True Precocious Puberty Research Articles

Diagnosis and constitutional and laboratory features of Korean girls referred for precocious puberty

PurposePrecocious puberty is defined as breast development before the age of 8 years in girls. The present study aimed to reveal the diagnosis of Korean girls referred for precocious puberty and to compare the constitutional and endocrinological features among diagnosis groups.MethodsThe present study used a retrospective chart review of 988 Korean girls who had visited a pediatric endocrinology clinic from 2006 to 2010 for the evaluation of precocious puberty. Study groups comprised fast puberty, true precocious puberty (PP), pseudo PP, premature thelarche, and control. We determined the height standard deviation score (HSDS), weight standard deviation score (WSDS), and body mass index standard deviation score (BMISDS) of each group using the published 2007 Korean growth charts. Hormone tests were performed at our outpatient clinic.ResultsThe PP groups comprised fast puberty (67%), premature thelarche (17%), true PP (15%), and pseudo PP (1%). Advanced bone age and levels of estradiol, basal luteinizing hormone (LH), and peak LH after gonadotropin-releasing hormone stimulation testing were significantly high in the fast puberty and true PP groups compared with the control group. HSDS, WSDS, and BMISDS were significantly higher in the true PP group than in the control group (P<0.05).ConclusionThe frequent causes of PP were found to be fast puberty, true PP, and premature thelarche. Furthermore, BMISDS were significantly elevated in the true PP group. Therefore, we emphasize the need for regular follow-up of girls who are heavier or taller than others in the same age group.

특발성 진성 성조숙증으로 진단된 소아의 원인 및 임상적 분석

Objectives: The purpose of this study is to estimate genetic and environmental factors, which can affect Idiopathic true Precocious puberty, and to evaluate the clinical and endocrinologic characteristics. Methods: Retrospective and Comparative analysis of 76 children (72 girls and 4 boys) has been diagnosed with idiopathic true precocious puberty, and treated with GnRHa from December 2008 to July 2011. Results: 1. The Average chronological age (CA. yr) of children diagnosed with idiopathic true precocious puberty was <TEX>$8.40{\pm}0.81$</TEX> (girls), <TEX>$9.93{\pm}0.12$</TEX> (boys). 2. The Average height & weight percentile (%ile) of the girls diagnosed with idiopathic true precocious puberty was <TEX>$67.38{\pm}22.04$</TEX>, <TEX>$67.69{\pm}23.20$</TEX>. 3. The girls' mothers have diagnosed with idiopathic true precocious puberty, and they were shorter than the average. This shows that mother's small height and idiopathic true precocious puberty are closely related to each other. 4. BMI percentile (%ile) of girls diagnosed with idiopathic true precocious puberty was <TEX>$63.26{\pm}24.86$</TEX>. 23.6% of children were diagnosed with overweight or obesity. This result shows that obesity and idiopathic true precocious puberty are proportionally related. 5. Birth weights (kg) of the children diagnosed with idiopathic true precocious puberty were <TEX>$3.16{\pm}0.43$</TEX> (girls), <TEX>$3.15{\pm}0.38$</TEX> (boys). 8.3% of children were diagnosed with Intrauterine growth retardation. 6. The Average bone ages (BA. yr) of the children diagnosed with idiopathic true precocious puberty were <TEX>$10.51{\pm}0.99$</TEX> (girls), <TEX>$12.10{\pm}0.97$</TEX> (boys). The Average BA-CA was <TEX>$2.11{\pm}0.81$</TEX> (girls), <TEX>$2.00{\pm}0.87$</TEX> (boys). 7. The Average predicted adults' height (PAH. cm) of the children diagnosed with idiopathic true precocious puberty was <TEX>$151.61{\pm}4.00$</TEX> (girls), <TEX>$163.50{\pm}2.15$</TEX> (boys). The Average MPH-PAH was <TEX>$6.84{\pm}4.91$</TEX> (girls), <TEX>$6.00{\pm}5.35$</TEX> (boys). 8. 23.6% of the children treated with GnRHa were co-treated with Growth Hormone. Conclusions: Estimated factors which cause Idiopathic true precocious puberty are mother's small height, obesity, and Intrauterine growth retardation. However, the studies of Oriental Medicine for Idiopathic true precocious puberty were lacking. Further clinical and experimental researches are needed.

