Precocious Puberty In Girls Research Articles

Central precocious puberty in girls: Internal genitalia before, during, and after treatment with long-acting gonadotropin-releasing hormone analogues

Pelvic ultrasonography was systematically performed on 33 girls with idiopathic central precocious puberty to investigate the impact of treatment with gonadotropin-releasing hormone analogues on female internal genitalia. All girls were treated with a long-acting gonadotropin-releasing hormone analogue (Decapeptyl Depot; Ferring Co., Copenhagen, Denmark) 75 μg/kg every 4 weeks. Before, during, and after treatment, pelvic ultrasonography was performed and ovarian and uterine volumes were calculated. The size of follicles > 5 mm were accurately measured. The results were related to a normative study of healthy Danish schoolgirls. Our data demonstrated that ovaries and uterus are enlarged in a significant number of girls (50%) with the diagnosis of central precocious puberty at the time of diagnosis. Median ovarian volume at time of diagnosis was 1.1 standard deviation scores (range –0.6 to 3.2 SD), median uterine volume was 1.8 standard deviation scores (range 0.0 to 3.5 SD). Within 3 months of treatment, both ovarian and uterine volumes decreased significantly ( p < 0.01) to normal values appropriate for age. Median ovarian volume after 3 months of treatment was 0.0 SD (range –2.4 to 1.5 SD); median uterine volume was 0.7 SD (range –0.6 to 4.1 SD). Ovarian and uterine volume remained within normal range (<2 standard deviation scores) after discontinuation of treatment. Follicles and macrocysts regressed during treatment. None of the girls' ovaries had a polycystic appearance during or after treatment with the gonadotropin-releasing hormone analogue. Our results confirmed pelvic ultrasonography as a reliable tool for investigation of internal genitalia in girls with precocious puberty and as a valid method for evaluation of the efficacy of treatment with gonadotropin-releasing hormone analogues. We suggest that repeated investigations be performed when evaluating treatment because the morphologic changes, including follicular maturation or regression, reflect ovarian stimulation or suppression. We found no evidence that girls with precocious puberty treated with long-acting gonadotropin-releasing hormone analogues have enlarged polycystic ovaries develop. (J Pediatr 1998;132:105-8)

Precocious Puberty: Changing Trends in Diagnosis and Treatment

Objective: the complications of precocious puberty may include premature menarche, shortened adult height due to accelerated bane maturation, and psychological distress. With advances in molecular biology and medical imaging techniques, and with a decade and a half of experience with the use of gonadotrophin-releasing hormone (GnRH) agonist analogue therapy to suppress central precocious puberty, the diagnosis and treatment of sexual precocity has been greatly refined. This paper discusses the recent advances in diagnostic and therapeutic interventions for central precocious puberty in girls, with emphasis on the following outcomes: final adult height, ovarian function, and psychological sequelae.Methods: we reviewed the literature on the diagnosis and therapy of precocious puberty. Data were abstracted from reports that included outcome measures of final adult height, ovarian/menstrual function or psychological assessments in treated and untreated female patients.Results: most reports demonstrate increased final adult height in women treated with GnRH analogues when compared to reports of untreated patients or those treated with cyproterone acetate or medroxyprogesterone acetate. This effect appears to be most marked in patients with extremely precocious pubertal onset, before age five to six years. Menarche occurs within two years of treatment cessation in nearly all patients. Limited data exist regarding the psychological consequences of sexual precocity or its treatment.Conclusion: GnRH analogues have become the treatment of choice for girls with central precocious puberty. Their ability to suppress chronically the central activation of the hypothalamic-pituitary-ovarian axis represents a major advance, and results in the slowing of bone maturation and the reversible delay of menarche and the progression of secondary sexual characteristics.

