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A 57-year-old man arrives at the hospital with nausea, dark urine, and decreased urine output for 2 days.  For the past week, the patient has had generalized fatigue, muscle pain, and weakness.  He reports no recent fever, chills, sore throat, skin infection, or abdominal pain.  Medical history is significant for coronary artery disease with stenting to the right coronary artery, hypertension, gout, and obstructive sleep apnea.  Current medications include aspirin, ticagrelor, simvastatin, metoprolol, lisinopril, and colchicine.  The patient does not use alcohol, tobacco, or illicit drugs.  Temperature is 37 C (98.6 F), blood pressure is 140/90 mm Hg, pulse is 88/min, and respirations are 18/min.  There is no orthostasis.  Skin turgor is normal.  Oropharynx is clear.  Cardiopulmonary examination shows no abnormalities.  The abdomen is soft, nontender, and without bruit; there are no masses felt.  There is no peripheral edema.  The right great toe is slightly inflamed.  Laboratory studies reveal the following: Complete blood count     Hemoglobin 13.8 g/dL     Platelets 260,000/mm3     Leukocytes 11,000/mm3 Serum chemistry     Sodium 136 mEq/L     Potassium 5.6 mEq/L     Chloride 94 mEq/L     Bicarbonate 18 mEq/L     Blood urea nitrogen 50 mg/dL     Creatinine 4.2 mg/dL     Glucose 100 mg/dL Urinalysis     Protein none     Blood 3+     White blood cells 1-2/hpf     Red blood cells 1-2/hpf Baseline laboratory studies conducted a month ago were normal.  Which of the following is most helpful to establish a diagnosis? A. 24 hour urine protein measurement B. Renal ultrasonogram C. Renal vascular imaging D. Serum complement levels E. Serum creatine phosphokinase

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A 32-year-old male presents to your clinic concerning about the two occasions over the past week during which he has noticed blood in his semen. He has never noticed this before. There is no pain with urination or ejaculation and no urinary frequency. He reports no anorexia, bone pain or weight loss. He has had several casual sexual relationships with women over the past 12 months. He has no significant past medical history and takes no regular medications. There is no family history or other risk factors for prostate cancer. On examination, his temperature is 36.8C and blood pressure is 135/85 mmHg and genital examination and digital rectal examination are unremarkable. Systems review shows no clinical signs of chronic liver disease, leukaemia or lymphoma. Which initial investigations would be most appropriate for him at this stage? A. Urine microscopy, culture & sensitivities; urine cytology; full blood count; coagulation studies; chlamydia & gonorrhoea PCR B. Urine microscopy, culture & sensitivities; full blood count; prostate specific antigen; chlamydia & gonorrhoea PCR; coagulation studies C. Urine microscopy, culture & sensitivities; urine cytology; prostate specific antigen; pelvic computed tomography; chlamydia & gonorrhoea PCR D. Urine microscopy, culture & sensitivities; full blood count; urine cytology; scrotal ultrasound; cystoscopy E. Urine microscopy, culture & sensitivities; chlamydia & gonorrhoea PCR; full blood count; pelvic computed tomography; cystoscopy

Correct Answer Is E This patient has evidence of von Hippel-Lindau (VHL) disease, an autosomal dominant disorder that results in benign and malignant multiorgan tumors.  The most common tumors associated with VHL are hemangioblastomas of the central nervous system (CNS) (particularly in the cerebellum, with a classic cystic nodular radiographic appearance) and retina.  Although the tumors are noninvasive, symptoms occur due to hemorrhage or compression of surrounding tissues.  Bleeding from retinal tumors can lead to retinal exudates and impaired vision or, if untreated, retinal detachment with vision loss.  Acute hemorrhage in a brain tumor can result in herniation and death (as likely occurred in this patient’s father). Malignant manifestations include renal cell carcinoma (RCC), which occurs in upward of 70% of patients by age 60.  RCCs are of the clear cell subtype and typically bilateral.  They are often preceded by the formation of multiple renal cysts, which are considered a premalignant condition.  Pheochromocytomas also occur with increased frequency and are characterized by paroxysms of hypertension, tachycardia, and diaphoresis.  Less common manifestations include vascular tumors of the endolymphatic sac in the ear and pancreatic disease (eg, cysts, neuroendocrine tumors).  Genetic testing for germline VHL mutations is key to diagnosis.  Management requires frequent tumor surveillance beginning in infancy or early childhood. Autosomal dominant polycystic kidney disease also manifests as CNS and renal disease.  However, the CNS disease is largely due to aneurysms (which would not appear as cystic nodules on imaging) rather than tumors; the renal disease is characterized by progressive parenchymal obliteration by cysts, which commonly leads to flank pain and hematuria; and the condition is not associated with retinal capillary hemangioblastomas. Patients with autosomal recessive polycystic kidney disease are typically diagnosed in infancy or childhood.  Although the disease is associated with multiple renal cysts, patients characteristically develop end-stage renal disease in early childhood, and hepatobiliary involvement is common (eg, hepatic fibrosis, liver cysts).  It is not associated with hemangioblastomas. Li-Fraumeni syndrome is an autosomal dominant disorder associated with alterations of the tumor protein p53 gene.  It usually results in early onset of malignancies such as sarcomas, breast cancer, and adrenal carcinomas.  CNS disease is characterized by gliomas and medulloblastomas, not hemangiomas. Neurofibromatosis type 2 is another autosomal dominant disorder with marked CNS and ophthalmologic features.  However, it is more commonly characterized by schwannomas, particularly of the vestibular nerve, and meningiomas.  Cataracts and retinal hamartomas are common ophthalmic manifestations. Von Hippel-Lindau disease is an autosomal dominant disorder resulting in benign and malignant multiorgan tumors.  The most common tumors are hemangioblastomas of the central nervous system and retina.  Other common manifestations include renal cell carcinoma (often preceded by the formation of premalignant renal cysts) and pheochromocytoma.

