The patient is experiencing Cushing’s disease, which is caused by excessive secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland, often due to a pituitary adenoma. Addison’s disease and acromegaly can be ruled out based on the patient’s symptoms. It is important to differentiate between Cushing’s triad, which includes irregular breathing, bradycardia, and systolic hypertension caused by increased intracranial pressure, and Cushing’s syndrome, a collection of symptoms resulting from prolonged exposure to cortisol. Cushing’s disease is a specific type of Cushing’s syndrome characterized by increased ACTH production due to a pituitary adenoma or excess production of hypothalamus CRH.

Understanding the Causes of Cushing’s Syndrome

Cushing’s syndrome is a condition that occurs when the body is exposed to high levels of cortisol for an extended period. While exogenous causes of Cushing’s syndrome, such as glucocorticoid therapy, are more common, endogenous causes can also occur. The causes of Cushing’s syndrome can be divided into two categories: ACTH dependent and ACTH independent.

ACTH dependent causes of Cushing’s syndrome include Cushing’s disease, which is caused by a pituitary tumor secreting ACTH and producing adrenal hyperplasia. Ectopic ACTH production, which is caused by small cell lung cancer, is another ACTH dependent cause. On the other hand, ACTH independent causes of Cushing’s syndrome include iatrogenic causes such as steroid use, adrenal adenoma, adrenal carcinoma, Carney complex, and micronodular adrenal dysplasia.

In addition to these causes, there is also a condition called Pseudo-Cushing’s, which mimics Cushing’s syndrome. This condition is often caused by alcohol excess or severe depression and can cause false positive dexamethasone suppression tests or 24-hour urinary free cortisol tests. To differentiate between Cushing’s syndrome and Pseudo-Cushing’s, an insulin stress test may be used. Understanding the causes of Cushing’s syndrome is crucial in diagnosing and treating this condition.

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.

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.

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.

Subacute (De Quervain’s) thyroiditis is the likely cause of this patient’s hyperthyroidism, as evidenced by symptoms such as heat intolerance, insomnia, and agitation, as well as a normal TSH and high T4 level. The presence of a tender goitre and recent viral illness further support this diagnosis. Conservative management, including observation and NSAIDs for pain relief, is the most appropriate course of action as subacute thyroiditis is typically self-limiting. Antithyroid drugs such as carbimazole and propylthiouracil are not indicated for this condition, as they are used to treat chronic hyperthyroidism such as Grave’s disease. Radioactive iodine therapy is also not appropriate for subacute thyroiditis.

Subacute Thyroiditis: A Self-Limiting Condition with Four Phases

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

To diagnose subacute thyroiditis, thyroid scintigraphy is used to show a globally reduced uptake of iodine-131. However, most patients do not require treatment as the condition is self-limiting. Thyroid pain may respond to aspirin or other NSAIDs, but in more severe cases, steroids may be used, particularly if hypothyroidism develops.

It is important to note that subacute thyroiditis is just one of the many causes of thyroid dysfunction. A Venn diagram can be used to show how different causes of thyroid dysfunction may manifest. It is interesting to note that many causes of hypothyroidism may have an initial thyrotoxic phase. Proper diagnosis and management of thyroid dysfunction are crucial to ensure optimal patient outcomes.

Hypocalcaemia: Symptoms and Signs

Hypocalcaemia is a condition characterized by low levels of calcium in the blood. Since calcium is essential for proper muscle and nerve function, many of the symptoms and signs of hypocalcaemia are related to neuromuscular excitability. The most common features of hypocalcaemia include muscle twitching, cramping, and spasms, as well as perioral paraesthesia. In chronic cases, patients may experience depression and cataracts.

An electrocardiogram (ECG) may show a prolonged QT interval, while Trousseau’s sign may be present when the brachial artery is occluded by inflating the blood pressure cuff and maintaining pressure above systolic. This causes wrist flexion and fingers to be drawn together, and is seen in around 95% of patients with hypocalcaemia and around 1% of normocalcaemic people. Chvostek’s sign, which is seen in around 70% of patients with hypocalcaemia and around 10% of normocalcaemic people, involves tapping over the parotid gland to cause facial muscles to twitch.

