lhrh--ala(6)-gly(10)-ethylamide- and Puberty--Precocious

Bone age (BA) indicates more clearly than chronologic age how far an individual has progressed toward full maturity, and predicts the potential for further growth. Single or serial skeletal age estimations help to confirm the diagnosis of normal puberty and normal pubertal variants such as constitutional delay of growth and puberty, premature therlache, and precocious adrenarche. BA can aid in the clinical workup of children whose sexual maturation is early or delayed. Although BA is considered a qualitative rather than quantitative measure, it serves to round out the clinical picture, providing information without which diagnosis could not be achieved.

Topics: Adolescent; Adolescent Development; Age Determination by Skeleton; Body Height; Bone Development; Child; Child Development; Epiphyses; Female; Gonadotropin-Releasing Hormone; Growth Disorders; Growth Hormone; Humans; Male; Puberty; Puberty, Delayed; Puberty, Precocious

Experiments of nature and clinical observations have provided indications that postponing puberty may increase final height in short children. In children with central precocious puberty, a GnRH analog (GnRHa) alone is efficacious in increasing final height, but in other conditions a combination of growth hormone (GH) and GnRHa is needed. In GH-deficient children with early onset of puberty and poor height prediction, the combination of GH and GnRHa increases final height by 1.0-1.3 s.d. In children with idiopathic short stature and persistent short stature after intrauterine growth retardation, the combination also appears to be beneficial. Potential side effects include weight gain, a negative effect on bone mineralization, and psychosocial consequences. More data on long-term safety have to be collected before the combination of GH and GnRHa in children with idiopathic short stature should be considered for clinical use outside clinical trials.

Topics: Adaptation, Psychological; Body Height; Body Weight; Calcification, Physiologic; Child; Drug Therapy, Combination; Fetal Growth Retardation; Gonadotropin-Releasing Hormone; Human Growth Hormone; Humans; Puberty; Puberty, Precocious; Weight Gain

Estrogens, GH and IGFs are essential in the development and growth of the skeleton and for the maintenance of bone mass and density. Treatment of precocious puberty with GnRH analogs (GnRHa), by reducing sex steroid levels, leads to a situation of hypoestrogenism that may theoretically have a detrimental effect on bone mass during pubertal development. A reduction in bone mineral density (BMD) during GnRHa treatment has been demonstrated, but GnRHa treatment in patients with central precocious puberty (CPP) does not seem to impair the achievement of normal peak bone mass (PBM) at final height. However, calcium supplementation is effective in improving bone densitometric levels and may promote better PBM achievement. In children and adolescents with GH deficiency (GHD), BMD assessed by dual-energy X-ray absorptiometry (DEXA) and bone turnover are significantly reduced, but they are stimulated by GH treatment. GH treatment leads to improved bone density, function of the dose and duration of treatment, and patients may require prolonged GH treatment beyond the time of growth to improve PBM. After the discontinuation of GH therapy, the more active population had higher bone mineral content (BMC) levels than patients with low physical activity. In our experience, the therapeutic association of GH and calcium also represents a valuable tool in pursuing a proper BMC in GHD patients. We concluded that nonhormonal factors, such as physical activity and nutritional factors, are important in determining bone metabolism and bone mass.

Topics: Adolescent; Bone Density; Bone Development; Child; Drug Therapy, Combination; Exercise; Gonadotropin-Releasing Hormone; Growth Disorders; Growth Hormone; Human Growth Hormone; Humans; Nutritional Physiological Phenomena; Puberty, Precocious

