Central precocious puberty secondary to peripheral precocious puberty due to a pineal germ cell tumor: a case and review of literature.

BACKGROUND: The pineal lesion affecting melatonin is a rare cause of central precocious puberty by decreasing the inhibition of hypothalamic-pituitary-gonadal axis. Germ cell tumor secreting human chorionic gonadotropin is a rare cause of peripheral puberty. CASE PRESENTATION: A 5.8-year-old male presented facial hair and phallic growth, deepened voice, and accelerated growth velocity for 6 months. The elevated human chorionic gonadotropin level with undetectable gonadotropin levels indicated peripheral precocious puberty. Brain imaging revealed a pineal mass and further pathology indicated the diagnosis of teratoma. During chemoradiotherapy with operation, the elevated human chorionic gonadotropin level reduced to normal range, while the levels of gonadotropins and testosterone increased. Subsequently, progressing precocious puberty was arrested with gonadotrophin-releasing hormone analog therapy. Previous cases of transition from peripheral precocious puberty to central precocious puberty were reviewed. The transitions were caused by the suddenly reduced feedback inhibition of sex steroid hormones on gonadotropin releasing hormone and gonadotropins. CONCLUSIONS: For patients with human chorionic gonadotropin-secreting tumors, gonadotropin levels increase prior to sex steroid decrease, seems a sign of melatonin-related central PP related to melatonin.

Precocious puberty related to Leydig cell testicular tumor: the diagnostic imaging keys.

BACKGROUND: We report the challenging case of a 6-year-old boy with precocious puberty related to histologically proven Leydig cell tumor. CASE PRESENTATION: Multiparametric ultrasound and magnetic resonance imaging (MRI) was performed. Interesting findings were scarcely or never reported in children and differed from adults Leydig cell tumors s such as the hyperechogenic halo surrounding the lesion and the dominant central vascularization using ultrasensitive Doppler. MRI revealed an enlarged testicle with strong enhancement of a tumor, a tumor apparent diffusion coefficient (ADC) of 600 × 10-3 mm2/s and a lower ADC value of the non-tumor parenchyma compared to the contralateral testis (ADC = 800 × 10-3 mm2/s vs 1100 × 10-3 mm2/s), attributed to the spermatogenesis induced by hormonal impregnation. CONCLUSION: We illustrate multiparametric US and MRI findings of a pediatric Leydig cell tumor, including the imaging changes attributed to local hormone secretion, which may be helpful in similar cases.

Feminizing adrenocortical oncocytoma presenting as precocious puberty: a case report and literature review.

OBJECTIVES: Feminizing adrenal tumors are rare in childhood. We present a case of a special category of adrenal tumor, an oncocytoma, causing isosexual peripheral precocity. CASE PRESENTATION: A 4-year old girl presented with breast development and menstrual bleeding over a period of 3-4 months. Her SMR staging was breast stage 4, pubic hair stage 3. Her bone age was advanced (6 year 10 months), stimulated LH 0.7 IU/L, estradiol 206 pmol/L and DHEAS >27.1 micromol/L. CT scan revealed a right adrenal mass with features of atypical adrenal adenoma. Laparoscopic adrenalectomy was done and histopathology revealed oncocytoma. Lin-Weiss-Bisceglia criteria classified it as likely benign, borne out till a 2 year follow up. CONCLUSIONS: Adrenal oncocytoma can be a cause of isosexual peripheral precocity in a young girl. Recognition and correct classification of this histological variant, which is more often benign, is important for prognostication and choice of therapy after surgery.

Case Report: Lipoma of the Tuber Cinereum Mimicking a Pituitary Gland Abnormality in a Girl With Central Precocious Puberty.

