Leptin levels in children with central precocious puberty

Several studies have suggested that sufficient serum leptin levels may be involved in the initiation of puberty. To assess further the relationship between leptin and the onset of puberty in humans, we measured the serum leptin concentration in children with central precocious puberty (CPP). We studied 65 children with either idiopathic (IPP; n = 50 girls and 3 boys) or neurogenic central precocious puberty (NPP; n = 5 girls and 7 boys). The serum leptin levels in these patients were compared with normative data from healthy children and adolescents using SD scores that adjust for body mass index (BMI) and Tanner stage. The mean SD scores of IPP and NPP girls were +0.4 +/- 0.1 and +1.0 +/- 0.5, respectively, compared with that of age-matched prepubertal girls and +0.7 +/- 0.2 and +1.6 +/- 0.6 compared with that of girls matched for pubertal stage. The CPP girls with lower BMIs contributed larger SD scores, such that the leptin SD score was negatively correlated with BMI. A similar, modest increase in leptin levels in the CPP girls was evident when additional normative data were considered. The mean leptin SD scores of IPP and NPP boys were -0.9 +/- 0.5 and +0.7 +/- 0.3, respectively, compared with that of normal boys at Tanner stage 3-4. Serum leptin levels in the boys with CPP were not different from those in healthy boys in any of the normative studies. These data should be interpreted cautiously, but they suggest that girls with CPP have modestly elevated serum leptin concentrations compared with those in healthy children and adolescents. In addition, the negative correlation between the leptin SD score and BMI suggests that sufficient leptin levels may be associated with initiation of puberty in girls.     

The impact of reversible gonadal sex steroid suppression on serum leptin concentrations in children with central precocious puberty

OBJECTIVE: Evaluation of clinical course and outcome of hypertrophic cardiomyopathy in a representative Greek population. BACKGROUND: Hypertrophic cardiomyopathy is characterized by unexplained left ventricular hypertrophy and varied clinical expression. Recent studies suggest ethnic differences. MATERIALS AND METHODS: One hundred seventy-four consecutive Greek patients (117 male, 57 female, age 47+/-16 years) from 143 different families were assessed at the Department of Cardiology of the University of Athens, Greece, and the State Cardiac Department, Hippokration Hospital, both located in Athens, Greece. To reduce selection bias, referral was based on disease diagnosis irrespective of clinical status or treatment needs. All patients were examined clinically, echocardiographically, and by ECG ambulatory monitoring at 6-month intervals for a period of 74+/-22 months (range, 8 to 108 months). RESULTS: Most patients (n = 156, 89.7%) were in New York Heart Association (NYHA) functional class I or II. The disease was familial (at least one affected first-degree relative) in 81 of the 143 families (56.6%), and in 19 of these (13.3%) there was familial history of sudden cardiac death. At initial examination, intraventricular septal thickness was 17.3+/-4.1 mm and posterior wall thickness was 13.7+/-3.8 mm and a left ventricular outflow gradient >30 mm Hg was present in 58 patients (33.3%). Similar were the findings during the last examination (17.5+/-4.3 mm, 13.5+/-4.4 mm, and 56 (32.2%, respectively, p = not significant). Episodes of nonsustained ventricular tachycardia were noted in 15 patients (8.6%). There were eight deaths during follow-up: four sudden deaths and four from intractable heart failure. Syncope was reported by all patients who died. The annual mortality in this study was 1%. Syncope and NYHA class were the only predictors of outcome. CONCLUSIONS: In this representative Greek patient cohort with hypertrophic cardiomyopathy, the arrhythmogenic substrate was modest and the clinical course benign. Sudden cardiac death was infrequent and syncope, functional class, and ventricular arrhythmias were the only predictors of a poor outcome.     

