Clinical efficacy of leprerelin acetate with different dosage forms in central precocious puberty girls

Objective:To observe the clinical efficacy of different dosage forms of lepraline acetate(LA)in the treatment of girls with central precocious puberty(CPP).Methods:72 CPP girls treated in the Department of Pediatrics of Huai'an First People's Hospital from February 2021 to August 2022 were included as subjects and divided into two groups:3-month LA group(n=34)and 1-month LA group(n=38).Both group girls were treated for 6 months.Serum hormone levels,body mass index(BMI),bone age/chronological age(BA/CA)and pelvic color ultrasound were detected at 0 and 6 months after treatment,and the changes of various indexes were compared before and after treatment.Results:1)There were no significant differences in baseline data between the two groups before treatment(P>0.05).2)After 6 months of treatment,BA/CA decreased,growth rate slowed down,and predicted adult height increased in both groups(P<0.05),but there were no significant differences between groups(P>0.05).3)After 6 months of treatment,there waere no significant differences in luteinizing hormone(LH)inhibition ratio between the 3 month and 1 month dosage groups(P>0.05).After treatment,the peak value of serum LH and FSH,estradiol level,uterine volume,bilateral ovarian volume,maximum follicle diameter and the number of follicles 4mm were significantly decreased in the two groups,but there were no significant differences between the two groups(P>0.05).4)There were no significant differences in the levels of thyroid hormone,fasting blood glucose and triglyceride between the two groups before and after treatment(P>0.05).Total cholesterol levels were increased after treatment(P<0.05),but there was no significant difference between groups(P>0.05).5)No serious adverse reactions occurred during the treatment of the two dosage forms of LA,but the 3-month dosage form of LA reduced the treatment cost and improved the treatment compliance.Conclusion:The short-term efficacy of 3-month LA in the treatment of CPP in girls is similar to that of 1-month LA.The 3-month dosage form LA is a safe,effective,and economical method for the treatment of CPP in girls.

Treatment of central precocious puberty by GnRH analogs： long-term outcome in men

In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.

Expression and significance of netrin-1 and its receptor UNC5C in precocious puberty female rat hypothalamus

Objective:To study expressions of netrin-1 and its receptor UNC5 C in female precocious puberty rat hypothalamus,and explore its effect on precocious puberty process.Methods:Forty female one-week-old SD rats were randomly divided into four groups:experimental group A(precocious puberty early youth),experimental group B(precocious puberty medium youth),group A(normal pre-puberty).group B(normal early youth) with 10 rats in each group.Precocious puberty experimental rats were induced with Danazol and rals in control group were injected with saline.Uterus and ovaries were removed,specimens were weighed,litems index and ovarian index were calculated,and amount of luteinizing hormone(LH) and follicle-stimulating hormone(FSH) were detected from the blood by ELISA.Real-time PCR was used to delect netrin-1 and its receptor UNC5 C.as well as hypothalamic gonadolropinreleasing hormone(GnRH) mRNA expression in hypothalamus tissues:and then,a coimmunoprecipitation study of interactions between netrin-1 and its receptor UNC5 C was carried out.Results:Relative target gene expression levels of control group A,control group B.experimental group A,and experimental group B(with,3-actin as an internal control for normalization) were as follows:Netrin-1:3.5±0.9,5.4±0.7.4.9±1.0.5.3±0.3:UNC5C:0.8±0.04.1.7±0.2.1.82±0.23.1.58±0.4:GnRH:1.2±0.3.2.7±0.3.2.4±0.7.3.2±0.4.Conclusions:LH and FSH concentrations,netrin-1 and its receptor expression are increased in precocious puberty animal models.

Efficacy of Subcutaneous Administration of Gonadotropin-releasing Hormone Agonist on Idiopathic Central Precocious Puberty

In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty （ICPP）, 46 girls with ICPP were treated with GnRHa. Triptorelin （Decapeptyl, 3.75 mg） was administered subcutaneously （SC） at 6-weeks intervals or intramuscularly （IM） at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage, bone age, uterine volume and ovarian size, serum levels of luteinizing hormone （LH）, follicle stimulating hormone （FSH） and estradiol （E2）, were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics. Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment. The height velocity was decreased significandy from 6.3±1.4 cm/year to 5.8：1：1.2 cm/year in group SC and 6.7±1.3 cm/year to 5.4±1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBAgdeltaCA was 1.2±0.2 or 1.3±0.3 at the onset of therapy and decreased significantly after the treatment to 0.7±0.2 or 0.9±0.1, respectively. The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in di- ameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients, which disappeared after 6- 12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was concluded that both IM and SC triptorelin administrations were clinically effective. They induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6-weeks intervals at a dosage of 3.75 mg be a safe and acceptable regimen for ICPP.

