Pubertad precoz relacionada con la pandemia por COVID-19. Encuesta a endocrinólogos pediátricos argentinos / Precocious puberty in relation to the COVID-19 pandemic. A survey among Argentine pediatric endocrinologists

Introducción. La pubertad se manifiesta inicialmente por la aparición de los caracteres sexuales secundarios, como consecuencia de cambios hormonales que progresivamente conducen a la madurez sexual completa. En Argentina y el mundo, la pandemia ocasionada por el coronavirus SARS-CoV-2 generó un confinamiento que pudo haber interferido en el inicio y tempo del desarrollo puberal. Objetivo. Describir la percepción de los endocrinólogos pediatras del país sobre las consultas por sospecha de pubertad precoz y/o pubertad de rápida progresión durante la pandemia. Materiales y métodos. Estudio descriptivo, observacional, transversal. Encuesta anónima a endocrinólogos pediatras pertenecientes a la Sociedad Argentina de Pediatría y/o a la Asociación de Endocrinología Pediátrica Argentina, en diciembre de 2021. Resultados. Respondieron la encuesta 83 de 144 endocrinólogos pediátricos (tasa de respuesta 58 %). Todos consideraron que aumentó la consulta por desarrollo precoz o temprano, ya sea en sus variantes telarca precoz (84 %), pubarca precoz (26 %) y/o pubertad precoz (95 %). El 99 % acuerda con que se ha dado en mayor medida en niñas. La totalidad de los encuestados también considera que aumentó el diagnóstico de pubertad precoz central. El 96,4 % considera que ha aumentado el número de pacientes tratados con análogos de GnRH. Conclusión. Nuestros resultados sobre la percepción de endocrinólogos pediatras coinciden con datos publicados en otras regiones sobre el aumento del diagnóstico de pubertad precoz durante la pandemia por COVID-19. Se reafirma la necesidad de generar registros nacionales de pubertad precoz central, difundir las evidencias para su detección y abordaje oportuno.

Introduction. Puberty is manifested initially by the onset of secondary sexual characteristics as a result of hormonal changes that progressively lead to complete sexual maturity. In Argentina and worldwide, the lockdown resulting from the SARS-CoV-2 pandemic may have interfered in the onset and timing of pubertal development. Objective. To describe the perception of pediatric endocrinologists in Argentina regarding consultations for suspected precocious and/or rapidly progressive puberty during the pandemic. Materials and methods. Descriptive, observational, cross-sectional study. Anonymous survey among pediatric endocrinologists members of the Sociedad Argentina de Pediatría and/or the Asociación de Endocrinología Pediátrica Argentina administered in December 2021. Results. Out of 144 pediatric endocrinologists, 83 completed the survey (rate of response: 58%). All of them considered that consultation for precocious or early puberty increased, either in terms of early thelarche (84%), early pubarche (26%), and/or precocious puberty (95%). Ninety-nine percent agreed that this has occurred to a greater extent in girls. All survey respondents also consider that the diagnosis of central precocious puberty has increased. In total, 96.4% of respondents consider that the number of patients treated with GnRH analogs has increased. Conclusion. Our results about the perception of pediatric endocrinologists are consistent with data published in other regions on the increase in the diagnosis of precocious puberty during the COVID-19 pandemic. We underscore the need to develop national registries of central precocious puberty, and to disseminate the evidence for a timely detection and management

Pubertad precoz y pubertad rápidamente progresiva durante el confinamiento por la pandemia por COVID-19 / Rapidly progressive precocious puberty during the COVID-19 lockdown

Introducción. Durante la pandemia por COVID-19, observamos un aumento de consultas por pubertad precoz (PP). Nuestro objetivo fue determinar la frecuencia de PP y su progresión antes y durante la pandemia. Métodos. Estudio retrospectivo, observacional y analítico. Se evaluaron las historias clínicas de los pacientes que consultaron en Endocrinología Infantil entre abril de 2018 y marzo de 2021. Se analizaron las consultas por sospecha de PP durante la pandemia (período 3) y se compararon con 2 años previos (períodos 1 y 2). Se recolectaron datos clínicos y estudios complementarios de la evaluación inicial y su progresión. Resultados. Se analizaron 5151 consultas. Se observó un aumento de consultas por sospecha de PP durante el período 3 (21 % vs.10 % y 11 %, p <0,001). Los pacientes que consultaron por sospecha de PP durante el período 3 aumentaron 2,3 veces (80 vs. 29 y 31, p <0,001). El 95 % fueron niñas; esa población fue analizada. Se incluyeron 132 pacientes que fueron similares en edad, peso, talla, edad ósea y determinaciones hormonales en los 3 períodos. En el período 3, se observó un menor índice de masa corporal, mayor porcentaje de estadio mamario Tanner 3-4 y mayor longitud uterina. Se indicó tratamiento al diagnóstico en el 26 % de los casos. En el resto, se controló su evolución. Durante el seguimiento, se observó una evolución rápidamente progresiva con mayor frecuencia durante el período 3 (47 % vs. 8 % vs. 13 %; p: 0,02). Conclusiones. Evidenciamos un aumento de la PP y una evolución rápidamente progresiva en niñas durante la pandemia.

