Exposure to excessive androgens is usually accompanied by premature epiphyseal maturation and closure, resulting in a final adult height that is typically significantly below that expected from parental heights.

congenital adrenal hyperplasia (CAH) is associated with precocious puberty caused by long term exposure to androgens, which activate the hypothalamic-pituitary-gonadal axis. Similarly, CAH is associated with hyperpigmentation and hyperreninemia due to sodium loss and hypovolaemia.

Lateral epicondylitis (tennis elbow) is an overuse injury of the hand and finger extensor tendons that originate in the lateral humeral epicondyle that occurs following repeated or excessive pronation/supination and extension of the wrist (e.g., in racquet sports). Clinical features include pain and tenderness over the lateral epicondyle and along extensor muscles, thickening of the tendons. The examiner holds the patient’s hand with the thumb placed over the lateral epicondyle – The patient makes a fist, supinates the forearm, deviates radially, and extends the fist against the examiner’s resistance which results in pain over the lateral epicondyle. Conservative treatment includes rest, physiotherapy and orthotic braces. If this fails corticosteroids and lidocaine injections are employed. Surgery is indicated in patients with persistent symptoms despite 6 months of conservative treatment. Excision of abnormal tendon tissue; longitudinal incisions (tenotomies) in scarred and fibrotic areas to promote healing.

Xeroderma pigmentosum is an X-linked recessive condition, which is caused by mutations in DNA gyrase which further encodes the XP gene. The defect may lead to skin cancer at an early stage of life, especially at photo exposed sites.

When you have a patient with HIV and diarrhoea on the exam, think Cryptosporidium. In those who are immunocompetent this organism doesn’t usually cause symptoms, but in immunocompromised people like those with HIV, it causes infection and diarrhoea. Typically those with CD4 counts of <100 cells/µL1 have the greatest risk for prolonged, severe, or extraintestinal cryptosporidiosis.

This woman is receiving methotrexate, an immunosuppressant, to control her rheumatoid arthritis. In such immunocompromised patients, BNF suggests clarithromycin as first-line management.

Lidocaine is an example of class IB antiarrhythmics.

The Vaughan-Williams classification of antiarrhythmics
I: Membrane stabilizing agents
IA: Quinidine, Procainamide, Disopyramide
IB: Lidocaine, Mexiletine
IC: Propafenone, Flecainide
II: β blockers – Propranolol, Esmolol
III: Agents widening AP – Amiodarone, Dronedarone, Dofetilide, Ibutilide, Sotalol
IV: Calcium channel blockers – Verapamil, Diltiazem
V: Miscellaneous – Digoxin, adenosine, magnesium

Alpha1-antitrypsin (AAT) deficiency, first described in 1963, is one of the most common inherited disorders amongst white Caucasians. Its primary manifestation is early-onset of pan acinar emphysema. In adults, alpha1-antitrypsin deficiency leads to chronic liver disease in the fifth decade. As a cause of emphysema, it is seen in non-smokers in the fifth decade of life and during the fourth decade of life in smokers.

Symptoms of alpha1-antitrypsin (AAT) deficiency emphysema are limited to the respiratory system. Dyspnoea is the symptom that eventually dominates alpha1-antitrypsin deficiency. Similar to other forms of emphysema, the dyspnoea of alpha1-antitrypsin deficiency is initially evident only with strenuous exertion. Over several years, it eventually limits even mild activities.
The serum levels of some of the common genotypes are:
•PiMM: 100% (normal)
•PiMS: 80% of normal serum level of A1AT
•PiSS: 60% of normal serum level of A1AT
•PiMZ: 60% of normal serum level of A1AT, mild deficiency
•PiSZ: 40% of normal serum level of A1AT, moderate deficiency
•PiZZ: 10–15% (severe alpha 1-antitrypsin deficiency)

When the aim of the randomized controlled trial (RCT) is to show that one treatment is superior to another, a statistical test is employed and the trial (test) is called a superiority trial (test).

The most likely complaint of this patient would be hot flushes.

Alopecia and cataracts are listed in the BNF as possible side-effects. They are however not as prevalent as hot flushes, which are very common in pre-menopausal women.

Tamoxifen is a Selective Oestrogen Receptor Modulator (SERM) which acts as an oestrogen receptor antagonist and partial agonist. It is used in the management of oestrogen receptor-positive breast cancer

Adverse effects:
Menstrual disturbance: vaginal bleeding, amenorrhoea
Hot flushes – 3% of patients stop taking tamoxifen due to climacteric side-effects.
Venous thromboembolism.
Endometrial cancer
Tamoxifen is typically used for 5 years following the removal of the tumour.

Raloxifene is a pure oestrogen receptor antagonist and carries a lower risk of endometrial cancer.

Although antagonistic with respects to breast tissue tamoxifen may serve as an agonist at other sites. Therefore the risk of endometrial cancer is increased cancer.

