Total body irradiation is a crucial risk factor for developing secondary carcinomas after allogeneic hematopoietic stem cell transplantation in childhood.

Allogeneic hematopoietic stem cell transplantation (HSCT) has become a standard part of therapy for a variety of malignant and non-malignant disorders. With improved outcomes after HSCT, increasing attention has been drawn to late complications in long-term survivors. The development of secondary malignancies is recognized as one of the most serious complications. We have evaluated data from 426 patients (272 males, 154 females) who underwent allogeneic transplantation at a median age of 7.9 years from 1989 till 2017 and were alive more than one year after transplantation for the occurrence of secondary solid tumors. We have documented the occurrence of secondary solid tumors in 20 patients (4.7%). The median duration of the development of secondary solid cancer from HSCT was 11.7 (range, 5.4-21.5 years). 18 out of 20 patients (90%) had total body irradiation (TBI) 12-14.4 Gy as a part of a conditioning regimen. All but two had transplantation for malignant disease. All patients underwent surgery and/or chemo-radiotherapy. Eighteen are alive, and two died due to the progression of their secondary malignancy. The most frequent solid cancer was thyroid carcinoma (n=9). Cumulative incidence of secondary solid cancer in all groups was 15.2±3.9%, in a group using TBI based regimen 34.7±8.9%, in non-TBI (only chemo) group was 1.5±1.1%. Overall, the cumulative incidence is statistically significantly different between the TBI based and non-TBI (chemo only) group. The incidence and number of complications following allogeneic HSCT in childhood are increasing in time. The early diagnosis of secondary malignancies is one of the key tasks of long-life multidisciplinary post-transplant care.

[Disorders of sex differentiation: genes responsible for development of genital system and final phenotype]. / Poruchy sexuální diferenciace s chybým vývojem gonád: dosud známé zodpovedné geny a výsledný fenotype.

OBJECTIVE: The study summarizes data on genes responsible for development of gonads and subsequently of additional structures of genital system in humans. It comprises the effect of gene defects on clinical phenotype. SUBJECT: Review article. SETTING: Department of Pediatrics, University Hospital Motol and 2nd Faculty of Medicine, Charles University in Prague. SUBJECT AND METHOD: We present the overview of genes that contribute to development of genital system. Special emphasis is given on patient's phenotype related with various genetic disorders. Data were mainly found on Pubmed or OMIM web-sites according to key words "sex development" and "sex determination". We focused on ten genes with known relation to gonadal development--SRY, SOX9, SF1, DAX1, WNT4, WT1, DMRT1, DHH, RSPO1, ATRX. CONCLUSION: Sex development is a complex process orchestrated by numerous genes. Here we collect information on gene defect (gene mutations or defective number of gene copies) that cause gonadal maldevelopment with effects on final phenotype. Currently, genetic background of numerous disorders can be detected. That allows not only to verify the diagnosis but also to predict the future sexual development and genetic risk for other family members.

[Psychomotor and cognitive development of children born after intracytoplasmic sperm injection]. / Psychomotorický a kognitivní vývoj detí narozených po mimotelním oplodnení metodou intracytoplazmatické injekce spermie.

OBJECTIVE: To analyse data on psychomotor and cognitive development of children born after intracytoplasmic sperm injection (ICSI). DESIGN: Open cross-section clinical study. SETTING: Institute for the Care of Mother and Child, Prague and Department of Paediatrics, Charles University, 2nd Medical School and University Hospital Motol, Prague. METHODS: In 133 children (75 boys and 58 girls) psychological examination was made at the age range 11 months - 8.5 years in the years 2004-2006. All children were born after intracytoplasmic sperm injection (ICSI). Psychomotor development of children aged from 11 months to 3.5 years was assessed using the Bayley Scales (BSID-II). In older children, Global Intelligence McCarthy Test was used. RESULTS: In our sample of ICSI-children, no significantly higher incidence of children delayed in mental (cognitive) as well as in motor development has been found as compared with the population norms. However, the results indicate a significantly lower average value of the Psychomotor Developmental Index (PDI) in the group of younger children as compared with the given norm (92.3 +/- 13.9 versus 100 +/- 15; p<0.01). In the group of older children, lower average value of the General Cognitive Index (GCI), as compared with corrected population norm has been found (105.1 +/- 14.7 versus 110 +/- 16; p<0.05). In the group of twins, a significantly higher number of mild developmental disorders was ascertained on the contrary in the group of singletons (64.7% versus 333%; p<0.01) in our older children conceived by ICSI. CONCLUSION: The results indicate only mild lowering of some performances in our ICSI-children: in motor domain in younger children, and in cognitive domain in older children. Children from multiple pregnancies are at greater developmental risk than singletons.

