Precocious Puberty Research Articles

Adrenocortical carcinoma (ACC) with massive liver metastases in a 4-year-old female patient: the significance of chemotherapy and imaging studies in treatment and diagnosis – a case report

Background: Adrenocortical carcinoma (ACC) is a retroperitoneal tumour, accounting for less than 0.2% of all malignancies in children. In pediatric patients, the most common clinical presentation is virilisation, either isolated or in combination with hypercortisolemia.
 Case report: A 4-year-old girl was admitted to the hospital for diagnostic evaluation of precocious puberty and features of hypercorticism. Ultrasonography revealed a heterogeneous neoplastic lesion between the left kidney and spleen. Computed tomography (CT) scan confirmed a pathological mass in the left adrenal region. The urine steroid profile was suggestive of adrenocortical carcinoma. The patient was qualified for surgery. Histopathological examination confirmed the diagnosis. A PET scan performed a few months later showed a metabolically active lesion in the left lobe of the liver. Due to the suspicion of a metastatic focus, it was proposed to implement systemic treatment, to which the patient's parents did not agree. After 15 months of no treatment and oncological follow-up, the girl was referred to the ED with symptoms of progression of the neoplastic process. In the face of a renewed lack of consent to the inclusion of treatment, the patient was referred to a home hospice, where she died a short time later.
 Conclusions: In the pediatric population, adrenocortical carcinoma is a rare neoplasm with a very poor prognosis. Prompt diagnosis enables early identification of the primary tumour and implementation of appropriate treatment. Imaging examinations are crucial in order to assess the size of the tumour, the extent of local invasion and the presence of potential metastases.

Clinical Management and Therapy of Precocious Puberty in the Sapienza University Pediatrics Hospital of Rome, Italy.

Puberty identifies the transition from childhood to adulthood. Precocious puberty is the onset of signs of pubertal development before age eight in girls and before age nine in boys, it has an incidence of 1/5000-1/10,000 with an F:M ratio ranging from 3:1 to 20:1. Precocious puberty can be divided into central, also known as gonadotropin-dependent precocious puberty or true precocious puberty, and peripheral, also recognized as gonadotropin-independent precocious puberty or precocious pseudopuberty. Thus, the main aim of this narrative report is to describe the standard clinical management and therapy of precocious puberty according to the experience and expertise of pediatricians and pediatric endocrinologists at Policlinico Umberto I, Sapienza University of Rome, Italy. In the suspicion of early sexual maturation, it is important to collect information regarding the age of onset, the speed of maturation of secondary sexual features, exposure to exogenous sex steroids and the presence of neurological symptoms. The objective examination, in addition to the evaluation of secondary sexual characteristics, must also include the evaluation of auxological parameters. Initial laboratory investigations should include serum gonadotropin levels (LH and FSH) and serum levels of the sex steroids. Brain MRI should be performed as indicated by the 2009 Consensus Statement in all boys regardless of chronological age and in all girls with onset of pubertal signs before 6 years of age. The gold standard in the treatment of central precocious puberty is represented by GnRH analogs, whereas, as far as peripheral forms are concerned, the triggering cause must be identified and treated. At the moment there are no reliable data establishing the criteria for discontinuation of GnRH analog therapy. However, numerous pieces of evidence suggest that the therapy should be suspended at the physiological age at which puberty occurs.

The effect of cognitive behavioral therapy on stress and anxiety of mothers of girls with precocious puberty symptoms: a randomized controlled trial

Introduction: Precocious puberty in girls has been associated with an increased risk of stress and anxiety in their mothers. This study aimed to investigate the effect of cognitive behavioral therapy (CBT) on perceived stress and anxiety of mothers of girls with precocious puberty symptoms.MethodsThis randomized controlled trial was conducted on 70 mothers of girls with precocious puberty symptoms in Tabriz-Iran, 2021. The participants were randomly assigned to CBT and control groups through blocked randomization. Group counseling was provided to the intervention group in eight sessions of 45–60 min weekly with 5 to 7 women. A booklet containing explanations about puberty was provided for the both groups. Data were collected using the questionnaires of socio-demographic characteristics, Spielberger State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS) and quality of life (SF-36). Independent t-test, ANCOVA, chi-square, and fisher’s exact tests were used to compare the outcomes between the groups.Findings: After the intervention, based on ANCOVA test with adjusting the baseline values, mean scores of stress (mean difference (MD): -10.75; 95% confidence interval (95% CI): -11.77 to -9.72; P < 0.001), state anxiety (MD: -14.36; 95% CI: -15.7 to -12.7; P < 0.001) and trait anxiety (MD: -12.8; 95% CI: -14.4 to -11.1; P < 0.001) were significantly lower in CBT group compared to the control group. Also mean score of quality of life (MD: 9.82; 95% CI: -6.74 to -12.90; P < 0.001) was significantly higher in CBT group compared to the control group.ConclusionBased on the results, group CBT is effective in reducing stress and anxiety and improving the quality of life of mothers of girls with precocious puberty symptoms. However, more studies are required to make a definite conclusion in this field.Trial registrationIranian Registry of Clinical Trials (IRCT): IRCT20110826007418N6. Date of registration: 11/10/2021. URL: https://en.irct.ir/trial/57346; Date of first registration: 11/10/2021.