Clinical and metabolic findings in a 6‐year‐old boy with a Leydig cell tumour

To analyse the urinary steroid metabolome in a boy who had true precocious puberty after a Leydig cell tumour. Case report and detailed description of clinical and metabolic findings in a 7-year-old-boy with a Leydig cell tumour. Before surgery, the urinary steroid metabolome showed an activation of an alternative route to gonadal androgens independent of dehydroepiandrosterone (DHEA). After surgery, the boy entered true precocious puberty. Under leuprolide acetate treatment, clinical and laboratory findings normalized. Central precocious puberty after precocious pseudopuberty may be more common than expected and should be considered in children with persistent or recurrent symptoms after initial treatment of precocious pseudopuberty. Patients with a Leydig cell tumour seem to reactivate the so-called 'back door pathway' of androgen production, which is independent of the classical route via DHEA.

Clinical Course of Childhood Onset Pseudoprecocious Puberty due to Autonomous Ovarian Cyst

Purpose: There are few reports about the natural history of patients with pseudoprecocious puberty due to autonomous ovarian cyst. We reviewed the clinical course of 7 patients who had autonomous ovarian cysts and signs of precocious puberty. Methods:We retrospectively evaluated 7 children, aged 2.8 to 7.9 years, who were diagnosed with pseudoprecocious puberty due to autonomous ovarian cysts from November 2005 to May 2011. The follow-up durations ranged from 0.5 to 6.3 years. Results: Four out of 7 patients showed elevated serum estrogen levels and all revealed prepubertal response of gonadotropin to GnRH stimulation at diagnosis. The size of the cysts was from 1.7 to 4.6 cm on pelvic ultrasound examination. After 1 to 3 months, the ovarian cysts disappeared in all patients. Three of the girls developed relapsing signs of precocious puberty (vaginal bleeding and breast budding). Two of them showed an increase in growth velocity and bone age due to recurrent ovarian cysts, and one of them was converted to true precocious puberty. Conclusion: In our cases, all patients with autonomous ovarian cysts resolved spontaneously. However, some showed frequent recurrence of ovarian cysts, and needed a longer follow up because of the possibility of conversion to true precocious puberty and signs of McCune-Albright syndrome. (J Korean Soc Pediatr Endocrinol 2011;16: 86-91)

The Relationship between Initial Body Mass Index and Body Mass Index after One Year of Gonadotropin-Releasing Hormone Agonist Therapy in Idiopathic True Precocious Puberty Girls

The Relationship between Initial Body Mass Index and Body Mass Index after One Year of Gonadotropin-Releasing Hormone Agonist Therapy in Idiopathic True Precocious Puberty Girls Ju Young Yoon, M.D., Min Jae Kang, M.D., Se Young Kim, M.D., Ji Young Seo, M.D., Sei Won Yang, M.D., Young Ah Lee, M.D., Ji Eun Lee, M.D., Hye Rim Chung, M.D and Choong Ho Shin, M.D. Department of Pediatrics , Seoul National University College of Medicine, Seoul, Department of Pediatrics, Bundang Jesaeng General Hospital, Seongnam, Department of Pediatrics, Eulji University School of Medicine, Seoul, Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea

Surgical excision of hypothalamic hamartoma in a twenty months old boy with precocious puberty

A twenty months old boy presented to our department with true precocious puberty due to hypothalamic hamartoma. Total surgical excision of pedunculated hypothalamic hamartoma was done successfully by the pterional trans-sylvian approach as he could not afford medical management. Patient had uneventful post-operative course with normalization of serum testosterone levels and regression of secondary sexual characters.