Introduction. During the COVID-19 pandemic, an increase in consultations for precocious puberty (PP) was observed. Our objective was to determine the frequency of PP and its progression before and during the pandemic. Methods. Retrospective, observational, analytical study. The medical records of patients who consulted with the Department of Pediatric Endocrinology between April 2018 and March 2021 were assessed. Consultations for suspected PP during the pandemic (period 3) were analyzed and compared to the 2 previous years (periods 1 and 2). Clinical data and ancillary tests done in the initial assessment and PP progression information were collected. Results. Data from 5151 consultations were analyzed. An increase in consultations for suspected PP was observed during period 3 (21% versus 10% and 11%, p < 0.001). Patients who consulted for suspected PP during period 3 increased 2.3-fold (80 versus 29 and 31, p < 0.001). In total, 95% were female; this was the population analyzed. We included 132 patients with similar age, weight, height, bone age, and hormonal characteristics in the 3 periods. During period 3, a lower body mass index, a higher percentage of Tanner breast stage 3­4, and a greater uterine length were observed. Treatment was indicated upon diagnosis in 26% of the cases. In the rest, their evolution was monitored. During follow-up, a rapidly progressive course was observed more frequently in period 3 (47% versus 8% versus 13%, p: 0.02). Conclusions. We observed an increase in PP and a rapidly progressive evolution in girls during the pandemic.

Análisis de la incidencia de pubertad precoz central tratada con análogos de hormona liberadora de gonadotrofina. Impacto de la pandemia por COVID-19 / Analysis of the incidence of central precocious puberty treated with gonadotropin-releasing hormone analogs. Impact of the COVID-19 pandemic

Introducción. Desde inicios de la pandemia por coronavirus 2019 (COVID-19), fue comunicado en varios países un incremento de las consultas de niñas con pubertad precoz central idiopática (PPCI), sin que contáramos con datos argentinos. Este aumento estaría vinculado con los cambios en el estilo de vida y los niveles de estrés resultantes del aislamiento que afectó particularmente a la población infantil. Objetivos. 1) Describir la evolución de la incidencia de PPCI con requerimiento de inhibición del eje hipotálamo-hipófiso-gonadal (EHHG) en niñas entre 2010 y 2021 en una cohorte del Área Metropolitana de Buenos Aires. 2) Comparar las características de las niñas, con dicho diagnóstico realizado durante la pandemia, con las de un grupo control. Métodos. Serie de tiempo interrumpida y estudio de casos y controles. Resultados. La incidencia anual fue estable entre 2010 y 2017. Desde 2017 hubo un ascenso anual que promedió el 59,9 % (IC95 % 18,6-115,5) y pareciera haberse acelerado durante la pandemia. Constatamos asociación entre haber desarrollado PPCI y haber requerido tratamiento inhibitorio entre el 01 de junio de 2020 y el 31 de mayo de 2021, y dos variables: edad de menarca materna (OR 0,46; IC95 % 0,28-0,77) y antecedente familiar de PPCI (OR 4,42; IC95 % 1,16-16,86). Conclusión. Evidenciamos desde 2017 un aumento significativo en la incidencia de PPCI con requerimiento de inhibición del EHHG. El incremento en la exposición a diversos desencadenantes ambientales durante la pandemia por COVID-19 podría haber ejercido mayor influencia en las niñas con alguna predisposición genética.

Introduction. Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, consultations of girls with idiopathic central precocious puberty (ICPP) increased in several countries, but there were no data from Argentina. This increase may be related to changes in lifestyle and stress levels resulting from the lockdown, which particularly affected the child population. Objectives. 1) To describe the progression of the incidence of ICPP requiring inhibition of the hypothalamic- pituitary-gonadal (HPG) axis in girls between 2010 and 2021 in a cohort from the Metropolitan Area of Buenos Aires. 2) To compare the characteristics of girls diagnosed with ICPP during the pandemic with those of a control group. Methods. Interrupted time-series and case-control study. Results. The annual incidence remained stable between 2010 and 2017. Since 2017, it increased to an average of 59.9% (95% CI: 18.6­115.5) and appears to have accelerated during the pandemic. We found an association between ICPP and requiring inhibitory treatment between June 1 st, 2020 andMay 31 st, 2021 and 2 variables: maternal age at menarche (OR: 0.46, 95% CI: 0.28­0.77) and family history of ICPP (OR: 4.42, 95% CI: 1.16­16.86). Conclusion. We evidenced a significant increase in the incidence of ICPP with requirement of HPG axis inhibition since 2017. Increased exposure to various environmental triggers during the COVID-19 pandemic may have had a greater influence in girls with some genetic predisposition.

Serum 25-hydroxyvitamin D levels and the risk of idiopathic central precocious puberty in girls

Abstract Introduction Prior studies have found inconsistent results regarding the relationship between vitamin D status and Idiopathic Central Precocious Puberty (ICPP). Objective To assess the role of serum 25-hydroxyvitamin D (25 [OH]D) levels in ICPP development. Method The authors retrospectively collected data from 221 girls with ICPP and 144 healthy girls between January 2017 and December 2019. The participants' serum 25(OH)D levels were measured using an automatic chemiluminescence method, and the association between serum 25(OH)D levels and the risk of ICPP was assessed using multivariate logistic regression analysis. Odds Ratios (OR) with 95% Confidence Intervals (95% CI) were calculated as effect estimates. Results Serum 25(OH)D levels in the ICPP group were significantly lower than those in healthy controls (p < 0.001). Multivariate analysis indicated that girls with insufficient vitamin D levels (OR = 0.201; 95% CI 0.094-0.428; p < 0.001) and sufficient vitamin D levels (OR = 0.141; 95% CI 0.053-0.375; p < 0.001) both had a lower risk of ICPP than girls with vitamin D deficiency. Moreover, the authors found that the height (p = 0.014), weight (p = 0.014), breast stage (p = 0.010), mother's height (p < 0.001), and luteinizing hormone/follicle-stimulating hormone ratio (p = 0.010) in girls with ICPP could be associated with levels of vitamin D. Conclusion This study found that a low serum 25(OH)D level is an independent risk factor for ICPP, and several characteristics of girls with ICPP could be affected by their vitamin D status.