A toddler with testosterone: where did it come from?

Precocious development of secondary sexual characters not involving pulsatile gonadotropin secretion is known as gonadotropin independent precocious puberty or peripheral precocious puberty (PPP). This form of sexual precocity in males can occur due to gonadal, adrenal, or other testosterone secreting tumors (teratomas, hepatomas, and choriocarcinomas), untreated congenital adrenal hyperplasia, testotoxicosis, and familial male limited precocious puberty. We report a case of a 2-year-old boy with PPP caused due to hepatoblastoma. Complete surgical resection of the tumor was done, and the child received cisplatin chemotherapy.

Precocious puberty – Are children maturing more rapidly?

Precocious puberty – Are children maturing more rapidly?

Alterations in Appetite-Regulating Hormones in Girls with Central Early or Precocious Puberty.

The prevalence of central precocious puberty (CPP) in girls has increased worldwide and is often associated with obesity in childhood as well as high fat/high glycemic index diets. Evidence suggests that subjects with obesity present with alterations in appetite-regulating hormones. The arcuate and paraventricular nuclei of the hypothalamus are the centers of action of appetite hormones, as well as the location of gonadotropin-releasing hormone (GnRH) neurons, the activation of which results in the onset of puberty. This anatomical proximity raises the question of possible alterations in appetite-regulating hormones in patients with CPP. Furthermore, diet-induced hypothalamic inflammation constitutes a probable mechanism of the pathophysiology of CPP, as well as alterations in appetite-regulating hormones in young children. In this article, we summarize the evidence investigating whether girls with CPP present with alterations in appetite-regulating hormones. We present evidence that leptin concentrations are elevated in girls with CPP, ghrelin concentrations are lower in girls with CPP, nesfatin-1 and orexin-A concentrations are elevated among girls with premature thelarche, and insulin concentrations are increased in girls with early menarche.

Characterization of Puberty in an Australian Population-Based Cohort Study

PurposeCurrent knowledge of the characteristics of puberty beyond age at menarche and thelarche is limited, particularly within population-based cohorts. Secular trends and concerns of the health effects of early puberty reinforce the value of contemporary studies characterizing the timing, tempo, duration, and synchronicity of puberty. MethodsThe Childhood to Adolescence Transition Study is a unique Australian cohort of individuals followed annually from late childhood to late adolescence, with up to eight assessments of pubertal stage from 9 to 19 years of age (N = 1,183; 636 females). At each assessment, females reported their Tanner Stage of breast and pubic hair development, while males reported on genital/pubic hair development. Nonlinear mixed-effects models characterized pubertal trajectories and were used to derive each individual’s estimates of timing, tempo, and synchronicity. Parametric survival models were used to estimate the overall duration of puberty. ResultsTiming of mid-puberty (Tanner Stage 3) ranged from 12.5 to 13.5 years, with females developing approximately 6 months before males. Pubertal tempo (at mid-puberty) was similar across sex (between half and one Tanner Stage per year), but the overall duration of puberty was slightly shorter in males. Most females exhibited asynchronous changes of breast and pubic hair development. DiscussionEstimates of pubertal timing and tempo are consistent with reports of cohorts from two or more decades ago, suggesting stabilization of certain pubertal characteristics in predominantly White populations. However, our understanding of the duration of puberty and individual differences in pubertal characteristics (e.g., synchronicity of physical changes) remains limited.

SAT398 Pubertal Status And Trends In Gender Affirming Treatment Of Transgender And Gender Diverse Youth

Abstract Disclosure: C. Lin: None. M. Oransky: None. R. Fader: None. N.R. Malhotra: None. E.M. Baldiserroto: None. C.J. Romero: None. J.D. Safer: None. M. Yau: None. Background: Transgender and gender diverse (TGD) youth seek care to affirm their gender identities and improve quality of life and mental health. Gender affirming care of youth includes pubertal assessment, pubertal suppression with gonadotropin-releasing hormone agonist (GnRHa) and gender-affirming hormone therapy (GAHT). Management choices are made collaboratively among the patient, the patient’s family, and the multidisciplinary treatment team. Objective: We sought to characterize the pubertal status of the TGD youth to consider medical intervention. Method: The medical records of 58 TGD youth referred to pediatric endocrinology from 2020-2022 were retrospectively analyzed. Pubertal assessments were made by visualization of pubic hair and breast development according to the Tanner scale and determination of testicular volume with an orchidometer. We labeled Tanner stage 1 as prepuberty; stages 2-3 as early puberty; and stages 4-5 as late puberty. Results: The median age was 15 years (range 8-18 years). 46.6% were trans girls (n=27), 44.8% were trans boys (n=26), and 8.6% were non-binary (n=1 natal male and n=4 natal female). Of the trans girls, 7.4% were prepubertal (n=2), 51.9% were in early puberty (n =14), and 40.7% were in late puberty (n=11). Of the trans boys, none were prepubertal, 3.6% were in early puberty (n=1), and 96.4% were in late puberty (n=25). Of the non-binary youth, 20% were in early puberty (n=1) and 80% were in late puberty (n=4).For the prepubertal patients, monitoring for onset of puberty without treatment was recommended. Of the 15 patients in early puberty, 73.3% started GnRHa (10 trans girls, 1 trans boy) and 26.7% started GAHT (4 trans girls). Of the 36 patients in late puberty, 2.8% received no treatment (1 trans boy), 25.0% started GnRHa (7 trans girls, 2 trans boys) and 72.2% started GAHT (4 trans girl, 22 trans boy). Of the 5 non-binary patients, 1 patient in early puberty (1 natal female) was treated with GnRHa, and 4 were in late puberty and initiated on GAHT (1 natal male, 3 natal female). Conclusion: In our multidisciplinary practice, trans feminine patients are evenly divided between those who present in early and late puberty. This presents possible implications for fertility preservation strategies. Trans masculine patients overwhelmingly present in late puberty, perhaps owing in part to earlier timing for typical “female” puberty. This means that even prompt initiation of GnRHa therapy cannot entirely prevent the potential future need for chest masculinization surgery. Presentation: Saturday, June 17, 2023