Evaluation of melatonin on the precocious puberty: a pilot study

Objective. To evaluate the effect of 6-sulphatoxymelatonin on the sleep quality of girls with precocious puberty. Study design. Ninety-nine girls were divided into three groups: GI, precocious puberty; GII, normal prepubescent; GIII, normal puberty. Questionnaires containing demographic and clinical data were applied. Blood was collected for hormonal evaluation for 6-sulphatoxymelatonin. The modified Rush Sleep Diary was used. Results. The levels of 6-sulphatoxymelatonin were highest in the group without pubertal development (75.23 ± 10.84 ng/ml), second highest in the group with normal puberty (45.66 ± 3.87 ng/ml, p < 0.001) and lowest in the group with true precocious puberty (37.04 ± 5.47 ng/ml). The amount of day sleep was greater in the group without pubertal development compared to other groups. Conclusion. Despite the sleep data, melatonin may be involved in the precocious puberty process.

Clinical research of luterinizi releasing hormone anogist with zhibaidihuang pill treatment for girls idiopathic true precocious puberty

目的 研究达那唑、知柏地黄丸联合治疗女孩特发性性早熟临床疗效.方法29例乳房在B3期以内的女孩特发性性早熟(ICPP)患儿,其中9例单独使用达那唑,12例采用达那唑、知柏地黄丸联合治疗,未治疗作为对照组8例.治疗前后分别进行生长速率、第二性征、骨龄的测定,子宫卵巢成熟度测定以及达必佳(LHRH)激发实验.结果两组患儿在治疗4个疗程后进行疗效对比结果:达那唑组患儿平均身高增速减慢不明显、最终身高的预测值增加不明显(P＞0.05)、第二性征减退、血LH峰值不同程度下降、骨龄无改变;达那唑、知柏地黄丸联合治疗组患儿,平均身高增速减慢、最终身高的预测值增加(P＜0.001);第二性征减退明显减退,骨龄/年龄比值(△BA/△CA)值下降(P＜0.001),提示骨龄增长速度减慢、血LH峰值显著下降(P＜0.001)、子宫卵巢均有不同程度的回缩.结论达那唑、知柏地黄丸联合治疗轻、中度女孩ICPP,可减慢骨骼生长,延缓骨龄成熟,改善最终身高,并且减轻患者的经济负担。

Evaluation of the true precocious puberty rats induced by neonatal administration of Danazol: therapeutic effects of nourishing "Yin"-Removing "Fire" Chinese herb mixture.

BackgroundNourishing "Yin"-Removing "Fire" Chinese Herb Mixture, a traditional herb-based formulation, has been successfully used for the management of idiopathic true precocious puberty (IPP) for more than thirty years. Precocious puberty rat model by neonatal administration of Danazol was used to investigate the effects of the herb mixture on the advanced sexual development of the rats, and the expression of hypothalamic gonadotropin-releasing hormone (GnRH), which is the important regulator for the hypothalamus-pituitary-gonadal axis, particularly at puberty.MethodsFemale Sprague-Dawley rats were divided into five groups: intact normal (N), IPP model (M), vehicle with no IPP (V), IPP model exposed to herb mixture (HM) and IPP model exposed to saline (S). Rats at 5 days of age were given a single subcutaneous injection of 300 microgram of Danazol dissolved in 25 microliter vehicle of propylene glycol-ethanol (1:1, v/v), to establish the precocious puberty model. From the day 15, rats in HM and S groups were continuously fed with either Nourishing "Yin"-Removing "Fire" Chinese Herb Mixture 2 ml or saline 2 ml, until 3 consecutive regular estrous cycles were established. The day of vaginal opening and the day of setup regular estrous cycle of the rats were observed. Blood concentration of estrogen was determined by radioimmunoassay. Immunohistochemistry and RT-PCR analysis were used to explore the expression of GnRH.ResultsThe day of vaginal opening and first estrous showed significant advancement in M compared with N and V (p < 0.05, respectively). The blood estrogen level increased significantly in M compared with those in other groups (about 28 days of age, at the time of vaginal opening in M rats) (p < 0.05, respectively). GnRH cells in rostral medial septum (MS), Broca diagonal band nucleus (DBB) and the medial preoptic area (MPOA), were calculated. The number in M was less than those in N and V (p < 0.05, respectively). The number was significantly higher in HM than that in M (p < 0.05). The GnRH mRNA expression increased significantly in M compared with that in N and V (p < 0.05).ConclusionThe true precocious puberty model by neonatal administration of Danazol in female rats showed augmented expression of hypothalamic GnRH; the Nourishing "Yin"-Removing "Fire" Chinese Herb Mixture down-regulated the increased GnRH expression, and significantly delayed the sexual development of the precocious puberty rat.