Introduction: Magnetic Resonance Imaging (MRI) is the best approach to investigate the hypothalamic-pituitary region in children with central precocious puberty (CPP). Routine scanning is controversial in girls aged 6-8 year, due to the overwhelming prevalence of idiopathic forms and unrelated incidentalomas. Cerebral lipomas are rare and accidental findings, not usually expected in CPP. We report a girl with CPP and an unusually shaped posterior pituitary gland on SE-T1w sequences. Case Description: A 7.3-year-old female was referred for breast development started at age 7. Her past medical history and physical examination were unremarkable, apart from the Tanner stage 2 breast. X-ray of the left-hand revealed a bone age 2-years ahead of her chronological age, projecting her adult height prognosis below the mid parental height. LHRH test and pelvic ultrasound were suggestive for CPP. Routine brain MRI sequences, SE T1w and TSE T2w, showed the posterior pituitary bright spot increased in size and stretched upward. The finding was considered as an anatomical variant, in an otherwise normal brain imaging. Patient was started on treatment with GnRH analogue. At a thorough revaluation, imaging overlap with adipose tissue was suspected and a new MRI scan with 3D-fat-suppression T1w-VIBE sequences demonstrated a lipoma of the tuber cinereum, bordering a perfectly normal neurohypophysis. 3D-T2w-SPACE sequences, acquired at first MRI scan, would have provided a more correct interpretation if rightly considered. Conclusion: This is the first evidence, to our knowledge, of a cerebral lipoma mimicking pituitary gland abnormalities. Our experience highlights the importance of considering suprasellar lipomas in the MRI investigation of children with CPP, despite their rarity, should the T1w sequences show an unexpected pituitary shape. 3D-T2w SPACE sequences could be integrated into standard ones, especially when performing MRI routinely, to avoid potential misinterpretations.

Precocious puberty in Korean girls with and without exposure to endocrine-disrupting chemicals in toy slime: a comparative analysis.

BACKGROUND: Toy slime is popular in Korea, and in parallel, pre-pubertal girls visit hospitals for early pubertal signs. Thus far, numerous studies have investigated the association of endocrine-disrupting chemicals (EDCs) with precocious puberty (PP). However, there is a lack of studies on the clinical manifestations and sex hormones. We aimed to investigate early pubertal development in Korean girls with or without a history of toy slime exposure and determine changes in bone age, Tanner stage, and sex hormones. METHODS: In this study, 140 girls underwent stimulation tests at Kyungpook National University Children's Hospital Endocrinology Department, during January 2018 and December 2020. Patients were divided into two groups for gonadotropin-releasing hormone (GnRH) stimulation test and frequency of exposure to toy slime (EDCs). GnRH stimulation test was conducted after an intravenous injection of 100 µg of luteinizing hormone-releasing hormone. Slime exposure was defined as Slime ≥ 3 times/week for ≥ 3 months. RESULTS: History of slime exposure was found in 14 of 58 and 65 of 82 patients in the central PP (CPP) and non-CPP groups, respectively. Slime-exposed patients had advanced bone age, although their Tanner stage was low. Patients with a history of toy slime exposure were 5.5 times more likely to be diagnosed with non-CPP than patients without slime exposure (p < 0.05). CONCLUSIONS: Exposure to toy slime in prepubertal girls may be associated with rapid clinical advancement of pubertal development and bone age, and the patients appear more likely to be diagnosed with non-CPP.

Association of Soy and Exclusive Breastfeeding With Central Precocious Puberty: A Case-Control Study.