A 26-year-old man comes to the office for follow-up related to painless progressive visual loss in the right eye. Recent ophthalmological evaluation revealed macular edema due to 2 retinal lesions consistent with capillary hemangioblastoma. He underwent laser photocoagulation treatment, and the vision in his right eye has improved. The patient has no other medical conditions. His father died from a cerebral hemorrhage at age 52. MRI of the brain with gadolinium reveals 2 small, cystic, enhancing nodules in the cerebellum. Renal ultrasonography reveals multiple cysts in both kidneys. Which of the following is the most likely diagnosis? A. Autosomal dominant polycystic kidney disease B. Autosomal recessive polycystic kidney disease C. Li-Fraumeni syndrome D. Neurofibromatosis type 2 E. Von Hippel-Lindau disease

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Correct Answer Is C Phenytoin is a commonly used, long-acting antiepileptic medication that inhibits voltage-gated sodium channels.  Acute toxicity initially manifests with signs of cerebellar dysfunction: horizontal nystagmus (ie, nystagmus on lateral gaze), ataxia (eg, wide-based gait), dysmetria (eg, on finger-nose testing), slurred speech, and nausea/vomiting are common, and hyperreflexia may occur.  Severe toxicity results in altered mental status (eg, lethargy, confusion), coma, paradoxical seizures, and death.  Rapid intravenous infusions of phenytoin or its prodrug fosphenytoin can also result in hypotension and bradyarrhythmia. Toxicity typically occurs after dosing adjustments or initiation of medications that interfere with the pharmacodynamics of phenytoin.  Because phenytoin is highly protein-bound and is hepatically metabolized by the cytochrome p450 system, medications that inhibit the cytochrome p450 system (eg, trimethoprim-sulfamethoxazole [as in this patient], fluconazole) or that displace phenytoin from plasma proteins (eg, valproic acid) increase the risk of drug toxicity.  Patients with renal or hepatic dysfunction are also at increased risk.  Management involves supportive care with gastric decontamination and possibly hemodialysis. Epidural abscesses (which may result from hematogenous spread of infection) may cause weakness and hyperreflexia; however, patients typically have fever, malaise, and back pain.  Lower extremity hyperreflexia is possible, but diffuse hyperreflexia would be unlikely.  In addition, epidural abscess is unlikely to cause cerebellar dysfunction and nystagmus. Folate deficiency (which is associated with phenytoin use) typically causes macrocytic anemia and mood disturbances or psychosis but may rarely cause paresthesias and weakness.  However, nystagmus and cerebellar dysfunction would be unexpected. Septic encephalopathy is characterized by delirium (waxing and waning altered mentation) and confusion.  Focal neurologic deficits, as seen in this patient, would be unexpected.  In addition, although the patient likely had a urinary tract infection, symptoms have improved and she does not have fever, tachycardia, tachypnea, or hypotension to suggest sepsis. Acute subdural hematoma usually occurs after trauma (eg, fall) and often causes coma at the time of injury (or shortly thereafter).  Chronic subdural hematoma has an indolent course with gradually worsening headache, cognitive impairment, and somnolence that occurs over a period of weeks.  This patient’s symptoms preceded the fall, and nystagmus would be unexpected. Phenytoin is highly protein-bound and metabolized hepatically by the cytochrome p450 system; medications that inhibit cytochrome p450 (eg, trimethoprim-sulfamethoxazole, fluconazole) or that displace phenytoin from plasma proteins (eg, valproic acid) increase the risk of drug toxicity.  Common symptoms of acute phenytoin toxicity include horizontal nystagmus, ataxia, and nausea/vomiting, and significant toxicity can result in altered mental status, coma, and death.