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.

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 recommended HbA1c goal for individuals with type 2 diabetes mellitus is 48 mmol/mol. According to NICE guidelines, this target is appropriate for patients who are managing their condition through lifestyle changes or a single antidiabetic medication. However, if a patient is prescribed a second medication or is taking a medication that increases the risk of hypoglycaemia (such as a sulphonylurea), the target may be adjusted to 53 mmol/mol. It is important to note that the HbA1c threshold for changing medications may differ from the target HbA1c level.

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.

According to the guidelines recommended by NICE Clinical Knowledge Summaries, this patient with subclinical hypothyroidism should be monitored at present based on both TSH and age criteria.

Understanding Subclinical Hypothyroidism

Subclinical hypothyroidism is a condition where the thyroid-stimulating hormone (TSH) is elevated, but the levels of T3 and T4 are normal, and there are no obvious symptoms. However, there is a risk of the condition progressing to overt hypothyroidism, especially in men, with a 2-5% chance per year. This risk is further increased if thyroid autoantibodies are present.

Not all patients with subclinical hypothyroidism require treatment, and guidelines have been produced by NICE Clinical Knowledge Summaries (CKS) to help determine when treatment is necessary. If the TSH level is above 10mU/L and the free thyroxine level is within the normal range, levothyroxine may be offered. If the TSH level is between 5.5 – 10mU/L and the free thyroxine level is within the normal range, a 6-month trial of levothyroxine may be considered if the patient is under 65 years old and experiencing symptoms of hypothyroidism. For older patients, a ‘watch and wait’ strategy is often used, and asymptomatic patients may simply have their thyroid function monitored every 6 months.

In summary, subclinical hypothyroidism is a condition that requires careful monitoring and consideration of treatment options based on individual patient factors.

Differentiating between causes of hypertension: A brief overview

One possible cause of hypertension is Conn syndrome, which is characterized by primary hyperaldosteronism due to a benign adrenal adenoma that secretes aldosterone. This leads to hypokalaemia, hypertension, and elevated sodium levels. Renin levels are reduced due to negative feedback from high aldosterone levels. Treatment options include surgical excision of the adenoma or potassium-sparing diuretics.

Acromegaly, on the other hand, is caused by excessive secretion of growth hormone, usually due to a pituitary tumor. While hypertension may be present, other clinical features such as visual field defects, abnormal increase in size of hands and feet, frontal bossing, and hyperhidrosis are expected. Abnormal electrolytes, renin, and aldosterone levels are not typically seen in acromegaly.

Cushing syndrome is characterized by hypercortisolism and may present with central obesity, skin and muscle atrophy, osteoporosis, and gonadal dysfunction. While hypertension may also be present, low renin levels and elevated aldosterone are not expected.

Phaeochromocytoma is a catecholamine-producing tumor that presents with episodic headaches, sweating, and tachycardia. While hypertension is also present, a low renin and elevated aldosterone are not expected.

Finally, renal artery stenosis is caused by renal hypoperfusion, leading to a compensatory increase in renin secretion, secondary hyperaldosteronism, and hypertension. This may result in hypokalaemia and hypernatraemia, but both renin and aldosterone levels would be raised.

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.

Investigating Hyperprolactinaemia: Tests and Imaging

Hyperprolactinaemia is a condition characterized by elevated levels of prolactin, often caused by a microadenoma in the pituitary gland. While no single test can determine the cause of hyperprolactinaemia, a prolactinoma is likely if the prolactin level is above 250 ng/ml. Inhibitory effects of raised prolactin may result in low levels of follicle-stimulating hormone (FSH), but this is not diagnostic. Magnetic resonance imaging (MRI) is the preferred imaging technique for investigating the cause of hyperprolactinaemia, rather than a skull computed tomography (CT) or X-ray, which may only show enlarged pituitary fossa with large adenomas. Additionally, thyroid function tests may be necessary to investigate mildly raised prolactin levels in the absence of pituitary pathology.

Targeting Hormones in Prolactinoma Treatment

Prolactinoma is a pituitary lesion that results in excessive prolactin secretion. To reduce prolactin levels, dopamine agonists like bromocriptine are used to target dopamine receptors in the anterior pituitary. While increased prolactin can indirectly decrease gonadotropin-releasing hormone (GnRH) secretion, GnRH receptors are not a therapeutic target in prolactin disorders. Corticotropin-releasing hormone (CRH) increases adrenocorticotropic hormone secretion and is not a target in prolactin disorders. Somatostatin decreases thyroid-stimulating hormone (TSH) and growth hormone secretion but does not affect prolactin levels. Thyrotropin-releasing hormone (TRH) increases prolactin and TSH release, but its use is limited due to side-effects on thyroid regulation and the superiority of dopamine agonists.

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.

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.

