

Hypoglycaemia – Incorrect: In the absence of insulin, hyperglycaemia would be expected to develop. Ketones are generated by the body as an alternative energy source to glucose, since to utilise glucose, insulin is required.

Undetectable ketones – Incorrect: A diabetic patient who is normally dependent on insulin is at risk of developing diabetic ketoacidosis (DKA) even with only a weekend of missed insulin doses.

Treatment of Diabetic Ketoacidosis: Continuing Long-Acting Insulin and Stopping Short-Acting Insulin

When a patient presents with diabetic ketoacidosis (DKA), it is important to provide prompt treatment. This involves fluid replacement with isotonic saline and an intravenous insulin infusion at 0.1 unit/kg per hour. While this takes place, the patient’s normal long-acting insulin should be continued, but their short-acting insulin should be stopped to avoid hypoglycemia.

In addition to insulin and fluid replacement, correction of electrolyte disturbance is essential. Serum potassium levels may be high on admission, but often fall quickly following treatment with insulin, resulting in hypokalemia. Potassium may need to be added to the replacement fluids, guided by the potassium levels. If the rate of potassium infusion is greater than 20 mmol/hour, cardiac monitoring is required.

Overall, the key to successful treatment of DKA is a careful balance of insulin, fluids, and electrolyte replacement. By continuing long-acting insulin and stopping short-acting insulin, healthcare providers can help ensure the best possible outcome for their patients.

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.

For a patient presenting with elevated fasting plasma glucose (6.8 mmol/L), indicating possible gestational diabetes, the recommended initial management is a trial of diet and exercise to control blood glucose without medication. The patient should be advised to consume a high-fibre diet with minimal refined sugars and monitor their blood glucose regularly. If the patient’s blood glucose remains elevated despite lifestyle interventions, insulin should be started if the initial fasting plasma glucose is 7 mmol/L or more. If there is no improvement within 1-2 weeks, metformin may be added, and if still inadequate, insulin may be required. It is important to note that pregnant women should not aim to lose weight and should maintain a balanced diet. Advising the patient to only monitor blood glucose without any interventions is inappropriate as lifestyle changes are necessary to manage gestational diabetes.

Gestational diabetes is a common medical disorder affecting around 4% of pregnancies. Risk factors include a high BMI, previous gestational diabetes, and family history of diabetes. Screening is done through an oral glucose tolerance test, and diagnostic thresholds have recently been updated. Management includes self-monitoring of blood glucose, diet and exercise advice, and medication if necessary. For pre-existing diabetes, weight loss and insulin are recommended, and tight glycemic control is important. Targets for self-monitoring include fasting glucose of 5.3 mmol/l and 1-2 hour post-meal glucose levels.

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.

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.

Complications of the hyperosmolar state, such as rhabdomyolysis, venous thromboembolism, lactic acidosis, hypertriglyceridemia, renal failure, stroke, and cerebral edema, contribute to the mortality of HONK. Identifying precipitants, such as a new diagnosis of type 2 diabetes, infection, high-dose steroids, myocardial infarction, vomiting, stroke, thromboembolism, and poor treatment compliance, is crucial.

Supportive care and slow metabolic resolution are the mainstays of HONK management. Patients with HONK often have a fluid deficit of over 8 liters, and caution should be exercised to avoid rapid fluid replacement, which can cause cerebral edema due to rapid osmolar shifts. In this scenario, fluid resuscitation should be the top priority, followed closely by initiating a sliding scale. Some experts recommend waiting for an hour before starting insulin to prevent rapid changes and pontine myelinolysis. However, the fluid alone can lower blood sugar levels, and some argue that administering insulin immediately can cause a precipitous drop in osmolality.

Understanding Hyperosmolar Hyperglycaemic State

Hyperosmolar hyperglycaemic state (HHS) is a medical emergency that can be life-threatening and difficult to manage. It is characterized by severe dehydration, electrolyte deficiencies, and osmotic diuresis resulting from hyperglycaemia. HHS typically affects elderly individuals with type 2 diabetes mellitus (T2DM).

The pathophysiology of HHS involves hyperglycaemia leading to increased serum osmolality, osmotic diuresis, and severe volume depletion. Precipitating factors include intercurrent illness, sedative drugs, and dementia. Clinical features of HHS include polyuria, polydipsia, signs of dehydration, lethargy, nausea, vomiting, altered level of consciousness, and focal neurological deficits.

