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PubMed1985

Puberty without gonadotropins. A unique mechanism of sexual development.

Recent evidence suggests that a group of children exists in whom premature sexual maturation occurs in the absence of pubertal levels of gonadotropins; that is, they have gonadotropin-independent precocious puberty. We compared six boys and one girl with this disorder with four boys and five girls with central precocious puberty, in which there is a pubertal pattern of gonadotropin release. The two groups were similar in age of onset, degree of sexual development, growth velocity, and rate of skeletal maturation. A family history of precocity was noted in four of the boys with gonadotropin-independent precocity, and the girl had McCune-Albright syndrome. Children with central precocious puberty demonstrated a pulsatile release of gonadotropins, pubertal responses to luteinizing hormone-releasing hormone, and complete suppression of gonadarche after exposure to an analogue of luteinizing hormone-releasing hormone (LHRHa). In contrast, children with gonadotropin-independent precocity demonstrated an absence of gonadotropin pulsations, variable responses to luteinizing hormone-releasing hormone, lack of suppression of puberty in response to LHRHa, and cyclic steroidogenesis. Tissue from testicular biopsies performed in five of six boys with gonadotropin-independent precocity showed a range from incipient pubertal development of the tubules with proliferation of Leydig cells to the appearance of normal adult testes. We conclude that gonadotropin-independent precocious puberty is a distinct syndrome, of unknown cause, that may be familial and may have been responsible for many previously reported cases of precocious puberty.

Child↗
PubMed2006

A seasonal variation of calcitropic hormones, bone turnover and bone mineral density in early and mid-puberty girls - a cross-sectional study.

The importance of the seasonal variation of calcitropic hormones to growing skeleton has not been established. We studied whether there exists a seasonal variation in calcitropic hormones, bone mineral density (BMD) and bone remodelling markers in early puberty girls. One hundred and ninety-six girls, mean age 11.4 (sd 0.4) years, in Tanner stage 2 (early puberty) and 3 (mid-puberty) were studied during September to March. The BMD was measured from the lumbar vertebrae and the left femur by dual-energy X-ray absoptiometry. Their serum 25-hydroxyvitamin D (S-25-OHD), serum intact parathyroid hormone (S-iPTH), serum osteocalcin, urinary pyridinoline and urinary deoxypyridinoline were analysed from fasting samples. The concentration of S-25-OHD and serum osteocalcin differed among months (P < 0.01), reflecting a seasonal variation. The parathyroid hormone correlated negatively with S-25-OHD (r -0.325, P < 0.001). Moreover, the BMD in the femur (P = 0.047) and to a lesser extent in vertebrae (P = 0.057) differed between months in early puberty girls but this was not seen in mid-puberty. Seasonal variation in S-25-OHD and bone remodelling markers accompanied by negative correlation between S-25-OHD and S-iPTH was seen in this cross-sectional study of adolescent girls. In addition, the seasonal rhythm contributed 7.0-7.6 % difference in the BMD of lumbar vertebrae and left femur in early puberty girls. This variation should be avoided since it could hamper peak bone mass attainment.

Adolescent↗
PubMed2000

Final height and body disproportion in thalassaemic boys and girls with spontaneous or induced puberty.