Gonadotrophin and prolactin secretory dynamics in girls with normal puberty, idiopathic precocious puberty and precocious puberty due to hypothalamic hamartoma

OBJECTIVE: This study was designed to test the hypothesis that hypothalamic hamartoma causes precocious puberty through a different neuroendocrine mechanism than that of normal puberty or of idiopathic precocious puberty. DESIGN AND PATIENTS: We compared the pattern of gonadotrophin secretion among 4 girls with precocious puberty due to hypothalamic hamartoma, 27 girls with idiopathic precocious puberty, and 14 girls with normal puberty. All subjects were breast stage 3 or 4. Blood samples were obtained every 20 min for 4 h during the day (1.000 hours to 1400 h) and night (22.00 hours to 0200 h). MEASUREMENTS: LH, FSH, and prolactin were measured in each blood sample. Girls also underwent LHRH-stimulation with measurement of LH and FSH before and after stimulation. RESULTS: There were no significant differences in mean LH level, LH peak amplitude, or LH or FSH peak frequency during either the day or the night among the three diagnostic groups. However, the mean +/- SD LHRH-stimulated peak LH levels were greater in girls with hypothalamic hamartoma than in girls with normal puberty or with idiopathic precocious puberty (194 +/- 142 vs 85 +/- 60 or 66 +/- 54 IU/l, respectively, P < 0.05). The LHRH-stimulated peak FSH level in girls with hypothalamic hamartoma exceeded the level for the normal pubertal girls (31 +/- 19 vs 17 +/- 7 IU/l, P < 0.05), but not the level for the girls with idiopathic precocious puberty (25 + 12 IU/l). The peak LH to peak FSH ratio in the girls with hypothalamic hamartoma exceeded the ratio for the girls with idiopathic precocious puberty (7.3 +/- 3.9 vs 2.6 +/- 3.0 IU/l, P < 0.05), but not the ratio for the normal pubertal girls (5.0 + 2.9). There were no significant differences in mean prolactin level, peak amplitude or frequency, or in the ratio of mean night to mean day prolactin, among the 3 diagnostic groups. CONCLUSIONS: We conclude that spontaneous gonadotrophin and prolactin secretion are similar among girls with hypothalamic hamartoma, idiopathic precocious puberty, or normal puberty. However, the increased LHRH-stimulated peak LH in the girls with hypothalamic hamartoma suggests subtle differences in neuroendocrine regulation that may underlie their more rapid pubertal maturation.     

Adult height in girls with idiopathic true precocious puberty

GnRH analogs are used to suppress pituitary-gonadal activity in children with true precocious puberty. The indications for therapy in this situation are not established, as some girls have a slow evolutive form, and the capacity of GnRH analogs to preserve the adult height has not been evaluated. This study analyzes the growth and adult heights of 2 groups of girls with idiopathic true precocious puberty, 1 with a predicted height of 155 cm or less (group 1, 19 cases) and the other with a predicted height of more than 155 cm (group 2, 15 cases). Group 1 patients were treated with a long-acting GnRH analog (D-Trp6-GnRH), and group 2 patients were followed without therapy. Group 1 showed greater clinical signs of estrogenization, vaginal maturation index (P < 0.03), plasma estradiol (P < 0.0004), and ratio of LH/FSH peaks (P < 0.01) at the initial evaluation than did group 2. The mean target heights were similar (difference, 0.9 cm). In group 1, the adult height (159 +/- 1.1 cm) was greater than the predicted height before therapy (152 +/- 1.4 cm; P < 0.0001). The difference between the adult height and the predicted height before therapy (mean, 6.5 cm) correlated positively with the bone age advance (P < 0.01), negatively with the predicted height (P < 0.05), and positively with the difference between the target and predicted heights (P < 0.001) before therapy. In group 2, the adult height (162 +/- 1.4 cm) was similar to the predicted height at the initial evaluation (162.5 +/- 1.4 cm). Adult heights correlated with target height in group 1 and with predicted height at the initial evaluation in group 2. In conclusion, some girls with true precocious puberty and poor adult height prediction who are treated with GnRH analog achieve an adult height more comparable to their target height. However, the lack of effect on height in girls with predicted height at the onset of therapy similar to their target height and preservation of the growth potential in the slow evolutive forms suggest that these forms might not require immediate therapy. Careful follow-up before therapy may be a better way of evaluating their natural course.     

Echographic and sonographic study of ovaries in girls with precocious puberty

The aim of this study is the biometrical and morphological evaluation of the ovaries by sonography and the study of the haemodynamics of the ovarian artery flow by doppler ultrasound in 14 girls with precocious puberty and in 33 control subjects. All people ranged in age from 5 to 7 years. The gonadian mean volume and the mean pulsatility index have been evaluated. A significant difference in the ovarian volume has been found between patients and controls. No index between the two groups. We conclude that the doppler ultrasound needs a larger number of cases to evaluate its validity in girls with precocious puberty.     

Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate

Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s-PIIINP changed significantly with age and pubertal development stages. For s-PIIINP, a peak was seen at 12 yr for girls and 13 yr for boys; no peak could be discerned for s-PICP. The prepubertal (Tanner stage 1) s-PICP value (mean +/- SD) for girls was 374 +/- 132 micrograms/L, the midpubertal value (stage 3) was 442 +/- 135 micrograms/L, and the postpubertal value (stage 5) was 203 +/- 103 micrograms/L. The mean s-PIIINP levels for girls were 9.1 +/- 2.4, 15.0 +/- 4.3, and 6.8 +/- 3.1 micrograms/L, respectively. For boys, levels were 362 +/- 119, 544 +/- 138, and 359 +/- 256 micrograms/L for s-PICP and 8.5 +/- 2.2, 14.5 +/- 5.0, and 8.6 +/- 3.8 micrograms/L for s-PIIINP (P < 0.001 for both propeptides in both boys and girls). There was, however, a large variation in normal values for both propeptides within the age groups and pubertal stages. There was a significant correlation of s-PICP and s-PIIINP levels to height velocity in girls (r = 0.35; P < 0.001 and r = 0.33; P < 0.001, respectively), while in boys, only s-PIIINP showed significant correlation to height velocity (r = 0.40; P < 0.001). In untreated girls with CPP, serum levels of s-PIIINP were elevated [PIIINP SD score (SDS), 2.13]. Levels of s-PICP were normal (PICP SDS, 0.39). Levels of both propeptides decreased within 2 months after initiation of therapy and remained below initial values (P < 0.01). The decrease in s-PIIINP after 2 months of therapy showed a significant correlation with the fall in height velocity SDS for chronological age after 6 months of therapy (r = 0.64; P < 0.01). We conclude that s-PIIINP and, to a lesser degree, s-PICP reflect growth in normal children, but due to the large variation, both propeptides seem unsuitable as markers for screening of growth disorders in children.     

A female case of the HCG-producing ectopic pinealoma associated with precocious puberty

Report on a 5 year old girl with the caracteristic features of the partial trisomy of the short arm of a chromosome no.4: short stature, microcephaly, hydrocephaly, enophthalmus, bulbous nose, deep set malformed ears, hypertrichosis, brachydactyly, hypoplastic ribs, abnormal EEG, imbecility. Trisomy originated from a reciprocal translocation in the father (46, XY, rcp (4;11) (p 13; q23)). q23)).     

Primary intrasellar mixed germ-cell tumor with precocious puberty and diabetes insipidus

A case-control study using data from the Baltimore-Washington Infant Study (BWIS) examined possible paternal risk factors in the etiology of isolated membranous ventricular septal defects (VSD). There were 641 total VSD case infants and 3,549 randomly selected control infants ascertained between 1981 and 1989. Isolated membranous VSDs were identified in 499 cases. Socio-demographic factors (such as parental age and race), social habits, and medical conditions were analyzed by multiple logistic regression in order to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Paternal age was not found to be a risk factor per se, but small positive associations were found for some social habits and maternal factors. Significant associations were found for paternal marijuana use (OR 1.36, 95% CI 1.05-1.76), African-American race of the infant (OR 1.34, 95% CI 1.09-1.65), and for cocaine use among older fathers (OR 3.92, 95% CI 1.30-11.86). These associations support a multifactorial etiologic hypothesis for isolated membranous VSDs and point to some interesting parental behavioral and medical considerations which may contribute to risk for this common birth defect.     

Hypothalamic hamartoma with skeletal malformations, gelastic epilepsy and precocious puberty

A child is described who has skeletal malformations, gelastic epilepsy, precocious puberty and a hypothalamic hamartoma. The skeletal abnormalities were detected at birth, she developed gelastic epilepsy at the age of 3 years 5 months and precocious puberty at 3 years 8 months. A hypothalamic hamartoma was found on MRI. The precocious puberty has been successfully medically managed, though her seizures are difficult to control. The combination of all four features has not been described previously.     

