Study On The Diagnosis And Treatment Of Peripheral Precocious Puberty

Background:Congenital adrenal hyperplasia（CAH）is a group of congenital autosomal recessive hereditary disease.The production of corticotropin hormone（CRH）and adrenocorticotropin hormone（ACTH）increases due to a defect in an enzyme that completely or partially blocks the production of corticotropin.21-hydroxylase deficiency（21-OHD）is the most common type in CAH,accounting for about 90%-95%.Depending on the degree of enzyme deficiency,21-OHD is classified as classical and non-classical,with the former divided into simple virilizing（SV）and salt wasting（SW）.Deficiency of glucocorticoid and/or mineralocorticoid,excessive androgen secretion and excessive accumulation of progesterone-related precursors are the main endocrine abnormalities of 21-OHD.The clinical treatment is to supplement the physiological needs of glucocorticoid replacement,to ensure the normal growth and development of the children,and to add the replacement of glucocorticoid with the presentation of salt loss.Due to the change of children’s hormone level in adolescence,the insufficient inhibition of adrenal male hormone leads to a great change in the relationship between hormones and the relationship between growth and development,which often results in abnormal youth development,adult height lagging behind the normal population and target height,and impaired reproductive function.Therefore,treatment also needs to focus on protecting growth potential and maintaining long-term reproductive health.In order to increase the acquisition of adolescent height in children with 21-OHD and improve the adult lifelong height of the patients,more optimized clinical indicators are needed for follow-up monitoring.In past studies,17-hydroxyprogesterone and androstenedione have been used to assess short-term efficacy;the patient’s height and bone age progression were used to evaluate the long-term treatment effect.But the clinical effect is not more ideal,so the treatment of adolescence is difficult and complex.Therefore,the selection of adolescent monitoring indicators and the evaluation of retrospective treatment effect are still the current issues of concern.Objects:The indicators with high specificity in diagnosis and treatment were selected in adolescent children with 21-OHD.Combined with the medication,height growth,bone age progression and body mass index of the children guide the adjustment of clinical drugs,early identification and early intervention of the transformation from peripheral precocious puberty to central precocious puberty,so as to improve lifelong height,reduce metabolic syndrome and maintain normal reproductive function in adulthood.Methods:Physical signs and laboratory indicators of height and weight of adolescent children admitted to 21-OHD in the pediatric endocrinology clinic of our hospital from June 2009 to October 2019 were collected and selected for inclusion.43 adolescents with 21-OHD in Pediatrics from Ruijin Hospital,Shanghai Jiaotong University School of Medicine were selected.The mean age of the children was 8.10±2.09 years,the follow-up interval was 3 months,and the mean observation period was 1.94±1.66 years.Fasting blood of each observation point was collected to monitor 17-OHP,ACTH,AD,T,DHEAS,LH and FSH in the morning.Height,weight and other indicators were also collected.The patients were divided into the control group（GC）and the control group（PC）according to the degree of masculinization and bone age.SPSS25.0 statistical software was used to analyze the relationship between steroid hormones,and differences in target height,BMI,hydrocortisone dose and levels of steroid hormones such as 17-hydroxyprogesterone,androstenedione and testosterone were compared among different treatment groups.The ROC curve was used to define the"poor control"cutting value.Results:A total of 43 children with 21-OHD were included in the study.The results showed that the difference of target height,change in body weight,change in BMI and hydrocortisone dose was not statistically significant.In men and women,the changes of Ht SDS_BA in different treatment groups were significantly different（P<0.01）.And the loss of bone age and height in the poor control group was greater than that in the good control group.The changes of Ht SDS_CA between different treatment groups were not statistically significant in men（P>0.05）,with significant difference in women（P<0.05）.Except for dehydroepiandrosterone sulfate,17-hydroxyprogesterone,corticotrophin,androstenedione and testosterone hormone levels in the good control group were lower than those in the poor control group.Combined with linear correlation analysis and ROC test,we found that there was a linear correlation between 17-OHP and AD,T and AD/T,and the diagnostic value of 17-OHP combined with AD/T was the highest.In males,when the cutting value of 17-OHP was 14.88ng/ml,AD/T=4.17,the sensitivity was 0.824,and the specificity was 889.In females,when the cutting value of 17-OHP was 27.23ng/ml,AD/T=4.63,the sensitivity was 0.848,and the specificity was 646.Greater than this value indicates that the androgen from the adrenal gland is too much,and the treatment effect is not good.Conclusions:In adolescence,there was a positive linear correlation between 17-OHP,AD,T and AD/T.There was no significant difference in the hydrocortisone dose and BMI between different treatment groups.In the poor control group,there was a large loss in height score of bone age,and there was a significant loss in height score of chronological age.The combination of 17-OHP and AD/T in steroid hormones has certain value as an alternative therapy for monitoring.However,since individualized regimentation is provided according to different types,genders and developmental periods,more sample data are needed to support the monitoring indicators in the treatment and follow-up of adolescence.Background: Fibrous osteodystrophy is also known as Mc Cune-Albright syndrome（MAS）.MAS is a rare sporadic disease.The clinical manifestations are peripheral precocious puberty,fibrous bone dysplasia（FD）,cafe-au-lait spot and a variety of endocrine disorders.Among them,the most common clinical manifestations are peripheral precocious puberty,especially in girls.Currently,estrogen receptor antagonist and aromatase inhibitor are the main drugs for the treatment of peripheral precocious puberty.The third-generation aromatase inhibitor letrozole reduces estrogen levels and prevents premature closure of epiphyses by inhibiting the conversion of androgens to estrogen.However,the main adverse reactions are liver damage and hyperandrogenemia.Therefore,the clinical efficacy and safety of letrozole in children and adolescents are controversial.Objects: To explore the efficacy and safety of the third-generation aromatase inhibitor letrozole in the treatment of Mc Cune-Albright syndrome（MAS）girls with peripheral precocious puberty.Methods: Twenty-one girls with MAS in Pediatrics from Ruijin Hospital,Shanghai Jiaotong University School of Medicine,were selected from March 2012 to June 2017.Peripheral precocious puberty by café-au-lait spots or dysplasia of bone fibers,and low levels of LH and FSH,exclude congenital adrenal hyperplasia,estrogen-producing tumors,and exogenous estrogen intake etc.Letrozole were treated with 0.5-2mg/m2.d.Treatment duration was 6 to 12 months.The patients were observed for changes in breast stage,vaginal bleeding,sex hormone levels,liver function and bone age changes,and changes in uterine and ovarian volume.Results: After treatment,BA/CA（1.23±0.30 to 1.11±0.18）slowed down,respectively（P=0.005）;The PAH increased from 156.18 ± 5.86 cm before treatment to 157.4 ± 2.06 cm after treatment,（P =0.023）.After treatment,E2 decreased significantly,and T did not increase significantly.After treatment,the uterus showed no significant increase,and no adverse reactions such as ovarian torsion occurred.Conclusions: Precocious puberty is one of the most common endocrine manifestations in MAS.Our findings suggest that letrozole may be an effective and safe therapy to precocious puberty in girls with Mc Cune-Albright Syndrome.