Uric acid less than 1 μmol/L?

foreword

foreword

Uric acid is the final product of purine metabolism, produced by xanthine oxidase oxidation in the liver, and most of it is excreted through the kidneys

Decreased uric acid concentrations are often overlooked because of fewer or less obvious clinical symptoms than hyperuricemia

What causes hypouricemia? What are the consequences? Who is prone to have extremely low uric acid? What potential risks will it bring to life? With a series of questions, please see the case of extremely low uric acid encountered by the author in actual work

case after

case after

Female, 32 years old, has a personal health examination once a year.

Laboratory tests showed: BUN 3.

The uric acid result was so low, which attracted the author's attention.

The biochemical reaction curve is shown in Figure 1 below.

Figure 1 The superimposed biochemical reaction curves of uric acid in patients (blue) and normal people (red)

Figure 1 The superimposed biochemical reaction curves of uric acid in patients (blue) and normal people (red)

This is the first time I have seen such a low uric acid result, and I can't help but wonder, is the result reliable? Will there be any interference? What test exclusions are needed?

1.

1.

1.

Table 1 The results of serum uric acid before and after mixing with patient serum

Table 1 The results of serum uric acid before and after mixing with patient serum

2.

2.

Table 2 Two different biochemical detection systems

It can be seen from the above two experiments that the patient's uric acid concentration is indeed very low.

3.

The patient complained of no discomfort, no medical history of taking medication, no family history of genetic disease, occasional nocturia, normal diet, no health supplements and vitamin tablets, neither thin nor fat, and a height of 1.

Figure 2 The patient's unit physical examination results in 2019

Figure 2 The patient's unit physical examination results in 2019

In order to further clarify the patient's condition and eliminate interference, the author contacted the nephrologist for the patient, and told the patient to eat normally, not to do strenuous exercise, and to come back for a review after a week's rest

One week later, the patient came to the laboratory on an empty stomach at 8:30 in the morning to take blood for re-examination.
The liver and kidney functions were basically the same as the previous results, only the blood uric acid was still low at 1.
7 μmol/L, and the four items of urine routine and renal damage (Figure 3) were tested.
are normal
.

24-hour urine collection, uric acid 31.
68 μmol/L (reference range: 1200-5900 μmol/24H), 24-hour urine creatinine: 15767 μmol/L, fractional excretion of uric acid (FEUA): 6.
43% (2-10% for normal people)
.
It can be seen that the 24-hour urine uric acid results are also low
.

Figure 3 Four results of random urinary renal damage in patients

Figure 3 Four results of random urinary renal damage in patients

case analysis

case analysis

A uric acid concentration below 120 μmol/L is called hypouricemia
.
Uric acid is mainly derived from nucleic acid and other purine compounds decomposed by cells and purines in food through the action of enzymes, and most of it can be reabsorbed by renal tubules, especially proximal convoluted tubules
.
Disorders of purine metabolism and impaired renal excretion can lead to changes in serum uric acid levels
.

There have been many studies on hyperuricemia, but with the increase in the prevalence of hypouricemia (less than 2% in the population [2]), more and more studies have shown the causes of hypouricemia Many, and its impact on all aspects of the body is no less than hyperuricemia
.
In 2021, the probability of occurrence of hypouricemia in outpatient and emergency department of our hospital is 0.
07%, that of inpatients is 2.
32%, and that of physical examination patients is 0.
02%.
The probability of low uric acid value distribution is shown in Figure 4:

Figure 4 Probability distribution of hypouric acid in our hospital in 2021

Figure 4 Probability distribution of hypouric acid in our hospital in 2021

It can be seen that the decrease of uric acid is not accidental and should not be ignored in clinical diagnosis.
The main causes of hypouricemia are: decreased synthesis and increased excretion.
The etiological classification is shown in Figure 5:

Figure 5 Classification of hypouricemia[3]

Figure 5 Classification of hypouricemia[3]

A reduction in synthesis

A reduction in synthesis

1.
Primary synthetic disorders: liver cell damage, hereditary xanthuria, purine nucleoside phosphorylase deficiency, the causes and clinical characteristics are shown in Table 3:

Table 3 Common autosomal recessive disorders of uric acid synthesis disorders

Table 3 Common autosomal recessive disorders of uric acid synthesis disorders

2.
Secondary synthesis reduction: the use of uric acid-lowering drugs such as xanthine oxidase inhibitors (allopurinol drugs), urate oxidase drugs (rasburicase Preikesi), etc.
, clinically used to treat hyperuricemia Blood and gout
.

2.
Increased excretion

2.
Increased excretion

1.
Primary renal tubular dysfunction: mainly seen in renal hypouricemia (RHUC)
.

2.
Excessive uric acid excretion secondary to other diseases: can be seen in Fanconi syndrome, inappropriate antidiuretic hormone secretion syndrome, diabetes, acquired immunodeficiency syndrome, certain drug applications such as benzbromarone, sulfonamides, Mannitol,
etc.

