A 35-year-old man is evaluated for progressive fatigue and shortness of breath. Recently, he has noticed bilateral leg swelling and abdominal distension despite overall weight loss. He does not use tobacco, alcohol, or illicit drugs. Despite treatment, the patient dies several weeks later. Autopsy reveals significant endocardial thickening with dense fibrous deposits around the tricuspid and pulmonary valves as well as moderate pulmonary valve stenosis. The left-sided cardiac chambers and valves are normal. Measuring the levels of which of the following substances would have helped in diagnosing this patient?

Question

A 35-year-old man is evaluated for progressive fatigue and shortness of breath.  Recently, he has noticed bilateral leg swelling and abdominal distension despite overall weight loss.  He does not use tobacco, alcohol, or illicit drugs.  Despite treatment, the patient dies several weeks later.  Autopsy reveals significant endocardial thickening with dense fibrous deposits around the tricuspid and pulmonary valves as well as moderate pulmonary valve stenosis.  The left-sided cardiac chambers and valves are normal.  Measuring the levels of which of the following substances would have helped in diagnosing this patient?

Quizplus · Accepted Answer

11ec160b_38c4_68a3_9249_0b751062feeb_MD0001_00 The autopsy findings - endocardial thickening and fibrosis of tricuspid and pulmonary valves - are characteristic of carcinoid heart disease. Carcinoids are well-differentiated neuroendocrine tumors found most commonly in the distal small intestine and proximal colon, with a strong propensity for metastasis to the liver. These tumors secrete several products (including histamine, serotonin, and vasoactive intestinal peptide) that are metabolized in the liver. In patients with liver metastasis, these hormones are released directly into the systemic circulation, leading to carcinoid syndrome. Carcinoid heart disease is caused by excessive secretion of serotonin, which stimulates fibroblast growth and fibrogenesis. Pathognomonic plaque-like deposits of fibrous tissue occur most commonly on the endocardium, leading to tricuspid regurgitation, pulmonic valvulopathy, and right-sided heart failure (eg, ascites, peripheral edema). Endocardial fibrosis and thickening are generally limited to the right heart as vasoactive products are inactivated distally by pulmonary vascular endothelial monoamine oxidase. 5-hydroxyindoleacetic acid (5-HIAA) is an end product of serotonin metabolism, and elevated 24-hour urinary 5-HIAA levels are helpful in diagnosing suspected carcinoid syndrome. (Choice A) Measurement of plasma cortisol levels is used for diagnosing adrenal insufficiency and Cushing syndrome. (Choice B) Inherited or acquired elevation of plasma homocysteine levels may contribute to arterial and venous thrombosis and to the development of atherosclerosis. (Choice C) Plasma phenylalanine may be elevated in patients with phenylalanine hydroxylase deficiency (phenylketonuria), resulting in central nervous system damage/intellectual disability. (Choice E) Urinary porphobilinogen may be elevated in the porphyrias, which are caused by deficiencies of the heme synthesis enzymes. The porphyrias may produce cutaneous lesions, skin photosensitivity, or attacks of abdominal pain and neurological disturbances (acute intermittent porphyria). (Choice F) Vanillylmandelic acid is a byproduct of norepinephrine and epinephrine, and can be used to detect neuroblastoma and other tumors of neural crest origin. Educational objective: Carcinoid syndrome typically presents with episodic flushing, secretory diarrhea, and wheezing. It can lead to pathognomonic plaque-like deposits of fibrous tissue on the right-sided endocardium, causing tricuspid regurgitation and right-sided heart failure. Elevated 24-hour urinary 5-hydroxyindoleacetic acid can confirm the diagnosis. __________ References: Prediction of prognosis by echocardiography in patients with midgut carcinoid syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/11412260)

A 35-Year-Old Man Is Evaluated for Progressive Fatigue and Shortness