UNLABELLED: The aim of the study was to evaluate whether sex hormone replacement therapy adversely affected final height and body disproportion in thalassaemic boys and girls. Thirty-six patients with spontaneous (SP) or induced puberty (IP) were studied in order to define the pattern of height growth through three observations: the first (A) at the age of 7-9; the second (B) at onset of spontaneous or induced puberty; and the third (C) when final height was reached. We examined 14 females with SP (f-SP) and 8 with IP (f-IP); 7 males with SP (m-SP) and 7 with IP (m-IP). Girls with IP reached the same final height of girls with SP (f-IP 153.8 (4.3) versus f-SP 154.4 (5.5) cm); p > 0.05) close to target height (f-IP 155.9 (5.2) cm versus f-SP 155.5 (3.6) cm). Girls with IP reached the final height at older chronological age (CA) (17.0 (0.6) y) than girls with SP (CA of 15.3 (0.7) y), but at the same bone age (BA) (f-IP 15.1 (0.9) y versus f-SP 14.8 (0.6) y). There was no difference between the two groups for pubertal growth (f-SP 16.2 (7.7) cm versus f-IP 12.2 (7.4) cm (p > 0.05)) that was negatively correlated with both prepubertal growth and BA at onset of puberty in both groups. Values of sitting height (sds) with respect to BA (SHsdsBA) were not significantly different between the two groups, and showed a worsening from the first observation to final height, reaching values around -2 SD, in both groups. Values of subischial leg length (sds) with respect to BA (SLLsdsBA) were in the normal range at both observations in all girls. High serum ferritin levels were observed in both groups (f-SP 3189 (2296) ng/ml and f-IP 3998 (2545) ng/ml; p > 0.05). Also boys with induced puberty reached the same final height of those with spontaneous one (m-IP 160.9 (5.5) cm versus m-SP 161.8 (2.4) cm; p > 0.05), but it was lower than target height in both groups (m-IP 168.1 (4.1) cm versus m-SP 169.6 (3.2) cm). Boys with IP reached final height at CA of 18.6 (1.1) y slightly older than boys with SP (CA 17.2 (0.9) y), but at the same BA (m-IP 15.9 (1.5) y versus m-SP 16.3 (0.8) y). Pubertal growth values were significantly different between boys with SP 18.9 (5.3) cm and those with IP 13.8 (4.9) cm (p < 0.05), but they were negatively correlated with prepubertal growth values in both groups (m-SP r = -0.91; p < 0.002 and m-IP r = -0.51; p < 0.05). SHsdsBA showed a worsening from the first observation to final height, reaching values around -3 SD in both groups, while SLLsdsBA were always in the normal range in all patients. Serum ferritin levels were higher in boys with IP (3400 (1179) ng/ml) than in those with SP (2020 (496) ng/ml). CONCLUSIONS: Our data showed that: (a) patients of both sexes with induced puberty reached the same final height of patients with spontaneous puberty; (b) all patients showed a body disproportion with truncal shortening and normal leg length that was more severe in boys of both groups at final height; (c) body disproportion was independent of pubertal or prepubertal period of greater height gain, suggesting that sexual steroids replacement therapy did not adversely affect either final height or body disproportion. Further studies, focused on the pathogenesis of the truncal shortening, are necessary in order to acquire more insight into the causes of this impairment.

Adolescent↗
PubMed1979

Twenty-four hour profiles of circulating androgens and oestrogens in male puberty with and without gynaecomastia.

The possible mechanisms involved in the development of transient gynaecomastia during male puberty have been investigated by studying 24 h profiles of circulating androstenedione (Ao) and testosterone (T) and their oestrogen pairs oestrone (E1) and oestradiol(E2), in eight boys with simple delayed puberty, eleven boys with pubertal gynaecomastia (three of whom were re-tested after its spontaneous resolution), and two normal adult men. No differences were observed between the 24h T and Ao profiles of pubertal boys with or without gynaecomastia; we confirmed that the initial T rise was nocturnal, associated with sleep. Late in puberty daytime T levels also rise. A small rise in 24 h Ao was seen, but this was not closely related to the stage of puberty. The major new finding was that E2 and to a lesser extent E1 levels are high relative to T for prolonged periods of the afternoon and evening (when T levels are lowest) in male puberty. A frequent finding, seen only in boys with gynaecomastia and one who later developed it, was of elevated and markedly fluctuating levels of plasma E2, and an absolute increase in the area under the 24 h E2 profile and between the E2 and T profiles. These fell towards normal in three boys who were re-tested after resolution of gynaecomastia. In a minority of subjects T and E2 were quite closely correlated, suggesting that in them rapid aromatization of T was occurring within or outside the testis. We conclude that normal male puberty is associated with relative oestrogen dominance particulary in the daytime. In boys with gynaecomastia there is in addition often an absolute elevation of E2 with or without E1, while 24 h T levels are submaximal. Normal men probably require sustained adult circulating T levels to prevent their oestrogens from stimulating breast development.

