Hyperuricemia Clinical Presentation

In patients with hyperuricemia, the history involves determining whether the patient is symptomatic or asymptomatic and identifying causative etiologies and comorbid conditions.

Symptoms are those of gout and nephrolithiasis.

• Gout typically manifests as an acute monoarthritis, most commonly in the great toe and less frequently in the tarsal joint, knee, and other joints.
• Uric acid nephrolithiasis may manifest with hematuria; pain in the flank, abdomen, or inguinal region; and/or nausea and vomiting.

Patients are usually asymptomatic, and no specific physical findings are recognized.

• In acute gouty arthritis, the affected joint is typically warm, erythematous, swollen, and exquisitely painful.
• Patients with chronic gouty arthritis may develop tophi in the helix or antihelix of the ear, along the ulnar surface of the forearm, in the olecranon bursa, or in other tissues.
• In uric acid nephrolithiasis, patients may present with abdominal or flank tenderness.

Hyperuricemia is generally divided into 3 pathophysiologic categories, ie, uric acid underexcretion, uric acid overproduction, and combined causes.

Underexcretion

• Idiopathic
• Familial juvenile gouty nephropathy: This is a rare autosomal dominant condition characterized by progressive renal insufficiency. These patients have a low fractional excretion of urate (typically 4%). Kidney biopsy findings indicate glomerulosclerosis and tubulointerstitial disease but no uric acid deposition.
• Renal insufficiency: Renal failure is one of the more common causes of hyperuricemia. In chronic renal failure, the uric acid level does not generally become elevated until the creatinine clearance falls below 20 mL/min, unless other contributing factors exist. This is due to a decrease in urate clearance as retained organic acids compete for secretion in the proximal tubule. In certain renal disorders, such as medullary cystic disease and chronic lead nephropathy, hyperuricemia is commonly observed even with minimal renal insufficiency.
• Syndrome X: This metabolic syndrome is characterized by hypertension, obesity, insulin resistance, dyslipidemia, and hyperuricemia. This is associated with a decreased fractional excretion of urate by the kidneys.
• Drugs: Causative drugs include diuretics, low-dose salicylate, cyclosporine, pyrazinamide, ethambutol, levodopa, nicotinic acid, and methoxyflurane.
• Hypertension
• Acidosis: Types that cause hyperuricemia include lactic acidosis, diabetic ketoacidosis, alcoholic ketoacidosis, and starvation ketoacidosis.
• Preeclampsia and eclampsia: The elevated uric acid associated with these conditions is a key clue to the diagnosis because uric acid levels are lower than normal in healthy pregnancies.
• Hypothyroidism
• Hyperparathyroidism
• Sarcoidosis
• Lead intoxication (chronic): History may reveal occupational exposure (eg, lead smelting, battery and paint manufacture) or consumption of moonshine (ie, illegally distilled corn whiskey) because some, but not all, moonshine was produced in lead-containing stills).
• Trisomy 21

Overproduction

• Idiopathic
• HGPRT deficiency (Lesch-Nyhan syndrome): This is an inherited X-linked disorder. HGRPT catalyzes the conversion of hypoxanthine to inosinic acid, in which PRPP serves as the phosphate donor. The deficiency of HGPRT results in accumulation of PRPP, which accelerates purine biosynthesis with a resultant increase in uric acid production. In addition to gout and uric acid nephrolithiasis, these patients develop a neurologic disorder that is characterized by choreoathetosis, spasticity, growth, mental function retardation, and, occasionally, self-mutilation.
• Partial deficiency of HGPRT (Kelley-Seegmiller syndrome): This is also an X-linked disorder. Patients typically develop gouty arthritis in the second or third decade of life, have a high incidence of uric acid nephrolithiasis, and may have mild neurologic deficits.
• Increased activity of PRPP synthetase: This is a rare X-linked disorder in which patients make mutated PRPP synthetase enzymes with increased activity. These patients develop gout when aged 15-30 years and have a high incidence of uric acid renal stones.
• Purine-rich diet: A diet rich in meats, organ foods, alcohol,^[1] and legumes can result in an overproduction of uric acid.
• Increased nucleic acid turnover: This may be observed in persons with hemolytic anemia and hematologic malignancies such as lymphoma, myeloma, or leukemia.
• Tumor lysis syndrome: This may produce the most serious complications of hyperuricemia.
• Glycogenoses III, V, and VII

Combined causes

• Alcohol^[1] : Ethanol increases the production of uric acid by causing increased turnover of adenine nucleotides. It also decreases uric acid excretion by the kidneys, which is partially due to the production of lactic acid.
• Exercise: Exercise may result in enhanced tissue breakdown and decreased renal excretion due to mild volume depletion.
• Deficiency of aldolase B (fructose-1-phosphate aldolase): This is a fairly common inherited disorder, often resulting in gout.
• Glucose-6-phosphatase deficiency (glycogenosis type I, von Gierke disease): This is an autosomal recessive disorder characterized by the development of symptomatic hypoglycemia and hepatomegaly within the first 12 months of life. Additional findings include short stature, delayed adolescence, enlarged kidneys, hepatic adenoma, hyperuricemia, hyperlipidemia, and increased serum lactate levels.