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PubMed1987

Clinical and endocrinologic study of precocious puberty in girls.

We describe 30 girls with precocious puberty whom we have seen during the last ten years. Modern procedures such as cerebral computer tomography and abdominal sonography increase diagnostic accuracy so that the incidence of idiopathic precocious puberty is likely to diminish. Abdominal sonography is of value in detecting and monitoring the growth of ovarian cysts and thus exploratory laparotomy can be avoided in those cases in which cysts regress rapidly. A modified classification of precocious is proposed.

Adrenal Cortex Hormones↗

PubMed2002

Ovarian and uterine findings in pelvic sonography: comparison between prepubertal girls, girls with isolated thelarche, and girls with central precocious puberty.

OBJECTIVE: To describe pelvic sonographic findings in girls as old as 7 years, to compare prepubertal girls with girls who had isolated thelarche or central precocious puberty, and to verify the accuracy of sonographic variables for distinguishing prepubertal girls from girls with central precocious puberty. METHODS: Ninety-six prepubertal girls and 2 reference groups (8 girls with isolated thelarche and 8 with idiopathic central precocious puberty) were included. Ovaries were classified morphologically as homogeneous, paucicystic, macrocystic, multicystic, and having isolated cysts. Receiver operating characteristic curves were used to choose the best cutoff points. RESULTS: Chronologic and bone age were correlated with uterine length, area, and volume and ovarian volume in prepubertal girls (P < .0001). Ovarian morphologic characteristics in prepubertal girls differed significantly from those of the reference groups (P < .0001). The best cutoff points were uterine length of 4.0 cm, uterine area of 4.5 cm2, uterine volume of 3.0 cm3, and ovarian volume of 1.0 cm3. CONCLUSIONS: Uterine and ovarian growth are proportional to age in prepubertal girls. Mean ovarian volume greater than 1 cm3 showed 100% sensitivity and specificity for discriminating between prepubertal girls and girls with central precocious puberty. Microcysts are common in prepubertal girls, but the presence of 6 or more follicles up to 10 mm in diameter may suggest central precocious puberty in girls younger than 8 years.

Child↗

PubMed1992

Predictive factors for the effect of gonadotrophin releasing hormone analogue therapy on the height of girls with idiopathic central precocious puberty.

The factors influencing the final height of central precocious puberty patients treated with gonadotrophin releasing hormone (GnRH) analogues remain a critical issue. This study compares the predicted final height before and after GnRH analogue therapy to identify predictive factors for final height. Fourteen girls with idiopathic central precocious puberty were treated with a GnRH analogue. All had an active non-regressive form before therapy, full and permanent suppression of oestrogenic activity during therapy (duration greater than 2 years, 3.1 +/- 0.3 years, mean +/- SEM), and the pubertal pituitary-ovarian axis had normalized in all of them 1 year after the cessation of therapy. The mean predicted final height increased from 152 +/- 1.8 cm before therapy to 162.2 +/- 1.2 cm (P less than 0.01) at the last evaluation performed 4.5 +/- 0.3 years after the onset of therapy. The mean gain in predicted final height between the onset of therapy and the last evaluation was 10.2 +/- 1.1 cm. It was correlated with the following data recorded at the onset of therapy: bone age advance over chronological age (r = 0.66, P less than 0.02), predicted final height at the onset of therapy (r = -0.76, P less than 0.001), and the difference between the target height and the predicted height at onset of therapy (r = 0.76, P less than 0.001). We conclude that GnRH analogue therapy is more likely to improve final height prognosis in girls who initially present with a markedly advanced bone age and a great difference between their target and predicted heights. Both these parameters reflect the severity of the disease at diagnosis.

Body Height↗

PubMed1979

Precocious puberty of cerebral origin.

Eighty-two cases of precocious puberty of cerebral origin were reviewed. All shared as a common factor the distortion, compression, or destruction of diencephalic structures. Attempts were made to parallel basic research findings with those derived from human pathology, hoping to gain further insight into the physiopathology of precocious puberty of cerebral origin.

Astrocytoma↗

PubMed2000

Etiology and age incidence of precocious puberty in girls: a multicentric study.