Rare mutation in MKRN3 in two twin sisters with central precocious puberty: Two case reports

BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis,there is increasing incidence of central precocious puberty(CPP),especially in girls.Makorin ring finger protein 3(MKRN3),a maternal imprinted gene with a highly conserved sequence,is the most common genetic etiology associated with CPP.Approximately 50 different mutations in MKRN3 have been found in CPP.CASE SUMMARY This case report involves identical twin sisters presenting with premature thelarche at the age of 6 years.The left hand bone age of both patients revealed advanced age(9 years).Pelvic B ultrasound indicated enlargement of the ovaries.Luteinizing hormone(LH)releasing hormone testing confirmed CPP.Wholeexome sequencing detected the c.841C>T mutation in MKRN3,leading to a single base substitution,in the twins.This mutation was inherited from the father and paternal grandmother.After 3 mo of treatment with a gonadotropin-releasing hormone analog,levels of LH,follicle-stimulating hormone,and estradiol in the proband’s sister returned to normal levels.CONCLUSION Here,we report a rare mutation(c.841C>T)in MKRN3 in identical twin sisters with CPP.

Precocious puberty: Pathology, related risks, and support strategies

Children are currently starting pubertal development much earlier than 20 to 30 years ago. Data from the National Health and Nutrition Examination Survey (NHANES III) conducted from 1988-1994 revealed that the median age for breast development in white girls was approximately 9.7 years and 8 years in African-American girls versus 10.9 years ago. More recent data, however, indicate that some children are starting pubertal development even earlier (age 7 or 8 in girls or age 9 in boys). Very early pubertal development is identified as precocious puberty, a phenomenon that brings great concern to others besides parents: the child, their peers, school nurses, teachers and counselors. This paper discusses precocious pubertal development, possible causes or relationships, related risks, treatment and helping strategies.

Investigation of the Cause of Precocious Puberty in an 8-Year-Old Girl Ended up in Juvenile Granulosa and Theca Cell Tumor of the Ovary

Isosexual precocious puberty in girls has several etiologies. Juvenile granulose cell tumor is one of the rarest causes that only stands for 1.5% of ovarian cancers. This tumor mostly encounters in first 2 decades of life. This paper is a report of an 8-year-old girl with precocious puberty that within five months developed breast enlargement followed by menarche. Works which are done to find the underlying cause of precocious puberty revealed juvenile granulosa cell tumor in her left ovary. She then under went laparoscopic surgery and 3 courses of chemotherapy. She did not experience any vaginal bleeding after that and the serum level of estradiol lay among its normal ranges, but after that the tumor relapsed and presented as abdominal pain and a huge mass which under went resection of all afflicted tissues. After 2 courses of chemotherapy, her status deteriorated and unfortunately she died after 6 months from the time of diagnosis. Treatment for this disease is consists of resection surgery and chemotherapy. If this tumor is diagnosed in its early stages, it will be curable, but in its advanced stages, up to 80% of patients die from recurrent tumors. The reported patient was diagnosed at stage IIIC that had poor prognosis.