In summary, hypocalcaemia can cause a range of symptoms and signs related to neuromuscular excitability, including muscle twitching, cramping, and spasms, as well as perioral paraesthesia, depression, and cataracts. Trousseau’s sign and Chvostek’s sign are also commonly observed in patients with hypocalcaemia.

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.

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.

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

Understanding Thyrotoxicosis: Causes and Investigations

Thyrotoxicosis is a condition characterized by an overactive thyroid gland, resulting in an excess of thyroid hormones in the body. Graves’ disease is the most common cause, accounting for 50-60% of cases. Other causes include toxic nodular goitre, subacute thyroiditis, post-partum thyroiditis, Hashimoto’s thyroiditis, amiodarone therapy, and contrast administration. The latter is rare but can occur in elderly patients with pre-existing thyroid disease. Patients with existing thyrotoxicosis should not receive iodinated contrast medium as it can result in hyperthyroidism developing over 2-12 weeks due to a large iodine load to the thyroid.

Investigations for thyrotoxicosis include measuring TSH, which is typically low, and T4 and T3, which are elevated. Thyroid autoantibodies may also be tested. Isotope scanning may be done in some cases, but other investigations are not routinely performed. It is important to note that many causes of hypothyroidism may have an initial thyrotoxic phase, as shown in a Venn diagram. Understanding the causes and investigations of thyrotoxicosis is crucial for proper diagnosis and management of this condition.

Differentiating Pituitary Disorders: Causes and Symptoms

Pituitary disorders can present with a variety of symptoms, making it important to differentiate between them for proper diagnosis and treatment. Here are some common causes and symptoms of pituitary disorders:

Prolactinoma: This is the most common functional pituitary tumor, which can cause headaches, visual field defects, and suppression of the normal hypothalamus-pituitary-gonadal axis, leading to loss of libido and gonadotrophin levels.

Craniopharyngioma: More common in children and adolescents, this tumor can lead to hypopituitarism, growth hormone deficiency, and visual changes. It can sometimes cause increased serum prolactin.

Idiopathic panhypopituitarism: This condition manifests with decreases in all anterior pituitary hormones, including prolactin.

Isolated LH deficiency: This can explain loss of libido and decreased plasma levels of LH and testosterone, but not the increase in prolactin or bitemporal hemianopia.

Pituitary infarction: This can occur in women who hemorrhage excessively during parturition, leading to varying degrees of hypopituitarism, but not hyperprolactinemia.

By understanding the specific causes and symptoms of pituitary disorders, healthcare professionals can provide appropriate treatment and improve patient outcomes.

Subacute Thyroiditis: A Self-Limiting Condition with Four Phases

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

To diagnose subacute thyroiditis, thyroid scintigraphy is used to show a globally reduced uptake of iodine-131. However, most patients do not require treatment as the condition is self-limiting. Thyroid pain may respond to aspirin or other NSAIDs, but in more severe cases, steroids may be used, particularly if hypothyroidism develops.

It is important to note that subacute thyroiditis is just one of the many causes of thyroid dysfunction. A Venn diagram can be used to show how different causes of thyroid dysfunction may manifest. It is interesting to note that many causes of hypothyroidism may have an initial thyrotoxic phase. Proper diagnosis and management of thyroid dysfunction are crucial to ensure optimal patient outcomes.

Differentiating between medical conditions based on breath scent

When a comatose patient presents with a distinct scent on their breath, it can be a helpful clue in determining the underlying medical condition. The smell of acetone is strongly indicative of diabetic ketoacidosis (DKA), which is commonly seen in patients with poorly controlled type I diabetes. In contrast, alcohol intoxication produces a scent of alcohol rather than a fruity odor. Diabetic hyperosmolar coma, typically seen in older patients with type II diabetes, does not produce a specific scent as there is no acetone production. Heroin overdose and profound hypoglycemia also do not result in a distinct breath scent. Understanding the different scents associated with various medical conditions can aid in prompt and accurate diagnosis.

If a person develops new onset diabetes at the age of 56 and has a strong interest in health and fitness, it is unlikely that they have type 2 diabetes. Therefore, it may be necessary to investigate secondary causes of pancreatic insufficiency, such as pancreatic cancer. In such cases, a CT scan is the most appropriate diagnostic tool, while abdominal X-ray and ultrasound are unlikely to be helpful. Repeating the urine dip test is not likely to provide any additional information, and delaying treatment by repeating blood tests in 120 days would be inappropriate. This person should be treated promptly, as they are symptomatic with an HBA1c level of over 48mmol.