Acupuncture combined with auricular point sticking for girls aged 3-8 years with incomplete precocious puberty: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the efficacy and safety of acupuncture combined with auricular point sticking for girls aged 3-8 years with incomplete precocious puberty (IPP).@*METHODS@#Sixty girls with IPP were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases were eliminated). The girls in the control group were treated with healthy diet and proper exercise for 12 weeks. On the basis of the treatment in the control group, the girls in the observation group were treated with acupuncture combined with auricular point sticking. The acupuncture was applied at Sanyinjiao (SP 6), Guanyuan (CV 4), Guilai (ST 29), etc., the needles were retained for 20 min, acupuncture was given twice a week (once every 3 days). The auricular point sticking was applied at Luanchao (TF2), Neishengzhiqi (TF2), Neifenmi (CO18), Yuanzhong (AT2,3,4i), etc., twice a week. The treatment was given for 12 weeks. Before treatment, after treatment and in follow-up after 12 weeks of treatment completion, the Tanner stage of breast, serum contents of sex hormone (luteinizing hormone [LH], follicle-stimulating hormone [FSH], estradiol [E2]) were observed. The ovarian volume, the number of follicles with diameter>4 mm, and the uterine volume were measured by abdominal color Doppler ultrasound. In addition, the safety of the observation group was evaluated.@*RESULTS@#Compared with before treatment, the Tanner stage of breast in the observation group was improved after treatment and in follow-up (P<0.05); after treatment and in follow-up, the Tanner stage of breast in the observation group was better than that in the control group (P<0.05). Compared with before treatment, the serum levels of LH and E2 in the observation group were increased (P<0.05), and the volume of bilateral ovaries was larger (P<0.05) in follow-up. Compared with before treatment, the serum contents of LH, FSH and E2 in the control group were increased (P<0.05), the volume of bilateral ovaries was larger (P<0.05), and the number of follicles was increased (P<0.05) after treatment and in follow-up. The serum levels of LH, FSH and E2 in the observation group were lower than those in the control group (P<0.05), the volume of bilateral ovaries was smaller than that in the control group (P<0.05), and the number of follicles was lower than that in the control group (P<0.05). Compared with before treatment, the uterine volume in the two groups was larger in follow-up (P<0.05). There was no statistically significant difference between the two groups after treatment and in follow-up (P>0.05). During the treatment, 3 cases in the observation group had slight abdominal pain and subcutaneous blood stasis, without serious adverse reactions.@*CONCLUSION@#Acupuncture combined with auricular point sticking could improve the Tanner stage of breast, reduce the level of sex hormone, slow down the development and maturation of ovary and follicle, and control the degree and speed of sexual development in girls aged 3-8 years with IPP.

Value of basal luteinizing hormone level combined with uterine volume measurement in the early diagnosis of central precocious puberty in girls with different Tanner stages / 中国当代儿科杂志

OBJECTIVES@#To study the value of basal luteinizing hormone (LH) level combined with uterine volume measurement in the early diagnosis of central precocious puberty (CPP) in girls with different Tanner stages.@*METHODS@#A retrospective analysis was performed on the girls who presented with breast development before the age of 8 years and attended the Third Affiliated Hospital of Zhengzhou University from January 2017 to September 2022. According to the results of gonadotropin-releasing hormone (GnRH) agonist test, the girls with peak LH ≥5.0 IU/L and peak LH/follicle stimulating hormone ≥0.6 were enrolled as the positive group, and the other girls were enrolled as the negative group. The two groups were compared in terms of the basal LH level and uterine volume. The receiver operating characteristic (ROC) curve was used to analyze their value in the early diagnosis of CPP.@*RESULTS@#For the girls with Tanner B2 and B3 stages, the positive group had significantly higher basal LH level and uterine volume than the negative group (P<0.05). The basal LH level had an optimal cut-off value of 0.325 IU/L and 0.505 IU/L respectively in the diagnosis of Tanner stage B2/B3 CPP, while uterine volume had an optimal cut-off value of 1.639 mL and 2.158 mL respectively. Basal LH level combined with uterine volume measurement had a significantly larger area under the ROC curve than uterine volume measurement alone (P<0.001), but with no significant difference compared with that of basal LH level measurement alone (P>0.05).@*CONCLUSIONS@#Basal LH level combined with uterine volume measurement is valuable in the early diagnosis of CPP in girls with different Tanner stages, which provides a basis and guiding significance for clinical diagnosis of CPP.