Diagnosis of HHS is based on the presence of hypovolaemia, marked hyperglycaemia, significantly raised serum osmolarity, no significant hyperketonaemia, and no significant acidosis. Management of HHS involves fluid replacement with IV 0.9% sodium chloride solution, potassium monitoring, and insulin administration only if blood glucose stops falling while giving IV fluids. Patients with HHS are at risk of thrombosis due to hyperviscosity, and venous thromboembolism prophylaxis is recommended.

Complications of HHS include vascular complications such as myocardial infarction and stroke. It is important to recognize the clinical features of HHS and manage it promptly to prevent mortality.

Overall, HHS is a serious medical condition that requires urgent attention and management. Understanding its pathophysiology, clinical features, and management is crucial in providing appropriate care to patients with HHS.

Endocrine Disorders: Congenital Adrenal Hyperplasia, Conn Syndrome, Addisonian Crisis, Cushing Syndrome, and Thyrotoxic Crisis

Endocrine disorders are conditions that affect the production and regulation of hormones in the body. Here are five different endocrine disorders and their characteristics:

Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive conditions caused by mutations in the enzymes involved in the production of steroids and hormones from the adrenal glands. It can affect both men and women equally, and symptoms include ambiguous genitalia at birth for women and hyperpigmentation and penile enlargement for men. Treatment involves hormone replacement therapy.

Conn Syndrome is a condition associated with primary hyperaldosteronism, which presents with hypernatraemia and hypokalaemia. It is more commonly seen in adult patients, but there are cases reported in childhood.

Addisonian Crisis occurs due to glucocorticoid and mineralocorticoid deficiency, usually occurring in adulthood. It is a potentially fatal episode that presents with hyponatraemia, hyperkalaemia, hypoglycaemia, and hypercalcaemia. Urgent intravenous administration of glucocorticoids is necessary for management.

Cushing Syndrome is due to cortisol excess, either exogenous or endogenous, and is usually diagnosed in adulthood. Symptoms include weight gain, hypertension, oedema, hyperglycaemia, hypokalaemia, and pigmentation of the skin in the axillae and neck.

Thyrotoxic Crisis, also known as a thyroid storm, is a life-threatening condition associated with excessive production of thyroid hormones. It can be the first presentation of undiagnosed hyperthyroidism in neonates and children. Symptoms include tachycardia, hypertension, fever, poor feeding, weight loss, diarrhoea, nausea, vomiting, seizures, and coma. Prompt treatment is necessary to prevent acute congestive heart failure, shock, and death.

To diagnose gestational diabetes, a fasting glucose level of >= 5.6 mmol/L or a 2-hour glucose level of >= 7.8 mmol/L can be used. A patient with a BMI of >30 kg/m² and symptoms of polydipsia and polyuria should undergo an oral glucose tolerance test during 24-28 weeks of pregnancy. In this test, the patient fasts for 8-10 hours, then drinks a glucose solution and has blood samples taken before and 2 hours after. A fasting glucose level of 5.9mmol/L or higher confirms the diagnosis of gestational diabetes.

Gestational diabetes is a common medical disorder affecting around 4% of pregnancies. Risk factors include a high BMI, previous gestational diabetes, and family history of diabetes. Screening is done through an oral glucose tolerance test, and diagnostic thresholds have recently been updated. Management includes self-monitoring of blood glucose, diet and exercise advice, and medication if necessary. For pre-existing diabetes, weight loss and insulin are recommended, and tight glycemic control is important. Targets for self-monitoring include fasting glucose of 5.3 mmol/l and 1-2 hour post-meal glucose levels.

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.

Diagnostic Tests for a Patient with Suspected Type II Diabetes Mellitus

Computed Tomography (CT) Abdomen:
A CT abdomen is recommended for any patient over the age of 60 with weight loss combined with a new onset of diabetes or abdominal or back pain, nausea, vomiting or change in bowel habit. This is because new-onset type II diabetes can be a presenting feature of pancreatic cancer in patients over the age of 60, especially those who have also experienced weight loss.

Pancreatic Autoantibodies:
Pancreatic autoantibodies include anti-glutamic acid decarboxylase, insulin autoantibodies and islet-cell antibodies, the presence of which would support a diagnosis of type I diabetes. These tests are usually carried out in secondary care for atypical presentations such as suspected type II diabetes in a child or a non-overweight person.

Glucose Tolerance Test:
Glucose tolerance test has a limited role in diagnosing type II diabetes now that HbA1c is an accepted diagnostic investigation. It is still used routinely to investigate pregnant women at risk of gestational diabetes.

Short Synacthen Test:
A short synacthen test is used to diagnose adrenal insufficiency. The history and investigation results do not suggest this as a likely diagnosis, so this test would not be indicated.

