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.

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.

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.

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.

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.

Choosing the Right Treatment for Hypoglycaemic Episodes in Type 2 Diabetes

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

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

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

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

Treatment Options for Addison’s Disease

Addison’s disease is a condition in which the adrenal glands do not produce enough hormones. To manage this condition, patients are typically given replacement therapy with both glucocorticoid and mineralocorticoid medications. Fludrocortisone is a common mineralocorticoid medication used in this treatment. However, dexamethasone, aspirin, and both types of contraceptive pills have no role in the treatment of Addison’s disease. It is important for patients to work closely with their healthcare provider to determine the best treatment plan for their individual needs.

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.

Endocrine Disorders: Addison’s Disease, Cushing Syndrome, and Conn Syndrome

Addison’s Disease:
Addison’s disease, or primary hypoadrenalism, is a condition characterized by chronic adrenal insufficiency. It is most commonly caused by autoimmune destruction of the adrenals in the UK, while tuberculosis is the most common cause worldwide. Other causes include long-term exogenous steroid use, cancer, or hemorrhage damage. Symptoms develop gradually, but patients can present in Addisonian crisis if there is a sudden deterioration in adrenal function or a physiological stress that the residual adrenal function cannot cope with. Treatment is with long-term replacement of corticosteroids and aldosterone.

Cushing Syndrome:
Cushing syndrome is a result of excess corticosteroid. It can be caused by exogenous steroids, primary hyperadrenalism, or secondary hyperadrenalism. Signs and symptoms include weight gain with moon facies and buffalo hump, hypertension, hyperglycemia, mood changes, hirsutism, baldness, and sleep disturbance.

Conn Syndrome:
Conn syndrome, also known as primary hyperaldosteronism, is caused most commonly by adrenal hyperplasia or adenomas. It results in excess aldosterone release, causing difficult-to-treat hypertension, hypernatremia, and hypokalemia.

Other Disorders:
Hypoglycemia occurs in insulinoma, but the other features are absent. Peutz-Jeghers syndrome is an autosomal dominant condition characterized by perioral freckling and small bowel polyps, which may present with vomiting secondary to intussusception from the small polyps but does not explain the hypoglycemia.

Thyroid eye disease can be triggered by radioiodine therapy, as has been extensively recorded, but most patients will ultimately need to undergo thyroxine replacement.

Management of Graves’ Disease

Despite numerous attempts, there is no clear consensus on the best way to manage Graves’ disease. The available treatment options include anti-thyroid drugs (ATDs), radioiodine treatment, and surgery. In recent years, ATDs have become the most popular first-line therapy for Graves’ disease. This is particularly true for patients who have significant symptoms of thyrotoxicosis or those who are at a high risk of hyperthyroid complications, such as elderly patients or those with cardiovascular disease.

To control symptoms, propranolol is often used to block the adrenergic effects. NICE Clinical Knowledge Summaries recommend that patients with Graves’ disease be referred to secondary care for ongoing treatment. If a patient’s symptoms are not controlled with propranolol, carbimazole should be considered in primary care.

ATD therapy involves starting carbimazole at 40mg and gradually reducing it to maintain euthyroidism. This treatment is typically continued for 12-18 months. The major complication of carbimazole therapy is agranulocytosis. An alternative regime, known as block-and-replace, involves starting carbimazole at 40mg and adding thyroxine when the patient is euthyroid. This treatment typically lasts for 6-9 months. Patients following an ATD titration regime have been shown to suffer fewer side-effects than those on a block-and-replace regime.

Radioiodine treatment is often used in patients who relapse following ATD therapy or are resistant to primary ATD treatment. However, it is contraindicated in pregnancy (should be avoided for 4-6 months following treatment) and in patients under the age of 16. Thyroid eye disease is a relative contraindication, as it may worsen the condition. The proportion of patients who become hypothyroid depends on the dose given, but as a rule, the majority of patients will require thyroxine supplementation after 5 years.

To avoid reducing the absorption of levothyroxine, it is important to give iron/calcium carbonate tablets at least four hours apart from the medication. Ferrous sulphate is the medication that can affect the absorption of levothyroxine and should also be given four hours apart. Patients should be advised to separate doses of calcium carbonate or antacids containing aluminium and magnesium from levothyroxine by at least four hours. It is recommended to review potential drug interactions before increasing treatment doses and refer to The National Institute for Health and Care Excellence (NICE) clinical knowledge summaries for a detailed list of potential drug interactions. The other medications listed do not have a known effect on the absorption of levothyroxine.