[Parental attitudes and socio-emotional development in children born after ICSI]. / Rodicovské postoje a socioemocní vývoj detí pocatých po ICSI.

OBJECTIVE: To analyze parental attitudes and socio-emotional development of children conceived by ICSI. DESIGN: Open cross-sectional study. SETTING: Department of Clinical Psychology, Thomayer University Hospital, Prague and Department of Paediatrics, Charles University, 2nd Medical School, University Hospital-Motol, Prague. METHODS: 133 children (75 boys, 58 girls) conceived by ICSI, age ranged from 11 months to 8.5 years were psychologically assessed between the years 2004-2006. Children's behavior was evaluated by 4 rating scales during the assessment. Parents answered questionnaires concerning children's temperament, behavioral problems (TBC) and the parental attitudes questionnaire (PARQ). RESULTS: Children's behavior during the psychological assessment was rated mostly as very good or good, although the children were often less communicative. Most of the children have mixed or easy temperament, a difficult type of temperament didn't report any of the parents. Most of the parents didn't describe significant behavioral problems in their children, in particular there were very few externalizing difficulties (opposition, aggression), but in 29.5% of the sample, there were found some social or emotional difficulties. We found surprisingly high frequency of milder forms of autism spectrum disorders and another social problems (social and other anxiety disorders) in the sample, other psychopathology was rare. Parental attitudes had a tendency to grater involvement with the child and high affection in relation with him. CONCLUSION: Socio-emotional development of ICSI children is good, although some have specific social difficulties, externalising problems were present only exceptionally. Parental attitudes toward ICSI children are positive, there is slight tendency to higher emotional involvement with the child.

[Children born after intracytoplasmic sperm injection (ICSI): factors of infertility, pregnancy complications, neonatal period and neonatal characteristics]. / Deti narozené po intracytoplazmatické injekci spermie: faktory neplodnosti, prubeh tehotenství a porodu, perinatální období.

OBJECTIVE: To analyze the type of infertility, pregnancy and neonatal outcome in children conceived after intracytoplasmic sperm injection (ICSI children). DESIGN: Prospective open cross-sectional clinical study. SETTING: University hospital and private IVF unit. METHODS: Type of infertility, pregnancy complications, neonatal period and neonatal characteristics were evaluated in 135 newborns conceived after ICSI from singleton and twin pregnancies and compared to general population. RESULTS: The percentage of twins was significantly higher after ICSI compared to general population (31% versus 1.7%; p<0.001) as well as the percentage of caesarean section deliveries (31% versus 17.8%; p<0.001). Some complication in neonatal period was found in 21.5% ICSI newborns (18 out of 42 twins and 12 out of 93 singletons; p< 0.001). Some complication during the course of pregnancy was found in 50.9% ICSI children. CONCLUSIONS: no differences in gestational age, birth weight and birth length were found when ICSI and spontaneously conceined (sc) singletons and ICSI and SC twins were compared. However, complications during the course of pregnancy and in the neonatal period were more frequent in ICSI conceived children.

[Birth defects, medical outcome and somatic development in children conceived after intracytoplasmic sperm injection (ICSI)]. / Vrozené vývojové vady, zdravotní stav a somatický vývoj detí narozených po intracytoplazmatické injekci spermie.

OBJECTIVE: To analyze the incidence of birth defects, medical outcome and somatic development in children conceived after intracytoplasmic sperm injection (ICSI). DESIGN: Prospective open cross-sectional clinical study. SETTING: University hospital and private IVF unit. METHODS: 135 Czech children (59 girls, 76 boys) from singleton and twin pregnancies conceived after ICSI (age 03-9.5 years; median 5.9) were assessed during the period 2004-2006. The incidence of birth defects, medical outcome and somatic development were evaluated and compared with data of general population and/or with control group matched for sex and age. RESULTS: Birth defects were found in 133% of ICSI children (compared to 4.6% in children after spontaneous conception; p<0.001). The general health of ICSI children did not differ significantly compared to general population. ICSI children required more surgery or hospitalization compared to general population data. There is high rate (69.6%) among ICSI children in the care of various specialised clinics. Body height and weight in ICSI children is in normal range and corresponds to their growth potential. Head circumference in ICSI children is larger compared to reference data (0.43 SD; p<0.001). CONCLUSIONS: No clinically important differences in somatic development between ICSI and general population of Czech children were found. Birth defects were more frequent in ICSI children. The overall general health in ICSI children seems satisfactory but ICSI children were more likely to need health care compared to general population.

