Gout is the result of the biochemical pathway of purine nucleotide metabolism, leading to the formation of monosodium Urate (MSU) crystals. With crystal formation,an intense inflammatory response develops leading to the clinical acute gouty attack. Uric acid is the end product of purine degradation. One-third of the daily urate load is dietary with the remainder generated endogenously.One-third of a rate is eliminated by GI tract, the remainder is handled primarily by the kidneys.

In primary gout, 10% of patients develop hyperuricemia from renal under secretion and 90% develop it from over production of enogenous uric acid. Both genetic and environmental factors contribute to hyperuricemia. These include hypertension, use of thiazide diuretics, obesity, high alcohol intake and dietary factors (high meat intake), all of which are modifiable risk factors. A strong correlation exists between obesity, hyperuricemia and gout. Hyperinsulinemia and insulin resistant syndrome have been estimated to occur in 95% and 76% of gout suppressors respectively.

Gout treatment should not ignore lifestyle and health factors. A diet of high-purine meats and shellfish is associated with increased risk of gout. Dietary intervention is important due to the association of hyperuricemia with insulin resistance.

Gout treatment should not ignore lifestyle and health factors. A diet of high-purine meats and shellfish is associated with increased risk of gout. Dietary intervention is important due to the association of hyperuricemia with insulin resistance.

It is estimated that more than half of gout sufferers drink alcohol excessively. Transient lactic acidemia from acute alcohol excess reduces renal urate excretion. Long-term alcohol ingestion stimulates purine production. Hypertension reduces renal excretion of urate and thiazide diuretics further increase serum urate levels by interfering with renal excretion. Low dose aspirin decreases renal urate excretion while high-dose aspirin actually has a uricosuric effect. Estrogen also exerts a uricosuric effect.

Treatment of acute gout is to rapidly resolve pain and inflammation. NSAID's are the treatment of choice. Use with caution in patients with renal impairment, congestive heart failure, peptic ulcer disease, anticoagulation therapy or hepatic dysfunction. Colchicine functions by interfering with tubulin dimers (leukocyte function) and mitigates the chemotaotic response of urate crystals. It's use is limited by nausea, vomiting, diarrhea and abdominal pain.

Corticosteroids are often used in patients where colchicine or NSAIDs' are contra-indicated, and are effective due to the direct anti-inflammatory effects. The treatment of chronic gout in these patients with anywhere from two to more than four gout attacks per year, will require urate-lowering therapy with a uricostatic agent such as Allopurinol. This drug inhibits Xanthine oxidase, decreasing the production of uric acid. Probenecid is a uricosurgic agent and acts to increase uric acid excretion in the urine. In all cases, urate-lowering drugs should not be started until after the acute attack has resolved.

• Consider the initiation of urate-lowering therapy in patients with more than 2 attacks per year.
• Do not start urate-lowering drugs during an acute attack. If a patient on a urate-lowering drug has an acute flare, do not discontinue the urate-lowering medication
• 24 hour urinary uric acid excretion is not routinely measured, although should be considered before initiating a uricosuric
• Allopurinol is usually the drug of choice for initial therapy, but uricosurics may be used in Allopurinol-allergic patients with normal renal function, uric acid under excretion, and no history of nephrolithiasis.
• Use of concomitant prophylaxis with oral colchicine or NSAIDS (if no contra-indications) when initiating urate-lowering therapy.
• Routinely measure serum uric acid levels (every 3-6 months) and adjust medications until a target uric acid of <6 mg/dt, is achieved.
• Consider and treat associated comorbidities such as obesity, hypertension, hyperlipidemia, and coronary artery disease.