Parathyroid hormone levels serve as a valuable tool in identifying the underlying causes of hypercalcaemia, with malignancy and primary hyperparathyroidism being the most prevalent culprits. If the parathyroid hormone levels are normal or elevated, it indicates the presence of primary hyperparathyroidism.

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.

The patient is likely suffering from Becker’s muscular dystrophy, a milder form of the condition compared to Duchenne muscular dystrophy (DMD). Both conditions are caused by mutations in the DMD gene, but Becker’s tends to present later in childhood or adolescence with slower progression of symptoms. The patient’s normal childhood development followed by slow onset of proximal weakness fits the typical picture of Becker’s. Limb-girdle muscular dystrophy (LGMD) is a possibility, but less likely given the patient’s presentation. DMD is unlikely as it typically presents in early childhood with rapid progression of symptoms. Facioscapulohumeral dystrophy is characterized by weakness and wasting of the face, scapula, and upper arms, and would not typically present with gait disturbance or lower limb weakness in childhood. Myasthenia gravis is also unlikely given the patient’s history.

Syphilis, Lymphogranuloma venereum (LGV), and donovanosis (granuloma inguinal) can all lead to the development of genital ulcers that are not accompanied by pain. However, in the case of the patient who has recently changed sexual partners and is not experiencing any other symptoms, herpes simplex is the more probable cause of the painful genital ulcers. Behcets may also cause painful genital ulcers.

STI Ulcers: Causes and Symptoms

Genital ulcers are a common symptom of several sexually transmitted infections (STIs). One of the most common causes of genital ulcers is the herpes simplex virus (HSV) type 2, which is responsible for genital herpes. The primary attack of genital herpes is usually severe and accompanied by fever, while subsequent attacks are less severe and localized to one site. The ulcers caused by genital herpes are multiple and painful.

Syphilis is another STI that can cause genital ulcers. It is caused by the spirochaete Treponema pallidum and is characterized by primary, secondary, and tertiary stages. The primary stage of syphilis is marked by the appearance of a painless ulcer, known as a chancre. The incubation period for syphilis is between 9-90 days.

Chancroid is a tropical disease caused by Haemophilus ducreyi. It causes painful genital ulcers that are associated with unilateral, painful inguinal lymph node enlargement. The ulcers typically have a sharply defined, ragged, undermined border.

Lymphogranuloma venereum (LGV) is caused by Chlamydia trachomatis and typically occurs in three stages. The first stage is marked by a small, painless pustule that later forms an ulcer. The second stage is characterized by painful inguinal lymphadenopathy, while the third stage is proctocolitis. LGV is treated using doxycycline.

Other causes of genital ulcers include Behcet’s disease, carcinoma, and granuloma inguinale, which is caused by Klebsiella granulomatis (previously called Calymmatobacterium granulomatis).

Sexually Transmitted Infections: Differential Diagnosis

Sexually transmitted infections (STIs) are a common cause of morbidity worldwide. When evaluating a patient with symptoms suggestive of an STI, it is important to consider a broad differential diagnosis. Here are some common STIs and their clinical presentations:

Gonorrhoea: This is a purulent infection of the mucous membranes caused by Neisseria gonorrhoeae. In men, symptoms include urethritis, acute epididymitis, and rectal infection. A diagnosis can be made by identifying typical Gram-negative intracellular diplococci after a Gram stain.

Crohn’s disease: This is an inflammatory bowel disease that presents with prolonged diarrhea, abdominal pain, anorexia, and weight loss. It is not consistent with a typical STI presentation.

Candidiasis: This is a fungal infection caused by yeasts from the genus Candida. It is associated with balanitis, presenting with penile pruritus and whitish patches on the penis.

Salmonella infection: This is often transmitted orally via contaminated food or beverages. Symptoms include a severe non-specific febrile illness, which can be confused with typhoid fever. There is nothing in this clinical scenario to suggest Salmonella infection.

Chancroid: This is a bacterial STI caused by Haemophilus ducreyi. It is characterised by painful necrotising genital ulcers and inguinal lymphadenopathy.

In summary, a thorough differential diagnosis is important when evaluating patients with symptoms suggestive of an STI.

Measles is a highly contagious disease that can affect people of all ages, although it is commonly associated with childhood. The disease is characterized by the appearance of Koplik spots, which are white-grey specks that develop on the buccal mucosa opposite the second molars about 1-2 days before the rash. The rash typically appears 14 days after exposure and consists of erythematous macules and papules that start on the face and spread to the trunk and extremities, including the palms and soles. The rash lasts for 5-7 days before fading into hyperpigmented patches that eventually desquamate.

Meningococcaemia is a condition where meningococci (Neisseria meningitidis) spread into the bloodstream. Patients with acute meningococcaemia may present with or without meningitis and typically have a non-blanching petechial rash that spreads rapidly and may develop into purpura. However, the rash described in this case is not typical for meningococcaemia.

Rubella is a communicable disease that is usually benign, with nearly half of infected individuals being asymptomatic. The disease can have teratogenic effects on pregnant women. The rash associated with rubella is a rose-pink maculopapular rash that may be pruritic in adults. The Forchheimer sign may be present on the soft palate, but the buccal lesions described in this case are typical of Koplik spots, which are pathognomonic for measles.

