RU2536288C1 - Diagnostic technique for adolescent's reproductive disorders accompanying chronic renal pathology - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: technique involves a blood serum examination for thyrotropic hormone, mcUnit/ml, free T4, pmole/l, prolactine, mIU/ml, follicle-stimulating hormone, mIU/ml, lutenizing hormone, mIU/ml, testosterone, nmole/l, dehydroepiandrosterone sulphate, mcg/ml, cortisol, nmole/l, oestradiol, pg/ml, 17-OH progesterone, nmole/l. Calculating an integral hormone state (HIS) by formula follows. If the HIS value is below 0.799, a habitual disorder is stated, which is accompanied by a minimum risk of the reproductive disorders. The HIS values falling from the range of 0.800 to 1.000 provides stating the tensed hormonal regulation reflecting a moderate risk of the reproductive disorders. The disturbed interhormonal cooperation corresponds to the HIS value falling within the range of 1.001 to ≤1.210 that represents a high risk of the reproductive disorders. The HIS value of more than 1.211 shows the lack of reserves that testifies to a very high risk of the reproductive disorders.

EFFECT: technique enables improving the diagnosis of the adolescent's reproductive disorders.

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Description

The invention relates to medicine, namely to pediatrics, nephrology, endocrinology, and can be used to predict disorders of reproductive function in adolescents by the value of the integral indicator of hormonal status (IPSG).

The physical and sexual development of adolescents is affected by a fairly large number of factors, including the presence of chronic kidney pathology that violates the formation of the reproductive system in the period of puberty, which in the future can lead to infertility, miscarriage, etc. (Perepelkina N.Yu. Ways to improve pediatric nephrological service: diss. Dr. med. - Moscow, 2003. - 372 p.).

It is known that violations in reproductive health lead to a change in the level of hormones (Zhukovsky MA Children's endocrinology. - M .: Medicine, 1995. - 656 p.). A reserve for improving reproductive health is the early diagnosis of its abnormalities.

There is a method for predicting reproductive health disorders by a screening assessment of reproductive health (RU No. 2271152 C1, 05/26/2008, RU No. 2393757 C1, 05/25/2009), which consists in determining a point indicator of occupational and production factors, anamnestic, biomedical points are additionally determined indicators and calculate diagnostic risk indicators according to the formulas.

The disadvantages of this method are restrictions on professional affiliation, age and gender, as well as lack of objectivity due to the lack of assessment of the hormonal profile.

The closest analogue is a method for determining hormonal status disorders in women (RU No. 2225009 C2, 05/13/2002), which recommends the identification of constitutional-phenotypic signs and obstetric-gynecological history, highlighting the stages of hormonal status violation.

The disadvantages of the prototype are:

- determination of the stage of hormonal status disorder by clinical manifestations, which may be absent in adolescents;

- lack of accounting for complex changes in the level of hormones involved in the formation of the reproductive function;

- the differentiated boundaries of the complex of hormone indicators were not determined in a comprehensive assessment of reproductive health disorders at the prenosological level.

The objective of the invention: improving diagnosis, simplifying the interpretation of data and improving the accuracy of pre-nosological diagnosis of reproductive health disorders in adolescents.

The technical result - the possibility of early preclinical diagnosis of reproductive health disorders in adolescents with chronic renal pathology by determining the norm and violation of hormonal status.

Positive effect: the method allows to diagnose reproductive health disorders in adolescents at the preclinical stage, which makes it possible to determine the tactics of therapeutic and preventive measures in the early stages of the disease.