Legius syndrome combined with central precocious puberty: a case report and literature review / 中华神经科杂志

Objective:To investigate the clinical phenotype and genotypic characteristics of Legius syndrome.Methods:The clinical data of a child with precocious puberty and scattered café-au-lait macules admitted to Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University in July 2021 were retrospectively analyzed. Trio-whole exome sequencing (trio-WES) was used for genetic analysis to confirm the molecular diagnosis of the family. The relevant literature was reviewed to summarize the clinical characteristics of the disease.Results:The proband was a 10-year and 9-month-old girl, presenting with more than 5 café-au-lait macules with diameter>5 mm on the face and trunk, freckles in the axillary, without Lisch tubercles of iris and tumor signs of neurofibromatosis type 1, diagnosed as central precocious puberty at the age of 8. trio-WES results of the family revealed a spontaneous heterozygous nonsense mutation c.751(exon7) C>T in SPRED1 gene, causing a nonsense mutation in the amino acid sequence p.Arg251Ter (p. Ter251 *). Literature review showed a total of 88 pathogenic mutations were reported in SPRED1 gene, including frameshift mutations (41/88), nonsense mutations (31/88), splice mutations (7/88), missense mutations (6/88), and others (3/88), and no mutational hotspots were found. Clinical phenotype was as follows:>5 café-au-lait macules accounted for 92.8% (168/181), armpit and inguinal freckles 43.5% (73/168), macrocephaly 21.4% (31/145), learning disability 18.0% (30/166), psychomotor retardation 13.8% (22/159), lipoma (adult) 13.7% (21/153), Noonan facial sign 12.1% (21/173), and tumor phenotype of neurofibromatosis type 1 was not reported. Conclusions:The central precocious puberty phenotype of Legius syndrome was not reported in China. The clinical phenotype of Legius syndrome was mild, with a large variation, but without neurofibromatosis type 1 tumor phenotype. Genetic testing can be beneficial for early diagnosis of Legius syndrome.

Caracterización clínica de pacientes chilenos con displasia fibrosa/síndrome de McCune-Albright / Clinical features of Chilean patients with Fibrous Dysplasia/McCune-Albright Syndrome

BACKGROUND: Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is characterized by a spectrum of manifestations that may include fibrous dysplasia of bone and multiple endocrinopathies. AIM: To describe the clinical spectrum, the study and follow-up of patients with FD/MAS cared at our institution. MATERIAL AND METHODS: Review of medical records of 12 pediatric and adult patients (11 women) who met the clinical and genetic diagnostic criteria for FD/ MAS. RESULTS: The patients' mean age at diagnosis was 4.9 ± 5.5 years. The most common initial clinical manifestation was peripheral precocious puberty (PPP) in 67% of patients and 75% had café-au-lait spots. Fibrous dysplasia was present in 75% of patients and the mean age at diagnosis was 7.9 ± 4.7 years. Ten patients had a bone scintigraphy, with an age at the first examination that varied between 2 and 38 years of age. The most frequent location of dysplasia was craniofacial and appendicular. No patient had a recorded history of cholestasis, hepatitis, or pancreatitis. In four patients, a genetic study was performed that was positive for the pathogenic variant of guanine nucleotide binding protein, alpha stimulating (GNAS). CONCLUSIONS: These patients demonstrate the variable nature of the clinical presentation and study of FD/MAS. It is essential to increase the index of diagnostic suspicion and adherence to international recommendations.

Differences in hormonal levels between heterozygous CYP21A2 pathogenic variant carriers, non-carriers, and females with non-classic congenital hyperplasia

ABSTRACT Objective: CYP21A2 mutation heterozygote carriers seem to have an increased risk of hyperandrogenism. However, the clinical relevance of the heterozygote carrier status and the reliability of hormonal testing in discriminating a carrier from a non-carrier are puzzling questions. We aimed to characterize a population of Portuguese females suspected of having non-classic congenital adrenal hyperplasia (NC-CAH) due to clinical and biochemical criteria and who have undergone CYP21A2 molecular analysis. Subjects and methods: Retrospectively, we have analyzed the clinical records of 131 females (32 girls aged 3-9 and 99 adolescents and premenopausal women aged 13-49) who underwent complete CYP21A2 molecular analysis due to suspicion of NC-CAH. We divided included participants into three groups according to the CYP21A2 molecular analysis: NC-CAH females (46), heterozygous carriers (49), and wild type (36). We then compared clinical signs and symptoms as well as biochemical and molecular data between carriers and NC-CAH individuals and between carriers and wild type females. We measured 17OHP by electrochemiluminescence immunoassay. Results: Clinical features were similar between groups. Heterozygous carriers presented higher basal and post-cosyntropin 17-hydroxyprogesterone (17OHP) than wild type individuals (p < 0.05) and lower basal and stimulated 17OHP levels than NC-CAH patients (p < 0.05). We discovered a considerable overlap between 17OHP levels among groups. The most common pathogenic variant we identified was p.Val282Leu. Conclusion: In this population of hyperandrogenic women and children, heterozygous carriers showed higher basal and stimulated 17OHP than non-carriers although normal basal and stimulated 17OHP responses do not exclude heterozygosity for CYP21A2 pathogenic variants. In this study, only the molecular analysis presented good sensitivity in identifying heterozygotes.