Precocious puberty in a girl with an hCG-secreting suprasellar immature teratoma

Although precocious puberty is common in boys with human chorionic gonadotropin (hCG)-secreting brain tumors, it is extremely rare in girls. The authors describe a 6-year-old girl with an hCG-secreting suprasellar immature teratoma who presented with diabetes insipidus, increased intracranial pressure, and precocious puberty. On admission, breast budding was observed. The serum hCG level was 1230 mIU/ml. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) remained below detectable levels, even after gonadotropin-releasing hormone stimulation. Serum estrogen and androgen were moderately elevated. After chemotherapy, breast budding disappeared with normalization of serum hCG. It has been believed that hCG does not produce precocious puberty in girls in the absence of FSH, and this has been used as an explanation for the rarity of precocious puberty in girls with hCG-secreting brain tumors. However, it has also been reported that hCG has not only LH activity but also intrinsic, although weak, FSH-like activity. In the present case, this FSH-like activity was considered to have played a role in the development of precocious puberty. It is speculated that a very high level of serum hCG can produce precocious puberty in girls. The rarity of intracranial germ-cell tumors with a high potential of hCG secretion may be one of the reasons why hCG-induced precocious puberty is uncommon in girls.

Factors associated with precocious puberty in girls with spina bifida cystica

Factors associated with precocious puberty in girls with spina bifida cystica

Precocious Puberty in Girls With Myelodysplasia

Myelodysplasia is a relatively common anomaly occurring in 1 to 5 per thousand live births. It is seen more frequently in girls. The severity of developmental defect and the resultant neurological impairment is variable; however, hydrocephalus is a common finding.1 True precocious puberty, premature activation of the hypothalamic-pituitary-gonadal axis, also occurs more frequently in girls.2,3 It has been our clinical impression that sexual precocity is more common in girls with myelodysplasia than in otherwise healthy children. To assess the degree and nature of this association, if any, we retrospectively studied 62 girls with myelodysplasia. MATERIALS AND METHODS All female patients with myelomeningocele attending our multidisciplinary myelodysplasia clinic at the New England Medical Center (Floating Hospital for Children) between September 1989 and May 1991 were studied.

Long-Term Testolactone Therapy for Precocious Puberty in Girls With the McCune-Albright Syndrome

Developemental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland

Long-term testolactone therapy for precocious puberty in girls with the McCune-Albright syndrome.

We used the aromatase inhibitor testolactone (40 mg/kg.day) to treat 12 girls with precocious puberty due to the McCune-Albright syndrome for periods of 0.5-5 yr. In the 7 girls who received testolactone for at least 3 yr, the mean +/- SD serum estradiol level was 618 +/- 268 pmol/L at the start of therapy and fell to 156 +/- 84 pmol/L at 1 yr, 116 +/- 48 pmol/L at 2 yr, and 241 +/- 260 pmol/L at 3 yr (P < 0.05 compared to the start of therapy), with recurrent ovarian cysts at 3 yr in 2 patients. These 7 girls averaged 8 menses/yr before therapy. The average frequency of menses decreased to 2 episodes/yr during the first year of treatment, 3/yr during the second year, and 4/yr during the third year. The mean +/- SD testosterone levels were slightly above the normal prepubertal range (0.51 +/- 0.2 nmol/L) before treatment and did not change significantly during treatment. The mean +/- SD androstenedione levels rose from 1.1 +/- 0.6 nmol/L before treatment to 2.1 +/- 0.1 nmol/L at 2 yr and 2.8 +/- 0.1 nmol/L after 3 yr of treatment (P < 0.05 compared to before treatment) and were consistent with normal adrenarche. The mean predicted adult stature was 143.0 +/- 7.8 cm before treatment and 147.3 +/- 11.5 cm at 3 yr (P = NS). In 3 of 12 girls, all with bone age greater than 12 yr, the gonadotropin responses to LHRH indicated early central precocious puberty after 1-4 yr of treatment. The adverse effects of testolactone were transient abdominal pain, headache, and diarrhea in 3 girls and elevated hepatic enzymes in 1 girl who had abnormal liver function before treatment. Six families acknowledged difficulty in adhering to the daily dosing schedule. We conclude that testolactone can be effective in the treatment of LHRH-independent precocious puberty in girls with McCune-Albright syndrome, but that some patients exhibit an escape from the effects of treatment after 1-3 yr.