Navigating Recent Articles on Girls' Puberty: Where Should Our Patients Go for Evaluation?

To the Editor .— This letter is written in response to the Herman-Giddens et al commentary “Navigating the Recent Articles on Girls' Puberty in Pediatrics : What Do We Know and Where Do We Go From Here?”1 We disagree with the authors on several key points. These authors state that we have made the “erroneous assumption that a girl needs to have both breasts and pubic hair to be considered as having true precocious puberty.”1(p914) Pubic hair development and breast development accompanied by a growth spurt has long been the conventional definition of true precocious puberty.2 We maintain that this traditional definition is clinically very helpful, because the development of all 3 before the age of 8 years should be viewed with …

Clinical characteristics of 104 children referred for evaluation of precocious puberty.

There is controversy over the age of onset of puberty in normal children and the risk of missing pathology if the recently proposed revised age guidelines for referring patients are followed. However, there is little recently published information on the frequency of different diagnoses in children referred for signs of early puberty. The purposes of this study were 1) to analyze the spectrum of diagnoses made in a consecutive group of children referred to a single clinician for signs of early puberty; 2) to see whether certain patient groups were more likely to be obese; and 3) to estimate the incidence of endocrine pathology in this sample. The charts of all children referred to the author for evaluation of signs of early puberty between October 1999 and October 2002 were reviewed. Criteria were developed to assign patients to one of seven diagnostic categories based on age, growth, and clinical findings, and differences from the population mean for height and percentage of ideal body weight in the different groups were determined. Most of the patients referred (87%) were female, and the two most common diagnoses made were premature adrenarche (46%) and premature thelarche (18%). Only 9% (all girls) were thought to have true precocious puberty. Two conditions not well described in the literature, pubic hair of infancy and premature menses, were found in 8 and 5%, respectively. Patients with premature adrenarche were significantly taller and more overweight than the general population; a subgroup had evidence of accelerated growth and bone maturation but no worrisome endocrine findings. Acanthosis nigricans was found in 13% of the girls in this study, but the incidence of true endocrine pathology was very low. The majority of children being referred for precocious puberty have benign normal variants, with a very low incidence of endocrine pathology. Most girls presenting with minimal breast or pubic hair development and normal growth velocity may be managed with observation and without a full endocrine evaluation.

Decreased hypothalamic aromatization in female rats of true precocious puberty

The true precocious puberty animal model induced by the single dose of danazol was used for investigating the expressions of hypothalamic aromatase in the advanced onset of puberty in rats. The day of vaginal opening and first estrus showed significant advancement in the model rats compared with the normal and vehicle rats ( P < 0.01, respectively). The hypothalamic gonadotropin-releasing hormone (GnRH) mRNA expression increased significantly in the model rats compared with that in the normal and vehicle ones ( P < 0.01). The levels of aromatase mRNA and protein expressions detected by RT-PCR and Western blot both decreased in the model rats compared with those in the normal and vehicle groups ( P < 0.05). The results suggested that the hypothalamic aromatization might diminish in the onset of true precocious puberty of female rats.

Adrenocortical tumors in childhood.