Peripheral precocious puberty with ovarian new growth: A case report

@#Precocious puberty is defined as appearance of secondary sexual characteristics that begins earlier than usual, and may be central or peripheral in origin. It is the physician’s duty to undertake a detailed investigation of the cause of the condition so as not to overlook a potentially correctable pathologic lesion, and prevent long-term somatic and psychosocial consequences in the child. This paper presents a case of 10 year old female with clinical signs and symptoms and laboratory results that point to a possible peripheral type of precocious puberty , and with a huge ovarian mass, which intraoperatively yielded inconclusive histopathologic findings due to massive necrosis. This paper aimed to discuss the possible etiologies for the development of precocious puberty in the index case, and the treatment options for both precocious puberty and ovarian new growth.

Clinical and genetic analysis of five patients with familial male-limited precocious puberty / 中华内分泌代谢杂志

Objective:To analyze the clinical and genetic characteristics of five patients with familial male-limited precocious puberty(FMPP).Methods:The clinical data, laboratory and imaging results of the five patients with FMPP were collected. Whole exome sequencing was carried out to identify the potential variants. Suspected variants were verified by Sanger sequencing of family numbers.Results:Of the five patients, four were children and one was an adult. All the four children presented to hospital with premature sexual development at age less than 4 years. Serum testosterone was elevated, luteinizing hormone(LH) and follicle stimulating hormone(FSH) basal values were at prepubertal levels, and gonadotropin-releasing hormone(GnRH) stimulation test suggested peripheral precocious puberty. Genetic analysis revealed the mutations of LHCGR genes in all the five patients. Patients 1, 2, 3, and 4 carried the same heterozygous mutation c. 1713G>C(p.M571I), and the patient 5 carried the c. 1741T>C(p.C581R)variation. The four children were treated with anti-androgen preparations and the third-generation aromatase inhibitors, all of which were effective.Conclusion:The c. 1713G>C mutation of LHCGR gene is a novel one which expands the mutation spectrum of LHCGR gene. Combined treatment with bicaluamide and the third generation aromatase inhibitors can improve clinical symptoms and delay epiphyseal closure in children with FMPP.

Research progress of the efficacy and safety of 3-month depot Leuprorelin in the treatment of central precocious puberty / 中华实用儿科临床杂志

Central precocious puberty (CPP) is a common pediatric endocrine disease caused by premature activation of the hypothalamic-pituitary-gonadal axis, featured by rapid development of internal and external reproductive organs and secondary sexual characteristics in girls before age 8 and boys before age 9.The gonadotropin-releasing hormone analogue (GnRHa) is the first choice for the treatment of CPP.Currently, 3.75 mg/ month sustained -release short-acting dosage form (1M depot formulations) is the most commonly used in China.The development of long-acting dosage form will reduce injection times and clinic visits.At present, the 3-month long-acting dosage form (11.25 mg 3M depot formulations) of Leprorelin microsphere has been approved in China.However, clinical practice experience of 3-month Leuprorelin acetate depot formulations is lacking in China.Therefore, in this paper, existing clinical evidence for this dosage form was reviewed to provide evidence-based medicine support for its clinical application.

Effects of Jiuwei Chushi Decoction on sex hormone and Kisspeptin protein expression of Central Precocious Puberty rats / 国际中医中药杂志

Objective:To observe the effect of Jiuwei Chushi Decoction on sex hormone level of serum and Kisspeptin protein expression in hypothalamus of Central Precocious Puberty (CPP) rats model.Methods:After sixty female rat were breeded from SD rats, they are randomly divided into six groups, which are normal control group, model group, Gonadorelin group, and high, medium and low dose group of Jiuwei Chushi Decoction, 10 in each group. In addition to the normal control group, the other groups were subcutaneously injected with N-methyl-DL-aspartic acid to establish CPP model. Gonadorelin group was subcutaneously injected with Gonadorelin 100 μg/(kg·d), and high, medium and low dose group of Jiuwei Chushi Decoction were intragastrated with Jiuwei Chushi Decoction extract at 5.75, 2.87 and 1.43 ml/(kg·d) respectively. The levels of Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH),Estradiol (E 2) were detected by ELISA, and the protein expressions of Gonadotropin-releasing Hormone (GnRH) and Kisspeptin in hypothalamus were detected by Western Blot. Results:Compared with the model group, the levels of LH and E 2 of the low, medium and high dose group of Jiuwei Chushi Decoction were significantly decreased ( P<0.05), while the FSH level was significantly increased ( P<0.05). The relative protein expression of GnRH (0.657±0.110, 0.536±0.152 vs. 0.912±0.219) and Kisspeptin (0.508±0.035,0.347±0.073 vs. 0.659±0.030) in the medium and high dose group of Jiuwei Chushi Decoction was lower than that of model group. Conclusion:Jiuwei Chushi Decoction could affect hypothalamic Kisspeptin protein expression, inhibite hypothalamic GnRH expression, and decrease LH and E 2 levels in the serum of CPP rats.