THU197 Peripheral Precocious Puberty In A 6-year-old Girl With Extreme Estradiol Elevation With Rapid Normalization: A Case Report

Abstract Disclosure: L. Meller: None. M. Marinkovic: None. M.E. Patterson: None. Background: Peripheral precocious puberty (PPP) in girls is typically associated with ovarian or adrenal tumors, ovarian cysts, McCune-Albright syndrome (MAS), or exogenous hormone exposure. We present an unusual case of PPP with extreme estradiol elevation and rapid normalization. Clinical Case: A 6.5-year-old previously healthy girl presented with two-month history of bilateral breast growth and tenderness, associated with daily cramping. Subsequently, she developed clear, odorless vaginal discharge. Two days prior to the visit she started light vaginal bleeding. Parents denied any medication intake or use of lavender or essential oils. She had no family history of early puberty. On the exam, she was tall for her age (95%) with a recent growth spurt. She had breast buds (Tanner 2) and vaginal bleeding without pubic hair (Tanner 1) or signs of hyperandrogenemia. There were no skin lesions or gross bone abnormalities. Bone age was equal to chronological age. She had an extreme elevation of estradiol of 156pg/mL and 170pg/mL (reference range&amp;lt;=16pg/mL) measured two weeks apart with prepubertal LH/FSH. Thyroid tests were normal. Pelvic ultrasound and abdomen/pelvis CT showed no abnormalities of ovaries and adrenal glands. Nine days after the onset, vaginal bleeding and cramping spontaneously resolved. Estradiol levels measured two days after cessation of vaginal bleeding normalized (7pg/mL) while LH/FSH remained prepubertal. Interestingly, two weeks after the bleeding stopped her pelvic ultrasound showed significantly enlarged ovaries (R 4.1mL, L 4.3mL), while her estradiol remained normal (5pg/mL). Conclusion: We describe an unusual presentation of PPP in a young girl with extreme estradiol elevation causing simultaneous premature breast development and vaginal bleeding. We suspect PPP was secondary to ruptured ovarian cyst that was not captured by imaging. Other differentials include MAS, exogenous hormone exposure, adrenal or ovarian tumors. These were unlikely due to lack of abnormal skin or bone findings, environmental hormone exposure and normal imaging. Her ovarian enlargement could be secondary to high endogenous estrogen exposure, and she may be at risk of developing central precocious puberty. This unique case emphasizes the importance of prompt assessment of children with precocious puberty and discusses the differential diagnosis process for PPP with markedly elevated estradiol with rapid normalization. Presentation: Thursday, June 15, 2023

SAT442 Increased Prevalence Of Precocious Puberty: What Is The Influence Of Endocrine Disruptors?

Abstract Disclosure: D.M. Bastos: None. J.F. Bastos: None. A.F. Bastos: None. Central precocious puberty (CPP) is defined by the onset of the pubertal process before 8 years old in girls and 9 years old in boys. Its main form is idiopathic, and its etiology is still unknown. Thus, several studies point to possible causative factors, from gestational age at birth to hormonal disruptors. Therefore, this work aims to collect the prevalence for the evaluation of the childrens profile who have this pathology in a private clinic in Brasília. Methodology: This is a retrospective and observational study that aims to evaluate the prevalence and analysis of the medical records of children with precocious puberty in a pediatric endocrinology clinic in the Federal District between 2020 and 2021. The medical records of children with genetic syndromes were excluded. Biological, family, nutritional variables and complementary exams were analyzed. Results: The following main characteristics were identified: higher prevalence in girls (90.6%), 23% had a body weight greater than expected for their age, the majority (80.3%) were diagnosed between 8 and 12 years and a difference of 6.7 centimeters was observed between target height and predicted final height according to bone age. Conclusion: The study concluded that among the patients with CPP, the majority were girls and almost quarter of the childrens were obese or overweight. A difference of almost 7 centimeters was found between the predicted final height and the target height of these patients, showing the need for investigation and early diagnosis of this condition. Presentation: Saturday, June 17, 2023