Table 4 Common diseases with increased uric acid excretion

Table 4 Common diseases with increased uric acid excretion

3.
Malignant tumors: Malignant tumors such as non-Hodgkin lymphoma have been found to be associated with significant hypouricemia as early as previous studies, and are caused by defects in uric acid reabsorption
.
A recent study in South Korea involved 426 patients with hypouricemia [4], of which 198 patients could find the cause of the decrease in uric acid, and 86 were malignant tumors.
Treatment-induced nutritional deficiencies and/or renal tubular damage are possible causes of hypouricemia
.

The patient in this case was found to have a very low uric acid result on physical examination.
Due to the 2019 physical examination report provided by him, the uric acid result was normal and congenital hereditary diseases could be ruled out
.
This B-ultrasound examination and other liver function, blood, urine routine, common tumor indicators, etc.
are all normal, and the influence of liver and diabetes can basically be ruled out
.

Considering the extremely low blood uric acid, normal uric acid excretion fraction, no medication, and female, additional tests related to endocrine diseases, such as thyroid function, sex hormones, PTH, cortisol, aldosterone, etc.
, were done
.
Surprisingly, the patient's aldosterone was elevated except for a slightly elevated testosterone of 0.
532 ↑ (reference range: 0.
084-0.
481 ng/mL for adult females), which resulted in a 674 pg/mL ↑ (reference range: supine position: 30- 160pg/mL, upright position: 70-300pg/mL), but the blood pressure is normal on physical examination, which is very confusing
.

Could it be a rare adrenal tumor or secondary aldosteronism without hypertension? (See Table 5 for common RAA system disorders.
) Or is it a patient-acquired genetic variation? When we contacted the patient again to explain the potential harm of hypouricemia to the body, and proposed to continue further examination and genetic screening, the patient was quite concerned and refused to do further testing
.

Table 5 Common RAA system disorders

Table 5 Common RAA system disorders

Summary

Summary

Under normal circumstances, the uric acid in the body (Figure 6) is about 1200 mg, and about 600 mg is newly generated every day, and 600 mg is excreted at the same time, which is in a balanced state.
Excessive uric acid retention, when the blood uric acid concentration is greater than 7 mg/dL, will cause the body fluids to become sour, and if left untreated for a long time, it will cause gout
.

Figure 6 7,9-dihydro-2,6,8(3H)trione-1H-purine, chemical formula is C5H4N4O3, molecular weight 168.
11, slightly soluble in water, easy to form crystals

Figure 6 7,9-dihydro-2,6,8(3H)trione-1H-purine, chemical formula is C5H4N4O3, molecular weight 168.
11, slightly soluble in water, easy to form crystals

On the contrary, due to the hyperactive excretion of uric acid, it is very likely that uric acid is too low or even undetectable, and patients with hypouricemia are mostly patients with various malignant tumors, followed by cardiovascular diseases, bone damage diseases, gallbladder diseases, etc.
Hypouricemia is related to the following diseases and may lead to various complications, which should be paid attention to by clinicians [2]
.

Figure 7 Serum uric acid concentration in patients with hypouricemia in different diseases[2]

Figure 7 Serum uric acid concentration in patients with hypouricemia in different diseases[2]

Hypouricemia refers to the level of uric acid in the blood that is lower than the normal value, and there is no recognized diagnostic cutoff value, which is artificially defined as <2mg/dl (120mmol/L)
.
Hypouricemia often indicates the existence of primary or secondary renal tubular disease or other diseases, and may induce serious complications such as acute renal failure, but for a long time, hypouricemia has been considered as a clinical Significance of biochemical abnormalities
.

In the above cases, although we did not really find out the cause of the patient, some special cases encountered in the clinic are worthy of our exploration, inference from one case to another, multi-dimensional thinking, and reminders to patients and clinics.
And warning, to truly fulfill the responsibility and spirit of the inspector is also a test for modern inspectors, and it is also the transformation of inspection technology to the direction of laboratory medicine.
When encountering special cases, we should pay enough attention and actively communicate with the clinic.

.

references

references

[1] Huang Huibin, Li Wenbin.
Analysis of uric acid results in 1364 hospitalized patients with hypouricemia [J].
Laboratory Medicine and Clinical, 2010, 7(001): 38-39.

[1] Huang Huibin, Li Wenbin.
Analysis of uric acid results in 1364 hospitalized patients with hypouricemia [J].
Laboratory Medicine and Clinical, 2010, 7(001): 38-39.

[2] Liu Deping.
Hypouricemia [J].
China Cardiovascular Journal, 2016, 21(2): 104-107.

[2] Liu Deping.
Hypouricemia [J].
China Cardiovascular Journal, 2016, 21(2): 104-107.

[3] Cai Lili.
Detection of serum uric acid in leukemia patients [J].
Practical Clinical Medicine, 2002, (4): 11-12.

[3] Cai Lili.
Detection of serum uric acid in leukemia patients [J].
Practical Clinical Medicine, 2002, (4): 11-12.

[4] SonCN, Kim JM, Kim SH, et al.
Prevalence and possible causes ofhypouricemia at a tertiary care hospital[J].
Korean J Intern Med, 2016, 31(5): 971.

[4]SonCN, Kim JM, Kim SH, et al.
Prevalence and possible causes ofhypouricemia at a tertiary care hospital[J].
Korean J Intern Med, 2016, 31(5): 971.


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