Detection of glucolipid metabolism and sex hormones among female children with precocious puberty / 预防医学

Objective@#To investigate glucolipid metabolism and sex hormone levels among female children with precocious puberty, so as to provide insights into the illustration of pathogenesis of precocious puberty. @*Methods@#A total of 110 female children with precocious puberty treated in Huzhou Maternity & Child Health Care Hospital during the period from May 2019 through May 2021 were enrolled and assigned into the idiopathic central precocious puberty (ICPP) group and the premature thelarche alone (PT) group according to the results of gonadotropin-releasing hormone stimulation tests. The follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), testosterone (T), prolactin (PRL), fasting insulin (FINS), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB) andlipoprotein-a [Lp (a)] levels were detected and compared in children between the ICPP and PT groups.@*Results@#There were 70 cases in the ICCP group, with a mean age of (7.62±1.13) years and a mean body mass index (BMI) of (16.30±2.21) kg/m2 and 40 cases in the PT group, with a mean age of (7.42±1.04) years and a mean BMI of (16.70±2.10) kg/m2 (both P>0.05). The FSH [(3.58±0.80) vs. (2.22±0.75) IU/L], LH [(1.40±0.28) vs. (0.25±0.12) IU/L], P [(0.29±0.12) vs. (0.18±0.08) ng/mL], E2 [(23.28±4.23) vs. (15.54±2.75) pg/mL] and PRL [(8.56±1.93) vs. (6.54±1.50) ng/mL], FINS [(13.24±2.54) vs. (11.10±2.49) U/L], TG [(1.36±0.17) vs. (1.21±0.27) mmol/L], LDL-C [(3.10±0.44) vs. (2.81±0.60) mmol/L], ApoB [(0.78±0.19) vs. (0.71±0.14) g/L] and Lp (a) levels [(252.45±52.10) vs. (202.60±41.28) mg/L] were significantly higher in the ICPP group than in the PT group (all P<0.05).@*Conclusion@#The levels of sex hormones and glucolipid metabolism parameters are significantly higher among female children with ICPP than among those with PT.

Dedicated sellar magnetic resonance imaging protocols without contrast enhancement in girls with central precocious puberty: prevalence of pathologic lesions and clinical correlation

ABSTRACT Objective: Contrast-enhanced brain magnetic resonance imaging (MRI) is routinely performed in children with central precocious puberty (CPP). We evaluated the value of a dedicated sellar MRI protocol without contrast enhancement in girls with CPP. Subjects and methods: This study included 261 girls diagnosed with CPP. We performed sellar MRI scanning without gadolinium enhancement of the hypothalamic-pituitary area (HPA) at the pituitary level, including additional T2-weighted imaging of whole-brain scans to check for other lesions. We evaluated the prevalence of intracranial lesions via this MR protocol. In addition,the correlation between the clinical parameters and morphology of the pituitary gland on the images was assessed. Results: Intracranial lesions were detected in 17 (6.5%) of the 261 girls. Of the 17 girls with abnormalities, 16 (94.1%) had findings in brain areas other than the HPA. The weight, height, Tanner stage of patients were significantly (p < 0.05) higher in the group with greater pituitary height. Patient weight and height, Tanner stage of breast development, and luteinizing hormone (LH) levels were significantly (p < 0.05) greater in those with a higher pituitary grade as determined on sellar MRI. Conclusion: A dedicated unenhanced sellar MRI protocol provides valuable information on brain lesions and pituitary morphology. We found a significantly low prevalence of brain lesions among girls with CPP. Analysis of the height or shape of the pituitary gland on sellar MRI revealed significant correlations with the weight, height, Tanner stage, and LH levels of the patients.

Variantes de la pubertad precoz en las niñas / Variants of precocious puberty in girls

Introducción: El inicio de la pubertad está determinado por la interacción entre factores genéticos y reguladores. En las niñas ocurre alrededor de los ocho años. Puede afectarse cuando existe una pubertad adelantada, pubertad precoz o una variante de la pubertad. Para su diferenciación los estudios imagenológicos se han convertido en una herramienta vital. Objetivo: Describir aspectos fisiopatológicos, clínico-epidemiológicos y del diagnóstico por imágenes de la pubertad precoz y de sus variantes puberales en las niñas. Métodos: Se realizó una revisión sistemática a través de términos de búsqueda según descriptores en ciencias de la salud. Se utilizaron artículos de libre acceso en las bases de datos de PubMed, SciELO y Google Académico. De un total de 125 artículos, se utilizaron 45 de mayor interés: 34 en idioma español y nueve en inglés, que incluyeron libros y revistas. Análisis e integración de la información: Constituye un desafío distinguir la pubertad precoz de la telarquia, pubarquia, adrenarquia o menarquia aislada de aparición precoz, ya que son variantes del desarrollo puberal. Para su diagnóstico es importante descartar una causa tratable subyacente. El examen físico, análisis de laboratorio y estudios por imágenes, permiten diferenciar las formas completas de sus variantes y las posibles causas que determinan la estimulación de la producción hormonal. Conclusiones: El conocimiento del desarrollo normal de la pubertad y la aparición de sus variantes en las niñas resultan de gran utilidad. Su detección temprana ayudaría a recibir atención médica y descartar mediante métodos de imágenes sus causas secundarias(AU)

Introduction: The start of puberty is determined by the interaction between genetic and regulatory factors. Among girls this occurs around the age of eight years. However, the process may be affected by the presence of early puberty, precocious puberty or a variant of puberty. Imaging studies have become a vital tool for their differentiation. Objective: Describe the pathophysiological, clinical-epidemiological and imaging diagnostic aspects of precocious puberty and its pubertal variants in girls. Methods: A systematic review was conducted using search terms obtained from health sciences descriptors. The documents reviewed were open access papers from the databases PubMed, SciELO and Google Scholar. Of a total 125 papers retrieved, a selection was made of the 45 of greatest interest: 34 in Spanish and 9 in English, including books and journals. Data analysis and integration: Distinguishing precocious puberty from thelarche, pubarche, adrenarche or isolated premature menarche is a challenge, for these are variants of pubertal development. Ruling out an underlying treatable cause is important for diagnosis. Physical examination, laboratory analysis and imaging studies make it possible to differentiate complete forms from their variants and the possible causes determining the stimulation of hormone production. Conclusions: Knowledge about the normal development of puberty and the emergence of its variants in girls is very useful. Early detection would pave the way for medical care, including imaging studies to rule out its secondary causes(AU)