THU227 Isosexual Peudo-precocious Puberty Due To Leydig Cell Tumor In A Prepubertal Child

Abstract Disclosure: M. Baby: None. A. Xu: None. N. Shacham: None. E. Shapiro: None. B.C. Shah: None. Background: Testicular tumors account for 2-4% of all childhood cancers. Leydig cell tumors are the most common form of sex cord stromal tumors and represent 1-3% of all testicular tumors. In the pediatric population, testicular Leydig cell tumors present with signs of precocious puberty. Workup reveals low gonadotropins with elevated testosterone and testicular mass on ultrasound. Treatment involves surgical enucleation (partial orchiectomy) in most cases. Clinical case: We present the case of a 4 year 10 month old male who presented to endocrine clinic for precocious puberty. He developed pubic hair three months prior with body odor. He did not have any CNS symptoms including headaches or visual changes. There was no use of exogenous androgens at home. He was born full term, small for gestational age with an uncomplicated postnatal course. There was no family history of precocious puberty. Height was at the 99th percentile (z-score 2.7), weight 98th percentile (z-score 2.07), and BMI 86th percentile (z-score 1.09). On exam, he was lean and appeared muscular. His testes were asymmetrical with the right testicle measuring 3 ml and the left testicle 2 ml. Scrotal hair was curly and sparse, Tanner III. Stretched penile length was 7 cm (90th percentile), width was 3.2 cm. Results: Bone age was advanced to 10 year 0 months with height age of 7 year 3 months. Serum gonadotropins were low, testosterone was pubertal at 115 ng/dl (Electrochemiluminescence Immunoassay). Serum 17-hydroxyprogesterone (221 ng/dl, ref range 0-90 ng/dl) androstenedione (163 ng/dl, ref range = &amp;lt; 51 ng/dl), and IGF-1 (368 ng/ml, ref range 108 – 293 ng/ml) were elevated. ACTH, cortisol, thyroid profile, and prolactin were normal. Beta-HCG and AFP were negative. ACTH stimulation test showed normal response. Testicular ultrasound with doppler was performed; right testicle measured 1.82 x 1.06 x 1.36 cm, volume of 1.4 ml, while left measured 1.27 x 0.72 x 0.87 cm, 0.4 ml. Within the right testicle, there was a mass that was hypoechoic, vascular (with a testicular artery feeding branch in the periphery), multinodular and measured 1.2 x 0.8 x 1.10 cm (0.53 ml). He was referred to urology and underwent enucleation of the right testicular mass through an inguinal approach. Grossly, the mass appeared tan and lobulated and surgical pathology confirmed a benign Leydig cell tumor. The patient recovered well and post-operative serum testosterone level at 2 weeks was &amp;lt;2.5 ng/dl. Conclusion: We present a case of a testicular Leydig cell tumor that presented as peripheral precocious puberty marked by low gonadotropins and elevated testosterone with ultrasound findings of a vascular mass with testicular artery feeding branch in the periphery. Early detection of a Leydig cell tumor is crucial as it can be treated by enucleation thus salvaging the testes. Presentation: Thursday, June 15, 2023

THU202 Peripheral Precocious Puberty In A 7-year-old Female As A Result Of Exposure To Bath Bombs

Abstract Disclosure: C.C. Gordner: None. Introduction: Recent studies have demonstrated a progressive decrease in the age of onset of puberty in children. Endocrine disrupters are increasingly being identified as an important contributing factor to this shift in pubertal timing. We present here a case of peripheral precocious puberty in a 7-year-old female after a brief intense exposure to bath bombs. Clinical Case: A healthy pre-pubertal 7-year-old female used daily bath bombs for 7 days. She developed tender Tanner II breast buds the following week with no other pubertal or adrenarchal signs. Growth chart review revealed stable linear growth without growth acceleration. Bone age x-ray was consistent with chronologic age (CA 7y0m, BA 6y10m). LH, ECL, was 0.058 miU/mL (ref: 0.02-0.3), Estradiol, LCMS, was 2.0 pg/mL (ref &amp;lt; 15), DHEA-Sulfate, LCMS, was 45 mcg/dL (ref: 6-7y: &amp;lt; 72). The breast buds started to resolve after 2 months and were completely gone after 3 months from the initial exposure. Clinical Lessons: Endocrine-disrupting chemicals are found in pesticides, plasticizers, lavender, fennel, and tea tree oils and can lead to precocious puberty, delayed puberty, and/or impact sexual differentiation. Consumer products are often not well labeled to identify these chemicals and often use confusing terminology like “all-natural” and “organic” which can be misleading. Conclusions: Bath bombs should now be added to the growing list of consumer products associated with precocious puberty. Leaders should advocate for better labeling of consumer products to help identify potentially harmful products. Presentation: Thursday, June 15, 2023

THU452 Polyostotic Fibrous Dysplasia Complicated By Aneurysmal Bone Cyst In A Patient With McCune-Albright Syndrome