Adolescent↗
PubMed1982

Serum immunoreactive melatonin in boys with delayed puberty.

Serum immunoreactive melatonin was measured in thirty-three male subjects with delayed puberty, thirty of whom had simple (idiopathic) delayed puberty (SDP) and three of whom were GH deficient. The results were compared with a control population of twenty-six subjects. Significantly elevated values of serum melatonin were demonstrated in both groups of abnormal subjects as compared with the control population (P less than 0.0001). No significant fall of serum melatonin was noted in the subjects with simple pubertal delay prior to the onset of puberty. However, there was a significant fall of serum melatonin in these subjects between mid and late puberty (P less than 0.025). The results suggest that whilst melatonin may inhibit puberty, a fall in serum levels is not essential for the commencement of puberty in man.

Adolescent↗
PubMed1995

A simplified gonadotrophin-releasing hormone test for precocious puberty.

BACKGROUND AND OBJECTIVE: The gonadotrophin-releasing hormone (GnRH) test is important for the evaluation of children with disorders of puberty. Traditionally, the test determines the peak LH and the peak FSH responses from 5 to 8 blood samples, which makes it cumbersome and costly. We suspected that the test could be simplified to require fewer hormonal measurements. DESIGN: A retrospective clinical study. PATIENTS: Subjects were 44 girls and 7 boys with signs of precocious puberty, of whom 39 were diagnosed as definite central precocious puberty. Fifty-five diagnostic tests and 39 tests for suppression during GnRH-analogue treatment were reviewed. MEASUREMENTS: LH and FSH were measured in serum samples obtained during a standard GnRH test. PARAMETERS: LH and FSH responses and the LH:FSH ratio at 30, 45 and 60 minutes, and the respective peak levels. For each parameter, the sensitivities and specificities were estimated and the receiver operating characteristic curve was constructed. RESULTS: The receiver operating characteristic curves for the LH responses at 30, 45 and 60 minutes and peak, were similar and showed high specificities and sensitivities for the diagnosis of central precocious puberty. A single LH cut-off (15 IU/I) had diagnostic sensitivity > 90% and specificity > 80% for LH concentrations at 30, 45 or 60 minutes and peak, and sensitivity > 90% to detect suppression. Calculations of the LH:FSH ratio did not improve the diagnostic accuracy of the GnRH test achieved by LH alone. CONCLUSIONS: A single LH determination 30 minutes after GnRH administration is as useful as the peak LH; FSH measurements are unnecessary for the differential diagnosis of central precocious puberty. We propose that for the diagnosis of central precocious puberty and for treatment monitoring, the GnRH test to be simplified to LH measurement in a single blood sample at 30 minutes.

Child↗
PubMed1994

A longitudinal study from prepuberty to puberty of gingivitis. Correlation between the occurrence of Prevotella intermedia and sex hormones.

A longitudinal study of 24 subjects progressing normally from prepuberty to puberty was undertaken to evaluate the effects of sex hormone levels on clinical and microbiologic parameters and on serum antibodies. During elementary school, at the beginning of the longitudinal monitoring, 2 groups, 12 subjects with gingivitis and 12 gingivitis-free subjects, were selected and observed through puberty. Bone ages and self-assessment of secondary sex characteristics were used to confirm puberty. A statistically significant increase in the proportions of Prevotella intermedia including Prevotella nigrescens and serum antibody levels against P. intermedia was seen in gingivitis group throughout the longitudinal study. Serum levels of testosterone in boys and estradiol and progesterone in girls was positively correlated with levels of P. intermedia and P. nigrescens. In puberty, a slight but significant increase in GI scores over prepuberty has been shown; however, there was no significant change in PlI from prepuberty to puberty. Our study confirmed that there was a statistically significant increase in gingival inflammation and in the proportion of P. intermedia and P. nigrescens in puberty relative to the baseline value, except in the gingivitis-free male group. Our findings suggest that these increases are correlated with elevation in systemic levels of the sex hormones.

