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

Diagnosis of Type 1 Diabetes Mellitus

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

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

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

If methotrexate and trimethoprim-containing antibiotics are used together, it may lead to severe or fatal pancytopenia and bone marrow suppression. This patient, who takes methotrexate for rheumatoid arthritis, has presented with pancytopenia and feeling unwell. Myelosuppression is a known adverse effect of methotrexate, which can be exacerbated by renal impairment and certain medications.

Methotrexate: An Antimetabolite with Potentially Life-Threatening Side Effects

Methotrexate is an antimetabolite drug that inhibits the enzyme dihydrofolate reductase, which is essential for the synthesis of purines and pyrimidines. It is commonly used to treat inflammatory arthritis, psoriasis, and some types of leukemia. However, it is considered an important drug due to its potential for life-threatening side effects. Careful prescribing and close monitoring are essential to ensure patient safety.

The adverse effects of methotrexate include mucositis, myelosuppression, pneumonitis, pulmonary fibrosis, and liver fibrosis. The most common pulmonary manifestation is pneumonitis, which typically develops within a year of starting treatment and presents with non-productive cough, dyspnea, malaise, and fever. Women should avoid pregnancy for at least 6 months after treatment has stopped, and men using methotrexate need to use effective contraception for at least 6 months after treatment.

When prescribing methotrexate, it is important to follow guidelines and monitor patients regularly. Methotrexate is taken weekly, and FBC, U&E, and LFTs need to be regularly monitored. The starting dose is 7.5 mg weekly, and folic acid 5mg once weekly should be co-prescribed, taken more than 24 hours after the methotrexate dose. Only one strength of methotrexate tablet should be prescribed, usually 2.5 mg. It is also important to avoid prescribing trimethoprim or co-trimoxazole concurrently, as it increases the risk of marrow aplasia, and high-dose aspirin increases the risk of methotrexate toxicity.

In case of methotrexate toxicity, the treatment of choice is folinic acid. Methotrexate is a drug with a high potential for patient harm, and it is crucial to be familiar with guidelines relating to its use to ensure patient safety.

In cases of iron-deficiency anemia, it is common for both the total iron-binding capacity (TIBC) and transferrin levels to be elevated. However, it should be noted that the transferrin saturation level is typically decreased.

Iron deficiency anaemia is caused by a lack of iron, which is needed to make haemoglobin in red blood cells. It is the most common type of anaemia worldwide, with preschool-age children having the highest prevalence. Causes include excessive blood loss, inadequate dietary intake, poor intestinal absorption, and increased iron requirements. Symptoms include fatigue, shortness of breath, palpitations, and nail changes. Diagnosis is made through a full blood count and serum ferritin test. Treatment involves identifying and managing the underlying cause, as well as taking oral iron supplements and consuming an iron-rich diet.

Premature menopause is characterized by irregular menstrual cycles occurring before the age of 45, along with elevated FSH/LH levels and low oestradiol levels in blood tests. The pituitary gland releases more hormones in an attempt to stimulate the failing ovary to produce oestrogen, resulting in a negative feedback loop. Therefore, options 1, 3, 4, and 5 are incorrect. Option 5 depicts primary pituitary failure.

Premature Ovarian Insufficiency: Causes and Management

Premature ovarian insufficiency is a condition where menopausal symptoms and elevated gonadotrophin levels occur before the age of 40. It affects approximately 1 in 100 women and can be caused by various factors such as idiopathic reasons, family history, bilateral oophorectomy, radiotherapy, chemotherapy, infection, autoimmune disorders, and resistant ovary syndrome. The symptoms of premature ovarian insufficiency are similar to those of normal menopause, including hot flushes, night sweats, infertility, secondary amenorrhoea, raised FSH and LH levels, and low oestradiol.

Management of premature ovarian insufficiency involves hormone replacement therapy (HRT) or a combined oral contraceptive pill until the age of the average menopause, which is 51 years. It is important to note that HRT does not provide contraception in case spontaneous ovarian activity resumes. Early diagnosis and management of premature ovarian insufficiency can help alleviate symptoms and improve quality of life for affected women.

A non-contrast abdomino-pelvic/KUB CT scan is the preferred imaging modality for diagnosing nephrolithiasis in patients with a history of gout. This test has a high sensitivity and specificity and can also detect other pathologies.
Intravenous urography is less sensitive and requires IV contrast material, which can cause allergic reactions or renal failure.
Renal ultrasonography is useful in pregnancy or in combination with a KUB radiograph but is less accurate for diagnosing ureteral stones.
Retrograde ureterography is rarely performed for diagnostic purposes but is essential when surgery is necessary.
Uric acid stones are associated with low urine pH, high purine intake, or malignancy, and can be treated with allopurinol or alkali therapy depending on the patient’s uric acid levels.