We review the etiology and age incidence of precocious puberty in 438 girls examined between 1988-1998; 428 (97.7%) had central precocious puberty (CPP), the remaining 10 (2.3%) gonadotropin-independent precocious puberty (GIPP) of ovarian origin. The majority of CPP girls (59.6%) were aged between 7-7.9 yr, 22.4% were 6 year olds, and only 18% were under 6 years old. Cranial CT and/or MRI performed in 304/428 girls, showed neurogenic abnormalities in 56/304 (18.4%) CPP girls; 30 (9.9%) were due to previously diagnosed intracranial abnormalities and the remaining 26 (8.5%) were detected at the diagnosis of CPP. The frequency of neurogenic CPP tended to be higher in girls under 4 years of age while the frequency of idiopathic CPP tended to be higher in girls aged between 7-7.9 years, but no statistically significant differences were found. Interestingly, some CNS anomalies either of tumoral or congenital origin were detected at presentation in 7% of the girls aged over 7 years. Other related or coincidental clinical anomalies, mainly due to genetic diseases, were observed in 22/304 (7.2%) patients. History of precocious maternal menarche was found in 12/304 (4%) girls. In conclusion, idiopathic CPP was observed in 74% of the girls in this study. Neurogenic anomalies or other coincidental or related clinical findings were observed in the remaining 26%. The increased frequency of idiopathic CPP in girls aged over 7 years may suggest an early, but otherwise normal onset of puberty in many of these girls as a consequence of the trend towards earlier maturation. Nonetheless, the finding of CNS anomalies also in the older patients, raises the question of whether these patients should undergo a complete diagnostic work-up.

Abnormalities, Multiple↗

PubMed1976

[Urocytogram and precocious puberty].

After a review of the technique of urocytogram the authors report the results obtained in 39 children between the ages of 3 and 12 years. Before the appearance of the first signs of puberty, urocytograms are similar in both girls and boys. Differences were seen in seven cases of male or female precocious puberty. Urocytograms are also different in patients with incomplete precocious puberty but less marked than in those with true precocious puberty. The authors consider the possibility of repeat urocytograms during the supervision or treatment of incomplete and complete precocious puberty.

Brain Neoplasms↗

PubMed2005

[Central precocious puberty in girls: prediction of the etiology].

Precocious puberty (PP) is defined in girls by the occurrence of pubertal development before the age of 8. This development raises 3 questions: 1) Is it abnormal puberty or variant of the normal? 2) If abnormal puberty, is it of central, hypothalamic-pituitary, or peripheral, ovarian or adrenal origin? 3) If central, is it idiopathic or due to a lesion, and is there indication to treat it? The PP in a girl with no previous medical history is usually of central and idiopathic origin. However, isolated central PP may reveal a CNS lesion, particularly an optic glioma with its risk of blindness. Two independent predictors of CNS lesion are the age at PP onset of less than 6 years old, and increased plasma estradiol concentration. The selection of the girls for neuroradiological imaging should be based on these two parameters. However, neuroradiological imaging remains necessary until the prospective confirmation of their predictive value.

Adolescent↗

PubMed2000

Near final height after GnRH agonist treatment in central precocious puberty.

The impact of treatment of central precocious puberty (CPP) with gonadotropin-releasing hormone agonists (GnRHa) on final height remains controversial. We analyzed the long term results of 23 girls with CPP treated with triptorelin or leuprolide. Their "near final height" (NFH) assessed at a bone age of at least 14 years and expressed as SDS, was compared either with predicted height before treatment (PAH) or with parental height (TH). We also compared NFH of 12 girls treated before 8 years of age (7.0 +/- 0.5 yr) with NFH of 11 girls treated after 8 years old (8.5 +/- 0.3 yr). The NFH of the 23 girls (-0.9 +/- 1.0 SDS) was not different either from PAH (-0.85 +/- 1.5 SDS) or from TH (-0.5 +/0.6 SDS). Earlier treated girls reached a NFH (-0.97 +/- 1.0 SDS) not different from later treated girls (-0.91 +/- 1.0 SDS; p = ns) and both groups reached parental height (NFH - TH = -0.44 +/- 1 and -0.09 +/- 0.83 SDS, respectively). In conclusion, our patients, treated either earlier or later, reached a near final height comparable to predicted height and familial target; however, these results might still improve further because the girls have not yet reached their final adult height.

Body Height↗

PubMed2001

Does GnRH analog improve the final height in Thai girls with idiopathic central precocious puberty?

