ACTA ENDOCRINOLOGICA (BUC)

Central precocius puberty (CPP) is characterized by abnormalities in the setting up of the gonadotropin ?pubertal? release, which occurs earlier. The gonadotropin releasing hormone (GnRH) was used initially to test the pituitary regarding FSH and LH release in both precocious and delayed puberty. Various GnRH superagonists were used for the same purpose, including triptorelin. A triptorelin test was applied to 14 girls with premature thelarche by using the subcutaneous administration of 0.1 mg/sqm and blood sampling at 2, 3 and 4 hours for serum LH and FSH and at 24 hours for serum estradiol. Serum mean levels of LH were >7.8 mIU/ml at all intervals, suggesting a ?pubertal? type of LH release. As concerns the individual levels of LH, only 5 out of 14 girls showed a value greater than 8 mIU/ml, which is the cutoff limit for the diagnosis of precocious puberty. These girls also met the other clinical and radiological criteria necessary for the diagnosis of precocious puberty. It was concluded that soluble triptorelin may be useful in detecting ?pubertal? type of LH release in girls exhibiting premature thelarche. Regarding the FSH and estradiol levels, they were considered irrelevant for the diagnosis.

Leptin seems to play a significant role in the regulation of pituitary GH secretion. In GH deficient children serum leptin level is higher than in GH sufficient ones. Administration of rhGH resulted in a significant decrease in serum leptin in GH deficient but also in children displaying idiopathic growth delay, small for gestational age at birth, Prader-Willi syndrome and other obese. LBA is in fact the soluble form of leptin receptor. It was previously shown that GH deficient children are mostly hyperleptinemic and that GH induces a reduction in leptin level within 3 weeks of therapy. Such a reduction could serve as a valuable marker of the long term growth response. Twenty short children whose GH status was previously assessed through GH provocative tests and auxological evaluation were explored as concerns IGF I, leptin and LBA. According to these criteria they were classified as GH-deficient and GH-sufficient. Blood samples for the assay of serum leptin and LBA and IGF I were drawn at 8 a.m. A daily dose of 0.35 mg of rhGH was given subcutaneously at 8 pm in 12 of them and the same sampling was done 12 hours after the last injection. A therapy with GH with the same preparation and in comparable weekly dosage was started in all children and the height gain was evaluated after six months. Total serum leptin was assayed by a commercially available sandwich ELISA kit. LBA was assayed by a sandwich ELISA kit using a human IgG-Fc fragment of leptin receptor. IGF I determination was performed by the OCTEIA kit in a two-site immunoenzymometric assay (IEMA). The means and SEM before and after 10 days of GH administration in the whole group were of 3.4 ? 0.71 ng/ml and 1.7 ? 0.16 (p< 0.02) for leptin 0.27.1 ? 0.92 U/ml and 23.6 ?1.66 (ns) for LBA, 48.9 ? 10.65 ng/ml and 84.3 ? 17.61 for IGF I (p> 0.05, ns). Comparison between GH deficient (def) and GH sufficient (suf) subgroups resulted in significant differences as regards initial values for IGF I (20.2 ? 4.21 in def vs 77.6 ? 16.7 in suf, p< 0.02) but not in leptin, LBA, height and weight z scores. After ten days of therapy no significant differences were noted in subgroups for leptin, LBA and IGF I (absolute values), but a striking difference was noted in percentual rise of IGF I in def children. There was a significant positive correlation between leptin basal level and the growth rate in the subsequent 6 months of GH therapy. No similar correlation was noted for IGF I and LBA. It was concluded that hyperleptinemic GH deficient children seem to be particularly sensitive to the growth promoting effect of rhGH at least in the first six months of therapy.

Background/Aims. Growth hormone deficiency (GHD) in children and adolescents is managed with growth hormone (GH) therapy and aims to achieve optimal height development. However, treatment adherence can be poor, reducing the likelihood of a successful outcome. Adherence varies between geographic regions. This observational study assessed satisfaction and adherence to NutropinAq (somatropin, recombinant human GH) treatment in Romanian children with GHD. Methods. Patients ≥3 years of age with GHD for which GH replacement therapy with NutropinAq had been initiated were recruited from 13 centres in Romania (protocol number: A-38-58035-016). The primary variable was patient/caregiver-reported treatment adherence (assessed at 3, 6 and 12 months on a 5-item Likert scale), secondary variables included treatment satisfaction assessed by the treating physician and patient/caregiver on a 5-point scale. Results. Most patients did not miss any treatment injections in any 3-month period between assessments (≥79.8% of patients were 100% compliant). The incidence of missed injections was higher among patients <7 years of age than older children, but no differences between genders was observed. At study end, 94.3% of patients/caregivers and 94.3% of physicians reported complete satisfaction with treatment. Conclusions. Overall treatment adherence to NutropinAq was high in the Romanian GHD paediatric population, and a high level of treatment satisfaction was reported by patients/caregivers. This suggests reliable treatment outcomes can be anticipated in this population.