Parvovirus B19 infection typically occurs in young children and is characterized by a bright red macular exanthema that appears on the cheeks (known as slapped cheek) and may be associated with circumoral pallor. However, the buccal lesions described in this case are typical of Koplik spots, which are not a feature of parvovirus B19 infection.

Secondary syphilis usually presents with a cutaneous eruption within 2-10 weeks after the primary chancre and is most florid 3-4 months after infection. The rash is typically rough red or red/brown papules or plaques on the trunk, palms, and soles. While there may be red patches on mucosal surfaces, the white patches described in this case are typical of Koplik spots.

When a condition has low genetic penetrance, it may not show many clinical signs or symptoms, and the patient may appear normal, despite having an abnormal genetic profile. This is because the severity of the phenotype is determined by the penetrance of the genotype. If the condition has high penetrance, the phenotype is more likely to be expressed, resulting in more signs and symptoms.

Autosomal Dominant Diseases: Characteristics and Complicating Factors

Autosomal dominant diseases are genetic disorders that are inherited from one parent who carries the abnormal gene. In these diseases, both homozygotes and heterozygotes manifest the disease, and both males and females can be affected. The disease is passed on to 50% of children, and it normally appears in every generation. The risk remains the same for each successive pregnancy.

However, there are complicating factors that can affect the expression of the disease. Non-penetrance is a phenomenon where an individual carries the abnormal gene but does not show any clinical signs or symptoms of the disease. For example, 40% of individuals with otosclerosis do not show any symptoms despite carrying the abnormal gene. Another complicating factor is spontaneous mutation, where a new mutation occurs in one of the gametes. This can result in the disease appearing in a child even if both parents do not carry the abnormal gene. For instance, 80% of individuals with achondroplasia have unaffected parents.

In summary, autosomal dominant diseases have distinct characteristics such as their inheritance pattern and the fact that affected individuals can pass on the disease. However, complicating factors such as non-penetrance and spontaneous mutation can affect the expression of the disease and make it more difficult to predict its occurrence.

Primary biliary cholangitis is a likely diagnosis for a middle-aged female patient with an obstructive liver injury picture and positive anti-mitochondrial antibodies, M2 subtype. This differential is important to consider, as alcohol abuse may not always be obvious and gallstones could produce a similar result on liver function tests. However, the absence of pain and positive anti-mitochondrial antibodies make these less likely. Paracetamol overdose is also a potential differential, but the liver function profile in this case is more consistent with an obstructive picture, with a higher ALP and bilirubin and a modest increase in ALT. Additionally, anti-mitochondrial antibodies are not associated with paracetamol overdose.

Primary Biliary Cholangitis: A Chronic Liver Disorder

Primary biliary cholangitis, previously known as primary biliary cirrhosis, is a chronic liver disorder that is commonly observed in middle-aged women. The exact cause of this condition is not yet fully understood, but it is believed to be an autoimmune disease. The disease is characterized by the progressive damage of interlobular bile ducts due to chronic inflammation, leading to cholestasis and eventually cirrhosis. The most common symptom of primary biliary cholangitis is itching in middle-aged women.

This condition is often associated with other autoimmune diseases such as Sjogren’s syndrome, rheumatoid arthritis, systemic sclerosis, and thyroid disease. Early symptoms of primary biliary cholangitis may be asymptomatic or may include fatigue, pruritus, and cholestatic jaundice. Late symptoms may progress to liver failure. Diagnosis of primary biliary cholangitis involves immunology tests such as anti-mitochondrial antibodies (AMA) M2 subtype and smooth muscle antibodies, as well as imaging tests to exclude an extrahepatic biliary obstruction.

The first-line treatment for primary biliary cholangitis is ursodeoxycholic acid, which slows down the progression of the disease and improves symptoms. Cholestyramine is used to alleviate pruritus, and fat-soluble vitamin supplementation is recommended. In severe cases, liver transplantation may be necessary, especially if bilirubin levels exceed 100. However, recurrence in the graft can occur, but it is not usually a problem. Complications of primary biliary cholangitis include cirrhosis, portal hypertension, ascites, variceal hemorrhage, osteomalacia, osteoporosis, and an increased risk of hepatocellular carcinoma.

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

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

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

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

Disorders Affecting the Eye: Symptoms and Causes

Horner Syndrome, Holmes-Adie Syndrome, Multiple Sclerosis (MS), Myasthenia Gravis (MG), and Riley-Day Syndrome are all disorders that can affect the eye. Horner Syndrome is caused by an interruption of the sympathetic nerve supply to the eye, resulting in a constricted pupil, partial ptosis, and a loss of hemifacial sweating. Holmes-Adie Syndrome is caused by damage to the postganglionic parasympathetic fibers or the ciliary ganglion, resulting in a tonically dilated pupil that reacts slowly to light. MS is characterized by optic neuritis, which causes decreased pupillary light reaction, visual reduction, abnormal contrast sensitivity, and changes to color vision. MG is an autoimmune disorder that causes muscle weakness, but does not affect the pupils. Riley-Day Syndrome, also known as familial dysautonomia, affects the development and survival of sensory, sympathetic, and some parasympathetic neurons in the autonomic and sensory nervous systems, but is not consistent with the presentation described.

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

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