A 36-year-old man presents to the physician with fatigue and “brown” urine. He has an unremarkable past medical history and endorses IV drug use in his early 20s. Family history is significant for breast cancer on his mother’s side and rheumatoid arthritis on his father’s side. He is afebrile, has a blood pressure of 132/72 mmHg, and a heart rate of 84 beats per minute. Physical examination reveals icteric sclera and skin and pain in the right upper quadrant to deep palpation. Laboratory results reveal the following.
Which of the following is the best next step in the diagnostic workup?
Abdominal ultrasonography. The patient in this question is presenting with conjugated hyperbilirubinemia. If he had presented with a high indirect bilirubin, this would be a mainly unconjugated hyperbilirubinemia (possible causes include hemolysis and a conjugation defect like Gilbert’s). He also presents with a nonspecific slightly increased AST and ALT and a highly increased alkaline phosphatase level (760 U/L). In this setting, elevated alkaline phosphatase signifies cholestasis with biliary obstruction. The best next step in this clinical scenario is to order an abdominal ultrasound to determine whether the cholestasis is extrahepatic (biliary dilatation) or intrahepatic (no sign of biliary dilatation). (A) Viral hepatitis, acute type, is typically associated with highly elevated AST and ALT levels; however, this patient has normal levels and likely does not have a viral hepatitis.
Nonetheless, it should be noted that chronic viral hepatitis that has led to cirrhosis could actually have mildly elevated, and even normal, levels of liver enzymes. This patient has normal albumin and coagulation studies, however, and therefore does not likely have cirrhosis. (B) ERCP is a procedure that can be both diagnostic and therapeutic by relieving obstruction and allowing for biliary drainage. Nonetheless, imaging must be performed first to determine the presence of obstruction before ERCP is considered. (D) Liver biopsy is not indicated at this time without radiologic clues to the underlying diagnosis.
A 28-year-old man presents with fatigue and cognitive deterioration. He reports that in the last 2 months he has forgotten several of his friends’ names. His girlfriend states that he has been “impulsive” and has made several poor decisions such as urinating in public and cursing (which he has never done before). Physical examination reveals nonspecific abdominal pain to deep palpation in the right upper quadrant in addition to the finding seen in the photo below.
Which of the following laboratory findings do you expect with this condition?
Decreased serum ceruloplasmin. The patient in this question is presenting with neuropsychiatric symptoms and the physical examination finding of Kayser–Fleischer rings (copper deposition in a ring around the cornea) consistent with a diagnosis of Wilson disease. Wilson disease is an autosomal recessive disorder in which copper accumulates in tissues due to mutations in the Wilson disease protein (ATP7B) gene; this causes a defect in incorporation of copper in hepatic lysosomes. The main sites of copper accumulation are the liver and the brain. Kayser–Fleischer rings are pathognomonic for the condition and result from copper deposition in Descemet membrane (the basement membrane between the stroma and the endothelial layer of the cornea).
The faulty incorporation of copper in the liver leads to defective synthesis of ceruloplasmin, a protein carrier of copper. The resulting high unbound copper in the serum causes deposits in the cornea, liver, and several neurologic structures (basal ganglia, brainstem, cerebral cortex, etc.). (C, D) The diagnosis of Wilson disease is based on laboratory findings: high urinary copper, low serum ceruloplasmin, low serum copper (the low ceruloplasmin causes the bound portion of copper to be low), and high hepatic copper content on liver biopsy. Treatment is with chelation with penicillamine. (A) Elevated ferritin is associated with hereditary hemochromatosis, an autosomal recessive disorder of iron overload (not copper).
A 47-year-old woman presents to the physician with fatigue, pruritus, and jaundice. Physical examination demonstrates xanthelasma, hepatosplenomegaly, and jaundice. Laboratory findings reveal elevated alkaline phosphatase and total bilirubin in addition to the presence of anti-mitochondrial antibody (AMA) and antinuclear antibody (ANA). Liver biopsy demonstrates inflammation of the bile ducts with intraepithelial lymphocytes.
What is the most likely diagnosis?