[Late (non-classic) adrenal hyperplasia]. / Pozdní (neklasická) forma kortikální adrenální hyperplazie.

OBJECTIVE: To summarize available data concerning adrenal hyperandrogenemia caused by 21-hydroxylase deficiency, non-classic adrenal hyperplasia (NCAH). DESIGN: Review article. SETTING: Department of Gynecology and Obstetrics, General Faculty Hospital and 1st Medical Faculty, Prague. METHODS: Compilation of published data from scientific literature. CONCLUSION: Although 21-hydroxylase deficiency is one of the most frequent autosomal recessive genetic disorders, prevalence of NCAH in the whole population and among hyperandrogenic women is very low. The measurement of 17OH-progesterone should be incorporated into the standard evaluation of all hyperandrogenic patients to establish or exclude the diagnosis of NCAH. There is no typical clinical sign of NCAH, and clinical symptoms are to similar to patients with PCOS. Corticoid substitution as a treatment modality of NCAH is derived from therapy of classic congenital adrenal hyperplasia (CAH). Anti-androgen therapy is effective in skin disorders (hirsutism). Due to normal cortisol value there is to use of combined oral contraceptives in the treatment of choice. An improvement of clinical symptoms is a key parameter for the evaluation of treatment effectiveness. There are no data about risk of late metabolic complications in NCAH patients.

[Hormonal suppression and sexual development in children with central precocious puberty in the first treatment cycle 12 weeks after injection of triptoreline 11.25 mg (Diphereline S. R. 11.25 mg): a pilot study]. / Hormonální suprese a pohlavní vývoj detí s centrální predcasnou pubertou v prvním lécebném cyklu 12 týdnu po injekci triptorelinu 11.25 mg (Diphereline S. R. 11.25 mg): pilotní studie.

OBJECTIVE: To evaluate hormonal suppression and pubertal development in children with central precocious puberty (CPP) after injection of triptoreline 11.25 mg (Diphereline S. R. 11.25 mg; Ipsen) in the first treatment cycle of 12 weeks. DESIGN: Pilot study. SETTING: Paediatric department, University Hospital Motol-Prague. METHODS: Serum levels of FSHmax and LHmax and basal levels of estradiol/testosterone were monitored in GnRH test before, 4, 8 and 12 weeks after triptoreline 11.25 mg injection in 3 girls and 2 boys with CPP (age 3.9-10.6 years) previously treated by triptoreline 3 mg every 4 weeks. Uterine and ovarian volume, hormonal cytology (vaginal smear), breast development and testicular volume were evaluated before and 12 weeks after triptoreline 11.25 mg injection. RESULTS: 8 weeks after triptoreline 11.25 mg, FSHmax in girls increased (2.3 IU/l vs. 1.7 IU/l before injection; median) without any other change in 12th week. In boys after initial decrease LHmax 12 weeks after injection rose to 1.7 IU/l (identical as LHmax before injection). Estradiol and testosterone levels were in prepubertal range. Pubertal development in girls did not progress, and testicular volume decreased in both boys (treated for CPP 0.3 and 0.7 years). CONCLUSIONS: Triptoreline 11.25 mg injection in 12 weeks interval can be considered as effective, useful and safe for therapy of CPP. The long-term follow-up will be necessary.