Precocious In-Vitro Flowering of Perennial Asparagus (Asparagus officinalis L.) Regenerants with a Chemical Inducer

A precocious flowering system of regenerants in asparagus (Asparagus officinalis) was achieved by treatment with a chemical inducer. Somatic embryos withered completely by being processed for 8 - 12 days with 200 μM n-propyl N-(3,4-dichloro-phenyl)carbamate that had been dissolved in distilled water. In contrast, precocious flowering occurred at an extremely low rate (3.4%) when somatic embryos were processed in carbamate dissolved in Murashige and Skoog’s liquid medium. To encapsulate the female and male embryos, we surveyed the optimum conditions of viscosity and concentration of sodium alginate for encapsulating the seeds, and we screened the values of 80 - 120 cps and 2% - 3%, respectively. The synthetic seeds produced also withered when they were processed with the carbamate dissolved in distilled water. However, when Murashige and Skoog’s liquid medium was used for the solvent, the flowering frequency of the synthetic seeds was enhanced (13.3%). Based on our morphological and histological observations, female and male regenerants that were processed with the carbamate solution produced individual flower organs. The conversion of sex expression did not occur. A precocious flowering system would allow a significant reduction in the time required for perennial seedlings to flower and can, therefore, save time required for further experiments that employ floral homeotic mutants.

A Rare Cause of Precocious Puberty and Massive Ovarian Cysts Associated with Hypothyroidism

Van Wyk-Grumbach syndrome (VWGS) is characterized by juvenile hypothyroidism, delayed bone age, isosexual precocious puberty and massive ovarian cysts. We report such a case in a 7-year-old girl who presented with a bilateral pelvic pain, abdominal distension and signs of hypothyroidism. Physical examination showed a breast development and lack of pubic and axillary hair. There was no clitoromegaly. Pelvic ultrasonography and CT scan showed enlarged bilateral multiloculared multicystics ovarian masses. The pituitary MRI was recommended before an elevated prolactin, revealed a large sellar and suprasellar mass. The patient was started on thyroid replacement using L-Thyroxine. Clinically, the patient’s fatigue, pelvic pain, and abdominal distension are resolved. During the follow-up, her thyroid functions and serum prolactin normalized within 8 months. Ultrasonography revealed regression of ovarian cysts in 2 months measuring, with normal sized ovaries in 14 months.

Effects of Nourishing “Yin”-Removing “Fire” Chinese Herb Mixture on the Differential Expression of GABA_AReceptor <i>α</i>Subunits in Hypothalamus of Precocious Puberty Female Rats

GABAergic input to Gonadotropin-releasing hormone (GnRH) neurons is necessary to initiate the onset of puberty and its action mainly depends on GABAA receptor of which the subunit composition, properties and consequently function varies during this period. Nourishing “Yin”-Removing “Fire” Chinese herb mixture, a Chinese herb-based formulation, has been proved that it may retard the initiation of pubertal development in female precocious puberty rats. Our objective is to investigate the effects of Nourishing “Yin”-Removing “Fire” Chinese herb mixture on the expression of GABAA receptor α subunits in hypothalamus. Female Sprague-Dawley rats were divided into normal (N), precocious puberty model (M) induced by danazol, model exposed to saline (MS) and model exposed to Chinese herb mixture (CHM) groups. All rats were administered by the Chinese herb mixture from P15 on. Coefficients of reproductive organs and serum gonadotropins and estradiol levels in M were significantly enhanced while they were significantly decreased in CHM. The hypothalamic GnRH mRNA was also significantly increased in M and in CHM, as well as ERα mRNA. At the mean time, the hypothalamic GABAA receptor α1 and α3 subunits mRNA were more significantly decreased in M than those of N, while they were more significantly enhanced in CHM than those in M (p 0.01), the protein expression of which in hypothalamus had the same trend as the mRNA expression. The evidence suggests that Nourishing “Yin”-Removing “Fire” Chinese herb mixture could significantly retard the sexual development of the precocious rats, and up-regulate the expressions of hypothalamic GABAA receptor α1 and α3 subunits. Our result indicated that GABAA receptor α1 and α3 subunits might involve in the effective treatment of herb mixture on idiopathic precocious puberty.

Unusual Presentation of Precocious Puberty and Alopecia Universalis in Saudi Patients with Autoimmune Polyglandular Syndrome Type 1(APS1) without Any Other Manifestation of the Disease: Case Report and a Brief Review of the Literature