Abstract Disclosure: E. Milazzo: None. K.L. Hermayer: None. Introduction: McCune-Albright Syndrome (MAS) is a rare mosaic disorder with GNAS mutations, encoding the alpha-subunit of the Gs G-coupled protein receptor, activating it, and inappropriately producing cAMP. The hyperfunctioning endocrinopathies associated with MAS are due to signaling through the TSH, LH, FSH, GHRH, and ACTH receptors. MAS clinical presentation occurs with café-au-lait skin macules, precocious puberty, and fibrous dysplasia (FD) of the bone. FD is a benign tumor that leads to increased rates of bone fractures and if it causes facial deformities, can be complicated with orbital neuropathies. An aneurysmal bone cyst (ABC) is a blood-filled cyst that can be a primary or secondary lesion due to co-existing lesions. ABC is a rare complication of FD. We report a rare case of ABC in a MAS patient who presented with acute visual disturbance and enlargement of the forehead and was successfully treated with surgery. Clinical Case: A 20-year-old female diagnosed with MAS at the age of 2 who had precocious puberty by the 3rd year of life and developed polyostotic FD in the right arm, left femur, cranial, and skull bones with multiple long bone fractures by the age of 5-6 and required numerous orthopedic surgeries. She presented with the characteristic café-au-lait skin macules on the back and right arm. In 2018, a slow decline of left eye vision required left cranial decompression of the optic nerve, with pathology showing fibrous tissue compatible with FD. In 2021, she complained of acute right forehead enlargement, compressing her right eye with blurry vision. An MRI showed FD involving the facial and skull bones with a new expansible lesion in the right frontal bone with internal layering fluid, exerting a mild mass effect on the frontal lobe and extending superiorly to the orbit with inferior displacement of the globe. These findings were consistent with an ABC. Right frontal craniectomy and cranioplasty were performed in 12/2021, with pathology showing a fibrous pseudocyst wall with associated lymphoplasmacytic inflammation and evidence of prior hemorrhage with Ki-67 in the cyst wall at 15%. Lab work showed chronic alkaline phosphatase elevation at 567IU/L (42-106IU/L), normal calcium at 9.2mg/dl (8.4-10.3mg/dl), phosphate at 3.3mg/dl (3.3-5.1mg/dl), and PTH at 26pg/ml (15-65mg/dl), with Vitamin D insufficiency at 25.1ng/ml (30-100ng/ml). Endocrinology workup was negative for thyroid, adrenal, gonadotrophic, and GH dysfunction. 5 months post-surgery, the patient demonstrated complete recovery, and MRI showed no recurrence of the ABC. Conclusion: ABC is a benign solitary tumor generally arising from the metaphysis of long bones and rarely involves the cranium. ABC associated with FD has only been reported in a few cases. The treatment is surgical excision, with radiation and cryotherapy used in nonorbital cases. Presentation: Thursday, June 15, 2023

THU190 Deletion Of The Glucocorticoid Receptor From GABAergic Neurons Causes Early Puberty In Male And Female Mice

Abstract Disclosure: S.A. Pereira: None. L. Arvizu-Sanchez: None. A.N. Fontes: None. R.S. Carroll: None. V.M. Navarro: None. U.B. Kaiser: None. Background and Objectives: Glucocorticoid (GC) secretion induced by various types of stress can negatively impact reproduction through effects at several levels of the hypothalamic-pituitary-gonadal (HPG) axis, including inhibition of gonadotrophin-releasing hormone (GnRH) secretion and suppression of luteinizing hormone (LH) release. KNDy neurons, expressing kisspeptin, neurokinin B and dynorphin A, are the GnRH and LH pulse generator and are key regulators of puberty. These neurons are proposed to play an important role in mediating the effects of stress and GC on reproduction. While the precise mechanisms by which stress affects regulation of KNDy neurons remain to be fully characterized, it is known that KNDy neurons are subject to regulation by multiple neural networks, among which GABAergic neurons appear to play a determinant role. Importantly, a large proportion of GABAergic neurons express glucocorticoid receptors (GR). We therefore hypothesized that stress, through the action of GC on GR in GABAergic neurons, affects the activity of KNDy neurons to impact puberty timing. Methods and Results: We generated mice with conditional deletion of GR in GABAergic neurons using VgatCre mice crossed with GRlox/lox mice to generate VgatCre;GRlox/lox mice (GABAGRKO). The pubertal phenotypes of these GABAGRKO mice and their littermate controls (GRlox/lox) were characterized. Male GABAGRKO mice had earlier preputial separation compared to GRlox/lox littermate controls (GABAGRKO 29.8 ± 0.45 days vs. GRlox/lox 33.5 ± 0.57 days; p &amp;lt; 0.0001). Female GABAGRKO mice had a similar age of vaginal opening (GABAGRKO 25.7 ± 0.76 days vs GRlox/lox 24.5 ± 0.87 days; p = 0.2810) but had significantly earlier first estrus compared to their GRlox/lox littermate controls (GABAGRKO 32.4 ± 0.76 days vs GRlox/lox 37.9 ± 0.79 days; p &amp;lt; 0.0001). Male and female mice were euthanized at 30 days of age and their mediobasal hypothalamus (MBH) were collected for mRNA measurement by RT-qPCR of genes known to be related to pubertal development, including Kiss1, Tac2, Pdyn, Agrp and Pomc. Kiss1 and Pdyn expression were significantly higher in the MBH of GABAGRKO males compared to controls; in contrast, Pdyn expression was significantly lower in the MBH of GABAGRKO females and Kiss1 expression was unchanged compared to controls. Agrp expression was lower in the MBH of both GABAGRKO male and female mice compared to controls. No differences were observed in Tac2 and Pomc expression. Data sets are mean ± SEM. Statistical significance was considered at p &amp;lt; 0.05. Conclusions: The deletion of GR in GABAergic neurons results in early puberty onset, sexually dimorphic changes in Pdyn mRNA levels and downregulation of Agrp mRNA expression in male and female GABAGRKO mice. These findings suggest a role of glucocorticoids acting on GR in GABAergic neurons upstream of KNDy neurons to restrain the timing of their activation to initiate puberty. Presentation: Thursday, June 15, 2023