The effects of long-term metformin treatment on adrenal and ovarian steroidogenesis in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate adrenal and ovarian steroidogenesis before and after long-term treatment with metformin in women with polycystic ovary syndrome (PCOS). DESIGN AND METHODS: Twenty-four women with PCOS were evaluated before and after treatment (27+/-4 weeks) with metformin (1000 mg/day) using adrenocorticotrophin (ACTH), GnRH analogue and oral glucose tolerance (oGTT) tests. For statistical evaluation, ANOVA and Wilcoxon's test were used. RESULTS: In 58% of the women a significant improvement in menstrual cyclicity was observed. No significant change in basal steroid levels was found. After ACTH stimulation, a significant decrease in the activity of 3 beta-hydroxysteroid dehydrogenase in C(21) steroids (P<0.05) and in 17 beta-hydroxysteroid dehydrogenase (P<0.01) was observed, as was an increase in the activity of C17,20-lyase in the Delta(4) pathway (P<0.01). A significant growth in the dehydroepiandrosterone (DHEA)/DHEA-sulfate ratio (P<0.05) was detected. With regard to ovarian steroidogenesis, a significant decrease in the stimulated levels of testosterone (P<0.05), index of free testosterone (P<0.01), LH (P<0.05) and oestradiol (P<0.01), and an increase in the levels of 17-hydroxypregnenolone (P<0.05) were detected. In the indices of ovarian enzyme activities, we observed a significant decrease in 3 beta-hydroxysteroid dehydrogenase in C21 steroids (P<0.01), in C17,20-lyase in the Delta 5 pathway (P<0.01), in 17 beta-hydroxysteroid dehydrogenase (P<0.05) and in aromatase. In glucose metabolism, a tendency towards reduction in the homeostasis model assessment (HOMA)-R (for insulin resistance) and HOMA-F (for beta cell function) was detected. In addition, an increase in the levels of C peptide during oGTT was observed (P<0.01). CONCLUSIONS: Long-term metformin treatment reduced various steroid enzymatic activities both in the ovary and the adrenal glands, without apparent changes in basal steroid levels and in insulin sensitivity.

Pregnancy in a woman suffering from type 1 diabetes associated with Addison's disease and Hashimoto's thyroiditis (fully developed Autoimmune Polyglandular Syndrome Type 2).

In this article the pregnancy of a woman suffering from the complete triad typical of Autoimmune Polyglandular Syndrome Type 2 (Addison's disease + type 1 diabetes + Hashimoto's thyroiditis) is reported. By using insulin pump therapy with insulin lispro, it was possible to balance diabetes control with changes of steroid replacement therapy. Pregnancy was uneventful until week 27, when signs of preeclampsia occurred. The boy was born without difficulty at gestational age 37 weeks by planned cesarean section but signs of diabetic fetopathy (macrosomia, hypoglycaemia and hypocalcaemia) were expressed. He required a short course of hydrocortisone therapy. He made a good and rapid recovery. The mother made a good post-operative recovery too, but 4 months after the delivery microalbuminuria as well as mild hyperuricemia are still present. Interdisciplinary approach and very careful observation of the mother as well as of the child enabled successful outcome of this highly risky pregnancy.

An analysis of the relationship between insulin resistance and the activity of steroid C17,20-lyase and 3beta-hydroxysteroid dehydrogenase in ovaries and adrenals in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is connected with insulin resistance (IR), and often with the hypersecretion of adrenal androgens. Mutual relationships between IR and adrenal and ovarian steroidogenesis were investigated in the group of 19 oligo/amenorhoeic women with PCOS. The age and body mass index (BMI) of the patients were 21+/-4.7 years and 26.4+/-5 kg/m2 (average+/-SD), respectively. All underwent a 60-minute adrenocorticotrophic hormone (ACTH) stimulation test, a gonadoliberin analogue (GnRHa) test with buserelin and an oral glucose tolerance test (oGTT) in the early follicular phase of the menstrual cycle. When absolute stimulated steroid levels after GnRHa were studied, a significant positive correlation between DHEA and area under curve during oGTT for C peptide (AUC-CP) (r=0.477, p= 0.039) and a borderline negative correlation (r=-0.404, p= 0.087) between AUC-CP and 17-OH progesterone, were found. Considering steroid values after ACTH, a significant positive correlation of IR index was found only with 17-OH-progesterone (r=0.499, p= 0.03). When stimulated enzymatic activities (expressed as product/ precursor ratios) were analyzed using factor analysis, a positive relationship between IR and ovarian C17,20-lyase in both delta4 and delta5 pathway was revealed. On the other hand, no relationship was confirmed between IR and enzymatic activities in the adrenals. The authors conclude that insulin resistance and/or hyperinsulinemia is probably not the primary factor responsible for the exaggerated adrenal androgen secretion found in a great number of patients with PCOS.

Severe hypoglycemia and reduction of insulin requirement in a girl with insulin-dependent diabetes mellitus: first sign of a craniopharyngioma.