Adrenocortical tumors (ACT) are rare in childhood. Determination of malignant potential is difficult. To assess the presentation, clinical behaviour, and histology of these tumors in our center, the records of nine patients with ACTs between 1989 and 2000 were analyzed. The age, sex, clinical presentation, investigations, treatment, follow-up data, and current status were determined. The pathological features were reanalyzed by our pathologist. The endocrine profile of the tumors was also retrieved from the records. There were two males and seven females; the median age at referral was 2.5 years. Two patients (one male, one female) presented with clinical features of Cushing's syndrome with hypertension. Four girls had features of Cushing's syndrome with associated virilization. One 11-year-old girl presented with hypertension, hypokalemia, and pseudoparalysis due to an aldosterone-secreting tumor. One girl presented with precocious pubic hair and clitoromegaly. One male had evidence of true precocious puberty. The endocrine profile was available in eight cases: cortisol levels were raised in four, testosterone in four, and aldosterone in one. One boy had pubertal levels of follicle-stimulating hormone and testosterone. Surgery was the only modality of therapy used. Histopathology showed capsular invasion in four patients and vascular invasion in two. The median tumor weight was 80 g (15-550 g) and the size ranged from 1.5 x 1.5 to 12 x 12 cm. Five patients are alive without tumor recurrence at a median follow-up time of 2 years. Tumor recurrence was seen in two patients, one with capsular rupture during surgery and another with a tumor weight of 16 g with associated capsular and vascular invasion. Atypical modes of presentation like pseudoparalysis must be kept in mind. Histologic criteria for malignancy in ACT are unreliable. Tumor weight may not always be accurate in predicting tumor behaviour. Complete surgical excision remains the only effective and potentially curative treatment.

Bilateral testicular enlargement due to adrenal remnant in a patient with C11 hydroxylase deficiency congenital adrenal hyperplasia

The case of a 15-yr-old boy with C11 hydroxylase deficiency congenital adrenal hyperplasia is reported who was diagnosed and treated as true precocious puberty at the age of 2 yr because of virilization and bilateral testicular enlargement. He later developed hyperpigmentation, hypertension and short stature and because of an increase in testes size he underwent testicular biopsy with the assumption of Leydig cell tumor. With the intake of glucocorticoids his testes size, hypertension and hyperpigmentation improved markedly. We could find only 6 such cases in the literature and have reviewed their clinical and laboratory data. All patients showed the picture of virilization with hypertension. Leydig cell tumor was proposed as the differential diagnosis in all cases except ours. Ultrasonography was able to show testicular adrenal-like tissue in all those in whom the procedure was undertaken. In the 5 patients of whom we could find enough data, 1 responded partially and 4 responded markedly to corticosteroid therapy with shrinkage of testicular tumors. We conclude that clinical findings and US are very important in the early diagnosis of these patients and with adequate treatment most cases show shrinkage in testicular tumors.

Consenso sobre el diagnóstico y tratamiento de la pubertad precoz central

The beginning of puberty is marked by breast growth in girls and testicular enlargement in boys. These occur at the age of 10.5 +/- 2.0 years in females and 11.5 +/- 2.0 years in males. Recent but controversial publications suggest that these events are being observed at younger ages, at least in the USA. There are no studies demonstrating that this is true in Chile. For this reason we still consider that puberty is precocious when it occurs before 8.0 years in girls and before 9.0 years in boys. True or central precocious puberty (CPP) must be distinguished from peripheral or pseudoprecocious puberty (PPP), from premature telarche and from premature adrenarche. We suggest that the workup of a patient with premature development should include an LHRH test to demonstrate if the hypothalamic-pituitary axis is activated, plasma levels of sex steroids, bone age and pelvic ultrasound in girls. All children with CPP should have a CAT scan or MNR of the brain, since a lesion of the central nervous system is observed in 15% of the girls and 50% of the boys with CPP. Additional studies are needed in cases of PPP. The aim of treating CPP is to avoid adult short stature that results from premature fusion of the epiphysis and to avoid eventual emotional and psychological stress. Treatment consists of monthly intramuscular injections of a depot preparation of LHRH analogs. Suppression of pituitary and gonadal activity produces regression of secondary sex characteristics and slowing down of growth velocity and bone maturation. The opportunity, duration of treatment and their effect on final stature are discussed.