Adolescent↗
PubMed1993

Melatonin and human puberty: current perspectives.

Many studies of melatonin in human puberty are difficult to interpret in light of methodological considerations such as the use of single blood samples collected either during the day or at night; a small number of observations; the failure to include the temporal characteristics of melatonin secretion; the definition of puberty by the use of broad clinical features without use of hormonal markers of puberty; the lack of control for the actual duration and intensity of light exposure during the days preceding the study; and the cross sectional nature of most studies. The few studies that have examined the plasma melatonin rhythm in humans by multiple blood sampling overnight or over 24 hr suggest that normal pubertal development (as well as normal ovarian function) are not linked to alterations in the plasma melatonin profile. There is, however, some evidence to suggest that disorders of the hypothalamic-pituitary-gonadal axis (delayed puberty, precocious puberty, hypothalamic amenorrhea) may be linked to altered plasma melatonin profile, at least in some cases. These findings, taken together with strong evidence for the role of the pineal gland in the reproductive function of other vertebrate species, render unlikely the inference that the pineal gland has no role in the development and function of the human reproductive axis. Thus, one may speculate that a pineal-puberty relation does exist in humans and that the research techniques applied to date have been inadequate to uncover this relation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1997

Longitudinal study of behavioral and affective patterns in girls with central precocious puberty during long-acting triptorelin therapy.

The aim of the present study was to evaluate the behavioral and affective characteristics and the changes in psychosocial functioning resulting from precocious puberty in 15 girls with central precocious puberty treated for 2 y using the GnRH agonist long-acting triptorelin, and in 5 untreated girls. After diagnosis of precocious puberty at 6.6-10.4 y of age, height, weight and pubertal development were evaluated at 3-month intervals over 2 y. Semi-structured interviews were carried out with the patient, the parents and the pediatric endocrinologists at 1, 8, 16 and 24 months after diagnosis. Standardized questionnaires (Child Behavior Checklist, Self-esteem Inventory) were administered at 1 and 24 months or 16 and 24 months, respectively. There was a mean 1.5-y delay between the observation of signs of puberty as reported by the parents and the diagnosis of precocious puberty at the first consultation of a pediatric endocrinologist. Before follow-up, all 20 girls were very concerned about physical differences from peers, particularly breast development. During therapy, breast regression to minimal or absent development occurred in 5/15 treated patients, who then no longer felt embarrassed about pubertal development in contrast to the other patients. Fear of sexuality remained obvious throughout the study in most patients. Feelings of loneliness and exemplary behavior were observed and tended to decrease in the treated patients and to increase in the untreated patients. Elevated scores of withdrawal, anxiety/depression and somatic complaints at Child Behavior Checklist were still observed after 2 y. These changes in behavioral and affective characteristics appeared to be related neither to height and weight, nor to development of pubic hair, which progressed in most patients. After 2 y, the physical differences remained a concern for 13 girls and the risk of short adult stature for 6. In summary, some behavioral and affective characteristics and particularities in psychosocial functioning are observed in girls with precocious puberty. During treatment with long acting triptorelin, problematic behavior and functioning decrease slightly, particularly in the few girls showing breast regression to minimal or absent development.

Affect↗
PubMed1985

Childhood asthma and puberty.

Thirty eight, chronic, perennial asthmatic children were prospectively examined every six months for a mean 8.9 years to clarify the relation between clinical asthma and puberty. Improvement in the disease occurred independent of puberty but the rate of improvement was appreciably greater during puberty. This led to speculation that improvement in childhood asthma could be associated with an immunological process capable of receiving a powerful stimulus from hormones active during puberty. In addition, children whose illness improved before any sign of puberty had developed could be confidently predicted to 'grow out' of their disease. Conversely, if no improvement was seen by the onset of puberty, a much more guarded prognosis was needed.

Age Factors↗
PubMed2002

Early puberty in adopted children.