A girl with a history of insulin-dependent diabetes mellitus since 5.5 years, and Hashimoto's thyroiditis since 12 years, developed episodes of severe hypoglycemia from the age of 12 years. This was associated with falling insulin requirements, from 0.78 U/kg/day at 11 years to 0.34 U/kg/day at 16 years. At 16 years she was found to have GH, gonadotropin, ACTH, and probably also TSH deficiency with hyperprolactinemia. MRI scan revealed a cystic intrasellar craniopharyngioma with moderate suprasellar extension. In spite of cortisol replacement at 17 years, insulin requirement fell further to 0.25 U/kg/day at 18 years. In this girl, decreasing insulin requirements represented an early manifestation of combined growth hormone and cortisol deficiency.

HLA-DQ polymorphisms modify the risk of thyroid autoimmunity in children with type 1 diabetes mellitus.

OBJECTIVE: Type 1 diabetes mellitus (DM1) is frequently accompanied by thyroid autoimmunity (TAI). The aims of the present study were to estimate the prevalence of TAI and to determine the contribution of HLA-DQA1 and -DQB1 polymorphisms to TAI susceptibility among children with DM1. PATIENTS AND METLHODS: Screening for TAI was performed in 285 children with DM1 by measuring autoantibodies against thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg). HLA-DQA1 and -DQB1 were genotyped using PCR-SSP. RESULTS: Repeated positivity of anti-TPO and/or anti-Tg was found in 45/285 children with DM1 (15.8%). The prevalence was significantly higher in girls than in boys (26.7% vs 6.7%; p<10(-5)). The HLA-DQB1*0302 allele conferred susceptibility to TAI in children with DM1 (OR 2.7, 95% CI 1.1-6.4), while the DQB1*05 alleles acted protectively (OR 0.2, CI 95% 0.08-0.7). CONCLUSIONS: HLA-DQ polymorphisms significantly modify the risk of TAI in children with DM1.

Premenarchal and postmenarchal girls with insulin-dependent diabetes mellitus: ovarian and other organ-specific autoantibodies, menstrual cycle.

STUDY OBJECTIVE: To estimate various organ-specific autoantibodies and detect other endocrine autoimmune disorders and menstrual cycle characteristics in girls with Type 1 insulin dependent diabetes mellitus (IDDM). DESIGN: Prospective cohort study from 1993 to 1998, duration 4.5 years. SETTING: Diabetes & Endocrine Clinic of the University Hospital, Motol, Prague. PATIENTS: 53 IDDM girls (group A--43 postmenarchal, group B--10 premenarchal), 15.5 +/- 2.5 (8-19) years old, 6.2 +/- 4.3 years after IDDM onset. MAIN OUTCOME MEASURES: Ovarian autoantibodies directed to ooplasm, zona pellucida, membrana granulosa, theca folliculi interna, and lutein cells, insulin autoantibodies, thyroid peroxidase and thyroglobulin autoantibodies. Menstrual cycle character, endocrine glands disturbance. Diabetes control, body mass index, duration of IDDM. RESULTS: Ovarian autoantibodies in at least one of the followed structures were found in 67.9% of the IDDM girls. In the control group of 21 healthy girls of corresponding age, the positive findings in lutein cells were found in only 4.8% of the girls (P < 0.01 versus IDDM girls). The lutein cells commonly associated with theca folliculi interna cells were the most frequent immunopositive structures in diabetic girls (P < 0.05 versus another positive ovarian autoimmune structure). Autoantibodies directed to ovarian steroid producing cells were frequent in IDDM patients with both irregular and normal menstrual cycles. Irregular menstrual cycles were diagnosed in 27.9% of IDDM girls, polymenorrhea in half of them, and oligomenorrhea in the remainder. Diabetes control in our patients (glycosylated hemoglobin HbA1c in postmenarchal girls 10.1 +/- 2.0%) did not differ between those with regular and those with irregular menstrual cycles. Over a follow-up period one-third of the girls with oligomenorrhea and a long-term noncompliance (HbA1c 13.5%) developed secondary amenorrhea. Insulin autoantibodies were found in 67.8%, thyroid peroxidase autoantibodies in 12.5%, and thyroglobulin autoantibodies in 10.4% of the IDDM girls. Autoimmune thyroiditis was diagnosed in 5 IDDM patients (9.4%); hypothyroidism developed in 3 of them. Menstrual cycle was irregular in 4 of the 5 girls with autoimmune thyroiditis (polymenorrhea in 1, oligomenorrhea in another 3 girls). CONCLUSIONS: An increased incidence of various circulating autoantibodies may be markedly demonstrated in IDDM girls. Their reproductive function might have an important relationship to an evidence of ovarian autoantibodies. Menstrual cycle disturbances could be linked to the poor diabetes control, to the presence of ovarian and other autoantibodies, and also to other autoimmune disease.