Ultrasound of the Urinary Tract:
Ultrasound is not indicated unless a structural problem is suspected. Although this man is experiencing polyuria, his urinalysis and PSA are both normal, which makes a urological cause for his symptoms less likely than the newly diagnosed diabetes. Diabetes can cause renal impairment, but this should be monitored with annual urine albumin : creatinine measurement and regular U&Es blood test.

Acromegaly: Excess Growth Hormone and its Features

Acromegaly is a condition characterized by excess growth hormone, which is usually caused by a pituitary adenoma in over 95% of cases. However, a minority of cases are caused by ectopic GHRH or GH production by tumours such as pancreatic. The condition is associated with several features, including a coarse facial appearance, spade-like hands, and an increase in shoe size. Patients may also have a large tongue, prognathism, and interdental spaces. Excessive sweating and oily skin are also common, caused by sweat gland hypertrophy.

In addition to these physical features, patients with acromegaly may also experience symptoms of a pituitary tumour, such as hypopituitarism, headaches, and bitemporal hemianopia. Raised prolactin levels are also seen in about one-third of cases, which can lead to galactorrhoea. It is important to note that 6% of patients with acromegaly have MEN-1, a genetic disorder that affects multiple endocrine glands.

Complications of acromegaly include hypertension, diabetes (seen in over 10% of cases), cardiomyopathy, and an increased risk of colorectal cancer. Early diagnosis and treatment of acromegaly are crucial to prevent these complications and improve patient outcomes.

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.

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.

Patients with heart failure should not take pioglitazone due to its potential to cause fluid retention.

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.

In the case of a patient with Addison’s disease who develops an additional illness, it is recommended to increase the dose of glucocorticoids while maintaining the same dose of fludrocortisone.

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.

Possible Causes of Hypertension, Hypercalcemia, and Low Magnesium in a Patient

One possible diagnosis for a patient with severe hypertension, hypercalcemia, and low magnesium is MEN 2a, also known as Sipple syndrome. This is because these symptoms can be explained by the presence of a phaeochromocytoma and hyperparathyroidism, which are both associated with MEN 2a.

Conn syndrome, which is characterized by asymptomatic hypertension and hypokalemia, is not the most likely diagnosis in this case since the patient is normokalemic and has high calcium levels. Phaeochromocytoma could explain the hypertension, but not the hypercalcemia and low magnesium.

MEN 1, also known as Wermer syndrome, is associated with hyperparathyroidism, pancreatic endocrine tumors, and pituitary tumors, but rarely with phaeochromocytoma. Wagenmann-Froboese syndrome, or MEN 2b, is associated with medullary thyroid carcinoma and phaeochromocytoma, but hyperparathyroidism is rarely present.

Therefore, based on the patient’s symptoms, MEN 2a or Sipple syndrome is the most likely diagnosis.

Managing Addisonian Crisis: Treatment Options and Considerations

Addisonian crisis is a life-threatening condition that requires prompt intervention. Patients with Addison’s disease are at risk of developing an Addisonian crisis if they forget to take their steroids or if steroids have not been increased appropriately during an accompanying illness. In such cases, the first-line treatment is to administer 100 mg hydrocortisone intravenously (IV) STAT. This should be followed by fluid resuscitation and IV glucose if hypoglycemia is present.

It is important to note that treatment should be initiated before biochemical results are obtained. Patients with Addison’s disease should carry an IM autoinjector in case of an emergency. If an Addisonian crisis is suspected, hydrocortisone should be administered immediately, and blood tests for cortisol, ACTH, urea and electrolytes, and glucose should be carried out urgently.

Oral hydrocortisone is not recommended in cases where the patient is vomiting. In such cases, IM hydrocortisone injection is the preferred treatment option. Additionally, glucose gel sublingually may be given for hypoglycemia, but the primary focus should be on restoring cortisol levels.

Fludrocortisone may be of use if the cause of the Addisonian crisis is adrenal disease. However, it should be noted that hydrocortisone is the first-line treatment as it acts mainly on glucocorticoid receptors to increase blood sugar levels and counteract insulin. Fludrocortisone, on the other hand, acts mainly at mineralocorticoid receptors.

In conclusion, managing Addisonian crisis requires prompt intervention and careful consideration of treatment options. Administering hydrocortisone, fluid resuscitation, and IV glucose if necessary should be the primary focus, with fludrocortisone being considered only if the cause is adrenal disease.

