Method for predicting diffuse toxic goiter clinical course

FIELD: medicine.

SUBSTANCE: method involves determining anti-inflammatory cytokines IL-1β and TNF-α and anti-inflammatory IL-4 content. K coefficient is calculated from formula K=(ln IL-1β + ln TNF-α)/ ln IL-4. K value being found greater than 2, recurrent clinical course of diffuse toxic goiter is to be predicted.

EFFECT: high prognosis accuracy.

1 tbl

 

The invention relates to medicine, namely to endocrinology and surgery, and can be used for early diagnosis of relapse of diffuse toxic goiter.

Diffuse toxic goiter (graves ' disease, graves ' disease-Graves') is an autoimmune disease characterized by persistent pathological hypersecretion Cherednik hormones, usually diffusely enlarged thyroid gland (thyroid). The basis of pathogenesis of graves ' disease lies in stimulating the development of autoantibodies to the TSH receptors, probably due to a congenital defect in the immune system. A genetic predisposition is evidenced by the detection of circulating autoantibodies in 50% of relatives graves ' disease, frequently detected in patients with the haplotype HLA DR3. Women have 5-10 times more often than men. As a rule, LED manifests in young and middle age [1].

According to the literature, the recurrence rate, particularly nodular goiter, at different times after surgery ranges from 0.3%to 39%. Causes and mechanisms of its development are not entirely clear, therefore, there is no clear system of measures to prevent the recurrence of the disease [2]. Relapses of graves ' disease according to various authors, are found in 62% of patients [3]. Meng et al. [4] reported the occurrence of relapses after treatment thyreostatics at 53-54% of patients during the year, Edwards et al. [5] give the figures 55-66% when observed for 2 is no, for longer observation reported 60-67% of cases of recurrence (according to Lucas et al. [6]).

When recurrence of graves ' disease the thyroid gland structure often repeats the structure of the first remote thyroid tissue, but it is often observed subcapsular and interstitial fibrosis, the tendency to uzloobrazova.

There is a method of diagnosing flow LED and relapse definition of antibodies inhibiting the binding of TSH in the blood. Studies have shown, TSI (thyrostimulin immunoglobulins) are detected in 80-90% of cases in untreated patients with diffuse toxic goiter. When saving the TSI over 35% within 1-1,5 years of treatment thyreostatics predict relapse of the disease and recommend surgical treatment. Maintaining a high index of TSI is a risk factor for recurrence of the disease [7]. These findings are confirmed by other authors who also determine the high level of antibodies to the TSH receptor in patients with relapsing course of thyrotoxicosis [8].

As the prototype was accepted method of determining the risk of recurrent flow of hyperthyroidism on the basis of the title thyrostimulin immunoglobulins [9]. Calculate the relative risk of thyrotoxicosis by the formula RR=Fn(1-Fk)/Fk(1-Fn), where Fn is the fraction of native antibodies among patients; Fk is the fraction of native antibodies in the control group, the highest risk identified in patients with high titer thyrostimulin immunoglobulins (+19,6). The combination of high levels of antibodies to receptor tireotropina in the presence of a genetic predisposition to diffuse toxic goiter increases the risk of postoperative recurrence, especially in patients of young age. However, the disadvantages of this method include the need for continuous monitoring of the dynamics of the level thyrostimulin immunoglobulins with repeated study of the concentration of TSI, as well as the determination of antigens HLA-B8 and HLA-DR3 to decide on the further treatment of the thyrotoxicosis.

To improve accuracy and simplify the method for the diagnosis of relapse of thyrotoxicosis in patients with diffuse toxic goiter determine the concentration of Pro-inflammatory (IL-1, TNF-α) and anti-inflammatory (IL-4) cytokines, logarithmorum the results and calculate the ratio, and if it is more than 2 predict the possibility of relapse of thyrotoxicosis in patients with diffuse toxic goiter.

The method is performed as follows.

Blood taken from a vein of the patient on an empty stomach at 8 am. The blood was collected in a test tube with EDTA at a final concentration of 1 mg/ml Concentration of cytokines in the serum was determined by ELISA with the use of Russian is built monoclonal antibodies in PCG/ml (research Institute of highly pure biopreparations, St.-Petersburg). The obtained quantitative values of the concentrations of the investigated substances are logarithmically (logarithm of this number is called the exponent to which you want to build another number, called the base of the logarithm to obtain this number) and calculate the ratio by the formula:

K=(ln IL-1β+ln TNF-α)/ln IL-4,

where ln IL-1β - the natural logarithm of a numeric value content of IL-1β;

ln-TNF-α - the natural logarithm of a numeric value content of TNF-α;

ln IL-4 - the natural logarithm of a numeric value content of IL-4,

and if the ratio is greater than 2 diagnose the presence of relapse in patients with diffuse toxic goiter. The method used in 38 patients with recurrent for graves ' disease. The data obtained are presented in table 1:

Table 1
CytokinesControl

n-14
LED, the manifest form n-57Graves ' disease, relapsing form n-38
ln IL-1β3,38-3,925,0-5,97*6,87-7,21*,**
ln IL-43,25-3,744,96 of 5.99*5,98-6,01*,**
ln TNF-α2,93-3,444,15-5,54*6,44-6,89*,**
*- p<0.05 the significance of differences compared to control

**- p<0.05 the significance of differences between groups of diffuse toxic goiter, the manifest form and diffuse toxic goiter, relapse.

Increasing the ratio of the amounts of proinflammatory cytokines (ln IL-1β and ln TNF-α) to anti-inflammatory cytokine (ln IL-4) increases the risk of relapse in patients with diffuse toxic goiter, the reliability of this method was 83%.

Examples of specific performance.

1. Patient R., 37 years old, came to the clinic with complaints shivering, palpitations with little exertion, increased irritability, weight loss of 5 kg in 6 months. From history revealed that the above complaints appeared in the last 7 months, honey. not treated and not treated. At objective inspection: low power; the skin is hot and humid. Peripheral lymph nodes are not enlarged. Thyroid palpation of enlarged, elastic consistence, homogeneous. There have been positive symptoms of Moebius, Salvage. The vesicular breathing, wheezing no, NPV - 18 in 1 minute. The rhythmic heart sounds, systolic murmur at the apex, HR - 106 in 1 minute, BP 120/80 mm Hg, with a hand on the natives of organs and systems pathology is not found. Laboratory tests: TSH - 0.3 mked/ml, St. T4 - 176 nmol/l, AT to TPO was not found. At ultrasound of the thyroid gland: the gland 23 ml, contours equal, structure homogeneous, echo is increased. When fine-needle aspiration biopsy revealed proliferation of the follicular epithelium, atypical cells are not found. The levels of cytokines were: IL-1β=175 PCG/ml - ln IL-1β - 5,1; TNF-α - 66 PCG/ml - ln TNF-α - 4,18; IL-4=251 PCG/ml - ln IL-4 - of 5.82; K=1,59. Prescribed treatment: thyreostatics (mercazole 30 mg/day), β-blockers, sedatives. On the background of therapy made autres, the patient was discharged in good condition with recommendations: the gradual reduction of the dose of thyreostatics (5 mg 1 time per week), monitoring by an endocrinologist every 3 months. Within 1.5 years, the patient's condition remained stable. During the control study, the levels of cytokines were: IL-1β=32 PCG/ml - ln IL-1β - of 3.46; TSR-α=19,2 PCG/ml - ln TNF-α - 2,95; IL-4=36 PCG/ml - ln IL-4 - 3,60; K=1,78.

2. Patient M., 34 years old, came to the clinic with complaints of palpitations, trembling hands, increased irritability, weight loss of 12 kg for 4 months. From history revealed that the above complaints have appeared within the last 6 months, honey. not treated and not treated.

At objective inspection: low power, protect skin what s hot, wet. Peripheral lymph nodes are not enlarged. Thyroid palpation of enlarged, elastic consistency, painless. There have been positive symptoms Graefe, Salvage, Marie. The vesicular breathing, wheezing no, NPV - 16 in 1 minute. The rhythmic heart sounds, systolic murmur at the apex, HR - 112 in 1 minute, BP 130/80 mm Hg, from other organs and systems pathology is not found. Laboratory tests: TSH - 0.2 mked/ml, St. T4 - 180 nmol/l, AT to TPO was not found. At ultrasound of the thyroid gland: the gland 26 ml, contours equal, structure homogeneous, echo is increased. When fine-needle aspiration biopsy revealed proliferation of the follicular epithelium, atypical cells are not found. The levels of cytokines were: IL-1β=1142 PCG/ml - ln IL-1β? 7.04 baby mortality; TSR-α=641 PCG/ml - ln TNF-α - 6,46; IL-4=401 PCG/ml - ln IL-4 of 5.99; K=2,25.