Síndrome de McCune-Albright, una forma poco frecuente de pubertad precoz: diagnóstico, tratamiento y evolución / McCune-Albright syndrome, a rare form of precocious puberty: Diagnosis, treatment, and follow-up

Introducción. El síndrome de McCune-Albright (SMA) es un trastorno genético caracterizado por displasia ósea fibrosa, manchas cutáneas color "café con leche" e hiperfunción autónoma de uno o varios órganos endocrinos. El SMA es producido por mutaciones activadoras del gen GNAS1. La endocrinopatía más frecuente es la gonadal, que se manifiesta como pubertad precoz periférica. Objetivo. Describir las características clínicas y los estudios de laboratorio e imágenes en el momento del diagnóstico y a lo largo de la evolución de la enfermedad, con énfasis en la tríada clásica del síndrome. Población y métodos. Estudio clínico observacional, descriptivo, retrospectivo de las historias clínicas de pacientes con SMA de la División de Endocrinología del Hospital de Niños Ricardo Gutiérrez desde 1974 hasta 2019. Resultados. Se presentan 12 niñas. Todas tuvieron pubertad precoz periférica (PPP) secundaria a quistes ováricos funcionantes. La edad de presentación fue temprana (2,6 ± 1,3 años). Los niveles de gonadotrofinas estuvieron suprimidos o en rango prepuberal con niveles de estradiol generalmente elevados. Diez niñas tuvieron manchas "café con leche" desde el nacimiento. Durante la evolución se detectó displasia fibrosa poliostótica en todas las pacientes. Los tratamientos utilizados para disminuir la recurrencia de los quistes ováricos y los efectos del hiperestrogenismo mostraron diferente eficacia. Conclusiones. En esta serie, la aparición de PPP contribuyó al diagnóstico temprano del SMA y fue de difícil tratamiento. En la evolución persistió la hiperfunción gonadal y empeoraron las lesiones óseas.

Introduction. McCune-Albright syndrome (MAS) is a genetic disorder defined by fibrous dysplasia of bone, café-au-lait skin spots, and autonomous hyperfunction of one or more endocrine organs. MAS is caused by activating mutations of the GNAS1 gene. The most frequent type of endocrinopathy is gonadal endocrinopathy in the form of peripheral precocious puberty. Objective. To describe the clinical characteristics, laboratory and imaging tests at the time of diagnosis and over the course of the disease, focusing on the classical triad of MAS. Population and methods. Observational, descriptive, retrospective clinical study of patients with MAS seen at the Department of Endocrinology of Hospital de Niños Ricardo Gutiérrez between 1974 and 2019. Results. Twelve girls are described, all of whom developed peripheral precocious puberty (PPP) secondary to functional ovarian cysts. Their age at presentation was early (2.6 ± 1.3 years). Gonadotropin levels were suppressed or in the prepubertal range with generally high estradiol levels. Ten girls had café-au-lait skin spots since birth. During the course of disease, polyostotic fibrous dysplasia was detected in all patients. The treatments used to reduce ovarian cyst recurrence and hyperestrogenism effects showed varied effectiveness. Conclusions. In this series, the onset of PPP helped to make an early diagnosis of MAS and was difficult to treat. The course of disease showed persistent gonadal hyperfunction and worsening of bone injuries

Displasia fibrosa poliostótica - síndrome de McCune-Albright: reporte de un caso / Polyostotic fibrous dysplasia - McCune-Albright syndrome: a case report / Displasia fibrosa poliostótica - síndrome de McCune-Albright: relato de um caso

Resumen: Introducción: la displasia fibrosa poliostótica es una patología de muy baja prevalencia, por lo que su diagnóstico pasa desapercibido en la mayoría de los casos. Cuando se asocia a endocrinopatías o a lesiones cutáneas hiperpigmentadas corresponde al síndrome de McCune-Albright. Caso clínico: escolar de 8 años, sexo femenino, que presentó una fractura patológica de fémur izquierdo traumática, en la cual se diagnosticó una displasia fibrosa poliostótica. Por presentarse acompañada de pubertad precoz periférica configura el denominado síndrome de McCune-Albright. El control y tratamiento fue multidisciplinario. El equipo de traumatología realizó osteosíntesis con placa y tornillos de la lesión ósea con evolución a la consolidación en plazos habituales (tres meses). A los seis meses de seguimiento la niña se encuentra sin dolor y sin repercusiones funcionales para la vida diaria. Del punto de vista endocrinológico se realizó tratamiento de su pubertad precoz con inhibidores de la aromatasa con el fin de mejorar su talla final y evitar repercusiones psicológicas y emocionales. En este estudio se analizan características de esta patología y su pronóstico vital y funcional.