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.

Familial hypercholesterolaemia can be diagnosed when there are tendon xanthomata and elevated cholesterol levels present.

Familial Hypercholesterolaemia: Causes, Diagnosis, and Management

Familial hypercholesterolaemia (FH) is a genetic condition that affects approximately 1 in 500 people. It is an autosomal dominant disorder that results in high levels of LDL-cholesterol, which can lead to early cardiovascular disease if left untreated. FH is caused by mutations in the gene that encodes the LDL-receptor protein.

To diagnose FH, NICE recommends suspecting it as a possible diagnosis in adults with a total cholesterol level greater than 7.5 mmol/l and/or a personal or family history of premature coronary heart disease. For children of affected parents, testing should be arranged by age 10 if one parent is affected and by age 5 if both parents are affected. The Simon Broome criteria are used for clinical diagnosis, which includes total cholesterol and LDL-C levels, tendon xanthoma, and family history of myocardial infarction or raised cholesterol levels.

Management of FH involves referral to a specialist lipid clinic and the use of high-dose statins as first-line treatment. CVD risk estimation using standard tables is not appropriate for FH. First-degree relatives have a 50% chance of having the disorder and should be offered screening, including children who should be screened by age 10 if there is one affected parent. Statins should be discontinued in women 3 months before conception due to the risk of congenital defects.

Overall, early diagnosis and management of FH are crucial in preventing cardiovascular disease and improving patient outcomes.

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.

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 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.

Understanding Prediabetes and Impaired Glucose Regulation

Prediabetes is a term used to describe impaired glucose levels that are higher than normal but not yet high enough to be diagnosed as diabetes mellitus. This includes individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Diabetes UK estimates that around 1 in 7 adults in the UK have prediabetes, and many of them will eventually develop type 2 diabetes mellitus (T2DM), putting them at risk of microvascular and macrovascular complications.

To identify patients with prediabetes, NICE recommends using a validated computer-based risk assessment tool for adults aged 40 and over, people of South Asian and Chinese descent aged 25-39, and adults with conditions that increase the risk of T2DM. Patients identified as high risk should have a blood sample taken, and a fasting plasma glucose of 6.1-6.9 mmol/l or an HbA1c level of 42-47 mmol/mol (6.0-6.4%) indicates high risk.

Lifestyle modifications such as weight loss, increased exercise, and changes in diet are recommended for managing prediabetes. NICE also recommends metformin for adults at high risk who are still progressing towards T2DM despite lifestyle changes.

There are two main types of impaired glucose regulation: impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). IFG is due to hepatic insulin resistance, while IGT is due to muscle insulin resistance. Patients with IGT are more likely to develop T2DM and cardiovascular disease than those with IFG.

To rule out a diagnosis of diabetes, people with IFG should be offered an oral glucose tolerance test. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn’t have diabetes but does have IGT. It is important to understand prediabetes and impaired glucose regulation to prevent the progression to T2DM and its associated complications.

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.

Sheehan’s syndrome, also known as postpartum hypopituitarism, is characterized by a decrease in pituitary gland function caused by ischemic necrosis resulting from hypovolemic shock after childbirth. The symptoms can be diverse and may take several years to manifest due to the pituitary damage. The patient’s presentation of amenorrhea, lactation difficulties, and hypothyroidism suggests pituitary dysfunction, which can be attributed to her complicated delivery, leading to a diagnosis of Sheehan’s syndrome.

Understanding Amenorrhoea: Causes, Investigations, and Management

Amenorrhoea is a condition characterized by the absence of menstrual periods in women. It can be classified into two types: primary and secondary. Primary amenorrhoea occurs when menstruation fails to start by the age of 15 in girls with normal secondary sexual characteristics or by the age of 13 in girls with no secondary sexual characteristics. On the other hand, secondary amenorrhoea is the cessation of menstruation for 3-6 months in women with previously normal and regular menses or 6-12 months in women with previous oligomenorrhoea.

There are various causes of amenorrhoea, including gonadal dysgenesis, testicular feminization, congenital malformations of the genital tract, functional hypothalamic amenorrhoea, congenital adrenal hyperplasia, imperforate hymen, hypothalamic amenorrhoea, polycystic ovarian syndrome, hyperprolactinemia, premature ovarian failure, Sheehan’s syndrome, Asherman’s syndrome, and thyrotoxicosis. To determine the underlying cause of amenorrhoea, initial investigations such as full blood count, urea & electrolytes, coeliac screen, thyroid function tests, gonadotrophins, prolactin, and androgen levels are necessary.