Anastrozole, an aromatase inhibitor, may lead to the development of osteoporosis. This medication is commonly used to treat oestrogen receptor-positive breast cancer in postmenopausal women by reducing the production of peripheral oestrogen. However, patients taking this medication are at an increased risk of developing osteoporosis. On the other hand, selective oestrogen receptor modulators (SERM) like tamoxifen may cause amenorrhoea, endometrial cancer, vaginal bleeding, and venous thromboembolism. Tamoxifen is typically used to treat oestrogen receptor-positive breast cancer in pre-menopausal women.

Anti-oestrogen drugs are used in the management of oestrogen receptor-positive breast cancer. Selective oEstrogen Receptor Modulators (SERM) such as Tamoxifen act as an oestrogen receptor antagonist and partial agonist. However, Tamoxifen can cause adverse effects such as menstrual disturbance, hot flushes, venous thromboembolism, and endometrial cancer. On the other hand, aromatase inhibitors like Anastrozole and Letrozole reduce peripheral oestrogen synthesis, which is important in postmenopausal women. Anastrozole is used for ER +ve breast cancer in this group. However, aromatase inhibitors can cause adverse effects such as osteoporosis, hot flushes, arthralgia, myalgia, and insomnia. NICE recommends a DEXA scan when initiating a patient on aromatase inhibitors for breast cancer.

Effects of Cortisol on the Body: Misconceptions and Clarifications

Cortisol, a hormone produced by the adrenal glands, plays a crucial role in regulating various bodily functions. However, there are some misconceptions about the effects of cortisol on the body. Here are some clarifications:

Hirsutism: Elevated cortisol levels can cause a condition called Cushingoid, which may result in hirsutism in women. This is characterized by excessive hair growth in areas such as the face, chest, and back.

Hypoglycemia: Contrary to popular belief, cortisol does not cause hypoglycemia. Instead, it increases gluconeogenesis (the production of glucose from non-carbohydrate sources) and reduces glucose uptake in peripheral tissues, resulting in hyperglycemia.

Enhanced glucose uptake: Cortisol actually has the opposite effect on glucose uptake. It reduces the uptake of glucose into peripheral tissues and accelerates gluconeogenesis.

Hypotension: Patients with adrenal hyperfunction (excessive cortisol production) often suffer from hypertension (high blood pressure), not hypotension (low blood pressure). This is because excessive mineralocorticoids are released, which can cause fluid retention and increase blood pressure.

Hypocalciuria: Cortisol can lead to osteopenia and osteoporosis by increasing bone breakdown. This may result in hypercalcemia (high levels of calcium in the blood), which can cause hypercalciuria (excessive calcium in the urine), not hypocalciuria.

To diagnose diabetes mellitus, fasting blood glucose levels should be above 7.0 or random blood glucose levels should be above 11.1. If the patient is asymptomatic, two readings are required for confirmation.

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.

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.

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.

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.

It is common for elderly patients who are unwell to have abnormal thyroid function tests, known as sick euthyroid. This is likely the case for the woman in question, as she has no history of thyroid disease and is not taking levothyroxine. It may be reasonable to consider starting levothyroxine, but it would be preferable to wait until her current illness has resolved. Discontinuing her antibiotics before completing her course is not appropriate, as they are unlikely to be causing the abnormal TFTs and she is currently asymptomatic. It is also unnecessary to perform a radio-isotope scan, as there is no suspicion of malignancy. Her thyroid function tests tomorrow are expected to be similar.

Understanding Sick Euthyroid Syndrome

Sick euthyroid syndrome, also known as non-thyroidal illness, is a condition where the levels of TSH, thyroxine, and T3 are low. However, it is important to note that in most cases, the TSH level is within the normal range, which is considered inappropriate given the low levels of thyroxine and T3. This condition is reversible and typically resolves upon recovery from the underlying systemic illness. As such, treatment is usually not necessary.

In summary, sick euthyroid syndrome is a condition where the thyroid hormone levels are low, but the TSH level is within the normal range. It is a reversible condition that typically resolves upon recovery from the underlying illness. No treatment is usually required for this condition.

Understanding the Causes of Hypercalcaemia

Hypercalcaemia is a medical condition characterized by high levels of calcium in the blood. In most cases, two conditions account for 90% of hypercalcaemia cases. The first is primary hyperparathyroidism, which is the most common cause in non-hospitalized patients. The second is malignancy, which is the most common cause in hospitalized patients. Malignancy-related hypercalcaemia may be due to various processes, including PTHrP from the tumor, bone metastases, and myeloma. For this reason, measuring parathyroid hormone levels is crucial when investigating patients with hypercalcaemia.

Other causes of hypercalcaemia include sarcoidosis, tuberculosis, histoplasmosis, vitamin D intoxication, acromegaly, thyrotoxicosis, milk-alkali syndrome, drugs such as thiazides and calcium-containing antacids, dehydration, Addison’s disease, and Paget’s disease of the bone. It is important to note that hypercalcaemia may occur with prolonged immobilization in patients with Paget’s disease of the bone, although this condition is usually normal.