Ten Thai girls with idiopathic central precocious puberty (ICPP) were treated with gonadotrophin releasing hormone (GnRH) analog for a mean period of 1.5+/-0.4 years. The predicted adult height at the end of treatment was significantly higher than that at the start of treatment (158.2+/-7.9 vs 153.0+/-8.7 cm, p=0.009). In addition, treatment with GnRH analog could significantly regress the breast staging from 3.4+/-0.8 to 2.6+/-1.0 (p=0.04),but not the pubic hair staging. Five of them reached a final height which was not significantly higher than the predicted adult height before treatment (153.1+/-4.8 vs 150.7+/-1.0 cm, p=0.5). In conclusion, treatment with GnRH analog in Thai girls with ICPP can improve the predicted adult height and regress the breast staging. However, the improvement of final height is not promising.

Adolescent↗

PubMed1995

[Long-term experiences with a long-acting gonadotropin releasing hormone analog in therapy of central precocious puberty: effect on body growth].

In central precocious puberty (CPP), characterised by premature but otherwise normal puberty, the early onset of the pubertal growth spurt with increased height velocity results in premature epiphyseal closure with reduced final height. We examined the growth pattern in 11 patients (9 girls and 2 boys) with CPP treated with a long-acting gonadotropin-releasing hormone analogue (GNRHa). Every 28 days 75 micrograms of the GNRHa Triptorelin (Decapeptyl CR, Fa. Ferring) per kg body weight are given intramuscularly. We observed body height, height velocity, bone maturation (dBA/dCA) and predicted adult height in these patients for up to 4 years. Before treatment body height was markedly elevated (2.5 +/- 4.4 SD above the age appropriate mean); after two years of therapy it reached the normal range. Height velocity decreased significantly within the first six months of treatment and remained subsequently low (F = 7.59; p < 0.0001). In the first year on treatment bone maturation (dBA/dCA) dropped from 1.8 +/- 0.42 to 0.7 +/ 0.27 and in the second year to its lowest value of 0.3 +/- 0.13 (F = 2.35; p < 0.05). The predicted adult height increased from 154.5 +/- 4.0 cm at the beginning of treatment to 160.3 +/- 3.9 cm at the most recent follow-up examination. The present data indicate that treatment with a long-acting GNRHa markedly affects body growth in CPP by reducing height velocity and delaying bone maturation. The predicted adult height appears to increase, consequently.

Adolescent↗

PubMed1994

[Treatment of central precocious puberty with sustained-release triptorelin].

Central precocious puberty is defined as the appearance of morphological and biological changes induced by the early maturation of the hypothalamic-pituitary-gonadal system before eight years of age in girls and ten years of age in boys. This early onset of the gonadotropin-releasing hormone pulse generator activation leads to secretion of gonadal steroids and therefore to the development of secondary sexual characteristics. The aim of medical treatment is to suppress the secretion of sex hormones. A dramatic improvement has been achieved with the development of gonadotropin releasing hormone agonists which induce a reversible suppression of gonadotropin secretion. Since 1986, triptorelin (Decapeptyl) (D-Trp6-LHRH) has been available for this indication as a sustained-release formulation allowing an intramuscular injection of 3.75 mg every 4 weeks. Results published up to now concern 352 children (325 girls and 27 boys). The pituitary-gonadal suppressive effect has been confirmed. The complete suppression of gonadal secretions induced a rapid regression of secondary sexual characteristics as early as the 3rd month of therapy, and decreased the growth rate acceleration which normalizes during the 3rd year of therapy. The progression of bone maturation clearly slowed down at the end of the first year of treatment so the final height prognosis significantly improved. Whatever length of the treatment period, the reversibility of the suppressive effect of triptorelin has been demonstrated. Puberty resumed 3 to 9 months after stopping the treatment. Tolerance of the medication was excellent. The rare side effects were minor and never led to treatment discontinuation: headaches (8% of the cases), hot flushes (12% of the cases). The percentage of drop out was very low.

Delayed-Action Preparations↗

PubMed1983

EEG and evoked potentials in precocious puberty.

We recorded brain stem auditory evoked potentials, pattern reversal visual evoked potentials and electroencephalograms in 19 children, 2-8 years old. Sixteen had precocious puberty and three had precocious adrenarche. Two of the children with precocious puberty had hypothalamic hamartomas, one had an optic glioma, and one had a history of hydrocephalus. The EEG was abnormal in 7 patients: three had diffuse slowing, and four showed possible paroxysmal features. BAEPs and VEPs were normal in all patients. This study showed no abnormalities in two conduction pathways of the central nervous system and no evidence of a deleterious effect of hormonal aberrations in patients with precocious puberty. Abnormal EEG in these patients is more likely to reflect occult diencephalic disease than widespread neurophysiological dysfunction.