Treatment Options for Aortic Stenosis

Aortic stenosis (AS) is a serious condition that requires prompt treatment. The gold standard treatment for symptomatic AS is surgical aortic valve replacement, which involves open-heart surgery and the use of mechanical or biological valves. However, for patients who are deemed too high risk for open-heart surgery, aortic balloon valvuloplasty or transcatheter aortic valve implantation (TAVI) may be considered as less invasive options.

Annual echocardiography monitoring is necessary to ensure the effectiveness of the treatment. It is important to note that oral nitrates are contraindicated in patients with AS as they can cause profound hypotension. Direct oral anticoagulants are also not licensed or indicated for the treatment of valvular heart disease. Overall, the choice of treatment depends on the patient’s individual risk factors and overall health status.

Differential Diagnosis for a Patient with Worsening Ascites

Worsening ascites can be a sign of various underlying conditions. One possible diagnosis is hepatocellular carcinoma (HCC), which is a primary malignancy of the liver that often occurs in patients with chronic liver disease and cirrhosis. Another possible diagnosis is chronic active hepatitis, which is caused by the hepatitis C virus and can result in joint and muscle pain, nausea, and exhaustion. Superimposed hepatitis B infection can also cause liver injury and jaundice. Alcoholism, which can lead to alcoholic hepatitis, is another possible diagnosis, but it is not consistent with the clinical scenario given if there has been no further alcohol consumption. Spontaneous bacterial peritonitis is an acute bacterial infection of ascitic fluid that can cause fever, abdominal pain, and other symptoms. It is important to consider these and other possible diagnoses when evaluating a patient with worsening ascites.

CA 19-9 and Pancreatic Cancer

Understanding Tumour Markers

Tumour markers are substances that can be found in the blood, urine, or tissues of people with cancer. They are often used to help diagnose and monitor cancer, as well as to determine the effectiveness of treatment. Tumour markers can be divided into different categories, including monoclonal antibodies against carbohydrate or glycoprotein tumour antigens, tumour antigens, enzymes, and hormones.

Monoclonal antibodies are used to target specific tumour antigens, which are proteins or other molecules that are found on the surface of cancer cells. Some common tumour markers include CA 125 for ovarian cancer, CA 19-9 for pancreatic cancer, and CA 15-3 for breast cancer. However, it is important to note that tumour markers usually have a low specificity, meaning that they can also be found in people without cancer.

Tumour antigens are proteins that are produced by cancer cells and can be detected in the blood or tissues of people with cancer. Some examples of tumour antigens include prostate specific antigen (PSA) for prostatic carcinoma, alpha-feto protein (AFP) for hepatocellular carcinoma and teratoma, and carcinoembryonic antigen (CEA) for colorectal cancer.

Enzymes and hormones can also be used as tumour markers. For example, alkaline phosphatase and neurone specific enolase are enzymes that can be elevated in people with cancer, while hormones such as calcitonin and ADH can be used to detect certain types of cancer.

In summary, tumour markers are an important tool in the diagnosis and monitoring of cancer. However, they should be used in conjunction with other diagnostic tests and imaging studies, as they are not always specific to cancer and can also be elevated in people without cancer.

Herpes Zoster Ophthalmicus: Symptoms, Treatment, and Complications

Herpes zoster, commonly known as shingles, is a reactivation of the varicella-zoster virus that causes chickenpox. Herpes zoster ophthalmicus (HZO) occurs when the virus affects the trigeminal nerve, resulting in eye involvement in about 50% of cases. Symptoms include patchy erythema and grouped herpetiform vesicles, which may extend to the tip of the nose. Other ophthalmic manifestations include conjunctivitis, scleritis, keratitis, and optic neuritis. Urgent referral to ophthalmology is necessary in the presence of eye involvement, as it poses a risk to vision. Treatment involves oral aciclovir and topical aciclovir for severe eye infection. There is no recommendation for the use of carbamazepine in the management of post-herpetic neuralgia. Topical steroids are not indicated for herpes zoster infection. Complications of HZO include post-herpetic neuralgia and scarring. Aggressive treatment and follow-up monitoring are required for HZO due to the possibility of eye involvement.

Cervico-cerebral arterial dissections (CADs) are a common cause of strokes in younger patients, accounting for almost 20% of strokes in those under 45 years old. The majority of cases involve the extracranial internal carotid artery, while extracranial vertebral dissections make up about 15% of cases. A high level of suspicion is necessary to diagnose CAD, and confirmation can be obtained through various imaging techniques such as Doppler ultrasonography, magnetic resonance imaging/magnetic resonance angiography (MRA), computed tomography angiography (CTA), or catheter angiography. CTA can reveal several characteristic features of CAD, including an abnormal vessel contour, enlargement of the dissected artery, an intimal flap, and a dissecting aneurysm. The traditional method of diagnosing arterial dissections is catheter angiography, which typically shows a long segment of narrowed lumen known as the string sign. Other conditions such as carotid-artery pseudoaneurysm, carotid-artery aneurysm, carotid-artery occlusion, and carotid-artery stenosis can also be identified through imaging techniques, but they are not evident in this particular angiogram.