Prescribed treatment: thyreostatics (mercazole 30 mg/day), β-blockers, sedatives. On the background of therapy made autres, the patient was discharged in good condition with recommendations: the gradual reduction of the dose of thyreostatics (5 mg 1 time per week), monitoring by an endocrinologist every 3 months. Within 1.5 years, the patient's condition remained stable, after acute respiratory illness symptoms of shivering, palpitations. B is supplemented flax has addressed to the endocrinologist, when tests: TSH - 0.4 mked/ml (at a rate of 0.5 to 5.0 mked/ml), St. T4 - 174 nmol/l (normal 60-160 nmol/l), AT to TPO was not found. The levels of cytokines were: IL-1β=1291 PCG/ml - ln IL-1β - 7,16; TKR-α=718 PCG/ml - ln TNF-α return of 6.58; IL-4=411 PCG/ml - ln IL-4 - 6,0; K=2,29. At ultrasound of the thyroid gland: the gland 32 ml, contours equal, structure homogeneous, echo is increased. Was diagnosed with a relapse of diffuse toxic goiter, after the post-operative patient preparation conducted Subtotal subfascial resection of the thyroid gland. After 3 months investigated the levels of cytokines were: IL-1β=32 PCG/ml - ln IL-1β - of 3.46; TNF-α=29,5 PCG/ml - ln TNF-α - 3,38; IL-4=223 PCG/ml - ln IL-4 - 5,41; K=1,26.

3. Patient, 41 years, turned in Endocrinology center with complaints of palpitations, trembling hands, sweating, insomnia and irritability, increased neck in volume. The patient reported a significant weight loss of 9 kg in 3 months. From history revealed that the above complaints have appeared within the last 6 months, honey. not treated and not treated. At objective inspection: low power; the skin is hot and humid. Peripheral lymph nodes are not enlarged. Thyroid palpation of enlarged, elastic consistency, painless. Marked position is positive symptoms Graefe, Salvage, Dalrymple, Marie. The vesicular breathing, wheezing no, NPV - 18 in 1 minute. The rhythmic heart sounds, systolic murmur at the apex, HR - 120 in 1 minute, BP 140/80 mm Hg, from other organs and systems pathology is not found. Laboratory tests: TSH - 0.12 mked/ml, St. T4 - 190 nmol/l, AT to TPO was not found. At ultrasound of the thyroid gland: the gland 34 ml, contours equal, structure homogeneous, echo is increased. When fine-needle aspiration biopsy revealed proliferation of the follicular epithelium, atypical cells are not found. The levels of cytokines were: IL-1β=1142 PCG/ml - ln IL-1β-7,04; TNF-α=641 PCG/ml - ln TNF-α - 6,46; IL-4=401 PCG/ml - ln IL-4 of 5.99; K=2,25.

After the treatment thyreostatics (mercazole 30 mg/day), β-blockers, sedatives conducted Subtotal subfascial resection of the thyroid gland. After 3 months studied, the levels of cytokines were: IL-1β=29 PCG/ml - ln IL-1β - 3,40; TNF-α=19,5 PCG/ml - ln TNF-α - 2,97; IL-4=34,5 PCG/ml - ln IL-4 - 3,54; K=1,79.

Literature

1. Janashia PH, Selivanov G.B. Age differences in dynamics of blood pressure, the condition of the renin-aldosterone system and lipid profile in hypertension due to thyrotoxicosis. // Russian cardiology journal. - 2003. No. 6. - P.16-24.

2. Soludo A.M., Semikov V.I., Ivanov N.A.,Gorbachev AV, Mironov M.V., Batalova A.R., Kulikov ACTING Recurrent goiter and ways of its prevention. // Russian medical journal. - 2002. No. 3. - S.

3. Petrova N, Khomyakov, VN, Melnichenko G.A. // Samples. endocr. V.46. No. 6. - P.12-18.

4. Meng W., Meng, S., Mannchen E. et al. // Exp. Clin. Endocrinol. - 1991. - Vol.97. - P.257-260.

5. Edwards C.J.Jellez M. // Eur. J. Endocrmol. - 1994. - Vol.131. - P.120-124.

6. Lucas, A., I. Salinas, F. Rius Et al. // J. Clin. Endocrinol. Metab. - 1997. - Vol.82. - P.2410-2413.

7. Clinical endocrinology, edited by NetStorage. - Moscow, Medicine, 1991.

8. Okamoto T., Fujimoto Y., Obara T. et al. // Nippon Geka Gakkai Zasshi. - 1993. - Vol.94. - P.1043.

9. Annobon, Asseseries, Amirudin. // Problems of endocrinology. - 2002. - T. No. 1.

A method of predicting the course of diffuse toxic goiter by biochemical analysis of the blood, characterized in that determine the content of Pro-inflammatory cytokines IL-1β and TNF-α and anti-inflammatory IL-4, calculate the factor K by the formula

K=(In IL-1β+ln TNF-α)/ln IL-4,

where ln IL-1β - the natural logarithm of a numeric value content of IL-1β;

ln TNF-α - the natural logarithm of a numeric value content of TNF-α;

ln IL-4 - the natural logarithm of a numeric value content of IL-4,

and when set To more than 2 predict relapsing course of diffuse toxic goiter.



 

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