THU196 Insulin-like Growth Factor-1 As A Screening Tool For Central Precocious Puberty

Abstract Disclosure: L. Chung: None. M. Im: None. Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard test for diagnosing central precocious puberty (CPP), which needs time and effort to perform. Recently, many studies confirmed that Insulin-like growth factor-1 (IGF-1) is involved in the initiation and progression of puberty. With this inspection, we assumed that the IGF-1 level might be correlated with the pubertal stage in central precocious puberty. This study aimed to investigate the value of IGF-1 levels in screening central precocious puberty. The medical records of 359 patients with a chief complaint of premature breast development and visited the pediatric endocrinology clinic in Myongji Hospital from January 2017 to October 2022 were reviewed. Two hundred thirty-three girls with central precocious puberty (CPP) and 126 girls with premature thelarche (PT) diagnosed were enrolled. Each subject had IGF-1 and GnRH stimulation test results. The anthropometric data between CPP and PT showed no statistical differences except for weight and the existence of lipomastia. The hormonal indicators including peak luteinizing hormone (peak LH), peak follicular stimulating hormone (peak FSH), and estradiol were statistically different between the two groups (P &amp;lt; 0.001). IGF-1 levels were significantly higher in CPP group than in PT group. The IGF-1 levels were positively correlated with peak LH, the diagnostic indicator of CPP. The area under the curve (AUC) of IGF-1 was 0.709. IGF-1 levels were correlated with the diagnostic indicator of CPP. IGF-1 would be a useful tool for screening CPP. Keywords: girls; IGF-1; GnRH stimulation test; precocious puberty. Presentation: Thursday, June 15, 2023

THU198 Peripheral Precocious Puberty In Girls Due To Ovarian Cyst

Abstract Disclosure: H. Lee: None. J. Hwang: None. Y. Shim: None. S. Heo: None. Objective: Peripheral precocious puberty (PPP) is precocious development of secondary sexual characteristics caused by mechanisms that do not involve activation of pulsatile GnRH secretion. PPP in girl is less frequent than central precocious puberty (CPP). it is caused by various disease such as gonadal and adrenal tumors, ovarian cysts, hypothyroidism and exposure to exogenous sex steroids. In particular, discordant pubertal development with vaginal bleeding within one year of breast development suggests hyperestrogenic state, and may be caused by autonomous ovarian cysts, McCune-Albright syndrome (MAS) and hypothyroidism. We aimed to investigate clinical characteristics and long-term clinical course of PPP in girls with ovarian cyst. Methods: This study was conducted through a retrospective medical record analysis. We studied 12 patients who were diagnosed with PPP due to ovarian cyst after pelvic sonography from January 2003 to May 2022. Patients were examined for pelvic sonography when there was vaginal bleeding and/or nipple pigmentation in PPP. pelvic sonography findings, clinical characteristics, management and prognosis of patients with ovarian cysts were investigated. Results: Ten out of 12 cases had vaginal bleeding and the 3 cases had nipple pigmentation. E2 was elevated to median value 36 pg/mL ([IQR], 19-61). There was a total of 18 episodes of ovarian cyst including recurrence. The median size of cyst was 28 mm ([IQR], 24- 34). Surgical management was performed in one patient with large cyst of 70 mm. Aromatase inhibitor was used in three cases. Follow-up pelvic sonography was performed to confirm regression of ovarian cyst. Median time to regression of ovarian cyst was 6 months ([IQR], 3-9). Five cases were diagnosed with MAS. Later, In 4 out of 12 cases were progressed to CPP and cyst was recurred more than 2 episodes in 3 cases. Median total follow-up duration of cases was 2.5 years ([IQR], 0.9-5.3). Conclusion: Most of ovarian cysts in PPP disappear spontaneously. However, It may appear as a one of findings with MAS or can progress to CPP in recurrent case. Therefore, careful follow-up is necessary in ovarian cysts of PPP. Presentation: Thursday, June 15, 2023

THU205 A Case Of Infant With Familial-Male Limited Precocious Puberty (FMPP) Inherited From Father Due To An Activating Mutation Of The Luteinizing Hormone/Chorionic Gonadotropin Receptor Gene