Early puberty is frequently observed in adopted children. In various studies, early puberty has been associated with decreased final height. In Europe, studies were undertaken to treat early puberty in adopted children with GnRH agonist. This article reviews the current understanding of early puberty in adopted children, including prevalence, background and treatment options. Data from the European studies are briefly described. Besides auxological aspects, psychological items are addressed as well. Studies on the psychological effect of early puberty in adopted children are reported. Future issues include further study in the mechanism of early puberty in adopted children, evaluation of final height results of the growth studies and quality of life assessments in this specific group of children.

Adoption↗
PubMed2002

Factors affecting onset of puberty.

In humans, foetal and early postnatal growth failure may have persistent consequences for growth and pubertal development in later life. During this period, the developing organs are still plastic to change their function, which may have long-lasting effects. At the time of onset of puberty, acute factors may also interfere with pubertal development. Malnutrition, as seen in anorexic patients, and chronic diseases with malabsorption or diseases with systemic effects result in a delayed onset of puberty. We have observed an earlier onset of puberty in girls with low birth weight; menarcheal age also tended to be earlier. In boys, a low birth weight tended to be associated with a later development. Two rat models with growth failure based on perinatal malnutrition have been examined, one with intrauterine growth retardation (IUGR) by ligation of the uterine arteries and one with postnatal food restriction (FR) by increasing the litter size postnatally. In both models, the rats had a persistent postnatal growth failure. The onset of puberty in female rats, defined by vaginal opening, was delayed only in the IUGR group. Despite a significantly lower weight, there was no difference in the timing of puberty onset in the FR group. In IUGR rats, the ovaries had fewer follicles, while FR rats had a normal number of follicles but an abnormal maturation pattern. In male rats, both models showed a delayed onset of puberty, defined by the balano-preputial separation, as well as impaired testicular function, shown by decreased testosterone levels. These data indicate that early malnutrition during a critical developmental time window may have long-lasting effects on pubertal development, including gonadal maturation in both humans and rats.

Adolescent↗
PubMed1994

Psychosocial aspects of precocious puberty.

This paper will deal with the psychologic correlates of abnormal puberty and the implications for assessment and treatment. The main areas of adolescent behavior, equally relevant to the child who undergoes normal or abnormal puberty, are psychosexual development, psychopathology and mental functioning in terms of level of intelligence and cognitive strengths and weaknesses. Regarding psychosexual development, the important findings are that adolescents with precocious puberty tend to be somewhat earlier in starting their adolescent sex life, though they still remain within the normal range of current standards. The reports on psychopathology in children with precocious puberty on a short-term or long-term basis are based on clinical case reports and systematic studies and suggest that a history of precocious puberty may carry with it an increased risk of psychopathology. IQ and school achievement are typically not negatively affected in precocious puberty; in fact, there is a suggestion of the opposite. It may be that there is an advantage in intellectual development associated with early pubertal maturation, which may be temporary rather than long-term.

Adolescent↗
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↗
PubMed2003

Puberty: a finishing school for male social behavior.

The classical view of steroid-dependent organization of brain and behavior holds that gonadal steroid hormones, acting during an early critical period of development, cause permanent structural changes in neural circuits that determine behavioral responses to hormones in adulthood. This classical view has been modified to incorporate evidence that organizational effects of steroids can occur outside of the established perinatal critical period and that multiple critical periods may exist during development. Experiments in this laboratory indicate that steroid-dependent organization of neural circuits underlying male social behaviors occurs during puberty. This work shows that adult-typical reproductive and flank marking behaviors cannot be activated by gonadal steroids in male Syrian hamsters prior to puberty, suggesting that developmentally timed processes during puberty render the nervous system responsive to activating effects of gonadal steroids in adulthood. Additional experiments demonstrate that the presence or absence of gonadal hormones during puberty is a major factor in the ability of steroids to activate reproductive and flank marking behavior in adult male hamsters and in androgen receptor expression within the neural circuit underlying these behaviors. Thus, gonadal hormones during puberty appear to exert long-lasting changes in neural circuits that are responsible for the programming of activational responses to steroids later in adulthood. A two-stage model for maturation of male social behaviors is proposed: a perinatal critical period for sexual differentiation of neural circuits, followed by the pubertal period, during which gonadal steroids further organize the circuits to enhance behavioral responsiveness to hormones in adulthood. Whether puberty is a critical period for the proposed second wave of steroid-dependent organization of behavioral circuits remains to be determined.