Autoimmune polyglandular syndrome type 1 (APS-1) is one of the rare inherited disorder that affects both sexes alike. Although in specific autoimmune dysfunction associated with this syndrome found to be more common in females than males. It has specific criteria usually presented at a specific age. The object of this clinical case report is to highlight this unusual presentation of such condition which is the presence of APS-1 with precocious puberty and alopecia Universalis without any associated symptoms of APS-1 and the gene variations that never had been found before. And up to our knowledge, this is the 1st case in our population and worldwide that has such combination and this is unusual clinical presentation. Autoimmune polyglandular syndrome type 1 (APS-1) is one of the rare inherited disorder that affects both sexes alike. Although in specific autoimmune dysfunction associated with this syndrome found to be more common in females than males. It has specific criteria usually presented at a specific age. The object of this clinical case report is to highlight this unusual presentation of such condition which is the presence of APS-1 with precocious puberty and alopecia Universalis without any associated symptoms of APS-1 and the gene variations that never had been found before. And up to our knowledge, this is the 1st case in our population and worldwide that has such combination and this is unusual clinical presentation.

Effects of Nourishing “Yin”-Removing “Fire” Chinese Herb Mixture on the Expression of GABAB Receptors in Hypothalamus of Precocious Puberty Female Rats

Objectives: To investigate the potential role of GABAB Receptors (GABABRs) involved in the effect of Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM) treatment on precocious puberty. Methods: Female Sprague-Dawley rats were randomly divided into four groups: normal (N), central precocious puberty (CPP) model (M), CPP fed with normal saline (S) and CPP fed with Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM). Rats of postnatal day 5 were given a single subcutaneous injection of 240 μg danazol to establish CPP model rats. Rats of S and TCM groups were continuously administered with saline or nourishing “Yin”-removing “Fire” Chinese herb mixture since postnatal day 15. The expression of GABABRs was detected by means of real-time PCR and immunohistochemistry. Results: The expression of hypothalamic GnRH mRNA in M was significantly increased on the day of pre-puberty when compared with that of N (P < 0.01). On the day of onset-puberty, LH levels were higher in M than those in N (P < 0.01), while the serum E2 and LH levels of TCM decreased when compared with those of M (P B1 receptor (GABABR1) immunoreactive cells in the arcuate nucleus (ARN) was decreased in M when compared with that of N (P < 0.05) and increased in TCM compared with that of M (P < 0.05);simultaneously, the expression of GABABR1 mRNA in hypothalamus was significantly decreased in M when compared with that of N (P < 0.01) and increased in TCM compared with that of M (P < 0.01). On the day of onset-puberty, the number of GABABR1 immunoreactive cells in medial septum (MS) was decreased in M compared with that in N (P < 0.05) and increased in TCM comparing with that of M (P < 0.05);meanwhile, the mRNA expression of GABABR1 in hypothalamus was decreased in M compared with that in N (P B2 receptor (GABABR2) immunoreactive cells in the ARN, MS and diagnonal band of broca (DBB) were decreased in M when compared with those of N (P < 0.05) and increased in TCM compared with those of M (P < 0.05) on the day of onset-puberty. At the same time, the mRNA expression of GABABR2 was significantly decreased in M compared with that of N (P < 0.01). Conclusions: These results indicated that the GABABRs might involve in the curative effect of Nourishing “Yin”-Removing “Fire” Chinese herbal mixture on CPP rats.

Efficacy and Safety of Domestic Leuprorelin in Girls with Idiopathic Central Precocious Puberty： A Multicenter,Randomized, Parallel, Controlled Trial

Background：In central precocious puberty （CPP）,the pulse secretion and release ofgonadotropin-releasing hormone （GnRH） are increased due to early activation of the hypothalamic-pituitary-gonadal axis,resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics.The CPP without organic disease is known as idiopathic CPP （ICPP）.The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin （GnRH analog） in girls with ICPP.Methods：A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups.One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate,79 girls in the control group were treated with imported leuprorelin acetate.They all were treated and observed for 6 months.After 6-month treatment,the percentage of children with peak luteinizing hormone （LH） ≤3.3 U/L,the percentage of children with peak LH/peak follicle stimulating hormone （FSH） ratio 〈0.6,the improvements of secondary sexual characteristics,gonadal development and sex hormone levels,the change of growth rate of bone age （BA） and growth velocity,and drug adverse effects between two groups were compared.Results：After the treatment,the percentage of children with a suppressed LH response to GnRH,defined as a peak LH ≤3.3 U/L,at 6 months in test and control groups were 96.80% and 96.20%,respectively,and the percentage of children with peak LH/FSH ratio ≤0.6 at 6 months in test and control groups were 93.60% and 93.70%,respectively.The sizes of breast,uterus and ovary of children and the levels of estradiol （E2） were significantly reduced,and the growth rate of BA was also reduced.All the differences between pre-and post-treatment in each group were statistically significant （P 〈 0.05）,but the differences of the parameters between two groups were not significant （P 〉 0.05）.Conclusions：Domestic leuprorelin is effective and safe in the treatment of Chinese girls with ICPP.Its effectiveness and safety are comparable with imported leuprorelin.