Understanding Pancreatic Cancer: Risk Factors, Symptoms, and Management

Pancreatic cancer is a type of cancer that is often diagnosed late due to its non-specific symptoms. Adenocarcinomas, which occur at the head of the pancreas, make up over 80% of pancreatic tumors. Risk factors for pancreatic cancer include increasing age, smoking, diabetes, chronic pancreatitis, hereditary non-polyposis colorectal carcinoma, and genetic mutations such as BRCA2 and KRAS.

Symptoms of pancreatic cancer can include painless jaundice, pale stools, dark urine, pruritus, anorexia, weight loss, epigastric pain, loss of exocrine and endocrine function, and atypical back pain. Migratory thrombophlebitis, also known as Trousseau sign, is more common in pancreatic cancer than in other cancers.

Diagnosis of pancreatic cancer can be made through ultrasound or high-resolution CT scanning, which may show the double duct sign – simultaneous dilatation of the common bile and pancreatic ducts. However, less than 20% of patients are suitable for surgery at diagnosis. A Whipple’s resection, or pancreaticoduodenectomy, may be performed for resectable lesions in the head of the pancreas. Adjuvant chemotherapy is usually given following surgery, and ERCP with stenting may be used for palliation.

In summary, pancreatic cancer is a serious disease with non-specific symptoms that can be difficult to diagnose. Understanding the risk factors and symptoms can help with early detection and management.

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.

Investigations for Acromegaly: Serum IGF1 Levels, CT/MRI Head, and Visual Field Testing

Acromegaly is a condition caused by excess growth hormone (GH) production, often from a pituitary macroadenoma. To diagnose acromegaly, insulin-like growth factor 1 (IGF1) levels are measured instead of GH levels, as IGF1 has a longer half-life and is more stable in the blood. If IGF1 levels are high, a glucose tolerance test is used to confirm the diagnosis. CT scans of the head are not as sensitive as MRI scans for detecting pituitary tumors, which are often the cause of acromegaly. Visual field testing is also important to determine if a pituitary tumor is compressing the optic chiasm, but it is not a specific investigation for acromegaly.

Thyroid storm is a medical emergency that can occur in patients with hyperthyroidism, such as those with Graves’ disease. It is characterized by symptoms such as high fever, rapid heartbeat, jaundice, and altered mental status. In such cases, IV beta-blockers, such as propranolol, are the first-line treatment to inhibit the peripheral adrenergic effects of excess thyroid hormone. However, propranolol should not be used in patients with asthma or reversible COPD, and caution should be exercised in patients with heart failure. Lugol’s solution can also be used to inhibit the release of stored thyroid hormone, but it is usually delayed until after antithyroid therapy has been initiated. Therapeutic plasma exchange may be considered for patients who do not respond to medical therapy. In this case, the patient’s jaundice is likely due to her hyperthyroid crisis, and there is no evidence of biliary disease or cholecystitis. Therefore, IV co-amoxiclav, which is the first-line antibiotic for community-acquired pneumonia, would be appropriate for this patient. If propranolol is contraindicated, a cardiac-specific beta-blocker or calcium-channel blocker may be used instead. However, in this patient, IV propranolol should be used as the first-line treatment.

Understanding Thyroid Storm

Thyroid storm is a rare but serious complication of thyrotoxicosis, which is characterized by an overactive thyroid gland. It is usually seen in patients who already have thyrotoxicosis and is not typically the first symptom. It is important to note that an excess of thyroxine caused by medication does not usually lead to thyroid storm.

There are several events that can trigger thyroid storm, including surgery, trauma, infection, and exposure to iodine, such as through CT contrast media. The clinical features of thyroid storm include fever, tachycardia, confusion, nausea, vomiting, hypertension, heart failure, and abnormal liver function tests.

The management of thyroid storm involves treating the underlying cause and providing symptomatic relief. This may include medications such as beta-blockers, anti-thyroid drugs, Lugol’s iodine, and dexamethasone. Paracetamol may also be used to manage fever.

In summary, thyroid storm is a serious complication of thyrotoxicosis that requires prompt medical attention. Understanding the triggers and clinical features of thyroid storm can help with early diagnosis and effective management.