Protocol combining GnRH agonists and GnRH antagonists for rapid suppression and prevention of gonadal damage during cytotoxic therapy.

PURPOSE OF INVESTIGATION: Infertility represents one of the main sequelae of cytotoxic therapy given for various malignant diseases. Because dividing cells are more sensitive to cytotoxic effects than are cells at rest, it has been hypothesized that inhibition of the pituitary-gonadal axis may facilitate the preservation of future gonadal function. The aim of our study was to find a quick, reliable and economic way to suppress the pituitary-gonadal axis by combining GnRH-agonists with GnRH-antagonists in order to preserve future gonadal function. METHODS: A combination of D-Trp6-GnRH-a (3.75 mg) and cetrorelix (3 mg) was used to achieve a quick downregulation in six postmenarchal young women (aged 15.4 +/- 0.7) years with haematological malignancies before the onset of cytotoxic chemotherapy. RESULTS: The combination of D-Trp6-GnRH-a and GnRH-antagonist cetrorelix induced a reliable and long-lasting suppression of gonadotrophin secretion within 96 hours in all patients allowing cytotoxic therapy to be started without any delay. CONCLUSIONS: The combination of GnRH-agonist and GnRH-antagonist enables a rapid, reliable and cost-effective suppression of the pituitary-gonadal axis to be achieved. Future gonadal function of treated patients will be monitored.

[Pregnancy and delivery after traumatic panhypopituitarism]. / Tehotenství a porod po traumatickém panhypopituitarismu.

OBJECTIVE: We describe a case of 23 years old woman who, with a history of car accident at the age of 11 and severe head injury, attended our Center of Reproductive Medicine complaining of primary infertility. The accident preceded menarche and the development of inner genitalia (uterus 46 mm, cervix:corpus ratio 1:1) as well as secondary sexual development was not fully accomplished. Ovarian failure was accompanied by amenorrhea, if not substituted. Under replacement therapy regular menstruation was established. Basal hormonal levels was extremely low (FSH and LH 0.2-0.3 IU/l, PRL 0.5 ng/ml, estrogens 0.08 nmol/l, PRGE was not detected). With oral administration of micronized estradiol (Check et al., 2001) endometrial thickness of 9 mm was achieved. All of five retrieved oocytes were fertilized with partner sperm (normospermy) and three embryos were transferred. Already the first attempt was successful. Patient suffered with transitional anorexia and vomiting which could be handled conservatively. Hormonals level were normal. Patient substituted with Hydrocortison and Euthyrox. On January 2, 2003 the pregnancy was finished by caesarian section, one week before the delivery term (girl, 2970, Apgar score 10-10-10). DESIGN: Case report. SETTING: Center of Reproductive Medicine, Zlin. CONCLUSION: This care report demonstrates that recent progress in assisted reproduction field enables to manage successfully even exceptional pathological conditions.

[Growth and development in untreated girls with slowly progressing idiopathic central or borderline-onset puberty]. / Rust a vývoj nelécených dívek s pomalou progresí idiopatické centrální predcasné nebo hranicne nastupující puberty.

OBJECTIVE: To analyse growth and development of girls with slowly progressive idiopathic precocious or early puberty. DESIGN: Long-term open clinical study. SETTING: Department of Obstetrics and Gynaecology, Second Faculty of Medicine, Charles University, Prague. METHODS: In 20 untreated girls with slowly progressive puberty starting at 6-9 years neurogenic aetiology was excluded. During follow-up period 4.7 +/- 2.2 (2-8.5) years (mean +/- SD; range), sexual development (Tanner criteria), age at menarche, menstrual cycle and auxological parameters were evaluated. RESULTS: 13 girls reached menarche at 11.1 +/- 0.9 years (3.7 +/- 1.1 years after the onset of puberty), earlier than in their mothers (12.9 +/- 1.1 years) and Czech standards (P < 0.05). Menstrual cycle 28 (24-29) days was regular in all 6 girls with gynaecological age > 2 years. In one girl microprolactinoma was diagnosed, therapy with bromocryptine started at the age 14.7 years (3.5 years after menarche). At the onset of follow-up, bone age (TW20) advancement was 1.8 +/- 1.4 years above the chronologic age. Initial prediction of final height (graphic method) was 162.3 +/- 5.5 cm vs final prediction 163.7 +/- 5.1 cm. Final height 162.2 +/- 5.7 cm achieved 7 girls vs target height 163.6 +/- 5.2 cm (NS). CONCLUSION: In untreated girls, menarche occurred later after the first signs of puberty than in normal population, menstrual cycle was regular. Height potential was preserved, final height corresponded with their target height. Not all girls with early and slowly progressive puberty should be treated. Therapy is necessary in organic aetiology, rapid progressive precocious puberty and impaired growth prognosis.