In a patient with abnormal LFTs and UC, think primary sclerosing cholangitis (PSC). MRCP and liver biopsy is the best answer. MRCP will show classically beads on a string – intra and extrahepatic stricturing and dilation. Remember this finding!! Liver biopsy is required for official diagnosis (need tissue!).

CMV is a common viral infection that can be transmitted from a pregnant woman to her unborn child, leading to congenital CMV infection. Congenital CMV infection can result in a range of symptoms and complications in newborns, including deafness. In fact, CMV is one of the leading causes of non-genetic sensorineural hearing loss in children.

Given the mother’s history of symptoms during pregnancy and the concern for deafness in the infant, CMV should also be considered as a potential cause.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition that can affect nearly any organ system: the pancreas, biliary tree, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes, meninges, aorta, breast, prostate, thyroid, pericardium, and skin. The histopathological features are similar across organs, regardless of the site. IgG4-RD is analogous to sarcoidosis, in which diverse organ manifestations are linked by similar histopathological characteristics. Raised concentrations of IgG4 in tissue and serum can be helpful in diagnosing IgG4 disease, but neither is a specific diagnostic marker.

Some IgG4-RDs are:
1. Autoimmune pancreatitis
2. Riedel’s Thyroiditis
3. Mediastinal and Retroperitoneal Fibrosis
4. Periaortitis/periarteritis/Inflammatory aortic aneurysm
5. Kuttner Tumour (submandibular glands)
6. IgG4-related Mikulicz disease (lacrimal, parotid, and submandibular glands)

An overall concordance rate in monozygotic twins was documented to be 25% as compared to dizygotic twins with 3%. First degree relatives have a chance of around 3% of developing the disease. Caucasians show an increase frequency of HLA-B8. The Japanese lupus patients had a stronger association with HLA-DR2.

A cohort study is a particular form of longitudinal study that samples a cohort (a group of people who share a defining characteristic, typically those who experienced a common event in a selected period, such as birth or graduation), performing a cross-section at intervals through time.
The relative risk (RR) or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. Relative risk is used in the statistical analysis of the data of experimental, cohort and cross-sectional studies, to estimate the strength of the association between treatments or risk factors, and outcomes.

The vas deferens is a long tube that connects the epididymis to the ejaculatory ducts. It acts as a canal through which mature sperm may pass through the penis during ejaculation.

Most men with CF (97-98 percent) are infertile because of a blockage or absence of the vas deferens, known as congenital bilateral absence of the vas deferens (CBAVD). The sperm never makes it into the semen, making it impossible for them to reach and fertilize an egg through intercourse. The absence of sperm in the semen can also contribute to men with CF having thinner ejaculate and lower semen volume.

Patients with diabetes often develop ophthalmic complications, the most common and potentially most blinding of these complications is diabetic retinopathy.
The following are the 5 stages in the progression of diabetic retinopathy:
1. Dilation of the retinal venules and formation of retinal capillary microaneurysms.
2. Increased vascular permeability.
3. Vascular occlusion and retinal ischemia.
4. Proliferation of new blood vessels on the surface of the retina.
5. Vitreous haemorrhage and contraction of the fibrovascular proliferation.
The first 2 stages of diabetic retinopathy are known as background or nonproliferative retinopathy. Initially, the retinal venules dilate, then microaneurysms (tiny red dots on the retina that cause no visual impairment) appear. As the microaneurysms or retinal capillaries become more permeable, hard exudates appear, reflecting the leakage of plasma.

Mild nonproliferative diabetic retinopathy (NPDR) or background diabetic retinopathy is indicated by the presence of at least 1 microaneurysm, while neovascularization is the hallmark of Proliferative Diabetic Retinopathy (PDR).

The patient is most likely to have Addison’s disease as he has a history of autoimmune disease, hyperkalaemia and hypotension.
It is important to keep an Addisonian crisis on the differential in cases of shock, especially since adrenal crisis can be the patient’s first presentation of adrenal insufficiency.
Patients with Addison’s disease are prone to developing hypoglycaemia due to loss of the glucogenic effect of glucocorticoids. Given the sudden deterioration, a glucose level must be checked.

Haemophilia B (Christmas disease), is the deficiency of clotting factor IX and is inherited in an X-linked recessive pattern. The factor IX level dictates the disease severity and established arthropathy is usually seen in those with severe disease.

The aforementioned patient’s history and presentation is consistent with the development of hemarthrosis. Joint aspiration is not recommended. The treatment, therefore, should be intravenous replacement of the deficient clotting factor with plasma-derived factor IX concentrate.

The other listed options are ruled out because:
1. Joint aspiration is not preferred over the administration of clotting factor as the first step of management.
2. DDAVP (desmopressin) can increase factor VIII levels transiently in those with mild haemophilia A and is useful prior to minor surgical procedures in such patients.
3. Cryoprecipitate is rich in fibrinogen, factor VIII, and von Willebrand factor and is used in the treatment of haemophilia A.