Prevalence of vitamin D deficiency in girls with idiopathic central precocious puberty

The relationship between vitamin D deficiency and idiopathic central precocious puberty （ICPP） has been recently documented. In this study, 280 girls diagnosed with ICPP and 188 normal puberty control girls of similar ages were enrolled and retrospectively studied. The ICPP group had significantly lower serum 25- hydroxyvitamin D （25[OH]D） levels than the control group. Furthermore, a nonlinear relationship was found between serum 25[OH]D and ICPP, and a cut-offpoint for serum 25[OH]D was found at 31.8 ng/ml for ICPP with and without adjusting the different confounding factors. Girls with serum 25[OH]D 〉~ 31.8 ng/ml had a lower odds ratio （unadjusted： OR 0.36, 95% CI 0.15 to 0.83, P 〈 0.05; height and weight adjusted： OR 0.44, 95~0 CI 0.18 to 1.08, P = 0.072; BMI adjusted： OR 0.36, 95% CI 0.16 to 0.84, P 〈 0.05）. The ICPP subjects with 25[OH]D deficiency had a higher body mass index （BMI） than the subjects from the two other subgroups. Correlation analysis showed that vitamin D level is correlated with BMI and some metabolic parameters in the ICPP group. Our study suggested that vitamin D status may be associated with ICPP risk and may have a threshold effect on ICPP.

Effectiveness of ZiYin Xiehuo granules and Zishen Qinggan granules on partial precocious puberty in girls: a multicenter, randomized, single-blind, controlled trial

OBJECTIVE: To evaluate the effect of ZiYin Xiehuo granules(ZYXH) and Zishen Qinggan granules(ZSQG) on partial precocious puberty(PPP).METHODS: This was a multicenter, randomized, single-blind, positive-controlled trial. A total of 143 pa-tients were assigned to either the ZYXH group or the ZSQG group using a random number table. The ZYXH group received ZYXH three times daily for 6 months and the ZSQG group received ZSQG three times daily for 6 months. Mammary nucleus diameter; the results of uterus, ovarian, and maximum follicle measures; and Chinese medicine symptom pattern scores were compared at baseline and after 3 months and 6 months of treatment.RESULTS: After 3 months' treatment, there were no significant differences between the two groups in mammary nucleus index changes(left 3.4 ± 3.1 vs3.5 ± 3.1, P = 0.790; right 3.0 ± 2.9 vs 3.6 ± 3.0, P =0.719). The uterine volume in the ZYXH group was smaller than that in the ZSQG group(2.1 ± 1.6 vs2.6 ± 2.2, P = 0.006). There were no significant between-group differences in ovarian volume and maximum follicular diameter on either side(ovarian volume: left 1.2 ± 0.7 vs 1.3 ± 0.6, P = 0.8; right1.2 ± 0.7 vs 1.4 ± 1.1, P = 0.984; maximum follicular diameter: left 3.9 ± 1.7 vs 3.5 ± 2.2, P = 0.158; right3.5 ± 1.7 vs 3.9 ± 2.1, P = 0.314).CONCLUSION: ZYXH granules and ZSQG granules both affected the size of the mammary nucleus in girls with PPP, and improved Chinese medicine symptom patterns. ZYXH granules showed slight advantages over ZSQG granules in terms of the decrease in the size of the uterus, ovaries, and ovarian follicles.