Introduction: While soy is suggested as a possible risk factor, exclusive breastfeeding (EBF) has a likely protective effect in precocious puberty. Our aim was to evaluate the association between both of these variables with central precocious puberty (CPP). Methods: We performed a retrospective, case-control study. A total of 161 girls were divided into two groups: 84 patients diagnosed with CPP composed the case group and 77 patients without the diagnosis of CPP (had gone through normal onset of puberty) were the control group. Results: Our control group had a higher presence of EBF >6 months, which was an important protective factor for CPP (OR: 0.5; IC 95%: 0.3-0.9, p = 0.05) and also correlated negatively with the presence of it (r = -0.2; p < 0.05). Oppositely, the use of soy was significantly higher in the CPP group, (OR: 3.8; IC 95%: 1.5-6, p < 0.05) and positively correlating (r = 0.2; p < 0.01) with the presence of CPP. Duration of soy intake (years) correlated with bone age (r = 0.415; p < 0.05). A logistic regression was performed to evaluate the effects of EBF duration and soy on CPP. The model was significant (x² (2) = 20,715, p = <0.001) and explained 12.2% (Nagelkerke R2) of the variance, correctly classifying 62.5% of cases. EBF was associated with a reduction of likelihood of having CPP [OR = 0,187 (CI = 0.055-0,635); Wald = 7,222, p = 0.007], while soy intake increased the risk [OR = 3.505 (CI) = 1,688-7,279, Wald = 11,319, p = 0.001]. Conclusion: Our data found the use of soy was associated with CPP. Additionally, EBF was pointed as a protective factor. However, future prospective studies are needed to clarify this issue.

Clinical characteristics and treatment patterns with histrelin acetate subcutaneous implants vs. leuprolide injections in children with precocious puberty: a real-world study using a US claims database.

OBJECTIVES: Gonadotropin-releasing hormone analogs are the treatment of choice for central precocious puberty (CPP). This study characterizes patients treated with histrelin implant or leuprolide injection. METHODS: A US claims database was used to identify patients aged ≤20 years with ≥1 histrelin or leuprolide claim (index treatment) between April 2010 and November 2017 and continuous enrollment ≥3 months before and ≥12 months after the index treatment date. RESULTS: Overall, 4,217 patients (histrelin, n=1,001; leuprolide, n=3,216) were identified. The percentage of patients with CPP diagnosis was greater in the histrelin (96.5%) vs. leuprolide (68.8%; p<0.0001) cohort. In patients with CPP (histrelin, n=966; leuprolide, n=2,214), mean age at treatment initiation was similar for histrelin (9.0 ± 2.0 years) and leuprolide (9.1 ± 2.3 years), with >50% of patients aged 6-9 years. Mean treatment duration was significantly longer for histrelin (26.7 ± 14.8 months) vs. leuprolide (14.1 ± 12.1 months; p<0.0001), and was longer in younger patient groups. More patients switched from leuprolide to histrelin (12.3%) than vice versa (3.6%; p<0.0001). Median annual total treatment costs were slightly lower for the histrelin cohort ($23,071 [interquartile range, $16,833-$31,050]) than the leuprolide cohort ($27,021 [interquartile range, $18,314-$34,995]; p<0.0001). CONCLUSIONS: Patients with CPP treated with histrelin had a longer duration of treatment, lower rates of index treatment discontinuation, and lower annual treatment costs vs. those treated with leuprolide.

Importance of individualizing treatment decisions in girls with central precocious puberty when initiating treatment after age 7 years or continuing beyond a chronological age of 10 years or a bone age of 12 years.

OBJECTIVES: Gonadotropin-releasing hormone agonist treatment is important for optimal growth in girls with central precocious puberty (CPP). Data are lacking regarding benefit to height outcome when treatment is started after chronological age (CA) of 7 years, and if continued beyond CA of 10 years or bone age (BA) of 12 years. METHODS: Forty-eight girls with CPP were treated with monthly leuprolide depot. Change in predicted adult height (PAH) during treatment was assessed. Changes in PAH and growth velocity were compared between girls initiating treatment at CA <7 vs. ≥7 years, and BA ≥12 vs. BA <12 years. RESULTS: Mean baseline CA was 6.8 years, BA, 10.2 years; and PAH, 156.4 cm. BA/CA ratio decreased from pretreatment values, averaging 1.5 to 1.2 at the end of treatment. Proportion of girls with >5 cm PAH change during treatment was similar, and PAH increased throughout treatment in most girls, regardless of age at treatment initiation. PAH continued to increase in 16/19 girls who continued treatment after BA of 12 years, and also in 16/22 girls who continued treatment after CA of 10 years. CONCLUSIONS: PAH improved in most girls who initiated treatment after CA of 7 years. It continued to improve in most girls with longer treatment, even past BA of 12 years or CA of 10 years, which suggests that no absolute CA or BA limit should define initiation or end of treatment. Treatment plans need to be individualized, and neither treatment initiation nor cessation should be based on BA or CA alone.