Meconium ileus equivalent (MIE) can be defined as a clinical manifestation in cystic fibrosis (CF) patients caused by acute intestinal obstruction by putty-like faecal material in the cecum or terminal ileum. A broader definition includes a more chronic condition in CF patients with abdominal pain and a coecal mass which may eventually pass spontaneously. The condition occurs only in CF patients with exocrine pancreatic insufficiency (EPI). It has not been seen in other CF patients nor in non-CF patients with EPI. The frequency of these symptoms has been reported as 2.4%-25%.

The treatment should primarily be non-operative. Specific treatment with N-acetylcysteine, administrated orally and/or as an enema is recommended. Enemas with the water soluble contrast medium, meglucamine diatrizoate (Gastrografin), provide an alternative form for treatment and can also serve diagnostic purposes. It is important that the physician is familiar with this disease entity and the appropriate treatment with the above mentioned drugs. Non-operative treatment is often effective, and dangerous complications following surgery can thus be avoided.

This patient has a high risk of sudden cardiac death due to a strong family history and non sustained VT. So the most appropriate management is implantable cardiovertor defibrillator.

The somatotroph cells of the anterior pituitary gland produce growth hormone (GH).
GH deficiency in adults usually manifests as reduced physical performance and impaired psychological well-being. It results in alterations in the physiology of different systems of the body, manifesting as altered lipid metabolism, increased subcutaneous and visceral fat, decreased muscle mass, decreased bone density, low exercise performance, and reduced quality of life.

Congenital CMV infection can occur when a pregnant woman is infected with the cytomegalovirus (CMV) and passes the virus to her unborn child. Infants infected with CMV during pregnancy can exhibit a range of symptoms, including jaundice, seizures, and microcephaly (abnormally small head size). These symptoms are consistent with congenital CMV infection.

Given the mother’s HIV-positive status, the infant may have been at increased risk of acquiring other infections, including CMV, due to potential immunodeficiency.

Carcinoembryonic antigen (CEA) is a known tumour marker for colorectal cancer. It is not used diagnostically, but in patients with a known diagnosis of colorectal cancer associated with raised CEA levels, it can be used to monitor disease activity and help with the early identification of disease recurrence.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

Reactive arthritis, (formerly known as Reiter’s syndrome), is an autoimmune condition that occurs after a bacterial infection of the gastrointestinal or urinary tract. It is categorized as a seronegative spondylarthritis because of its association with HLA-B27. Reactive arthritis primarily affects young men and usually presents with musculoskeletal or extra‑articular symptoms. The characteristic triad consists of arthritis, conjunctivitis, and urethritis. The diagnosis is based on clinical features such as patient history and physical examination; there are no specific tests for reactive arthritis. Treatment is primarily symptomatic and consists of the administration of NSAIDs, as most patients recover spontaneously. extraarticular dermatologic manifestations include skin lesions of the glans resembling psoriasis (balanitis circinata); hyperkeratinisation of the palms and soles (keratoderma blenorrhagicum), oral ulcers.

Ramipril is an ACE inhibitor that blocks the conversion of angiotensin I to angiotensin II as well as preventing the breakdown of bradykinin, leading to blood vessel dilatation and decreased blood pressure. However, bradykinin also causes smooth muscles in the lungs to contract, so the build-up of bradykinin is thought to cause the dry cough that is a common side-effect in patients that are on ACE inhibitors.

Acute angle closure glaucoma can manifests itself with severe headache, nausea or vomiting, very blurry or hazy vision, seeing rainbows or halos around lights and redness in the white part of the affected eye. It is caused by a rapid or sudden increase in pressure inside the eye – intraocular pressure (IOP). In order to establish the diagnosis and start treatment immediately, IOP should first be measured.

Ostium secundum atrial septal defects are known to cause stroke due to the passage of emboli from the right sided circulation to the left sided circulation. ECG shows tall, peaked P waves (usually best seen in leads II and V2) and prolongation of the PR interval, rSR pattern in leads V3 R and V1 as well as right axis deviation.

This case has hypercalcaemia most likely associated with the bony metastases from her pre-existing breast carcinoma. The most appropriate next step is to give Pamidronate 60mg intravenously, a bisphosphonate, to immediately inhibit bone resorption and formation.

Causes for right axis deviation:
-Right ventricular hypertrophy and Left posterior fascicular block
-Lateral myocardial infarction.
-Acute or chronic lung diseases: Pulmonary embolism, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), cor pulmonale.
-Congenital heart disease (e.g., dextrocardia, secundum atrial septal defect).
-Wolff-Parkinson-White syndrome.
-Ventricular ectopic rhythms (e.g., ventricular tachycardia).

Chvostek and Trousseau signs can be elicited in patients with hypocalcaemia. Chvostek sign is the twitching of the upper lip with tapping on the cheek 2 cm anterior to the earlobe, below the zygomatic process overlying the facial nerve. Trousseau sign (a more reliable sign present in 94% of hypokalaemic individuals and only 1% to 4% of healthy people) is the presence of carpopedal spasm observed following application of an inflated blood pressure cuff over systolic pressure for 3 minutes in hypokalaemic patients.