If blood glucose targets are not achieved through diet and metformin in gestational diabetes, insulin should be added. Pregnant women with GDM should aim to keep their CBGs below specific levels, including fasting at 5.3mmol/L and 1 hour postprandial at 7.8 mmol/L or 2 hours postprandial at 6.4 mmol/L. If these targets are not met, insulin should be offered as an additional therapy. Gliclazide is not recommended, and the use of any sulphonylurea in GDM is an off-license indication. Gliptins are not recommended due to insufficient evidence of their safety in pregnancy. It is not appropriate to continue the same management or de-escalate treatment by stopping metformin if CBG readings are above target levels. Failure to achieve glycaemic control can result in serious risks to both mother and fetus, including pre-eclampsia, pre-term labour, stillbirth, and neonatal hypoglycaemia, even if fetal growth appears normal.

Gestational diabetes is a common medical disorder affecting around 4% of pregnancies. Risk factors include a high BMI, previous gestational diabetes, and family history of diabetes. Screening is done through an oral glucose tolerance test, and diagnostic thresholds have recently been updated. Management includes self-monitoring of blood glucose, diet and exercise advice, and medication if necessary. For pre-existing diabetes, weight loss and insulin are recommended, and tight glycemic control is important. Targets for self-monitoring include fasting glucose of 5.3 mmol/l and 1-2 hour post-meal glucose levels.

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.

Cholestasis can be caused by sulphonylureas.

Understanding Drug-Induced Liver Disease

Drug-induced liver disease is a condition that occurs when certain medications or drugs cause damage to the liver. This condition is generally divided into three categories: hepatocellular, cholestatic, or mixed. However, there is often overlap between these categories, as some drugs can cause a range of changes to the liver.

Hepatocellular drug-induced liver disease is characterized by damage to the liver cells. Some of the drugs that tend to cause this type of damage include paracetamol, sodium valproate, phenytoin, MAOIs, halothane, anti-tuberculosis medications, statins, alcohol, amiodarone, methyldopa, and nitrofurantoin.

Cholestatic drug-induced liver disease, on the other hand, is characterized by a reduction in bile flow from the liver. Some of the drugs that tend to cause this type of damage include the combined oral contraceptive pill, antibiotics such as flucloxacillin, co-amoxiclav, and erythromycin, anabolic steroids, testosterones, phenothiazines such as chlorpromazine and prochlorperazine, sulphonylureas, fibrates, and rare reported causes such as nifedipine. Methotrexate, methyldopa, and amiodarone can cause both hepatocellular and cholestatic damage.

It is important to note that drug-induced liver disease can be a serious condition and can lead to liver cirrhosis if left untreated. Therefore, it is important to be aware of the potential risks associated with certain medications and to seek medical attention if any symptoms of liver damage occur.

Sulfonylureas attach to a KATP channel on the cell membrane of pancreatic beta cells that is dependent on ATP.

Sulfonylureas are a type of medication used to treat type 2 diabetes mellitus. They work by increasing the amount of insulin produced by the pancreas, but they are only effective if the pancreas is functioning properly. Sulfonylureas bind to a specific channel on the cell membrane of pancreatic beta cells, which helps to increase insulin secretion. However, there are some potential side effects associated with these drugs.

One of the most common side effects of sulfonylureas is hypoglycaemia, which can be more likely to occur with long-acting preparations like chlorpropamide. Weight gain is another possible side effect. In rare cases, sulfonylureas can cause hyponatraemia, which is a condition where the body retains too much water and sodium levels become too low. Other rare side effects include bone marrow suppression, hepatotoxicity (liver damage), and peripheral neuropathy. It is important to note that sulfonylureas should not be used during pregnancy or while breastfeeding.

SIADH is a frequent endocrine complication associated with small cell lung cancer.

SIADH is a condition where the body retains too much water, leading to low sodium levels in the blood. This can be caused by a variety of factors, including malignancies such as small cell lung cancer, neurological conditions like stroke or meningitis, infections such as tuberculosis or pneumonia, and certain drugs like sulfonylureas and SSRIs. Other causes may include positive end-expiratory pressure and porphyrias. Treatment for SIADH involves slowly correcting the sodium levels to avoid complications like central pontine myelinolysis. This can be done through fluid restriction, the use of demeclocycline to reduce responsiveness to ADH, or the use of ADH receptor antagonists. It is important to note that certain drugs, such as glimepiride and glipizide, have been reported to cause SIADH according to the BNF.

The patient exhibits hypothyroidism, indicated by low free T4 and elevated TSH levels. Considering her age, it is recommended to gradually introduce levothyroxine at a starting dose of 25mcg once daily.

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.

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.