,The technical result is achieved in that in the blood serum in the first phase of the cycle, the method of enzyme-linked immunosorbent assay (ELISA) determines the sex, thyroid hormones and hormones of the adrenal glands, reflecting reproductive function in adolescents (Levenets S.A. Clinical and anamnestic and hormonal features of oligomenorrhea and secondary amenorrhea in adolescent girls with systemic dysplasia of the connective tissue / S.A. Levenets, L.F. Kulikova, T.A. Nachetova // Obstetrics and gynecology. - 2006. - No. 1. - P.39-41). Then, the integral indicator of hormonal status (IPGS) is calculated by the formula

,

where Xi is the value of the indicator in a particular patient, X is the average value of the indicator in healthy patients; / Xi-X / is the difference in indicators without regard to the sign, σ is the standard deviation of the indicator in the group of healthy people; n is the number of indicators studied.

Based on the results obtained, an analysis of the gradation of indicators is carried out and ranges of values of the IPGS function are calculated. Using cluster analysis (k-means method), 4 clusters were identified with different gradation ranges of the integral indicator:

Cluster 1: in this group, teens were united, who in 92.5% of cases had no reproductive health disorders, which made it possible to determine hormonal status indicators in adolescents as “habitual deviations” with an IPSG indicator in this group of up to 0.799, when there is a minimal risk of deviations in reproductive health.

In adolescents, 2 clusters of reproductive health disorders were detected in 13.5% of cases, which made it possible to determine hormonal status indicators in adolescents as “tension in the processes of hormonal regulation” and IPSG ranged from 0.800 to 0.999, which reflects the average risk of deviations in reproductive health.

Teenagers were united in cluster 3, in which reproductive health disorders requiring observation and correction were detected in 31% of cases. In adolescents of this group, IPHC corresponds to values from 1,000 to 1,210 (violation of inter-hormonal cooperation) and indicates a high risk of developing reproductive health disorders.

Cluster 4 was made up of adolescents, in whom 48% of cases identified diseases of the reproductive sphere that need treatment and control. IPGS in adolescents was equal to or higher than 1,210 (lack of reserve capacity). This indicator indicates a very high risk of deviations in the reproductive health of adolescents with CPD.

To disclose the essence of the invention, the results of a study of 139 adolescents with chronic renal pathology for the diagnosis of reproductive health disorders and hormonal status indicators are presented. According to the study protocol, reproductive health and hormonal status of adolescents were compared. Indicators of the hormonal profile in 39.8% of girls and 41.3% of boys fit into the usual deviations of hormone levels (Table 1). A fifth of children (18.3% of girls and 21.7% of boys) were identified as lacking in reserve capacity. With the growth of IPSG, the frequency of deviations in reproductive health increases (Table 2): if in the group of children with “usual deviations” reproductive health disorders were detected in 7.5% of adolescents, then in the group “lack of reserve capacity” - 48%.

Using the proposed method for the determination of IPGS, characterizing changes in hormonal status, allows you to identify children with functional stress of the body systems for early prenosological diagnosis of deviations in reproductive health in a particular teenager, and timely prescribe treatment and preventive measures.

As a result of the processing of analytical data, it was found that hormonal status is a rather sensitive indicator of the reproductive and general health status of a teenager. On the basis of the data obtained, the prospect of timely detection of reproductive health disorders or their predisposition to them opens up and, based on the value of IPGS, it is possible to draw up a screening and treatment plan for adolescents with chronic kidney disease.

The advantages of the proposed method:

1. changes in hormonal status are ahead of the clinical picture or other data of other diagnostic methods;

2. an integral assessment of hormonal status simultaneously for a number of indicators for the most complete diagnosis of reproductive health disorders in adolescents;

3. the possibility of isolating the most significant hormones for the violation of health from the totality of the studied.

Example 1. Patient Alexei P., 15 years old. Medical history of admission: In 1 g, 7 months. examined in the urology department of the regional hospital, where the diagnosis was made: the only right kidney. At 3 years old - received treatment in a hospital for exacerbation of chronic pyelonephritis; at 11 years - again exacerbation of the disease. After discharge, it is observed on an outpatient basis - for 4 years in urine tests - without pathology.