Clinical Utility of Serum E2 Assayed by Means of a High-Sensitivity Kit in Children

To evaluate the usefulness of a high-sensitivity assay kit for E2, we measured the serum E2 levels in children. The value in a girl with true central precocious puberty was also evaluated before the LH-RH analogue treatment. The study subjects were 36 boys, ranging in age from 1 yr and 9 mo to 17 yr and 6 mo and 46 girls, ranging in age from 1 yr to 15 yr and 6 mo. The minimal detection limit was 1.4 pg/ml. The serum E2 level in the boys and that in girls were 10.8 ± 3.1 pg/ml (mean ± SEM) and 20.7 ± 10.7 pg/ml, respectively. The E2 level was correlated closely with bone age and chronological age. Even when the range of serum E2 was limited to an undetectable level (<10 pg/ml) by the conventional assay, the logarithmic value for the E2 concentration was correlated with bone age in boys (r=0.734, p<0.05) and in girls (r=0.404, p<0.05). The E2 level in girls with partial and true precocious puberty ranged from 2.6 to 8.7 pg/ml. In a patient, who was originally considered as premature thelarche and later turned out to be true central precocious puberty, the serum E2 level was 3.7 pg/ml before therapy, suggesting that high sensitivity to estrogen was the cause of the condition. With LH-RH analogue treatment, the E2 level declined to below the detection limit and the bone age did not change for 1 yr without loss of linear growth. These results suggest that the high-sensitivity kit is useful for monitoring the pathophysiology of E2 in children.

Diagnóstico Laboratorial da Puberdade Precoce

A avaliação de uma criança com puberdade precoce implica numa anamnese e exame físico cuidadosos, que já podem, por si só, fornecer elementos importantes para o diagnóstico etiológico. Um aspecto de fundamental importância é a caracterização do processo como central (puberdade precoce verdadeira) ou periférico (pseudo-puberdade precoce), pois tanto do ponto de vista etiológico como terapêutico a abordagem difere nas duas situações. Com uma avaliação laboratorial coerente, baseada nas probabilidades etiológicas, é possível chegar-se a um diagnóstico com bastante precisão. No entanto, principalmente em meninas, ainda as formas idiopáticas constituem um número apreciável de casos. Nos meninos, a grande preocupação são os processos neoplásicos, que devem ser sistematicamente procurados. Este trabalho aborda aspectos de conceito e etiologia, bem como aborda detalhes da avaliação laboratorial tanto nas formas centrais quanto nas formas periféricas de puberdade precoce.

Sexual precocity in boys: accelerated versus slowly progressive puberty gonadotropin-suppressive therapy and final height.

The indication for GnRH analog treatment in boys with central sexual precocity is based mainly on the age of onset of puberty. Our aim was to determine whether the rate of pubertal progression should also be taken into consideration. Included in the study were 81 boys with central sexual precocity: 27 with true precocious puberty (onset at <9 yr) and 54 with early puberty (onset at 9-10.5 yr). At the time of analysis, all had completed puberty, and 66 (22 central precocious puberty, 44 early puberty) had achieved final height. Progression of puberty (Tanner stage 2 to 3) was accelerated (0.5-1.32 yr) in 42 boys (16 central precocious puberty, 26 early puberty) and slow (1.7-2.9 yr) in 39 (11 central precocious puberty, 28 early puberty). The boys with accelerated puberty had significantly elevated T levels (central precocious puberty and early puberty, P < 0.001), faster growth rate (change in height SD score/duration: central precocious puberty, P < 0.05; early puberty, P < 0.01), and faster bone maturation rate (change in bone age/duration: central precocious puberty, P < 0.05; early puberty, P < 0.001). All 42 boys with accelerated puberty were treated with GnRH analog for 2.3-4.2 yr; the duration to completion of puberty and the height gain after therapy was discontinued were similar for the boys with central precocious puberty and early puberty. The 39 boys with slow puberty received no treatment and had a prolonged course of puberty (central precocious puberty, 5.05 +/- 0.3 yr; early puberty, 4.72 +/- 0.77 yr; average normal, 3.5 yr). The final height achieved in the 35 (11 central precocious puberty, 24 early puberty) untreated boys was within the range of their respective target height. The 31 (11 central precocious puberty, 20 early puberty) treated boys also achieved their genetic target height. Predictions based on the Bayley-Pinneau method at Tanner stage 3 for all boys and at discontinuation of therapy for treated boys overestimated the achieved final height (P < 0.001). In conclusion, boys with sexual precocity, whether central precocious puberty or early puberty, may have either accelerated or slow pubertal development. The decision to institute suppressive therapy should be based also on the rate of pubertal progression. Treatment should be offered only to those (either central precocious puberty or early puberty) with accelerated growth and bone maturation rates and rapid increase in T levels. Suppression therapy apparently converts accelerated puberty into nonsustained slow puberty and probably prevents compromised final height.

