The role of AHS in the patient’s death is unclear. He was at high risk for stroke considering his age, comorbidities, and evidence of an old lacunar infarct. Myocardial infarctions have been reported as one cause of death in AHS, but we have found no reports of associated stroke. However, the temporal proximity of the CVA suggests a contributing effect of AHS. The adequacy of treatment is also brought into question. Early withdrawal of glucocorticoids can be associated with relapse of AHS; in retrospect, the prednisone dose may have been too low or the taper too short, or both.
Therapeutic alternatives to allopurinol were available. The most appropriate initial option for this patient likely was no pharmacologic intervention at all but a focus on weight loss and diet. The risk of gouty attacks in men increases as body mass index rises above normal (≥25 kg/m2) and decreases with weight loss. Lower calorie diets with decreased saturated fat, higher complex carbohydrates, and allowed proteins (low-fat dairy products) are more palatable and more effective than strict low-purine diets.
A urate-lowering antihypertensive may have been a better option—specifically, losartan rather than irbesartan and triamterene/hydrochlorothiazide.8,13 Losartan has uricosuric properties at the 50-mg dose.14 When compared in different studies with irbesartan, enalapril, and candesartan, losartan alone lowered serum urate levels. Increasing losartan to 100 mg could provide better hypertensive control but has not been found to lower urate levels more dramatically than the lower dose.13
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been found to blunt the urate-elevating effects of thiazides. Therefore, if the patient’s blood pressure was not adequately controlled on losartan alone, the combination of losartan/hydrochlorothiazide would be a reasonable choice because minimal or no change in serum uric acid levels would be expected.15
Febuxostat, a nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol in patients with gout. It is a more potent urate-lowering agent than allopurinol and can be used without dosage reduction in mild (creatinine clearance [CrCl], 60-89 mL/min) to moderate (CrCl, 30-59 mL/ min) renal insufficiency. Febuxostat is metabolized primarily in the liver—in contrast to allopurinol, which is excreted by the kidneys—and may increase liver transaminase levels.10 Although febuxostat was not available at the time our patient developed AHS, it would not have been indicated in asymptomatic hyperuricemia.
This compelling case reminds us to carefully consider the indications and risk factors in using allopurinol, and to be aware of the rare but sometimes devastating consequences of this commonly used drug.
CORRESPONDENCE
Tahirah Tyrell, MD, Rochester General Medical Group, 1425 Portland Avenue, Rochester, NY 14621;
tahirah.tyrell@rochestergeneral.org.