Mediastinal germ cell tumor in a child with precocious puberty and Klinefelter syndrome

An 8-year-old boy presented with precocious puberty and a mediastinal mass. A computer search showed that this rare presentation is most common with germ cell tumor of the mediastinum in children with Klinefelter syndrome. The tumor was completely resected after preoperative chemotherapy, and the patient is well 2 years after the operation. In patients with Klinefelter syndrome, germ cell tumors are 50 times more common than in patients without Klinefelter syndrome, usually contain nonseminomatous elements, present at an earlier age, and are seldom testicular in location.     

Hepatocellular carcinoma associated with precocious puberty and oral contraceptives. A case report

A 36-year-old woman presented with sudden abdominal pain and vomiting. Computed tomography showed a tumour of the right hepatic lobe with possible signs of acute haemorrhage. Her medical history revealed precocious puberty when she was a 5-year-old and the use of oral contraceptives for 18 years. Bisegmentectomy was performed and histological examination revealed hepatocellular carcinoma. The role of male and female sex hormones in the development of hepatic tumours has been well documented but, to our knowledge, association with precocious puberty has not yet been described.     

A super long-acting LH-RH analogue induces regression of hypothalamic hamartoma associated with precocious puberty

We treated a 1-year-old female with a hypothalamic hamartoma and precocious puberty with leuprolide acetate depot, a super long-acting hormone-releasing hormone analogue (Tap-144-SR; [D-Leu6-[des-Gly10-NH2] LH-RH ethylamide acetate). The infant's major symptoms were genital bleeding and gynaecomastia. The LH-RH analogue (30 micrograms/kg) was injected subcutaneously once every 4 weeks. Clinical and laboratory manifestations of precocious puberty showed marked improvement. A follow-up after 16 months of treatment, the size of the tumour decreased significantly and remained unchanged for 2 years of further follow-up. To the best of our knowledge, this is the first hypothalamic hamartoma case in whom a decrease of tumour size under treatment with LH-RH analogue has been documented. But, because diagnosis of hamartoma is only based on neuroradiological and not on histological examinations, the possibility of a gangliocytoma cannot be excluded with certainty.     

Luteinizing hormone secreting adrenal tumour as a cause of precocious puberty

OBJECTIVE: This study examined whether a selective serotonin reuptake inhibitor (paroxetine) had comparable efficacy but greater tolerability than a tricyclic antidepressant (imipramine) in depressed patients with HIV infection. METHOD: Seventy-five HIV-positive patients (45% of whom had AIDS) were blindly and randomly assigned to receive paroxetine (N = 25), imipramine (N = 25), or placebo (N = 25) in a 12-week trial. The Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, the Clinical Global Impression scale, and the SAFETEE general inquiry (for safety and tolerability) were administered at weeks 2, 4, 6, 8, and 12. RESULTS: Fifty-six (75%) of the 75 patients completed 6 weeks and 34 (45%) completed 12 weeks of the trial. The mean daily doses of both paroxetine (33.9 mg) and imipramine (162.5 mg) were significantly more effective than placebo; they were comparably effective at weeks 6, 8, and 12 according to the intent-to-treat analysis and at week 8 according to the analysis for the subjects who completed the trial (for them, only imipramine was superior to placebo at week 12). There were significantly more dropouts due to side effects from imipramine (48%) than from both paroxetine (20%) and placebo (24%). CONCLUSIONS: Depressed patients with HIV infection responded to imipramine or paroxetine at a higher rate than to placebo irrespective of severity of immunosuppression. Because paroxetine was much better tolerated than imipramine, its overall effectiveness may be greater. However, because of the small study group and the high attrition rate, these findings cannot be generalized and may need replication in a larger study group.     

46,XX/69,XXX diploid-triploid mixoploidy with hypothyroidism and precocious puberty

We report a 20 month old female patient with diploid-triploid mixoploidy (46,XX/69,XXX) syndrome with hypothyroidism and precocious puberty. The triploid cell line was only expressed in the fibroblast culture and comprised the majority (95%) of the cells. Chromosome analysis of the fetal blood sample and peripheral blood sample were normal. The patient shows typical features of full triploidy (growth and severe mental retardation, cranial and facial dysmorphism, complete syndactyly of fingers 3/4, partial syndactyly of toes 2/3) and facial but no body asymmetry. At the age of 5 months central hypothyroidism and precocious puberty were diagnosed. Thin pigmented streaks were visible on the wrists and legs of the patient at the age of 16 months. This is the first patient reported so far with 46,XX/69,XXX mixoploidy suffering from hypothyroidism and precocious puberty.     