Differential Diagnosis: Polyuria, Polydipsia, Constipation, and Loin-to-Groin Pain

Possible Causes and Clinical Features

Primary Hyperparathyroidism: This condition can cause hypercalcemia, leading to symptoms such as bone pain, osteopenia, kidney stones, constipation, nausea, vomiting, abdominal pain, fatigue, depression, and memory impairment. In severe cases, cardiac and metabolic disturbances, delirium, or coma may occur. Diagnosis is made by measuring serum-adjusted calcium and parathyroid hormone (PTH) levels at the same time.

Acute Pancreatitis: This condition can cause severe epigastric pain radiating to the back, vomiting, epigastric tenderness, ileus, and low-grade fever. Aetiological factors include alcohol and gallstones.

Addison’s Disease: This condition can cause generalised fatigue, abdominal pain, anorexia, nausea, vomiting, weight loss, ‘salt craving’, hyperpigmentation, vitiligo, loss of pubic hair in women, hypotension, hypoglycaemia, hyponatraemia, and hyperkalaemia.

Anxiety Attack: This condition can cause chest pain, palpitations, nausea, vomiting, sweating, insomnia, flushing, tremor, and urinary frequency. It typically occurs in an individual who is excessively worried about a number of different events, causing increased tension.

Diabetic Ketoacidosis (DKA): This condition can cause polyuria, polydipsia, abdominal pain, Kussmaul respiration, and pear-drops-smelling breath.

Differential Diagnosis of Polyuria, Polydipsia, Constipation, and Loin-to-Groin Pain

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.

Urinary Metabolites as Diagnostic Markers for Adrenal Tumors and Disorders

The urinary excretion of certain metabolites can serve as diagnostic markers for various adrenal tumors and disorders. For instance, metanephrines, vanillylmandelic acid (VMA), and homovanillic acid (HVA) are the principal metabolic products of adrenaline and noradrenaline. Normal individuals excrete only minimal amounts of these substances in the urine. However, in phaeochromocytoma and neuroblastoma, urinary excretion of adrenaline and noradrenaline, and their metabolic products, increases intermittently.

Similarly, increased urinary excretion of the serotonin metabolite 5-hydroxyindoleacetic acid is seen in functioning carcinoids. Free urinary cortisol levels are elevated in Cushing syndrome, which is characterized by weight gain, fatty tissue deposits, moon face, buffalo hump, striae, thin skin, and acne. Urinary dehydroepiandrosterone excretion is often increased in congenital adrenal hyperplasia, while urinary pregnanetriol excretion is often increased in congenital adrenal hyperplasia caused by 21-hydroxylase deficiency.

It is important to note that elevated excretion of these compounds may also occur in other conditions such as coma, dehydration, extreme stress states, medication use, and ingestion of certain foods. Therefore, careful interpretation of urinary metabolite levels is necessary for accurate diagnosis of adrenal tumors and disorders.

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.

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.

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.

The patient is suffering from Cushing’s syndrome, which is characterized by an excess of cortisol. This can be caused by exogenous glucocorticoid therapy, autonomous overproduction by the adrenal glands, or increased production of adrenocorticotrophic hormone. High levels of cortisol can mimic the effects of aldosterone, leading to increased sodium and water retention and increased potassium excretion, resulting in hypokalemia. The increased resorption of bicarbonate in the tubules due to potassium depletion causes metabolic alkalosis. Hyperkalemic metabolic acidosis is not expected because cortisol’s effect on the mineralocorticoid receptor causes a loss of potassium. Hyperkalemic respiratory alkalosis is also not expected because cortisol’s effect on the mineralocorticoid receptor leads to potassium excretion. Additionally, any acid-base disturbance in Cushing’s syndrome is likely to be metabolically mediated rather than respiratory. Hypokalemic metabolic acidosis is not expected because the concomitant loss of potassium and reabsorption of bicarbonate causes metabolic alkalosis.

Investigations for Cushing’s Syndrome

Cushing’s syndrome is a condition caused by excessive cortisol production in the body. There are various causes of Cushing’s syndrome, including iatrogenic, ACTH-dependent, and ACTH-independent causes. To diagnose Cushing’s syndrome, doctors typically perform tests to confirm the condition and determine its underlying cause.