The calculation of IPGS in this child:

Blood hormones The indicator of the child (X _i ) The average value of the indicator in healthy (X) Standard deviation
(σ _i ) Function TSH (μU / ml) 2.03 1.68 0,558011 0.0142 ST ₄ (pmol / l) 14.10 18.95 3.561098 0,030957 PRL (mMe / ml) 293.40 233.71 64,29977 0.021096 FSH (mMe / ml) 1.06 2.80 1,71361 0,023128 LH (mMe / ml) 1,03 2.28 0.912372 0,031221 T (nmol / L) 10.08 25.27 11.80447 0,029257 E ₂ (PG / ml) 68.74 71.58 35.01883 0,001846 DHEA-s (μg / ml) 4.08 3.37 1.559048 0,010237 Cortisol (nmol / L) 546.71 516.71 225,273 0,003026 17-OCG (nmol / L) 4.46 2.26 0.947667 0.052561 IPGS: 0.21753 - “habitual deviations”

IPGS in a child - 0.21753. The teenager is included in the group of “habitual deviations”. Examination of narrow specialists did not reveal violations in reproductive health.

Example 2

Patient Maria F., 14 years old. Anamnesis of the disease: changes in urine tests were first detected in a child in 2002 in the form of erythrocyturia up to 10-12 in the SC, microleukocyturia. Subsequently, microhematuria was noted in urinalysis. The girl was examined in 2010, where she was first diagnosed with chronic tubulointerstitial nephritis, toxic-allergic genesis, and the active phase.

Complaints at admission: on changes in urine tests, swelling of the eyelids in the morning, rare urination; headaches mainly in the evening. Deviation in organs and systems: the skin is clean, dry, pale, periorbital shadows. Body weight 45 kg; length 167 cm; OGK 66 cm; Exhaust gas 53 cm. Physical development of the mesosomatic disharmonious. Sexual formula: Ma3, P3, Ax3, Me0.

The calculation of IPGS in this child:

Blood hormones The indicator of the child (X _i ) The average value of the indicator in healthy (X) Standard deviation (σ _i ) Function TSH (μU / ml) 1.77 1.41 0.71333 0,04987 ST ₄ (pmol / l) 14.08 19.09 2,51872 0.19891 PRL (mMe / ml) 178.57 295.57 94,0452 0.12441 FSH (mMe / ml) 4.28 4.00 1,32433 0,02054 LH (mMe / ml) 2 5.18 2,35014 0.135535 T (nmol / L) 0.08 1.98 1,09082 0.174518 E ₂ (PG / ml) 16.3 119.58 62.57851 0.16505 DHEA-s (μg / ml) 0.68 2.90 1,98023 0,11242 Cortisol (nmol / L) 311.4 625.25 242.82 0.12925 17-OCG (nmol / L) 0.92 2.54 1,86775 0,08718 IPGS: 1,19768 "violation of inter-hormonal cooperation"

IPGS in adolescents is 1.19768, which corresponds to “disruption of inter-hormonal cooperation” due to the low level of estradiol, which is significantly lower in the girl compared to both the control group and the established standards.

The girl was examined by specialists, infantility of secondary sexual characteristics was established. Ultrasound of the small pelvis (uterus, ovaries) revealed no pathology.

Example 3

Patient Ksenia E., 15 years old. Medical history of admission: child at 4 months. pyelonephritis was first diagnosed. After a comprehensive examination, the diagnosis was established: Congenital malformation of the urinary system: iliac dystopia, hypoplasia, doubling of the right kidney. Bilateral PMR of 2-3 degrees (state after endoscopic correction of PMR on the right). Secondary obstructive pyelonephritis of a chronic continuously recurring course, stage of remission. Partial decrease in renal function. Dysmetabolic oxalate phosphate nephropathy. Enuresis of mixed genesis.

Complaints at admission: periodically - enuresis, ultrasound changes in the kidneys, lag in physical and mental development, periodically pain in the right hypochondrium, headaches with overwork and weather changes.