Brain Diseases↗

PubMed2005

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

BACKGROUND: Nourishing "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. METHODS: Female 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. RESULTS: The 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). CONCLUSION: The 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.

Animals↗

PubMed1996

Maternal uniparental isodisomy of human chromosome 14 associated with a paternal t(13q14q) and precocious puberty.

Cytogenetic and molecular investigation of a boy with precocious puberty and motor developmental delay revealed a 45,XY,t(14q14q) or i(14q) karyotype with no paternal chromosome 14 contribution. VNTR analysis of loci on four other chromosomes excluded non-paternity with greater than 99% confidence. Results of VNTR and CA repeat analyses of ten loci along the entire length of chromosome 14 were consistent with homozygosity at all loci, suggesting that the chromosomal rearrangement was a maternal isochromosome for 14q. As the proband's father had a balanced Robertsonian translocation, t(13q14q), we suggest that the origin of the maternal uniparental disomy (UPD) was fertilization by a nullisomy 14 sperm with formation of the isochromosome in the early embryo. Also, the proband has several clinical features in common with six previously reported liveborn cases of maternal UPD 14: hypotonia and motor developmental delay, mild dysmorphic facial features, low birth weight and growth abnormalities, and, more specifically, precocious puberty among the four cases old enough to assess. The emergence of a syndrome associated with maternal UPD 14 suggests the possibility of genomic imprinting of regions of chromosome 14, especially a gene involved in the onset of puberty.

Adolescent↗

PubMed1989

Precocious puberty in girls: early diagnosis of a slowly progressing variant.

An attempt was made to identify the less severe cases of precocious puberty and to describe their natural course. A group of 17 girls with precocious puberty and a bone age advance over chronological age of less than two years (group 1) was compared with a group of 19 patients with severe precocious puberty and bone age advance of two years or more (group 2). Mean (SEM) plasma oestradiol concentrations were 82 (30) pmol/l and 164 (21) pmol/l (p less than 0.05), vaginal maturation indexes were 16 (5) and 41 (4), and plasma somatomedin C concentrations were 1.0 (0.2) U/ml (n = 8) and 2.1 (0.3) U/ml (n = 16) in groups 1 and 2, respectively. The time between onset and diagnosis of secondary sexual characteristics was about one year in both groups. After two years' follow up the untreated patients in group 1 had maintained their predicted final height. These changes were in contrast to those observed at first examination in patients in group 2 who had a mean (SD) predicted final height of -1.3 (0.2) and a mean bone age advance of 3.0 (0.2) years. These data show that bone age advance to chronological age, and plasma somatomedin C concentrations measured at initial evaluation are helpful in identifying less severe and potentially slow progressing forms of central precocious puberty.

Age Determination by Skeleton↗

PubMed2000

Serum inhibin A and inhibin B in central precocious puberty before and during treatment with GnRH agonists.

Serum levels of the gonadal hormones inhibin A and inhibin B are undetectable or low in prepubertal girls, and rise during puberty. In girls with central precocious puberty (CPP) the hypothalamic-pituitary-gonadal axis is prematurely activated, if the girl is thereafter treated with GnRH agonists both gonadotropins and estradiol levels become suppressed. We therefore investigated serum levels of inhibin A and inhibin B in girls with CPP at diagnosis and during treatment in order to test the hypothesis that inhibin secretion would increase and decrease in parallel with the activation and suppression of the hypothalamic-pituitary-gonadal axis. Serum levels of inhibin A and inhibin B were significantly (p < 0.0005) elevated in 42 girls at diagnosis of CPP (inhibin A: 7 pg/ml (<7--139), inhibin B: 80 pg/ml (<20--294) (median, range)) compared to levels in age-matched healthy schoolgirls (inhibin A: all values <7 pg/ml, inhibin B: 21 pg/ml (<20--122) (median, range)), but were appropriate for Tanner stage. During treatment with GnRH agonist (intranasal buserelin and oral cyproterone acetate, treatment group 1, n = 23, or triptorelin depot injections, treatment group 2, n = 19) levels of both hormones fell significantly (p = 0.002). There was a significantly (p = 0.003) greater fall in inhibin B levels during treatment in group 2 compared to group 1, with inhibin B levels now lying below (group 2: <20 pg/ml (<20--68)) rather than within (group 1: 34.5 pg/ml (<20--93)) the age-appropriate range. It is concluded that levels of inhibin A and inhibin B are elevated and suppressed in concert with activation and suppression of the hypothalamo-pituitary-gonadal axis in girls with CPP, supporting the concept that ovarian inhibin secretion is dynamically regulated by gonadotropin stimulation.