Long-term testolactone therapy for precocious puberty in girls with the McCune-Albright syndrome

Long-term testolactone therapy for precocious puberty in girls with the McCune-Albright syndrome

CRANIAL IRRADIATION AND EARLY PUBERTY

Low doses of cranial irradiation (1800-2400 cGy) employed in the management of acute lymphoblastic leukaemia may cause early or precocious puberty in girls but not boys. To determine if this sexual dichotomy exists at higher irradiation doses (2500-4700 cGy) the onset of puberty was identified in 46 children (30 male), previously irradiated for a brain tumour not involving the hypothalamic-pituitary axis, and compared with the normal pubertal standards of Tanner. Regression analysis was employed to assess whether tumour diagnosis, sex, age at irradiation, chemotherapy, use of GH before puberty and radiotherapy protocol influenced age at pubertal onset. The onset of puberty occurred at an early age in both sexes (mean 8.5l years in girls and 9.21 years in boys plus 0.29 years for every year of age at irradiation). In the context of GH deficiency which is usually associated with a delay in the onset of puberty this is abnormal. There was a significant linear association between age at irradiation and age at onset of puberty in both sexes. At each age of irradiation the estimated age at the onset of puberty was approximately 0.7 years earlier in girls than boys. A similar trend was seen for bone age, which was abnormally early at the time of pubertal onset (mean 7.39 years in girls and 8.66 years in boys plus 0.25 years for every year of age at the time of irradiation). Radiation induced early puberty is not restricted to females at the doses of irradiation employed in the treatment of brain tumours. The clinical consequence of early puberty in the management of poor growth associated with radiation induced GH deficiency is to foreshorten the time available for treatment with GH.

Precocious puberty in girls: pituitary height as an index of hypothalamo-pituitary activation.

The pituitary heights in 47 girls having breast development before 8 yr were measured by magnetic resonance imaging and compared to the normal values for age and to clinical and laboratory data. They were classified into 3 groups: 1) premature thelarche (PT), isolated breast development with plasma estradiol less than 74 pmol/L (8 cases); 2) mild form of central precocious puberty (CPP1) with an LH/FSH peak ratio after the LH-releasing hormone test less than 1 (22 cases); 3) classical form of CPP (CPP2) with an LH/FSH peak ratio greater than 1 (17 cases). All girls with CPP had breast and pubic hair development before 8 yr, accelerated growth velocity, and no intracranial lesion. The mean ages at breast development [7.2 +/- 0.4 (SE), 6.5 +/- 0.4, and 7.2 +/- 0.3 yr] and the mean times between breast development and magnetic resonance imaging evaluation (0.8 +/- 0.1, 0.8 +/- 0.2, and 0.9 +/- 0.1 yr) were similar in the 3 groups. The mean pituitary heights were 4.9 +/- 0.2 in PT, 5.1 +/- 0.2 in CPP1, and 6.2 +/- 0.2 mm in CPP2. They were not significantly different in PT and CPP1 but were significantly greater in CPP2 than in PT (P < 0.001) or CPP1 (P < 0.001). Individual values of pituitary height were compared to those of age-matched girls: they were greater than or equal to mean +/- 2 SD in 8% of PT, 32% of CPP1, and 70% of CPP2. In the CPP group, the pituitary height was correlated with the LH/FSH peak ratio [correlation coefficient (r = 0.52, P < 0.01] and plasma estradiol (r = 0.60, P < 0.01). Four patients with high pituitary height despite LH/FSH peak ratios less than 1 had an increase of their breast development within 1 yr. We conclude that the pituitary height is normal for age in girls with premature thelarche or a mild form of CPP. Conversely, pituitary height is in the pubertal range in girls with the classical form of CPP. Its correlation with LH/FSH peak ratio suggests that pituitary height reflects changes in the degree of hypothalamo-pituitary activation and may provide an indication of its future development. It may therefore help in decisions on LH-releasing hormone analog therapy in certain cases.