Summary: Introduction: polyostotic fibrous dysplasia is a low prevalence disease, and for this reason, it often goes undetected. When associated to endocrinopathies and/or hyperpigmented skin lesions we speak about McCune Albright syndrome. Clinical case: eight-year old school girl who presented pathological fracture of the left femur, which was diagnosed as polyostotic fibrous dysplasia. As it was accompanied by peripheral precocious puberty it constituted an indicative clinical picture of the so-called McCune Albright. Control and treatment were multidisciplinary. The traumatology team performed osteosynthesis with plaques and nails to fix the bone lesion, and evolution consolidated in a regular time frame (3 months). Upon six months follow-up, the girl has no pain and presents no functional repercussion in daily life. From the endocrinological perspective, the girl received precocious puberty treatment with aromatase inhibitors with the purpose of improving her final size and avoid psychological and emotional implications. The study presents the characteristics of this condition, as well as its vital and functional prognosis.

Resumo: Introdução: a displasia fibrosa poliostótica é uma doença de prevalência muito baixa, por isso seu diagnóstico passa despercebido na maioria dos casos. Quando associada a endocrinopatias e / ou lesões cutâneas hiperpigmentadas, corresponde à síndrome de McCune Albright. Caso clínico: estudante do sexo feminino, 8 anos, com quadro de fratura patológica traumática do fêmur esquerdo, com diagnóstico de displasia fibrosa poliostótica. Por estar acompanhada de puberdade precoce periférica, configura a chamada síndrome de McCune Albright. O controle e o tratamento foram multidisciplinares. A equipe de trauma realizou osteossíntese de placa e parafuso da lesão óssea com progressão à consolidação nos prazos usuais (3 meses). Aos 6 meses de seguimento, a paciente não apresenta dor e tampouco repercussões funcionais no dia a dia. Do ponto de vista endocrinológico, sua puberdade precoce foi tratada com inibidores da aromatase para melhorar sua altura final e evitar repercussões psicológicas e emocionais. Este estudo analisa as características desta patologia, seu prognóstico vital e funcional.

Ausencia de beneficio de la terapia combinada con análogo de hormona liberadora de gonadotropina (GnRHa) y hormona de crecimiento humana recombinante (rhGH) en pacientes con pubertad temprana o precoz / Lack of benefit from combined therapy with gonadotropin-releasing hormone analog (GnRHa) and recombinant human growth hormone (rhGH) in patients with early or precocious puberty

RESUMEN Conclusiones del estudio: El análisis general no indica beneficio de la terapia combinada (análogo de hormona liberadora de gonadotropina [GnRHa] + hormona de crecimiento humana recombinante [rhGH]) versus solo GnRHa, solo rhGH o ausencia de tratamiento. Sin embargo, hay beneficios en mayor o menor medida en ciertas subpoblaciones. Comentario crítico: El artículo es relevante al no haber previamente un meta-análisis sobre la terapia combinada. Por otro lado, es importante ya que la terapia combinada implica el uso de rhGH, el cual puede ser costoso, de difícil adherencia y conllevar a efectos adversos. Además, la conclusión general del artículo - no usar terapia combinada - es aplicable. Sin embargo, falta la evaluación de sesgo de publicación y de reporte selectivo, y hay conclusiones secundarias que requieren una mejor explicación. La presente revisión crítica no encuentra evidencia suficiente para sugerir que la terapia combinada pueda ser efectiva en alguna subpoblación.

ABSTRACT Study conclusions: The overall analysis does not indicate benefit of combination therapy (gonadotropin-releasing hormone analog [GnRHa] + recombinant human growth hormone [rhGH]) versus GnRHa alone, rhGH alone, or no treatment. However, there are benefits to a greater or lesser extent in certain subpopulations. Critical comment: The article is relevant as there was no previous meta-analysis on combination therapy. On the other hand, it is important since combination therapy involves the use of rhGH, which can be expensive, difficult to adhere to, and lead to adverse effects. Furthermore, the general conclusion of the article - do not use combination therapy - is applicable. However, the assessment of publication bias and selective reporting is lacking, and there are secondary conclusions that require better explanation. The present critical review does not find sufficient evidence to suggest that combination therapy may be effective in any subpopulation.

A case of Van Wyk-Grumbach syndrome: clinical analysis / 中华全科医师杂志

The clinical data of a child with Van Wyk-Grumbach syndrome (VWGS) who visited Capital Institute of Pediatrics in 2019 were retrospectively analyzed. The patient was a seven year old girl, her main clinical manifestations included short stature (well below -2 standard deviations), obesity and breast development. The results of laboratory testing indicated that the level of thyrotropin (TSH)>100 mIU/L and the level of free thyroxine (FT 4) was 5.15 pmmol/L; serum estradiol and prolactin levels were significantly elevated; the gonadotropin-releasing hormone(GnRH) stimulation test showed that the gonad axis was not activated. She had giant ovarian cyst, pituitary hyperplasia, anemia and pericardial effusion. Bone age was delayed; and her blood lipids had increased. Therefore, she was diagnosed as Van Wyk-Grumbach syndrome. The patient received the treatment of levothyroxine, the drug does was gradually increased from 25 μg per day to 75 μg per day, vaginal bleeding was followed by medication for 3 days. Three months later, her thyroid function was back to normal, and giant ovarian cyst regressed, but the ovaries were bulky,pericardial effusion was absorbed. The levothyroxine dose was adjusted to 50 μg per day according to the test result of thyroid function. And 1 year late the thyroid function was normal, pituitary magnetic resonance imaging(MRI) showed the hyperplastic adenohypophysis was back to normal, no more vaginal bleeding occurred, and the giant ovarian cyst was shrunk.