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hyperuricemia

Etiology: 1) tumor lysis syndrome - chemotherapy-induced - spontaneous (Burkitt lymphoma) [12] 2) overproduction a) primary defect in purine metabolism - PRPP synthetase overactivity - HGRPT deficiency b) myeloproliferative disorders - polycythemia vera - myeloid metaplasia - chronic myelocytic leukemia (CML) c) lymphoproliferative disorders - chronic lymphocytic leukemia (CLL) - multiple myeloma d) disseminated cancer (carcinoma & sarcoma) e) chronic hemolytic anemia - sickle cell anemia - thalassemia - ineffective erythropoiesis f) psoriasis g) infectious mononucleosis h) obesity i) increased dietary intake of purines - shellfish, red meat, potatoes, poultry j) hyperalimentation k) alcoholic beverages & high-fructose corn syrup may increase uric acid production - beer, spirits, wine, soft drinks l) growth factor treatment: GM-CSF, G-CSF, erythropoietin m) non-adherence to allopurinol - likely cause in patients previously well-controlled on allopurinol [12] 3) underexcretion a) hereditary, renal tubule-based [4] b) intrinsic renal disease - chronic renal insufficiency - lead nephropathy c) pharmaceutical agents - aspirin (low-dose) - ethacrynic acid - loop diuretics, furosemide - thiazides - ethambutol - pyrazinamide - cyclosporine - nicotine - laxative abuse - levodopa - vitamin B12 [3] - niacin [3] d) endocrine disorders - adrenal insufficiency - nephrogenic diabetes insipidus - hyperparathyroidism - hypoparathyroidism - pseudohypoparathyroidism - hypothyroidism e) metabolic disorders - diabetic ketoacidosis (DKA) - lactic acidosis - starvation - alcoholism - type I glycogen storage disease - Bartter's syndrome f) dietary purines or purine-inducing foods - contributory, insufficient alone - red meat, shellfish, high-fructose corn syrup g) sarcoidosis h) Down's syndrome i) berylliosis j) gouty arthritis Genetics: - more important than diet [11] Clinical manifestations: 1) gouty arthritis 2) tophi 3) nephropathy: tumor lysis syndrome Laboratory: - see ARUP consult [5] Complications: - gout - nephrolithiasis (including tumor lysis syndrome) - no convincing association between hyperuricemia & any other health outcome [9] Management: - do not treat patients for asymptomatic hyperuricemia (see gout) [4] - hypertension: - HCTZ may increase serum urate [4] - losartan (unique among ARBS) has uricosuric effect - calcium channel blockers also lower serum urate [4] - allopurinol is associated with less chronic renal failure than febuxostat [10] - Healthy Eating, DASH diet, & Mediterranean diet associated with lower serum uric acid [11] - eggs, peanuts, cold cereal, skim milk, cheese, brown bread, margarine, & non-citrus fruit associated with lower serum uric acid [11]

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gout uric acid in serum

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sign/symptom

References

  1. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 831
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 858-61
  3. Prescriber's Letter 10(10):58 2003
  4. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018.
  5. ARUP Consult: Hyperuricemia - Gout The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/hyperuricemia
  6. Prescriber's Letter 19(12): 2012 GUIDELINES: 2012 American College of Rheumatology Guidelines for Management of Gout. Part 1: Systematic Nonpharmacologic and Pharmacologic Therapeutic Approaches to Hyperuricemia Detail-Document#: 281224 (subscription needed) http://www.prescribersletter.com
  7. Mandell BF. Clinical manifestations of hyperuricemia and gout. Cleve Clin J Med. 2008 Jul;75 Suppl 5:S5-8. PMID: 18822469
  8. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011 Oct;63(10):3136-41 PMID: 21800283
  9. Li X, Meng X, Timofeeva M et al Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies. BMJ. 2017 Jun 7;357:j2376. Review. PMID: 28592419 Free PMC Article
  10. Singh JA, Cleveland JD. Comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in older adults: An analysis of Medicare claims data. Ann Rheum Dis 2017 Jun 5 PMID: 28584186
  11. Major TJ, Topless RK, Dalbeth N, Merriman TR. Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population based cohorts. BMJ 2018;363:k3951. Oct 10. PMID: 30305269 https://www.bmj.com/content/363/bmj.k3951 - Watson L, Roddy E The role of diet in serum urate concentration. BMJ 2018;363:k4140. Oct 10. PMID: 30305276 https://www.bmj.com/content/363/bmj.k4140
  12. NEJM Knowledge+ Hematology