The management of amenorrhoea depends on the underlying cause. For primary amenorrhoea, it is important to investigate and treat any underlying cause. Women with primary ovarian insufficiency due to gonadal dysgenesis may benefit from hormone replacement therapy to prevent osteoporosis. For secondary amenorrhoea, it is important to exclude pregnancy, lactation, and menopause in women 40 years of age or older and treat the underlying cause accordingly. It is important to note that hypothyroidism may also cause amenorrhoea.

If a person has undergone a splenectomy, their HbA1c level may be falsely elevated due to the longer lifespan of their red blood cells. HbA1c testing is commonly used to determine diabetes, as it provides an average blood glucose level over a three-month period, which is the lifespan of a typical red blood cell. A higher HbA1c reading can be caused by either a higher average blood glucose concentration or a longer red cell lifespan. Therefore, only a splenectomy would result in an overestimation of blood sugar levels, as it increases the lifespan of red blood cells, while all other conditions would decrease their lifespan and lower the HbA1c reading.

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 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.

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.

Management of Diabetic Ketoacidosis (DKA)

Diabetic ketoacidosis (DKA) is a serious complication of diabetes that requires prompt treatment. The key principles of DKA management include initial fluid resuscitation with normal saline, followed by an IV insulin infusion at a fixed rate of 0.1 unit/kg per hour. Once the blood glucose level reaches 15 mmol/l, an infusion of 5% dextrose is added. Correction of electrolyte disturbance, particularly hypokalaemia, is also essential.

Empirical IV antibiotics are not useful in DKA unless triggered by an infection, in which case emergency DKA treatment should be started first. An insulin sliding scale is not used in DKA management.

It is important to note that IV 10 units Actrapid and 50 ml 50% dextrose are not used in DKA management. Similarly, IV sodium bicarbonate bolus is not recommended. Instead, careful monitoring of electrolyte levels and appropriate fluid and insulin therapy are crucial for successful management of DKA.

The primary treatment for hypercalcaemia is IV fluid therapy.

Managing Hypercalcaemia

Hypercalcaemia is a condition where there is an excess of calcium in the blood. The initial management of hypercalcaemia involves rehydration with normal saline, typically 3-4 litres per day. This helps to flush out the excess calcium from the body. Once rehydration is achieved, bisphosphonates may be used to further lower the calcium levels. These drugs take 2-3 days to work, with maximal effect being seen at 7 days.

Calcitonin is another option for managing hypercalcaemia. It works quicker than bisphosphonates but is less commonly used due to its short duration of action. Steroids may be used in sarcoidosis, a condition that can cause hypercalcaemia.

Loop diuretics such as furosemide may also be used in hypercalcaemia, particularly in patients who cannot tolerate aggressive fluid rehydration. However, they should be used with caution as they may worsen electrolyte derangement and volume depletion.

In summary, the management of hypercalcaemia involves rehydration with normal saline followed by the use of bisphosphonates or other medications depending on the underlying cause of the condition. It is important to monitor electrolyte levels and adjust treatment accordingly to prevent complications.

The measurement of insulin-like growth factor 1 (IGF-1) is now the preferred method for screening and monitoring suspected cases of acromegaly, replacing the oral glucose tolerance test (OGTT). IGF-1, also known as somatomedin C, is produced by the liver and plays a crucial role in childhood growth and has anabolic effects in adults. OGTT with growth hormone assay is no longer the first-line investigation for acromegaly diagnosis, but can be used as a second-line test to confirm the diagnosis if IGF-1 levels are elevated. The insulin tolerance test is used to assess pituitary and adrenal function, as well as insulin sensitivity, and is not useful for diagnosing acromegaly. Random growth hormone assay is also not helpful in diagnosing acromegaly due to the pulsatile nature of GH secretion. Elevated serum prolactin levels may also be present in up to 20% of GH-secreting pituitary adenomas, but this is not diagnostic.

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.

The HbA1c is a reliable indicator of good glycaemic control and should be used to determine any necessary changes to diabetes medications. It reflects average glucose levels over a period of 2-3 months, rather than a single reading. It is possible that the recent use of steroids has temporarily worsened glycaemic control in this case.

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.

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.

Explanation of Hypertension and Possible Causes

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

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.

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.