Abstract Disclosure: H. Yoo: None. J. Ha: None. M. Jung: None. Y. Choi: None. E. Yoo: None. We present an extremely rare case of FMPP with an activating mutation of the LHCGR gene in a Korean infant. A 16-month-old-boy was brought to the out-patient clinic with complaints of pubic hair, acne and rapid growth acceleration. His father had become aware of the symptoms 4 month before. His grandfather and father had a family history of precocious puberty and profound short stature (Height of grandfather and father: 148 cm and 158 cm respectively). At physical examination, his height was 83 cm (+1.2 SDS) and his weight was 14.3 kg (+2.8 SDS). The testicular volume was 2 mL and pubic hair was appropriate for Tanner stage 2. Stretched penile length was 7 cm (&amp;gt;2 SDS). He did not have any café au lait spots or hyperpigmentation. His bone age was significantly advanced to that of a 4 year old. Laboratory findings showed abnormally elevated serum testosterone (5.74 ng/mL) and slightly elevated α-fetoprotein (14.1 ng/ml; reference 0-10 ng/mL) with suppressed LH level (&amp;lt;0.07 mIU/mL). Serum levels of β-human chorionic gonadotropin, cortisol, 17-hydroxyprogesterone, androstenedione and dehydroepiandrosterone sulfate were within normal range. A gonadotropin releasing hormone (GnRH) stimulation test revealed a prepubertal response(peak LH 0.52). Brain magnetic resonance imaging study was reported to be normal. Ultrasound of the scrotum and adrenal gland were both normal. Due to the patient’s classic presentation and his family history of male-limited precocious puberty, a genetic analysis for LHCGR gene was performed. Molecular genetic analysis identified a pathogenic variant of LHCGR (c.1730 C&amp;gt;T, p.Thr577Ileu), which was previously reported in a FMPP patient. His father and paternal grand father also carry the same mutation. Anti-androgen treatment with bicalutamide (25mg/day) and aromatase inhibition with anastrozole (1mg/day) were initiated. After treatment, there was improvement in pubertal progression, accelerated growth velocity and rate of skeletal maturation without any specific side effects. Presentation: Thursday, June 15, 2023

THU194 Growth Pattern And Related Predictors Of Gonadotropin-releasing Hormone Analog Treatment In Girls With Precocious Puberty

Abstract Disclosure: L. Ouyang: None. F. Yang: None. Purpose: The purpose of this study was to analyze the height growth pattern during gonadotropin-releasing hormone analog (GnRHa) treatment in girls with central precocious puberty (CPP) and early and fast puberty (EFP), calculate the incidence of prominent height deceleration and explore the relevant predictors of prominent height deceleration, which may provide useful information for the application of GnRHa as treatement and other adjunctive treatments such as growth hormone (GH). Methods: Ninety-nine girls diagnosed with CPP and 47 girls with EFP were enrolled in this retrospective analysis, they were treated with GnRHa from 6 months to 2 years. Clinical indicators such as hormone levels, bone age (BA), and B-ultrasound indicators were included and shown every 6 months. The growth velocity (GV) of height and the change of height standard deviation score (SDS) were shown every 6 months and once a year. The incidence of height deceleration was calculated in both the first and second years of GnRHa treatment. Multivariate logistic regression analysis was used to explore the predictive indicators of height deceleration. Results: There was a statistically significant difference between girls with CPP and EFP in physical growth indicators, hormone levels, BA, BA advancement, and B-ultrasound indicators at the time of diagnosis (P &amp;lt; 0.05); however, these statistical differences gradually disappeared as treatment progressed. The treatment of GnRHa decreases the GV, BA, and levels of hormones in girls with CPP and EFP. The GV during GnRHa treatment in two groups reached a trough at 18 months, followed by a gradual rebound, but the rebound was significantly greater in CPP than in girls with EFP. The GV of girls with CPP was higher than that of girls with EFP, and the decrease in height-SDS of girls with EFP was more than girls with CPP during the entire of GnRHa treatment. The incidence of growth deceleration in CPP in the first and second year of treatment was 17.35% (17/98) and 42.86% (24/56), and EFP was 25.53% (12/47) and 76.92% (10/13), respectively. No significant indicators predicted the occurrence of growth deceleration (P&amp;lt;0.05). Conclusions: GnRHa is effective in slowing the GV of height, the maturation of BA, and hormone levels in patients with precocious puberty, and the treatment time of 2 years or more can lead to an adult height benefit. The girls with EFP seem to suffer more damage in GV, which might affect AH, so the use of GnRHa in treating EFP should be done with more caution than in CPP. An adequate period of observation in CPP is needed before adjunctive treatments such as GH are used due to the height ascent in the later stage of treatment (18 months to 24 months). None of the factors we studied predicted the incidence of height deceleration during the period of GnRHa treatment. Presentation: Thursday, June 15, 2023