In summary, hypercalcaemia can be caused by various medical conditions, with primary hyperparathyroidism and malignancy being the most common. Measuring parathyroid hormone levels is essential in investigating patients with hypercalcaemia. Other causes of hypercalcaemia include sarcoidosis, tuberculosis, histoplasmosis, vitamin D intoxication, acromegaly, thyrotoxicosis, milk-alkali syndrome, drugs, dehydration, Addison’s disease, and Paget’s disease of the bone.

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.

Management of Phaeochromocytoma: Medications and Interventions

Phaeochromocytoma is a neuroendocrine tumor that secretes adrenaline and noradrenaline, leading to sympathetic stimulation and clinical symptoms such as tachycardia, hypertension, anxiety, diaphoresis, and weight loss. Diagnosis is made through the measurement of catecholamines and metanephrines in plasma or urine. Surgery is required, but patients are at high risk due to potential life-threatening tachycardia and hypertension. The following medications and interventions are used in the management of phaeochromocytoma:

Alpha-adrenergic receptor blockers: Phenoxybenzamine or doxazosin are used to dampen sympathetic stimulation by blocking alpha-adrenoceptors.

Beta-adrenergic receptor blockers: Beta-blockers are used after alpha-blockers to avoid unopposed alpha-receptor stimulation, which can cause a hypertensive crisis.

Calcium channel blockers: These are not commonly used in phaeochromocytoma management but may be used as an antihypertensive in certain populations or as an anti-anginal drug.

Intravenous fluids: IV fluids should be readily available for all surgeries to address potential blood loss and hypotension following surgery.

Low-salt diet and low fluid intake: These interventions are not typically used in phaeochromocytoma management but may be used for chronic hypertension or fluid overload.

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

Diabetic foot disease is a significant complication of diabetes mellitus that requires regular screening. In 2015, NICE published guidelines on diabetic foot disease. The disease is caused by two main factors: neuropathy, which results in a loss of protective sensation, and peripheral arterial disease, which increases the risk of macro and microvascular ischaemia. Symptoms of diabetic foot disease include loss of sensation, absent foot pulses, reduced ankle-brachial pressure index (ABPI), intermittent claudication, calluses, ulceration, Charcot’s arthropathy, cellulitis, osteomyelitis, and gangrene. All patients with diabetes should be screened for diabetic foot disease at least once a year. Screening for ischaemia involves palpating for both the dorsalis pedis pulse and posterial tibial artery pulse, while screening for neuropathy involves using a 10 g monofilament on various parts of the sole of the foot. NICE recommends that patients be risk-stratified into low, moderate, and high-risk categories based on factors such as deformity, previous ulceration or amputation, renal replacement therapy, neuropathy, and non-critical limb ischaemia. Patients who are moderate or high-risk should be regularly followed up by their local diabetic foot centre.

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.

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.

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.

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.

Understanding the Different Causes of Cushing Syndrome

Cushing syndrome is a condition that occurs when the body is exposed to high levels of cortisol for an extended period. There are several different causes of Cushing syndrome, including iatrogenic, pituitary-dependent, ectopic ACTH secretion, primary adrenal disorder, and pseudo-Cushing’s syndrome.

The most common cause of Cushing syndrome is iatrogenic, which is related to the use of corticosteroid medication. This risk is higher in people who take oral corticosteroids, but it can also affect those who misuse inhaled or topical corticosteroids.

Pituitary-dependent Cushing’s disease is a much rarer cause of Cushing syndrome that arises from a pituitary tumour. Ectopic ACTH secretion is a very rare cause of Cushing syndrome that arises due to ACTH secretion from a carcinoid tumour.

Primary adrenal disorder is an unusual cause of Cushing syndrome that arises from primary hypercortisolism. Finally, pseudo-Cushing’s syndrome describes hypercortisolism arising as a result of a separate condition, such as malnutrition or chronic alcoholism, resulting in the same phenotype and biochemical abnormalities of Cushing syndrome.

Understanding the different causes of Cushing syndrome is important for proper diagnosis and treatment.

Causes of Metabolic Acidosis with Normal Anion Gap

Metabolic acidosis with a normal anion gap can be caused by various medical conditions. One such condition is an Addisonian crisis, which occurs due to severe adrenal insufficiency. This results in reduced activity of aldosterone, causing sodium loss and potassium retention, leading to hyperkalaemia and metabolic acidosis with a normal anion gap.

Burns can also cause hyperkalaemia due to rhabdomyolysis, resulting in a raised anion gap metabolic acidosis. Diabetic ketoacidosis is another condition that presents with hyperkalaemia and metabolic acidosis, but with an increased anion gap due to ketone bodies.

Diarrhoea can cause hypokalaemia, hyponatraemia, loss of bicarbonate, and metabolic acidosis with a normal anion gap. However, excessive thiazide treatment would result in hypokalaemia and not hyperkalaemia.

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.

To avoid reduced absorption of levothyroxine, iron/calcium carbonate tablets should be administered four hours apart.

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.

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).