A novel stop-loss DAX1 variant affecting its protein-interaction with SF1 precedes the adrenal hypoplasia congenital with rare spontaneous precocious puberty and elevated hypothalamic-pituitary-gonadal/adrenal axis responses.

The case study unveils the likely mechanism of a novel stop-loss DAX1 variant preceding the prolonged precocious puberty in the adrenal hypoplasia congenital (AHC) boy. A boy aged five years and nine months initially examined for the primary adrenal insufficiency symptoms. Next-generation sequencing confirmed the X-linked inheritance of a novel stop-loss DAX1 variant: c.1411T>C/p.Ter471Gln associated with AHC in the patient. The patient was subjected to a brief clinical follow-up from 11 to 15.1 years of age. The effect of the mutant-DAX1 variant (p.Ter471Gln) on DAX1-steroidogenic factor 1 (SF1) (protein-protein) interaction was studied by protein-protein docking using the ClusPro-online tool. At 5.9 yrs of age, the patient exhibited precocious puberty with the secondary sexual characteristics of Tanner 2 stage (of 9-14 yrs of age). The patient showed primary adrenal insufficiency with diminished cortisol concentrations at blood serum (25 ng/ml) and urine (3.55 µg/24 h) levels. Upon steroidal exposure, the patient showed normalized serum cortisol levels of 45-61 ng/ml. However, the precocious puberty got prolonged with the increased penis length of 8.5 cm and the bone age of 18 yrs old during the follow-up. The patient showed increased basal serum adrenocorticotropic hormone (110->2000 pg/ml) and follicle-stimulating hormone (18.4-22.3 mIU/ml) concentrations. Following an elevated hypothalamic-pituitary-gonadal axis activity witnessed upon gonarellin stimulation. Protein-protein docking confirmed a weaker interaction between the mutant-DAX1 (p.Ter471Gln) protein and the wild-SF1 protein. Overall, we hypothesize the weakened mutant-DAX1-SF1 (protein-protein) interaction could govern the prolonged precocious puberty augmented with the elevated hypothalamic-pituitary-gonadal/adrenal axis responses via SF1-induced neuronal nitric oxide synthetase activation in the patient.

Precocious sexual development in a male toddler caused by unrecognized transdermal exposure to testosterone: case report and review of the literature.

OBJECTIVES: Exogenous exposure to transdermal testosterone is often overlooked as a cause of precocious sexual development in children. CASE PRESENTATION: A 16-month-old male presented for a second opinion consultation before commencing treatment with bicalutamide and anastrozole for a presumptive diagnosis of familial gonadotropin-independent male-limited sexual precocity. Enlargement of the penis was first observed at four months of age. The initial evaluation showed isolated elevation of his plasma testosterone level; however, by 16 months, his testosterone level was prepubertal and no pathogenic variants in the LHC GR gene were identified. The history revealed that his grandfather, who had cared for him regularly in the first year of life, had used testosterone gel for treatment of hypogonadism. CONCLUSIONS: Despite the 2009 "black box" warning issued by the United States Food and Drug Administration (FDA) regarding potential consequences of transdermal testosterone exposure to women and children, this continues to be an important cause of sexual precocity in children. Children are often subjected to unnecessary and costly evaluation before this exposure is recognized, underscoring the importance of obtaining a thorough medical, family, and social history tailored to the differential diagnosis.

Serum level of NPTX1 is independent of serum MKRN3 in central precocious puberty.