Studies have reported that women with early menarche (≤10 years) have lower lung function.. To investigate lung function in women with a history of idio pathic central precocious puberty (ICPP) treated during childhood with gonadotropin-releasing hormone agonist (GnRHa).. ICPP women (n = 23) were compared with healthy age-matched controls (n = 23). Subjects were clinically evaluated by means of a questionnaire, baseline and post-β₂ agonist spirometry, impulse oscillometry (a measure of airway resistance), and measurement of fractional exhaled nitric oxide (FeNO).. Patients had lower lung function values than controls: forced expiratory volume in 1 s (FEV₁) (median 97.90 vs. 109.45; p = 0.011), FEV₁ after β₂ agonist (100.80 vs. 114.10; p = 0.013), peak expiratory flow (92.90 vs. 97.95; p = 0.031), and maximum mid-expiratory flow (MMEF) (80.80 vs. 106.30; p = 0.008). FeNO was significantly lower in the patients (p < 0.001). Significant reversibility of FEV₁ after β₂ agonist was observed in 8.7% of the patients. FEV₁/forced vital capacity and MMEF after β₂ agonist correlated negatively with hysterometry at diagnosis (p = 0.009 and p = 0.03, respectively). There was a negative correlation between age at diagnosis and airway resistance.. Women with ICPP seem to have lower lung function despite treatment with GnRHa. Further research on the effects of sex hormones on the airways should take into account potential interplay with factors affecting the start of puberty.
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Topics: Adolescent; Adult; Female; Gonadotropin-Releasing Hormone; Humans; Lung; Pilot Projects; Puberty, Precocious; Respiratory Function Tests

To investigate the effects of treatment with gonadotropin-releasing hormone analog (GnRHa) on final height in girls who experienced moderately early puberty with symptoms beginning at 7-8.5 years of age.. Female cases diagnosed with moderately early puberty which had started between ages 7 to 8.5 years were included in the study. In the treatment groups, all cases with a bone age ≤10.5 years constituted group 1 (n=18) and those with a bone age >10.5 years constituted group 2 (n=23). The 8 patients for which treatment approval could not be obtained constituted group 3. The 49 cases in all three groups were observed until they reached their final height.. Target height, target height standard deviation score (SDS), final height, and final height SDS values were similar in all 3 groups. Final height showed a significant positive correlation with target height (p=0.000, r=0.54) and height at diagnosis (p=0.003, r=0.467) in all groups. Linear regression analysis revealed that a 1 cm longer height at diagnosis increased the final height 0.213 fold, and a 1 cm longer target height at diagnosis increased the final height 0.459 fold.. We found that GnRHa did not make a positive contribution to final height in cases of moderately early puberty.

Topics: Body Height; Child; Female; Gonadotropin-Releasing Hormone; Growth Disorders; Humans; Puberty, Precocious

Gonadotropin-releasing hormone analogues (GnRHa) are the accepted treatment of idiopathic central precocious puberty. As it has been found that growth velocity may be decreased with GnRHa treatment, clinical trials with GnRHa combined with growth hormone (GH) have been carried out. In a recent study 46 adopted girls with early or precocious puberty were randomly assigned to treatment with either GnRHa or GnRHa combined with GH, and followed to final height (FH). It was found that FH was significantly higher in the combined treatment group, 158.9 compared with 155.8 cm in the GnRHa treated group. In order to select the patients who could benefit from added GH, predictions of FH at the start of treatment according to the methods of bone age determination of Greulich-Pyle (GP) and Tanner-Whitehouse 2 (TW2) were compared. It was found that the GP method was the most useful method for patient selection. Recently, a revision of the Tanner-Whitehouse method, named Tanner-Whitehouse 3 (TW3), has been developed. The present study examined the usefulness of the TW3 method in selecting suitable patients for combined treatment.. The TW3 method bone age determinations of the 46 girls were compared to the GP and TW2 method determinations, using the differences between actual FH and predicted adult height (PAH). Beside accuracy of prediction of FH, the criteria of efficiency of selection and replicability were applied in the comparison.. We found that the GP method, also when compared to the TW3 method, gave the most accurate prediction of the FH on only GnRHa treatment. This gives the best ground for selection of patients who can benefit from combined treatment. The GP method was also the most efficient in selecting patients, i.e., it could select the least number of patients that needed the combined treatment. The only drawback of the GP method was that it requires an experienced pediatric radiologist. Automated methods are being developed and may soon facilitate the use of the GP method for those less experienced. The FH after combined treatment could be predicted with an equation including PAH GP as well as PAH TW3 as variables.. The GP method remains the most useful method for selection of those patients who will benefit most from the addition of GH to GnRHa in the treatment of idiopathic central precocious or early puberty. FH prediction after combined treatment requires PAH GP as well as PAH TW3.