Primary biliary cirrhosis. The patient in this question is demonstrating signs, symptoms, and laboratory findings consistent with a diagnosis of primary biliary cirrhosis, a disease involving autoimmune destruction of intrahepatic bile ducts. The disease commonly affects women and presents with fatigue, pruritus, jaundice, and sometimes fat malabsorption. Diagnosis is suggested by a highly elevated alkaline phosphatase and total bilirubin, but the most specific finding is the presence of anti-mitochondrial antibodies. Liver biopsy is performed to confirm the diagnosis and determine the stage of the disease. Treatment involves minimizing the associated cholestasis with ursodeoxycholic acid. (A) Autoimmune hepatitis is associated with antismooth muscle antibody. (B) Primary sclerosing cholangitis is often seen in inflammatory bowel disease and is associated with p-ANCA antibodies. (D) α1-antitrypsin deficiency usually affects both the liver and the lungs and is diagnosed by the absence of α1-antitrypsin on serum protein electrophoresis (SPEP).
A 33-year-old man presents with diarrhea for the last 6 weeks. He reports that his stools float and have an oily appearance. They have also been particularly foul smelling. He also endorses a nonspecific and diffuse abdominal pain as well as a 2.3-kg (5-lb) weight loss during this time period. Physical examination is unremarkable and laboratory results reveal a mild iron deficiency anemia. Antibody assays are positive for antiendomysial antibody.
Which of the following is the recommended treatment for this condition?
Gluten-free diet. The patient in this question is presenting with several nonspecific symptoms (abdominal pain, weight loss, chronic diarrhea) as well as iron deficiency anemia that are consistent with a diagnosis of celiac sprue (celiac disease). The presence of antiendomysial antibody suggests the diagnosis; however, tissue biopsy is still considered the gold standard in the diagnosis of celiac sprue. Tissue biopsy will demonstrate flattening or villous atrophy and inflammation. The only effective treatment is a lifelong gluten-free diet. Gluten is present in most grains in the Western world including wheat, barley, several additives, and processed foods, so patients should receive dietary counseling to ensure compliance with the gluten-free diet. (A) In the case of refractory disease in which alternative causes have been ruled out, corticosteroids may be considered. (B) Although the patient in this question presents with chronic diarrhea (>4 weeks), his other clinical symptoms and positive antiendomysial antibody make the diagnosis of Clostridium difficile unlikely. Therefore, treatment with metronidazole is not indicated. (D) Although loperamide will improve the diarrhea, it does not treat the underlying cause of the patient’s constellation of symptoms, which is celiac sprue.
A 44-year-old man with a recent diagnosis of diabetes mellitus type 2 presents with joint pain, fatigue, and jaundice. He reports that his wife has noted that he looks “tanner” than usual. Physical examination demonstrates clubbing of the fingers, splenomegaly, and gynecomastia. Laboratory results reveal mildly increased AST and ALT, as well as an increased transferrin saturation (72%) and an increased ferritin level (410 ng/mL).
Periodic phlebotomies. The patient in this question is presenting with the classic triad of cirrhosis, bronze skin, and diabetes consistent with a diagnosis of hereditary hemochromatosis. Hereditary hemochromatosis is an autosomal recessive disorder of iron overload and typically affects middle-aged Caucasian men. Patients usually present with a mild transaminitis, diabetes mellitus, arthritis, infertility, and sometimes heart failure. Transferrin saturation is commonly used as a screening test for hereditary hemochromatosis and will be elevated. Other laboratory values include increased ferritin levels and increased iron saturation. If suspicious of the diagnosis, the presence of the HFE gene mutation can serve as diagnostic confirmation. Treatment includes periodic phlebotomies to decrease the iron load. These are usually scheduled at weekly intervals until ferritin levels are within the normal range. If phlebotomy treatment is not feasible for the patient, longterm administration of an iron-chelating compound such as deferoxamine is helpful. (A) N-acetylcysteine is used in the treatment of acetaminophen toxicity. (B) Penicillamine is a copper chelator used in the treatment of Wilson disease. (C) Ursodeoxycholic acid reduces cholesterol absorption and is used to dissolve gallstones; it is also used in the treatment of primary biliary cirrhosis and primary sclerosing cholangitis.
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