Cognitive abilities and hemispheric lateralization in females following idiopathic precocious puberty.

Compared 12 right-handed adolescent females with a history of idiopathic precocious puberty (IPP) to 12 closely pair-matched normal controls of similar maturational status. All Ss were aged 13–20 yrs. Cognitive abilities were assessed by subtests of the WISC and Primary Mental Abilities Test, and by combination scales derived from these subtests. Brain hemispheric lateralization was measured by 2 dichotic listening tests. Results show that IPP Ss and controls did not differ in verbal abilities or in dichotic consonant–vowel discrimination. IPP was associated with lower spatial ability. It is concluded that pubertal maturation is associated with spatial but not verbal ability. Left-hemisphere functioning does not seem to constitute a mediating mechanism for this association but a slight weakness of right-hemisphere functioning is suggested by poor left-ear performance on the staggered spondaic word test. (47 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Irreversible increase of serum IGF-1 and IGFBP-3 levels in GnRH-dependent precocious puberty of different etiologies: implications for the onset of puberty

Contemporary prostheses have developed from small iterations on moderately successful archetypes. This has resulted in modern designs that can either be termed cosmetic or functional, with neither attribute being fully satisfied. A new strategy is needed to develop a generation of upper-limb prostheses that will integrate both cosmetic and functional requirements in a single device. It is hypothesized that design principles applicable to a new generation of prostheses will result from exploring close analogies to the human upper limb. A method of practice led design research has been adopted to explore appropriate analogies, using the production of physical models to elucidate the design problem to the design team and other interested parties. This method uses a consciously iterative approach whereby criticisms and lessons learnt in the development of early models are embodied in subsequent models. This paper describes the first iterative cycle. It includes a critical review of the devices currently available and a study of mechanical analogies to original anatomy which form two of the inputs to the development of a skeletal model hand. It details the lessons learnt from this study and concludes on the wider application of practice led design research in medical engineering.     

Use of an ultrasensitive recombinant cell bioassay to determine estrogen levels in girls with precocious puberty treated with a luteinizing hormone-releasing hormone agonist

Although treatment of girls with precocious puberty should ideally restore estradiol levels to the normal prepubertal range, treatment effectiveness has usually been monitored by gonadotropin levels because estradiol RIAs have lacked sufficient sensitivity to monitor treatment effectiveness. We hypothesized that a recently developed ultrasensitive recombinant cell bioassay for estradiol would have sufficient sensitivity to demonstrate a dose-dependent suppression of estradiol during LH-releasing hormone agonist treatment and to determine whether currently used doses are able to suppress estradiol levels to the normal prepubertal range. Twenty girls with central precocious puberty were assigned randomly to receive deslorelin for 9 months at a dose of 1, 2, or 4 micrograms/ kg.day. A significant dose-response relationship was observed, with mean +/- SD estradiol levels of 16.7 +/- 6.1, 7.9 +/- 1.6, and 6.5 +/- 0.7 pmol/L at the doses of 1, 2, and 4 micrograms/kg.day, respectively (P < 0.01). The highest dose suppressed estradiol levels to just above the 95% confidence limits for normal prepubertal girls (< 0.07-6.3 pmol/L). We conclude that the ultrasensitive bioassay for estradiol has sufficient sensitivity for monitoring the response to LH-releasing hormone agonist treatment of central precocious puberty. Additionally, the observation that the deslorelin dose of 4 micrograms/kg.day did not fully restore estradiol levels to the normal prepubertal range suggests that some girls with precocious puberty may require higher doses to receive the maximal benefit of treatment. We suggest that restoration of estradiol levels to the normal prepubertal range should be the ultimate biochemical measure of efficacy, as estradiol is the key hormone that accelerates growth rate, bone maturation rate, and breast development in girls with precocious puberty.