Animals↗
PubMed2003

Puberty in growth hormone-treated children born small for gestational age (SGA).

Seventy-five small for gestational age (SGA) children were studied in a randomized, double-blind, dose-response GH trial with either 1 or 2 mg GH/m(2).d. Mean (SD) age at the start of GH therapy was 7.3 (2.2) yr. Data were compared with Dutch reference data. In SGA boys, mean (SD) age at onset of puberty was 12.0 (1.0) and 11.6 (0.7) yr, and in SGA girls it was 10.9 (1.1) and 10.6 (1.2) yr when treated with 1 and 2 mg GH/m(2).d, respectively. SGA boys treated with the lower GH dose started puberty later than the appropriate for gestational age (AGA) controls; for the other GH-dosage groups there was no significant difference in age at onset of puberty compared to AGA controls. The age at menarche and the interval between breast stage M2 and menarche were not significantly different for GH-treated SGA girls compared to their peers. The duration of puberty and pubertal height gain of GH-treated SGA boys and girls were not significantly different between the two GH-dosage groups and were comparable with untreated short children born SGA. In conclusion, long-term GH therapy in short SGA children has no influence on the age at onset and progression of puberty compared to AGA controls, regardless of treatment with a dose of 1 or 2 mg GH/m(2).d. Duration of puberty and pubertal height gain were not significantly different between the GH-dosage groups.

Aging↗
PubMed2004

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.

Aging↗
PubMed1988

Premature thelarche and central precocious puberty: the relationship between clinical presentation and the gonadotropin response to luteinizing hormone-releasing hormone.

Premature thelarche is a benign condition that affects young girls. In contrast, central precocious puberty is considered a more serious disorder that causes progressive secondary sexual development, accelerated growth and skeletal maturation, early epiphyseal fusion, and short adult stature. Differentiation between these 2 conditions is important, but may be difficult on clinical grounds, since patients with both disorders may present initially as isolated breast development. To examine the potential usefulness of gonadotropin measurements in distinguishing early central precocious puberty from premature thelarche, we measured basal and LHRH-stimulated plasma gonadotropin levels in 58 girls with idiopathic premature breast development. The girls were divided into six clinically distinct groups, based on the severity of clinical presentation, ranging from isolated breast development (group A) to complete secondary sexual development and accelerated growth and skeletal maturation (group F). The mean basal plasma LH levels and the peak LH response to LHRH stimulation were significantly less in girls with isolated thelarche (group A) than in girls with complete sexual development (group F). The mean basal plasma FSH levels did not differ between these groups, but the peak FSH response to LHRH was greater in girls with isolated thelarche than in girls with complete sexual development. Thus, girls with isolated premature thelarche had a FSH-predominant response to LHRH [mean ratio of peak LH to peak FSH, 0.29 +/- 0.10 (+/- SD)], while girls with complete sexual development had a LH-predominant response (peak LH/FSH, 4.16 +/- 1.80). All girls with isolated thelarche had peak LH/FSH ratios less than 1, and all girls with complete sexual development had a ratio greater than 1. Girls with early or intermediate manifestations of central precocious puberty, who had features of puberty in addition to breast development but lacked all of the features of group F, comprised groups B-E. These girls also had intermediate peak LH/FSH ratios, ranging from 0.29 +/- 0.10 (group B) to 3.35 +/- 2.66 (group E). We conclude that girls with early central precocious puberty frequently have LH and FSH responses to LHRH that are indistinguishable from the FSH-predominant responses of girls with isolated thelarche. These data are consistent with the hypothesis that premature thelarche and central precocious puberty may represent different positions along a continuum of hypothalamic LHRH neuron activation.

Breast↗