OBJECTIVES: Makorin ring finger protein 3 (MKRN3) is associated with the initiation of puberty, and loss of function mutation of MKRN3 is the most common genetic cause of central precocious puberty (CPP). A recent study reported that MKRN3 interacts with and suppresses neural pentraxin-1 precursor (NPTX1) activity via polyubiquitination during early puberty in the mouse hypothalamus. This study investigated the correlation between serum NPTX1 and MKRN3 in CPP girls and predicted the potential role of NPTX1 in pubertal progression. METHODS: In this case-control study, we examined 34 girls diagnosed with CPP and 34 healthy prepubertal girls. Anthropometric and hormonal parameters were measured and serum levels of NPTX1 and MKRN3 were evaluated with commercial enzyme-linked immunosorbent assay kits. RESULTS: Serum MKRN3 level decreased significantly in CPP patients compared to controls (344.48 ± 333.77 and 1295.21 ± 780.80 pg/mL, respectively, p<0.001). Serum MKRN3 tended to decrease as Tanner breast stage increased. However, no significant difference was observed in serum NPTX1 levels between patients and controls (20.14 ± 31.75 ng/mL and 12.93 ± 8.28 ng/mL, respectively, p=0.248). The serum level of NPTX1 did not change significantly with the Tanner breast stage. Serum NPTX1 was correlated with the height standard deviation score (r=0.255; p<0.05), but was not correlated with serum MKRN3 level or the others. Conclusion: Although serum NPTX1 level was independent of serum MKRN3 level, the possibility they might be involved in the progression of puberty or CPP remains. Further research is needed to determine their role in the hypothalamus.

Effectiveness of basal LH in monitoring central precocious puberty treatment in girls.

OBJECTIVES: Treatment of central precocious puberty (CPP) is based on administration of GnRH agonists in order to suppress hypothalamic-pituitary-gonadal axis and thus induce the stabilization or regression of pubertal development. Our aim was to determine whether the single basal serum LH and/or FSH concentration could be an effective tool to assess the efficacy of treatment to suppress activation of hypothalamic-pituitary axis. PATIENTS AND METHODS: Serum LH and FSH were measured before and after the GnRH injection, as well as E2 basal levels in 60 girls with documented idiopathic CPP at diagnosis and 18 and 30 months after the beginning of therapy. RESULTS: At diagnosis, peaks of >5 IU/L of LH and of FSH were observed in 100 and 91.6% of girls, respectively, with basal LH values of <1 IU/L in 70% and basal FSH levels of <1 IU/L in 10%. E2 were <20 pg/mL in 36.6%. After 18 months, a suppressed peak (i.e. <3 IU/L) was recorded in 85% of girls (p<0.01) for LH and in 98.3% for FSH (p<0.01). Basal LH <1 IU/L was detected in 85% (p<0.01) and basal FSH ≤1 IU/L in 40% (p<0.01). Serum E2 ≤20 pg/mL was recorded in 61.6% (p<0.01). After 30 months, all patients showed LH suppressed peak (p<0.01) and 98.3% suppressed FSH peak (p<0.01). 100% showed basal LH concentrations <1 IU/L (p<0.01) and 38.3% FSH basal values <1 UI/mL (p<0.01). E2 ≤20 pg/mL was observed in 32.72% (p=NS). CONCLUSIONS: Basal LH values are a reliable indicator of the efficacy of GnRHa therapy after 30 months of GnRHa therapy.

Puer barbatus: Precocious Puberty in Early Modern Medicine.

During early modernity, medico-legal concerns with timing puberty gave way to physiological and medical-hygienic concerns with pubertal timing. Sixteenth- and seventeenth-century medical-jurisprudential tracts isolated rare cases of conception before the legal marriage age. Scattered reports of "monstrously" early menarche and "prodigious" male puberty were offered from the latter half of the seventeenth century. Tied to excess heat, moisture, plethora and climate since antiquity, in the second half of the eighteenth century pubertal timing attracted sustained commentary regarding the purported role of social stressors, from novel-reading to diet and trousers. Both the known variability and strikingly outlying instances of pubertal timing thus provided an inroad to unravelling such perennial explanatory devices as temperament, constitution, and life style. Despite and in part because of its explanatory significance in early modern physiology, leading eighteenth-century nosologists did not yet itemize precocious puberty. One precocious boy described in the 1740s, the Willingham Prodigy, provided the best documented early medical and public response. Formal nosological interest followed by the 1760s, initially under Haller's heading of excessive growth (incrementum nimium, tied to enhanced circulation) and only much later under Meckel the Younger's heading of premature development (vorschnelle Entwicklung).