Topics: Administration, Intranasal; Adoption; Age Determination by Skeleton; Body Height; Child; Diagnostic Techniques, Endocrine; Drug Combinations; Female; Gonadotropin-Releasing Hormone; Human Growth Hormone; Humans; Predictive Value of Tests; Prognosis; Puberty, Precocious

Hypothalamic hamartoma (HH) represents the commonest cause of organic central precocious puberty (CPP). Follow-up of these patients in adulthood is scarce.. To describe the anthropometric, metabolic, and reproductive parameters of patients with CPP due to HH before and after treatment with gonadotropin-releasing hormone analog (GnRHa).. We performed a retrospective and cross-sectional study in a single tertiary center including 14 patients (7 females) with CPP due to HH.. The mean duration of GnRHa treatment was 7.7 ± 2.4 years in boys and 7.9 ± 2.1 years in girls. GnRHa treatment was interrupted at the mean chronological age (CA) of 12.1 ± 1.1 years in boys and 10.7 ± 0.5 years in girls. At the last visit, the mean CA of the male and female patients was 21.5 ± 3.2 and 24 ± 3.9 years, respectively. Eleven of the 14 patients reached normal final height (FH) (standard deviation score -0.6 ± 0.9 for males and -0.6 ± 0.5 for females), all of them within the target height (TH) range. The remaining 3 patients had predicted height within the TH range. The mean body mass index and the percentage of body fat mass was significantly higher in females, with a higher prevalence of metabolic disorders. All patients presented normal gonadal function in adulthood, and 3 males fathered a child.. All patients with CPP due to HH reached normal FH or near-FH. A higher prevalence of overweight/obesity and hypercholesterolemia was observed in the female patients. Finally, no reproductive disorder was identified in both sexes, indicating that HH per se has no deleterious effect on the gonadotropic axis in adulthood.

Topics: Adiposity; Body Height; Body Mass Index; Cross-Sectional Studies; Female; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Diseases; Longitudinal Studies; Male; Puberty, Precocious; Reproduction; Retrospective Studies; Treatment Outcome; Young Adult

Central precocious puberty (CPP) is fairly common in girls. In most girls, the etiology for the CPP is unknown. Among the more rare causes of CPP in girls are central nervous system tumors and hamartomas. Osteolipoma of the tuber cinereum, which is the most commonly diagnosed at autopsy, has been reported as a cause of CPP. We describe an 8-year-old girl with central precocious puberty in whom MRI demonstrated a lesion compatible with osteolipoma. Her symptom was breast development that begun at age 7 years and 9 months. Her case history, laboratory studies and imaging are presented. Her puberty was rapidly progressive. She was treated successfully with a GnRHa (Triptorelin 3.75 mg IM q 4 weeks). Her case brings to the forefront the need to perform an MRI in children with rapidly progressing puberty.

Topics: Adrenal Gland Neoplasms; Algorithms; Child; Diagnosis, Differential; Female; Fibrous Dysplasia of Bone; Gonadotropin-Releasing Hormone; Humans; Hypothalamic Neoplasms; Lipoma; Magnetic Resonance Imaging; Ovarian Cysts; Ovarian Neoplasms; Puberty, Precocious; Treatment Outcome; Tuber Cinereum

Improving the final adult height is one of the most important aims for treatment of central precocious puberty. Stanozolol (ST) is a synthetic derivative of androgen. In this study, we investigated the effects and the mechanisms of ST on the proliferation of growth plate chondrocytes isolated from adolescent rats treated with gonadotropin-releasing hormone analogue (GnRHa). Treatment with ST resulted in time- and concentration-dependent effects on proliferation as determined by MTT and proliferating cell nuclear antigen (PCNA) assays. Western blotting showed that ST increased the phosphorylation level of the estrogen receptor alpha (ERalpha), but not the androgen receptor (AR). Pharmacological inhibition of ERalpha and mitogen-activated protein kinase (MAPK) attenuated the effects of ST on the proliferation of growth plate chondrocytes. A molecular dynamics simulation showed hydrophobic interactions between ST and ERalpha. These results suggested that ERalpha, but not AR, partially mediates the ST-driven proliferation of growth plate chondrocytes, and that multiple pathways may be involved in the mechanism of action of ST.