Postnatal feeding with high-fat diet induces obesity and precocious puberty in C57BL/6J mouse pups： a novel model of obesity and puberty

Childhood obesity and obesity-related metabolic complications are induced by a high-fat postnatal diet. The lack of a suitable animal model, however, remains a considerable challenge in obesity studies. In the current study, we provided high-fat diet （HFD） to dams during lactation and to pups after weaning. We also developed a novel model of C57BL/6J mouse pups with HFD-induced postnatal obesity. Results showed that feeding with HFD induces fat deposition and obesity in pups. Furthermore, HFD more potently increased the body weight （BW） of male than female pups. HFD-fed female pups were obese, underwent precocious puberty, and showed increased kisspeptin expression in the hypothalamus. However, parental obesity and precocious puberty exerted no synergistic effects on the HFD-induced postnatal weight gain and puberty onset of the pups. Interestingly, some HFD-fed litters with normal BW also exhibited precocious puberty. This finding suggested that diet composition but not BW triggers puberty onset. Our model suggests good construction validity of obesity and precocious puberty. Furthermore, our model can also be used to explore the mutual interactions between diet-induced postnatal childhood obesity and puberty.

Research on Treatment of Female ldiopathic Precocious Puberty withCombined Traditional Chinese Medicine and Megestrol Acetate

Objective: To find effective therapeutic approach for treating true idiopathic precocious puberty suitable to our national condition and different from gonadotrophin releasing hormone analogue. Methods: One hundred and six girls with idiopathic precocious puberty were divided into 3 groups. The 51 girls in the TCMWM group were treated with Chinese herbal medicine combined with megestrol acetate (MA), 35 girls in the MA group treated with megestrol acetate alone, and 20 girls were taken as control group and given no treatment at all. Luteinizing hormone releasing hormone (LHRH) stimulating test were performed before and after treatment, and the size of the uterus and ovary, linear growth rate, X-ray bone age measurement and final height prediction were also observed simultaneously. Results: After treated with TCM-WM for 2.7 years in average,the luteinizing hormone (LH) peak value of LHRH stimulating test was reduced from 48. 5 ± 5. 2 IU/L to 12.2 ± 1. 3 IU/L, size of uterus and ovary decreased, secondary sexual characteristics regressed, the bone age difference/chronological age difference value (ΔBA/ΔCA) reduced from 1. 35 ± 0. 09 to 0. 65 ± 0. 05 and predictive final height increased from 153. 3 ± 0. 5 cm to 158. 5 ± 0. 6 cm. Conclusion: TCM-WM therapy could not only modulate the function of hypothalamic-pituitary-ovarian axis and the development of internal genitalia, but also could decelerate skeletal growth, delay skeletal maturation, and thereby prevent premature epiphyseal fusion and increase the final height of patients.

Central precocious puberty as a prelude of gonad dysplasia

There is increasing evidence that patients with gonad dysplasia,as characterized by absent or incomplete puberty,can also exhibit central precocious puberty(CPP).Herein,we review the reported cases that manifest with both gonad dysplasia and CPP.Further,we examine the hypothesis that these patients exhibit a normal hypothalamic-pituitarygonadal axis,hypogonadism,and the presence of residual gonadal function,and that the onset of disease is related to early initiation of the hypothalamic-pituitary-gonadal axis.Thus,we suggest that CPP is a prelude of some partial hypogonadism.

Central precocious puberty as a prelude to hypogonadism in a patient with Klinefelter syndrome

Introduction:Incomplete pubertal development is a common phenomenon found in patients with Klinefelter syndrome (KFS).KFS combined with central precocious puberty (CPP) rarely occurs.We herein report a rare case of KFS with CPP and review several studies to determine the possible mechanism underlying this condition.Case presentation:An 8-year,5-month-old male patient was admitted to our hospital because of enlargement of the penis and small testes.Laboratory evaluation revealed high luteinizing hormone and follicle-stimulating hormone levels,a high testosterone level,and the 48,XXYY karyotype.He was treated with triptorelin.One year later,the patient's testosterone level decreased and pubertal arrest occurred.Conclusion:The literature review in this study showed that the occurrence of hypogonadism combined with CPP is not unique to patients with KFS;it has also been reported in individuals with Turner syndrome,adrenal hypoplasia congenita,and other diseases.Such individuals share common features including partial hypogonadism and a normal hypothalamic-pituitary-gonadal axis.CPP is considered a prelude to hypogonadism,and treatment with a gonadotropin-releasing hormone agonist may prevent gonadal failure.