THU200 Three Cases Of Prepubertal Vaginal Bleeding

Abstract Disclosure: H. Doi: None. M. Igarashi: None. T. Kashima: None. N. Ujita: None. H. Konno: None. A. Fujioka: None. H. Miyagi: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None. Introduction: Children with prepubertal vaginal bleeding (PVB) are usually referred to pediatric endocrinologists, because precocious puberty is one of the important causes of PVB. However, the diagnosis remains challenging due to a wide variety of causative diseases beyond endocrinological disorders. We present three illustrative cases of children with PVB in our institution. Case presentations: Case 1. A 2-year-old girl had suppressed serum LH and FSH levels and elevated estradiol level. She had café-au-lait spots with jagged “coast of Maine” borders on her left chest and back. Her bone X ray showed multiple fibrous dysplasia. The diagnosis of McCune-Albright syndrome was made by a triad of skin, bone and hyperfunctioning endocrinopathy. Case 2. A 5-year-old girl had low serum LH, FSH, and estradiol levels. Her pelvic MRI showed a mass in her vagina and contrast enhancement of the vaginal membrane. Although some malignant tumor had been suspected, vaginal observation using cystoscopy revealed a foreign body of a sponge that seemed to be part of a toy. Her vaginal bleeding disappeared after removal. Our multidisciplinary team concluded that this case was not child abuse. Case 3. A 4-year-old girl had been misdiagnosed as central precocious puberty due to slightly elevated gonadotropin levels. She was referred to our hospital because gonadal suppression therapy with leuprorelin didn’t stop her PVB. Although the observation of her urethra, bladder, vagina, and uterus using cystoscopy revealed no abnormal findings, a small fistula on the membrane of her vaginal opening was noted. Finally, the diagnosis of von Willebrand’s disease type I was made by low level of von Willebrand factor. We speculated that her repeated bleeding was triggered by minor trauma with the background of bleeding tendency. When severe bleeding occurs or is expected to occur, factor VIII containing von Willebrand factor should be administered. Discussion: There are various etiologies of PVB. Detailed history taking and physical examination are quite important, but might be difficult for young pediatric patients. Neoplasms and sexual abuse must be ruled out. In case of suspicion of abuse, the patient’s safety should be guaranteed. Inspection using cystoscopy under general anesthesia is a useful option in recurrent PVB cases. It is critical to make the correct diagnosis because the treatments can be totally different. Conclusion: In PVB cases we need to perform detailed assessments including careful history taking, physical examination and necessary testing considering a broad range of possible diseases. Presentation: Thursday, June 15, 2023

FRI243 Hypertension And Virilization In A 4 Year Old Female

Abstract Disclosure: E. Ismail: None. J.L. Miller: None. A.V. Bernier: None. Background: Congenital adrenal hyperplasia (CAH) is the most common cause of virilization of an XX female neonate. More than 95% of CAH cases are due to 21 hydroxylase deficiency which is detected in the newborn screen by detection of elevated 17 hydroxyprogesterone (17 OHP). 11 beta hydroxylase deficiency (11 BOHD) is the second most common cause of CAH, but considered extremely rare accounting for only 0.2-8% of cases. 11-BOHD is not part of the newborn screen, as it does not present with life-threatening salt wasting crisis. Hypertension (HTN) is observed in 2/3 of cases and is due to mineralocorticoid excess in the form of deoxycorticosterone (DOC). Therefore, 11-BOHD should be strongly considered in a virilized female with HTN and accelerated growth. Clinical case: 4-year-old female admitted for evaluation of severe persistent HTN. She had surgical repair of posterior labial fusion at 5 months of age. She was seen at 21 months of age for concerns of precocious puberty and virilization. Her work up included XX karyotype, 17 OHP and electrolytes within normal limits, however, she had an elevated DHEAS and testosterone level, with a bone age of 5 years at 21 months of age. Hypertension was recorded at the visit, but she was lost to follow up. At a primary care appointment her blood pressure was notably elevated, so she was sent to the ED. On admission, she was found to have both weight and height &amp;gt;99% for age, hyperpigmentation of gums and scars, and virilization (clitoromegaly with tanner 3 pubic hair). She had no thelarche. Initial hormonal evaluation revealed prepubertal gonadotropins, low aldosterone and low plasma renin activity. High dose ACTH stimulation test revealed elevated 11 deoxycortisol and 11 deoxycorticosterone levels. Her peak stimulated cortisol was inadequate at 8.7 mcg/dl (normal=&amp;gt;18 mcg/dl). Genetic testing for CAH revealed compound heterozygosity for 2 variants in the CYP11B1 gene, confirming the diagnosis of 11-BOHD. She was started on hydrocortisone replacement (12 mg/m2/day) and required spironolactone to achieve adequate blood pressure control. At the time of diagnosis, her father reported that he also had hypertension before 10 years of age, as well as early puberty, and significantly darker skin color than his family members. Conclusions: The HTN seen with 11-OHD is associated with suppressed aldosterone/renin activity and hypokalemia and is responsive to glucocorticoid therapy. However, this cause of CAH is not included in the newborn screen so can go unrecognized until features of virilization and rapid growth with bone age advancement are noted. If HTN is persistent despite glucocorticoid treatment, spironolactone is the preferred antihypertensive, as it is both a mineralocorticoid and androgen receptor antagonist. This case serves as a reminder to pay attention to BP at every clinic visit. Presentation: Friday, June 16, 2023