Precocious puberty in girls: pituitary height as an index of hypothalamo-pituitary activation

Precocious puberty in girls: pituitary height as an index of hypothalamo-pituitary activation

Recurrent Ovarian Cysts in Childhood: Diagnosis of McCune-Albright Syndrome by Bone Scan

During the past decade, it has become clear that precocious puberty is a complex disorder with multiple pathophysiologic causes. Although gonadotropin-releasing hormone (GnRH)-dependent mechanisms account for the vast majority of precocious puberty in girls, GnRH-independent processes play an important role in a minority of patients. The recent availability of specific therapies for both GnRH-dependent and GnRH-independent precocious puberty has made it increasingly important for pediatricians to distinguish between these two subsets.1,2 Although most patients with precocious puberty neatly fall into one or the other subset, a significant minority of patients may present a diagnostic challenge even after an extensive evaluation is undertaken.

Luteinizing Hormone-Releasing Hormone (LHRH)-Independent Precocious Puberty Unresponsive to LHRH Agonist Therapy in Two Girls Lacking Features of the McCune-Albright Syndrome

Two girls with precocious puberty (chronological age, 1 and 4 yr; bone age, 3 and 6 yr, respectively) were initially given the diagnosis of idiopathic, central precocious puberty and treated with the LHRH agonist deslorelin (D-Trp6-Pro9-NEt-LHRH) for 5 yr. Unlike other girls with central precocious puberty, both had persistently elevated rates of growth and bone maturation, and both menstruated during therapy. One girl had episodic ovarian enlargement and markedly elevated serum estradiol levels due to recurrent unilateral ovarian cysts. Although the bone and skin manifestations of McCune-Albright syndrome were absent, we hypothesize that the underlying defect of McCune-Albright syndrome was expressed in the ovaries, but not in the skin or bones, of these two girls. One of these girls appeared to benefit from the aromatase inhibitor testolactone, which is effective in suppressing precocious puberty in girls with the McCune-Albright syndrome.

Idiopathic Central Precocious Puberty in Girls as a Model of the Effect of Plasma Estradiol Level on Growth, Skeletal Maturation and Plasma Insulin-Like Growth Factor I

Girls suffering from idiopathic central precocious puberty (CPP) may have different levels of estrogenic activity. This study was performed to evaluate the relationship between the estrogenic activity and the hypothalamopituitary activation and the effect of various plasma estradiol (E2) levels on growth, skeletal maturation and plasma insulin-like growth factor I (IGF-I). Fifty-eight girls with CPP were divided into 2 groups: group I with E2 less than 25 pg/ml (13 +/- 1 pg/ml, mean +/- SEM, n = 26) and group II with E2 greater than or equal to 25 pg/ml (52 +/- 3 pg/ml, n = 32). The mean ages at onset and at evaluation were lower in group I (5.9 +/- 0.4 and 6.8 +/- 0.4 years) than in group II (6.8 +/- 0.3 and 8.1 +/- 0.2 years, p less than 0.01), but the durations since onset (greater than 0.5 and less than 2 years) in the two groups were similar. The mean peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratios were lower in group I (0.8 +/- 0.2) than in group II (1.7 +/- 0.2, p less than 0.001) and correlated with E2 (r = 0.41, p less than 0.01). The mean height gains during the year preceding the initial evaluation were similar in the two groups (8.7 +/- 0.5 vs. 9.2 +/- 0.4 cm). They were independent of the plasma E2 level. Conversely, the mean plasma IGF-I values were lower in group I (2.4 +/- 0.3 U/ml) than in group II (4.2 +/- 0.6 U/ml, p less than 0.01) and correlated with E2 (r = 0.52, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Intranasal nafarelin: An LH-RH analogue treatment of gonadotropin-dependent precocious puberty

