Peer Reviewed
Asymptomatic Hyperuricemia Discovered in a 55-Year-Old Man: What’s the Best Approach?
Author:
Ronald N. Rubin, MD—Series Editor
Citation:
Rubin RN. Asymptomatic hyperuricemia discovered in a 55-year-old man: what’s the best approach? Consultant. 2017;57(6):360-361.
A 55-year-old man has matriculated into a general medicine practice for his ongoing routine care, since he has passed his 50th birthday and feels as if he should be seeing a doctor on a regular basis now. He feels well and is unaware of any medical problems. His past medical and surgical histories are rather bland, with a remote appendectomy and several orthopedic problems earlier in life, all of which are now resolved. He takes no chronic medications. He works in sales at a local hardware outlet. Other than “heart problems” that his parents encountered in old age, his family history is negative. He drinks 2 or 3 glasses of wine per week. His diet is not extreme regarding specific food intakes.
Physical examination reveals a healthy-appearing if slightly overweight (body mass index, 26 kg/m2) man with normal vital signs. Findings of a head, ears, eyes, nose, and throat examination are normal. There are no bruits in the neck or abdomen. The chest is clear, and the heart shows regular rhythm without murmurs or gallops. His abdomen is negative for masses or tenderness. Neurologic examination findings are nonfocal.
Results of a battery of laboratory tests include totally normal complete blood cell count findings. Results of a comprehensive metabolic panel show a glucose level of 94 mg/dL, a creatinine level of 1.0 mg/dL (creatinine clearance, 80 mL/min/1.73 m2), a urea nitrogen level of 14 mg/dL, and normal levels of transaminases. The uric acid level was 9.3 mg/dL. Urinalysis findings were negative for blood cells.
Answer on next page
Answer: D, withhold therapy until a gout flare or other indication for uric acid lowering occurs.
The case of asymptomatic hyperuricemia presented in this clinical vignette represents a very common situation.1 The major importance of such hyperuricemia is that it is the primary risk factor for gout. Although there are exceptions, hyperuricemia is essentially a requirement for gout, its presence having an adjusted hazard ratio approaching 50 for the development of clinical gout in the next 5 years.2
However, the risk is not total, since only 22% of people with hyperuricemia will develop clinical gout in that 5-year period—meaning that the vast majority will not develop gout.2 This results in the difficult clinical judgment situation of having an easily measured biochemical marker for disease on one hand, and the need to titrate that against the risks of therapy on the other hand. There is a reasonable body of data and opinion to help make a decision.
Gout Risk Factors
An important fact of basic science is that the primary driver of hyperuricemia is renal urate underexcretion, with a genetic component attached.3,4 Therefore, although addressing a long list of other risk factors can help lower hyperuricemia, the level of power of these interventions is very limited. Such risk factors include obesity, renal insufficiency, the use of diuretics (especially thiazides), alcohol consumption, and dietary factors such as meat consumption. Some of these risk factors matter more than others; for example, heavy alcohol use and thiazide use have higher hazard ratios than most dietary habits. And in any event, good studies testing for bona fide efficacy of lifestyle changes to lower uric acid levels do not really exist.
Approach to Management
The patient presented here takes no medications, consumes very modest amounts of alcohol, is not extreme in any dietary intakes, and is only very modestly overweight. Thus, to more stringently modify his already modest lifestyle would seem to be too extreme for the amount of uric acid lowering benefit expected, meaning that Answer C is not the best approach.
Answer A and Answer B invoke using pharmacologic interventions that may or may not be able to more effectively lower his uric acid level. Answer A can be quickly dismissed, since low-dose aspirin actually increases the gout risk in that it competitively inhibits the renal excretion of uric acid and results in uricoretentive effects (in contrast with high-dose aspirin, which is uricosuric but is far too toxic for prophylactic use).4
Allopurinol interferes with xanthine oxidase and decreases the synthesis of uric acid and thus the degree of hyperuricemia. However, the medication has enough toxicity—a 2% to 5% incidence of rash, some cases of which can degenerate into the serious conditions of Stevens-Johnson syndrome and toxic epidermal necrolysis—such that most authorities conclude that putting the entire hyperuricemic population on this agent to prevent gout in the 20% who will go on to develop clinical disease does not pass the risk-to-benefit ratio analysis.
The situation with colchicine is even more asymmetric on the risk side of the ledger. Colchicine is not an easy medicine to use. Dosage is critical, and strict attention must be paid to liver function and renal status (thus requiring monitoring), lest toxic levels accrue in the patient. And the toxicity is not trivial, with diarrhea as the most common adverse effect, and life-threatening cytopenia the most serious. An additional issue is that a clever pharmaceutical firm took advantage of an interesting aspect in the Food and Drug Administration’s regulatory process to secure market exclusivity for a 100-plus-year-old drug and raise its price very substantially.5 The author has not prescribed the medication since then. In any event, colchicine even more so than allopurinol has too many issues to justify its use in people with asymptomatic hyperuricemia. Thus, Answer B does not represent the best approach.
What is left, therefore, is the statement that mirrors the current guidelines for the management of asymptomatic hyperuricemia. The current indications for the use of urate-lowering therapy are as follows: the presence of 2 or more flares of clinical gout in a year; the presence of tophi; the presence of stage 2 or higher chronic kidney failure; and/or a past history of nephrolithiasis.2,3 Answer D best summarizes these indications and is the correct statement.
Patient Follow-Up
The patient was advised to try moderate lifestyle changes, such as eating meat 1 or 2 fewer times per week and avoiding sweetened soft drinks (especially with fructose) as much as possible. He will have screening with a metabolic panel at reasonable intervals with a focus on the uric acid level and renal function measurements. He was educated about the common and usual symptoms of an acute gouty flare, and he received a prescription for oral corticosteroids with taper to have available and be filled if needed.
Ronald N. Rubin, MD, is a professor of medicine at the Lewis Katz School of Medicine at Temple University and is chief of clinical hematology in the Department of Medicine at Temple University Hospital in Philadelphia, Pennsylvania.
References:
- Zhu Y, Pandya BS, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63(10):3136-3141.
- Neogi T. In the clinic: gout. Ann Intern Med. 2016;165(1):ITC1-ITC16.
- Neogi T. Clinical practice: gout. N Engl J Med. 2011;364(5):443-452.
- Merriman TR, Choi HK, Dalbeth N. The genetic basis of gout. Rheum Dis Clin North Am. 2014;40(2):279-290.
- Kesselheim AS, Solomon DH. Incentives for drug development—the curious case of colchicine. N Engl J Med. 2010;362(22):2045-2047.