Topics: Animals; Binding Sites; Body Height; Cell Proliferation; Child; Chondrocytes; Disease Models, Animal; Estrogen Receptor alpha; Female; Gonadotropin-Releasing Hormone; Growth Plate; Humans; Male; MAP Kinase Signaling System; Molecular Dynamics Simulation; Phosphorylation; Puberty, Precocious; Rats; Receptors, Androgen; Stanozolol

The objective of the study was to determine whether height gain after discontinuation of gonadotropin-suppressive (GnRHa) therapy differs in girls with sexual precocity diagnosed at various ages and assess its influence on final height (FHt) outcome.. We compared data on post-GnRHa treatment course and FHt of 115 girls [22 diagnosed before chronological age of 6 yr; 38 between ages 6 and 8 yr; and 55 early fast puberty (EFP) between ages 8 and 9 yr] treated with GnRHa from Tanner stage 2-3 to chronological age 11-12 yr and bone age 12-12.5 yr.. Despite comparable bone age at cessation of treatment, similar time to resumption of puberty (0.6 +/- 0.7, 0.5 +/- 0.7, and 0.5 +/- 0.7 yr), and age at menarche (12.6 +/- 0.5, 12.6 +/- 0.6, and 12.7 +/- 0.9 yr), height gain from cessation of therapy to FHt was greater and time to epiphyseal fusion was longer in the younger central precocious puberty (CPP) than in the older CPP (P < 0.05) and EFP (P < 0.001) groups. The percentage of residual growth predicted at discontinuation of treatment was achieved only by the younger CPP (6.6 +/- 1.6% vs. 6.7 +/- 1.6%), whereas in older CPP and EFP, it was significantly lower (6.2 +/- 1.6% vs. 4.6 +/- 2.7% and 6.3 +/- 1.5% vs. 3.6 +/- 1.5%, respectively). FHt of these two groups was compromised, compared with FHt predicted at discontinuation of treatment (P < 0.01 and P < 0.001, respectively).. Girls with sexual precocity diagnosed after the age of 6 yr exhibit earlier epiphyseal fusion with diminished posttreatment height gain and compromised FHt. Because recovery of gonadal axis was similar in all girls, differences were probably due to pretreatment intrinsic changes in the growth plate. Prediction of residual growth at discontinuation of treatment is unreliable in these girls.

Topics: Body Height; Child; Child Development; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Puberty, Precocious; Retrospective Studies; Withholding Treatment

Topics: Adolescent; Child; China; Female; Genitalia, Female; Genitalia, Male; Gonadotropin-Releasing Hormone; Humans; Male; Puberty, Precocious

Hypothalamic hamartoma (HH) is one of the most frequent causes of organic central precocious puberty (CPP). We compared the clinical presentation and the magnetic resonance images (MRI) of 19 patients with HH aged 5.7 +/- 4.1 (SD) years at the first endocrine evaluation. They had isolated CPP (group 1, n = 9), CPP plus gelastic seizures (group 2, n = 5), isolated seizures (group 3, n = 4), and 1 patient was asymptomatic.. All patients without neurological symptoms (group 1 and the asymptomatic patient) had pedunculated lesion (diameter 6.4 +/- 3.6 (3-15) mm), suspended from the floor of the third ventricle. All patients with neurological symptoms (groups 2 and 3) had sessile lesion (diameter 18.3 +/- 9.6 (10-38) mm, p = 0.0005 compared to the others), located in the interpeduncular cistern with extension to the hypothalamus. Seven patients were overweight. The growth hormone peak, free thyroxine, cortisol and prolactin concentrations, and the concomitant plasma and urinary osmolalities were normal in all the cases evaluated. The mean predicted or adult heights of 10 patients treated 5.2 +/- 3.3 years for CPP with gonadotropin hormone releasing hormone (GnRH) analog were -0.3 +/- 1.7 SD, similar to their target height -0.1 +/- 0.9 SD.. The clinical presentation of HH depends on its anatomy: small and pedunculated HH are associated with CPP, while large and sessile HH are associated with seizures. The hypothalamic-pituitary function in these cases is normal, which suggests that the absence of CPP is not due to gonadotropin deficiency. GnRH analog treatment preserves the growth potential in those with CPP.

Topics: Adolescent; Child; Child, Preschool; Epilepsies, Partial; Epilepsy; Female; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Infant; Magnetic Resonance Imaging; Male; Puberty, Precocious

Topics: Bone Density; Buserelin; Child; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Puberty, Precocious; Receptors, Estrogen