Effects of acute stanozolol treatment on puberty in female rats.

The effects of anabolic-androgenic steroid (AAS) abuse on the onset of puberty in female adolescents are largely unknown. This study assessed the acute effects of one AAS, stanozolol, on pubertal onset in the female rat. A single injection of stanozolol (5 mg/kg) on Postnatal Day (PN) 21 advanced vaginal opening but did not alter the onset of vaginal estrus. Higher doses of stanozolol treatment (10 and 25 mg/kg) also advanced vaginal opening but had no effect on vaginal estrus. The advancement of vaginal opening by stanozolol (5 mg/kg) was prevented by the concomitant administration of the pure antiestrogen ICI 182,780 (1 mg/kg) on PN20-22. Administration of the androgen receptor antagonist flutamide (10 mg/kg twice daily) on PN20-22 had no effect on the advancement of vaginal opening by stanozolol. Stanozolol treatment also advanced vaginal opening in ovariectomized rats. Perivaginal injections of a low dose of stanozolol (0.05 mg) on PN21 and PN23 also advanced vaginal opening. These results suggest that stanozolol is acting directly at estrogen receptors in the vaginal epithelium to advance vaginal opening and that prepubertal stanozolol treatment does not induce true precocious puberty.

Central Precocious Puberty in A 20-week Old Female Born Prematurely: A Case Report (and Clinical Clue?)

<h3>Background</h3> Over the past decade. newer gonadotropin assays have enhanced our understanding of the "GnRH pulse generator" and GnRH analogues have revolutionized the treatment of central precocious puberty. If allowed to progress, precocious puberty can have serious consequences both physically and psychosocially. Premature birth has been recognized as a risk tactor for early sexual maturation in the temale child but to our knowledge there have been no prior reports of this condition manifesting as early as infancy. <h3>Case</h3> T.D. was born at 26 weeks gestation and had suffered many expected complications of premannity including: sepsis, retinopathy and bronchopulmonary dysplasia. At 20 weeks of age. (6 weeks corrected age), while still in hospital, she was referred to paediatric gynaecology because of blood in her diaper. At the time of this initial assessment, she had Tanner II breast buds and a protruding estrogenized hymen with physiologic leukorrhea. The blood was telt to be secondary to local irritation of the prominent and exposed hymen but the features of estrogenization were Surprising. Her only medications were iron and vitamins, but a brief course of Aldactazide had been discontinued one month prior. During the month prior to presentation there was an apparent acceleralion in the rate of growth involving body length and head circwnterence. Investigations revealed a markedly elevated estradiol of 250pmol/L, an FSH of 7U/L, and a normal TSH. Abdominopelvic imaging showed bilaterally enlarged ovaries (2.4cm) with multiple tollicles, but the uterus was not well seen and the adrenal glands were nonnal. Bone age was not advanced. CT and MRI of the head showed diffuse atrophy and bilateral retinal detachment, but no localized lesion otherwise. An LHRH stimulation test demonstrated a positive response yielding an LH level of 16U/L (prepubertal <8). Three months later there had been neither regression nor progression of the tindings on examination. A repeat work up is scheduled for April/98 - stay tuned! <h3>Conclusion</h3> As no focal cause has been identitied for the apparenl central activation of the hypothalamic pituitary ovarian (HPO) axis, we have generated two possible explanations. # 1) This is a rare case of true precocious puberty, whether idiopathic or brain injury related, and it will self-resolve or progress or, #2) the patient is manifesting physiological events that have not yet succumbed to "central restraint" She was old enough that maternal and placental estrogen effects should have regressed but the HPO axis can remain active and pulsatile for several years before undergoing the mid-childhood nadir. In the former scenario, treatment (LHRH analogue) will be withheld unless bone age advancement and/or progression are detected. In other scenario, this case may provide more insight into control mechanisms of the HPO axis, the GnRH pulse generator after birth and the onset of puberty.