Buserelin↗

PubMed1985

True precocious puberty: a long-term complication in children with shunted non-tumoral hydrocephalus.

In 4/37 (10.8%) children, adolescents and young adults with successfully shunted hydrocephalus, puberty occurred or was occurring precociously, at an age ranging from 7.5 to 8.6 years, with a consequent impairment of their effective or predicted adult height as compared to the familial target height. All four patients had undergone a surgical intervention for the insertion of a ventricular-atrial or a ventricular-peritoneal shunt during the first year of life; since the last surgical shunt revision (at the age of 5 years) no relapse of hydrocephalus had been recorded. The authors conclude that precocious puberty is to be regarded as a not infrequent long-term complication in patients with successfully shunted hydrocephalus.

Adolescent↗

PubMedDate not supplied

Precocious puberty: clinical and endocrine profile and factors indicating neurogenic precocity in Indian children.

The objective of this study was to evaluate the clinical and endocrine profile of patients with precocious puberty followed up in a tertiary care hospital. Records of 140 patients (114 girls, 26 boys) with precocious puberty were reviewed. Clinical features including age of onset, stage of pubertal development, presenting symptoms, features suggestive of CNS involvement and family history were analyzed. Endocrine investigations included basal and GnRH-stimulated levels of LH and FSH as well as 17OHP, DHEA, hCG and thyroid profile. Abdominal and pelvic ultrasonography and CNS imaging were correlated with clinical features. Girls outnumbered boys in this series (4.4:1). Neurogenic central isosexual precocious puberty (CIPP) was more common in boys (10 out of 18, 55.6%) than girls (16 out of 77, 20.8%). The most common cause of neurogenic CIPP was hypothalamic hamartoma present in five girls and four boys. Other causes of neurogenic CIPP included neurotuberculosis, pituitary adenoma, hydrocephalus, post radiotherapy, CNS tumors and malformations. Peripheral precocious puberty (PPP) was secondary to adrenal causes in boys and ovarian cysts in girls. Benign variants of precocious puberty, such as premature thelarche and premature adrenarche, were present in 23 and six girls, respectively. Hypothyroidism was present in four girls and McCune-Albright syndrome in one girl. Girls with neurogenic CIPP had a lower age of onset as compared to idiopathic CIPP (3.6 +/- 2.7 years vs 5.4 +/- 2.5 years, p = 0.014). The lowest age of onset was seen in girls with hypothalamic hamartoma (1.6 +/- 0.9 years). Forty-seven girls with CIPP (seven neurogenic and 40 idiopathic) presented after the age of 6 years. Features of CNS involvement, in the form of seizures, mental retardation, raised intracranial tension or focal neurological deficits, were present in seven girls (43.8%) and four boys (40%), and gelastic seizures were present in three children. Girls with CIPP had greater bone age advancement (3.4 +/- 1.5 years) and negative height standard deviation for bone age (-2.7 +/- 1.5) than those with PPP (1.9 +/- 1.6 years and -1.3 +/- 1.3) and premature thelarche (0.4 +/- 0.4 years and -0.8 +/- 0.8). Patients with neurogenic CIPP had significantly higher levels of baseline and GnRH-stimulated levels of LH and FSH and LH:FSH ratio than those with idiopathic CIPP. Occurrence of neurogenic CIPP in seven girls with an age of onset after 6 years emphasizes the need for CNS imaging in these girls contrary to the current recommendations. The fact that 65.6% cases of idiopathic CIPP presented after the age of 6 years raises the possibility that these patients may be physiological variants of normal puberty. Pointers to neurogenic CIPP included early age of onset in girls, clinical features of CNS involvement, and elevated basal and stimulated LH levels and LH:FSH ratio.

Age Determination by Skeleton↗