The agonistic analogues of luteinizing hormone releasing hormone decrease biochemical findings and clinical signs of gonadotropin-dependent precocious puberty. We tested a new analogue, nafarelin acetate, in 15 girls with gonadotropin-dependent precocious puberty. The hydrophobic nature and potency of this compound allow it to be administered by intranasal inhalation. Laboratory assessment of vaginal cytology, estradiol and urinary gonadotropin levels, and growth velocity revealed that nafarelin acetate 800 to 1200 micrograms/day diminished these values during a 6-month treatment period. These results suggest gonadotropin-dependent precocious puberty in girls can be treated with intranasal administration of nafarelin acetate.

Idiopathic precocious puberty in girls: Long-term effects on adolescent behavior

Precocious puberty in girls has endocrinological as well as behavioral implications. We present data from a first systematic controlled follow-up study of 16 adolescent girls with a history of idiopathic precocious puberty (IPP) compared to closely pair-matched adolescent control subjects of comparable pubertal status and normal pubertal history. Findings in four areas of behavior are reported: Psychiatric sequelae: the IPP sample showed an increase in minor psychopathological symptoms. Psychosexual development: The IPP sample was advanced in sociosexual milestones, albeit mostly within the normal range for adolescents. Intelligence: IQ was not different from controls. However, school achievement was accelerated during childhood. Cognitive pattern: The IPP sample had lower spatial perception scores than controls.

UNSUSTAINED CENTRAL SEXUAL PRECOCITY IN GIRLS

It is assumed that idiopathic central precocious puberty in girls is progressive and leads to sexual maturity. Its natural course, however, is not well defined. Four girls presented with breast enlargement (B3) at age 4.0-6.0 yrs and have been followed for up to 3.5 yrs. All had normal CT brain scans. Stimulation of LH and FSH by LHRH was excessive for age in all. Estradiol (E2) was 62-122 pmol/L. Bone age was advanced by 1.8 and 2.8 yrs in 2 girls and progressed rapidly in all. Ultrasound visualized follicular ovarian cysts in 3/4. In 2 girls, E2 fell slowly to levels around 40 pmol/L and breast enlargement decreased 1.0 to 1.5 yr after the initial work-up. The other 2 girls showed a regression of clinical signs with normalization of E2 levels after 6 and 10 months, respectively. Another 6 months later, puberty was progressing clinically and biochemically in both. As illustrated, central precocious puberty can be transient and regressing, or fluctuating in its course. This has to be considered when new drugs to control precocious puberty are evaluated for their effectiveness.

BREAST CONTACT THERMOGRAPHY IN DIFFERENTIAL DIAGNOSIS OF PREMATURE THELARCHE AND PRECOCIOUS PUBERTY

In order to contribute to the differential diagnosis between idiopathic Premature Thelarche (PT)and true Precocious Puberty (PP) we performed Breast Contact Thermography (BCT, cholesteric liquid crystal plates) in 13 girls with PT and 12 with PP (previously diagnosed) and in 105 control girls (Tanner's 81-5). We evaluated the 4 principal components (fundus, vascularization, nipple and periareolar heat changes). Arbitrary gradual scores (0,1,2…) were attributed to the maturative signs. A Thermographic Index (TI= sum of the 4 scores of a single breast) and the higher TI (hTI = between the 2 breasts of single girls) were calculated.Results: in controls, single scores, TI and hTI had a positive correlation (r, p<0.001) with B stages. In PT, all signs of vascularization were always (100%) absent, while in PP they were always present, although in some cases monolaterally. The TI of PT was not different from B1 girls and significantly lower (p<0.001) than PP girls and B>1 controls. The hTI ranged from 0 to 3 in PT, from 4 to 13 in PP girls.We conclude that low hTI (≤ 3)and no signs of vascularization indicate PT, while vascular hyperthermia and hTI ≥ 4 indicate PP. We emphasize the useful diagnostic aid of the noninvasive imaging technique of BCT in evaluating the pathophysiology of pubertal breast development.