General lab findings consistent with Cushing’s syndrome include hypokalaemic metabolic alkalosis and impaired glucose tolerance. Ectopic ACTH secretion, which is often associated with small cell lung cancer, is characterized by very low potassium levels.

The two most commonly used tests to confirm Cushing’s syndrome are the overnight dexamethasone suppression test and the 24-hour urinary free cortisol test. The overnight dexamethasone suppression test is the most sensitive test and is used first-line to test for Cushing’s syndrome. Patients with Cushing’s syndrome do not have their morning cortisol spike suppressed. The 24-hour urinary free cortisol test measures the amount of cortisol in the urine over a 24-hour period.

To localize the cause of Cushing’s syndrome, doctors may perform additional tests such as high-dose dexamethasone suppression test, CRH stimulation, and petrosal sinus sampling of ACTH. An insulin stress test may also be used to differentiate between true Cushing’s and pseudo-Cushing’s. Overall, a combination of these tests can help diagnose Cushing’s syndrome and determine its underlying cause.

The patient’s symptoms of general fatigue and polyuria suggest the possibility of type I diabetes, which can lead to diabetic ketoacidosis (DKA). DKA can occur as a complication of existing type I diabetes or as the first presentation of the disease. In rare cases, extreme stress can also cause DKA in patients with type II diabetes. DKA is caused by uncontrolled lipolysis, resulting in excess free fatty acids that are converted to ketone bodies. Common triggers include infection, missed insulin doses, and myocardial infarction.

Anxiety attacks can cause heavy breathing and abdominal pain, but they do not explain the polyuria, polydipsia, and pear-drops-smelling breath. Symptoms of anxiety attacks include chest pain, palpitations, nausea and vomiting, sweating, insomnia, flushing, tremor, and urinary frequency.

Acute pancreatitis should be ruled out in cases of central abdominal pain. Symptoms of acute pancreatitis include severe epigastric pain radiating to the back, vomiting, epigastric tenderness, ileus, and low-grade fever. Cullen’s sign and Grey-Turner’s sign are rare.

Addison’s disease, the most common cause of primary hypoadrenalism in the UK, can present similarly to this case with general fatigue and abdominal pain. Other symptoms of Addison’s disease include anorexia, nausea and vomiting, weight loss, salt-craving, hyperpigmentation, vitiligo, loss of pubic hair in women, hypotension, hypoglycaemia, hyponatraemia, and hyperkalaemia.

Hyperparathyroidism can also cause polyuria, polydipsia, and abdominal pain, but the Kussmaul respiration and pear-drops-smelling breath suggest a likely diagnosis of DKA. Symptoms of hyperparathyroidism include bone pain, osteopenia and osteoporosis, increased risk of kidney stones, constipation, nausea, vomiting and abdominal pain, and fatigue, depression, and memory impairment, all of which are symptoms of underlying hypercalcaemia.

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.

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.

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).

Understanding Carbimazole and Its Mechanism of Action

Carbimazole is a medication used to manage thyrotoxicosis, a condition characterized by an overactive thyroid gland. It is typically administered in high doses for six weeks until the patient becomes euthyroid, or has a normal thyroid function. The drug works by blocking thyroid peroxidase, an enzyme responsible for coupling and iodinating the tyrosine residues on thyroglobulin, which ultimately reduces thyroid hormone production.

In contrast to propylthiouracil, another medication used to treat thyrotoxicosis, carbimazole only has a central mechanism of action. Propylthiouracil, on the other hand, also has a peripheral action by inhibiting 5′-deiodinase, an enzyme that reduces peripheral conversion of T4 to T3.

While carbimazole can be effective in managing thyrotoxicosis, it is not without its adverse effects. One of the most serious side effects is agranulocytosis, a condition characterized by a severe reduction in white blood cells. Additionally, carbimazole can cross the placenta, but may be used in low doses during pregnancy.

Overall, carbimazole is a medication that can be effective in managing thyrotoxicosis, but it is important to be aware of its mechanism of action and potential adverse effects. Patients should always consult with their healthcare provider before starting any new medication.

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.

Gliclazide is not the preferred initial treatment for type 2 diabetes. Due to the patient’s inability to tolerate metformin and a QRISK score of >10, there is now a higher likelihood of cardiovascular disease.

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.