Role of Body Weight in the Onset and the Progression of Idiopathic Premature Pubarche.

BACKGROUND: The term premature pubarche (PP) refers to the appearance of pubic hair before age 8 in girls and before age 9 in boys. Although idiopathic PP (often associated with premature adrenarche) is considered an extreme variation from the norm, it may be an initial sign of persistent hyperandrogenism. Factors contributing to PP onset and progression have not been identified to date. AIMS: The objectives of this study are to describe a group of Italian children with PP, to identify potential factors for its onset, and to define its clinical and biochemical progression. METHODS: We retrospectively enrolled all infants born between 2001 and 2014 with PP. Children with advanced bone age (BA) underwent functional tests to determine the cause of PP. Hormonal analysis and BA determination were performed annually during a 4-year follow-up period. RESULTS: A total of 334 children with PP were identified: idiopathic PP (92.5%, associated with premature adrenarche in some cases); related to precocious puberty (6.6%); late-onset 21-hydroxylase deficiency (0.9%). Low birth weight was associated with premature adrenal activation. Body mass index (BMI) was the only factor that influenced the progression of BA during follow-up. CONCLUSIONS: Low birth weight is a predisposing factor for premature adrenal activation. The increase in BMI in patients with idiopathic PP during the 4-years of follow-up was responsible for BA acceleration. We recommend prevention of excessive weight gain in children with PP and strict adherence to follow-up in order to prevent serious metabolic consequences.

MKRN3 inhibits the reproductive axis through actions in kisspeptin-expressing neurons.

The identification of loss-of-function mutations in MKRN3 in patients with central precocious puberty in association with the decrease in MKRN3 expression in the medial basal hypothalamus of mice before the initiation of reproductive maturation suggests that MKRN3 is acting as a brake on gonadotropin-releasing hormone (GnRH) secretion during childhood. In the current study, we investigated the mechanism by which MKRN3 prevents premature manifestation of the pubertal process. We showed that, as in mice, MKRN3 expression is high in the hypothalamus of rats and nonhuman primates early in life, decreases as puberty approaches, and is independent of sex steroid hormones. We demonstrated that Mkrn3 is expressed in Kiss1 neurons of the mouse hypothalamic arcuate nucleus and that MKRN3 repressed promoter activity of human KISS1 and TAC3, 2 key stimulators of GnRH secretion. We further showed that MKRN3 has ubiquitinase activity, that this activity is reduced by MKRN3 mutations affecting the RING finger domain, and that these mutations compromised the ability of MKRN3 to repress KISS1 and TAC3 promoter activity. These results indicate that MKRN3 acts to prevent puberty initiation, at least in part, by repressing KISS1 and TAC3 transcription and that this action may involve an MKRN3-directed ubiquitination-mediated mechanism.

[Mothers' Experiences of Caring for Children with Precocious Puberty: A Q-Methodological Approach].

PURPOSE: This study explored experiences of mothers caring for children with precocious puberty. METHODS: Q-methodology was used for analyzing individual subjectivity. Seventy Q-statements were selected and scored by 50 participants on an 11-point scale. The collected data were analyzed using the PC QUANL program. RESULTS: The following eight types of care experiences of mothers of children with precocious puberty were identified: Type I-1: hypersensitive and best-result oriented, Type I-2: treatment burden, Type II-1: treatment-oriented, Type II-2: self-blame, Type III-1: accepting and compliant, Type III-2: treatment confused, Type IV-1: serious and engaged, and Type IV-2: naturalism-oriented. CONCLUSION: These results can help develop specific education programs based on types of care experiences for the promotion of care among mothers of children with precocious puberty.