[Effect of estrogens on final body height in girls with a constitutionally tall stature--risk or benefit?]. / Ovlivnení definitivní telesné výsky estrogeny u dívek s konstitucne vysokým vzrustem--rizika nebo prínos?

OBJECTIVE: Investigation of the effect of a long-term oestrogen treatment on the growth and development of children, elaboration of a theoretical model for remaining growth of girls on a long-term oestrogen therapy predicting reduction of the final height in girls with constitutionally tall stature, analysis of early and late side-effects of therapy. TYPE OF STUDY: Open clinical study. NAME AND PLACE OF DEPARTMENT: Endocrine out-patient clinic of the Second Paediatric Department and gynaecological out-patient clinic for children and adolescents of the Gynaecological-Obstetric Department, Second Medical School--Charles University and University Hospital Prague--Motol. METHOD: Elaboration of theoretical model for remaining growth of girls on a long-term oestrogen therapy was based on an analysis of the remaining growth of upper and lower body segment of healthy Czech girls. RESULTS: The extent of assumed reduction of the final height in girls with constitutionally tall stature treated with oestrogen declines with advancing age at the onset of treatment. The optimal age for the onset of treatment is between 10 and 11 years. CONCLUSION: Treatment can be recommended only in girls with growth prediction above 185 cm and serious psychological difficulties resulting from excessive height, always after careful analysis of the biological development and growth prediction. In every case it is necessary to evaluate the possible benefit of treatment in relation to potential risks. The greatest problem is according to the authors late onset and overrating of the therapeutic possibilities.

[Protection of reproductive functions in patients with tumors]. / Ochrana reprodukcních funkcí u nemocných s nádorovým onemocnením.

BACKGROUND: Survival from cancer continues to improve. Antimitotic therapy can induce failure of spermatogenesis and oogenesis, gonadal disturbances and infertility. Recent advances in reproductive medicine have opened opportunities for the preservation of reproductive potential of patients with cancer. The aim of our study was to analyse by a multidisciplinary team the contemporary state of art and proposal of the Czech model of fertility preservation starting in childhood and continuing through the whole reproductive period. METHODS: This paper highlights the problems associated with gonadal failure as a consequence of therapy for malignancy in childhood, adolescence and adulthood. Analysis of these problems served as a principle for the management strategy for fertility preservation. CONCLUSIONS: Patients undergoing treatment for malignancy are at the high risk of gonadal damage and infertility. Therefore, alternative treatments with less gonadal toxicity and different treatment protocols were evaluated. Fertility can be preserved with the freezing and banking of spermatozoa, embryos, and oocytes obtained prior to the cancer treatment. In female patients (starting in puberty) pharmacological preservation of gonads with gonadoliberin analogues is also possible. Chance for the future fertility preservation for children offers freezing and thawing of primordial follicles and spermatozoa obtained during the gonadal biopsies. Long-term follow-up study by a multidisciplinary medical team is necessary.

[Reproductive medicine from childhood to adulthood]. / Reprodukcní medicína od detství po dospelost.

Modern era brought new diagnostic and therapeutic methods to endocrinology and changed the approach to many diseases and developmental disorders. Explosion of new findings brought about the possibility of examinations on subcellular level. Possibility to study structure and function of various genes is not any more the futurology. However, still in medicine romain a roas which are considered as less important. It is usually assumed that questions of fertility will be dealt by the specialist for adults. We suppose that the given problems should be well advised by an interdisciplinary co-operating team in the paediatric patients already. However, it should be recognised that some reproduction disorders have their origin in the early age. The aim of this paper is to give an overview on endocrine disorders in relation to reproduction impairments and to outline possibilities of co-operation between different specialist treating patients from childhood trough adulthood.