The calculation of IPGS in a child determined its value to -13.2124.

The adolescent revealed a “lack of reserve capacity” due to an excess of FSH and LH. With an additional examination and consultations of a gynecologist and endocrinologist, the diagnosis was established: hypergonadotropic hypogonadism, ovarian agenesis, rudimentary uterus. The teenager is taken under supervision and treatment by specialists.

The calculation of IPGS in this child:

Blood hormones The indicator of the child (X _i ) The average value of the indicator in healthy (X) Standard deviation (σ _i ) Function TSH (μU / ml) 1.7 1.41 0.71333 0,04006 ST ₄ (pmol / l) 16.45 19.09 2,51872 0.10481 PRL (mMe / ml) 282.35 295.57 94,0452 0,00163 FSH (mMe / ml) 148.45 4.00 1,32433 10.9068 LH (mMe / ml) 42.83 5.18 2,35014 1,60180 T (nmol / L) 0.26 1.98 1,09082 0.15801 E ₂ (PG / ml) 11.3 119.58 62.57851 0.17304 DHEA-s (μg / ml) 2,32 2.90 1,98023 0,02960 Cortisol (nmol / L) 406.16 625.25 242.82 0,09023 17-OCG (nmol / L) 0.56 2.54 1,86775 0.10646 IPGS: 13,2124 - "lack of reserve capacity"

Thus, the clinical examples cited indicate that the proposed method provides the ability to assess reproductive health by hormonal profile. Due to the fact that an integral indicator of hormonal status is used, including an assessment of the state of various endocrine glands, the reliability of the diagnosis of deviations in the reproductive health of adolescents suffering from chronic renal pathology increases.

Table 1 An integral indicator of the hormonal status of adolescents with ronic kidney disease Surveyed
IPGS Girls The boys Abs. % Abs. % Up to 0.799 37 39.8 19 41.3 0.800 to 1,000 23 24.7 8 17.5 From 1.001 to 1.209 16 17,2 9 19.5 Equal to or more than 1,210 17 18.3 10 21.7

table 2 Reproductive health disorders in adolescents in groups with different values of IPSG (%) Surveyed IPGS Girls The boys Up to 0.799 8 7 0.800 to 1,000 12 fifteen From 1.001 to 1.209 33 29th Equal to or more than 1,210 47 49

Claims (1)

A method for diagnosing abnormalities in the reproductive health of male and female adolescents with chronic renal pathology, including determining the level of thyroid-stimulating hormone (TSH, μU / ml), free thyroxine (CT _4, pmol / l), prolactin (PRL, mIU / ml), follicle-stimulating hormone (FSH, mMe / ml), luteinizing hormone (LH, mMe / ml), testosterone (T, nmol / L), dehydroepiandrosterone sulfate (DHEA-s, μg / ml), cortisol (nmol / L), estradiol ( E ₂ pg / ml), 17-OH progesterone (17-OPG, nmol / l) in blood serum, characterized in that the calculation is carried out and integrand hormonal status indicator by the formula

where Xi is the value of the indicator in a particular patient, X is the average value of the indicator in healthy patients; / Xi-X / is the difference in indicators without regard to the sign, σ is the standard deviation of the indicator in the healthy group, n is the number of studied parameters, and with IPSH up to 0.799, habitual deviations in hormonal status are diagnosed when there is a minimal risk of deviations in reproductive health, IPGS from 0.800 to 1.000 indicate the intensity of hormonal regulation processes that reflect the average risk of deviations in reproductive health, inter hormonal cooperation is diagnosed for IPGS values from 1.001 to ≤1.210, which This indicates a high risk of developing reproductive health disorders, a lack of reserve capacity is diagnosed when IPHI is equal to or exceeds 1.211, which reflects a very high risk of deviations in the reproductive health of adolescents with chronic renal pathology.