Rapid progressive central precocious puberty: diagnostic and predictive value of basal sex hormone levels and pelvic ultrasound.

Objectives Data on the predictive values of parameters included in the diagnostic work-up for precocious puberty (PP) remain limited. We detected the diagnostic value of basal sex hormone levels, pelvic ultrasound parameters and bone age assessment for activation of the hypothalamic-pituitary-gonadal axis in girls with PP, in order to help in the decision to perform GnRH testing. Patients and methods We retrospectively considered 177 girls with PP. According to puberty evolution, the girls were divided into two groups: rapid progressive central precocious puberty (RP-CPP) and non/slowly progressive/transient forms (SP-PP). In all patients we considered Tanner stage, basal luteinizing hormone (LH) and estradiol (E2) values, bone age, and pelvis examination. We assessed the diagnostic value of each variable and identified the number of pathological parameters that best identify patients with RP-CPP. Results Basal LH ≥ 0.2IU/L, E2 level ≥ 50 pmol/L, uterine longitudinal diameter ≥ 3.5 cm, transverse uterine diameter ≥ 1.5 cm, endometrial echo and ovarian volume ≥ 2 cm3 were significantly associated with RP-CPP (p ≤ 0.01). The ability to diagnose RP-CPP was enhanced with increasing number of pathological hormonal and instrumental parameters (p < 0.001). With more than three parameters detected, sensitivity and specificity reached 58% (95%CI 48-67) and 85% (95%CI 74-92), respectively, with a PPV = 86% (95%CI 76-93) and PPN = 54% (95%CI 43-54); the area under the ROC curve was 0.71 (95%CI 0.65-0.78). Conclusion Despite the availability of different tests, diagnosing RP-CPP remains difficult. A diagnosis model including at least three hormonal and/or ultrasound parameters may serve as a useful preliminary step in selecting patients who require GnRH testing for early detection of RC-PP.

Long-term effects of GnRH agonist treatment on body mass index in girls with idiopathic central precocious puberty.

Introduction Studies evaluating effects of gonadotropin-releasing hormone agonist (GnRHa) on weight and body-mass-index (BMI) in girls with idiopathic central precocious puberty (iCPP) include short-term effects. The aim of this study is to investigate changes in BMI during and 2 years after completion of GnRHa to determine the factors that may impact BMI in girls with iCPP. Methods Medical files of 138 girls who completed GnRHa were evaluated. All patients had weight and height measurements at the beginning and end of treatment, and 111 patients had anthropometric measurements 2 years after the completion of treatment. Results In the beginning, 82 (59.4%) had normal weight (NW), 42 (30.4%) were overweight (OW), and 14 (10.2%) were obese (OB). Analysis of BMI-standard deviation score (SDS) in the whole group showed an overall increase during GnRHa treatment (0.92 ± 0.74 vs. 1.20 ± 0.51, p < 0.001). Changes in BMI-SDS (ΔBMI-SDS) during GnRHa differed between NW and OW/OB (0.45 ± 0.31 vs. 0.03 ± 0.20, p < 0.001). BMI-SDSs of both groups returned to baseline scores (or initial levels) 2 years after the completion of treatment. Two factors affecting ΔBMI-SDS in multiple linear regression analyses were baseline BMI and Δheight-SDS, both correlated negatively with ΔBMI-SDS. Conclusions The present study is one of the studies evaluating BMI change over a long period of time in girls with CPP. Although BMI-SDS increased during GnRHa in NW girls, it was reversible in follow-up after treatment. However, BMI-SDS did not change during and in follow-up in OW/OB girls. Conserving BMI-SDS in OW/OB girls may be related to the fact that weight management programs were recommended for these patients. Dietary recommendations should be provided for children with NW who undergo GnRHa, as is the case for OW patients.