Serotonergic 5HT2A receptors constitute the sole subtype identifiable in platelets, their sole location outside CNS. They may intervene in intra-CNS pathways involved in GHRH and GH release, mainly during sleep. To gain information about such a subtype receptor in GH deficiency and, indirectly, on its role in GH release, studies on the platelets membrane binding sites of labelled LSD were undertaken in dwarf, GH-deficient children, assuming that the platelets sites number is parallel to their number in the brain. Five dwarf (Dw) children (3 boys) aged 7-13, having no signs of puberty, with a peak GH level under 5 ng/ml during ITT, no tumor in the hypothalamic and pituitary area and no previous rhGH therapy were compared with ten normally statured, non-obese children serving as controls (C). Fifty mL of platelet membrane preparation of pooled samples were incubated at 25?C with radioiodinated lysergic acid diethylamide ([125I] LSD) in concentrations of 0.35-3.5 nM/L. The reaction kinetics was followed up within 60 min weekly for 4 weeks. Bmax and Kd were calculated as means of 4 repetitions. Competitive inhibition curves were also drawn by using ketanserin (KET), mianserin (MIA) and cyproheptadin (CYP) in concentrations of 10-4 mM- 1nM/L and the inhibition constant (Ki) was calculated. The results showed that Bmax was (mean ? SEM) 33.0 ? 3.06 fmol/mg protein in C group versus 64.06 ? 13.82 fmol/mg protein in Dw group (F test in covar p<.05). Kd was 0.76? 0.166 nM in C and 2.0? 0.48 nM in Dw (t test p<0.01). The earliest time of 100% binding (Tmin) was 20 min in C and 5 min in Dw groups. Ki in C was 0.1 nM for KET, 18 nM for MIA and <0.1 nM/L for CYP. In Dw children Ki was 1.85 nM for KET, 18 nM for MIA and <0.1 nM for CYP. The results indicated that the number of 5HT2A receptors in platelets was significantly greater in GH-deficient children than in controls, as well as Kd. Tmin indicated an earlier steady state in Dw patients. Ki values pleaded to some extent in favour of the presence of excess 5HT2A receptors. In conclusion, excessive binding of labelled LSD and its inhibition by specific antagonists proves excess of 5HT2A receptors in platelets preparations collected from dwarf children.

There are no new national growth references for the Romanian population and the current recommendations for short stature evaluation is the use of the Swiss growth charts developed based on a longitudinal study. The aim of the present paper is to present the new synthetic growth references for Romanian children. Material and methods. We used local Romanian data from 9 studies with information on height and weight obtained between 1999 and 2016. Based on their plausibility and methodology six studies were selected for generating the National Synthetic Growth References for Romanian Children based on the specific methodology described previously. The selected studies included 8407 subjects measured in schools/kindergartens. Age is reported in years covering a range from 3-18 years. Height and weight were measured at a precision of 0.1 cm and 0.1 kg. All children were measured at normal temperature, in light clothes, without footwear. Results. We present the charts and tables with the common centiles for height, weight and body mass index for boys and girls. Conclusion. We suggest synthetic growth references based upon recent growth data from 6 different Romanian regions as new National Growth Charts for Romanian children.

We report the case of a 6.6 years old boy, born to healthy unrelated parents, from a normal pregnancy, admitted for severe growth retardation. His height was 71 cm\r\n(-9.3 SD), with a weight of 6.6 kg and he presented a triunghiular face, mycrognatia, proeminent nose and hypertelorism resulting in a ?bird headed? profile. He associated clinodactyly of the 5th finger and a slightly longer left leg. Tanner stages were P1 G1. The\r\nbiochemical panel was normal, but he presented mild hypocromic anemia. The thyroid function was normal, and the IGF1 low. The karyotype was 46 XY and the bone age 4.5\r\nyears. The pituitary computed tomography revealed empty sella. Based on the clinical picture, the possible diagnosis of Seckel syndrome was suspected. A short course of treatment with Metandienonum 0.04 mg/kg/day for 3 months was recommended, without success (growth speed of 6 cm/year - -0.14 SD)

Thyroid carcinoma is rare in children and adolescents and has a relatively favorable prognosis. As in adults, the incidence in girls is double than in boys. It has a little risk of mortality, but a high risk of recurrence. Patients younger than 15 years old at diagnosis are considered more likely to have more extensive tumor at diagnosis than patients who are 15 years and older. We report two patients: an 11 years old girl with Fallot tetrallogy and papillary thyroid cancer and a 13 years old girl with Graves&#8217; disease treated with antithyroid drugs for three years and thyroidectomized at 17 years old with an incidental thyroid microcarcinoma. Those unusual associations are discussed regarding therapy and follow-up issues.

Individuals with male phenotypes and 46 XX karyotype appear in about 1 of 20,000 births\r\nwith clinical features varying from normal male appearance to sexual ambiguity and\r\nhermaphroditism. More than 80% of these patients present a spontaneous translocation of the\r\nSRY gene from the Y to the X chromosome in the paternal germinal cells.\r\nWe present a case of a 2 years old boy diagnosed with minor hypospadias, bifid scrotum,\r\nnormal penis and palpable gonads in the scrotum. The karyotype is 46 XX and FISH analysis\r\nreveals SRY translocation on one of the X chromosomes. Ultrasound exam does not reveal any\r\nmullerian structures and a hCG test proves the testes to be functional. A short course of\r\ntreatment with hCG is recommended in order to induce the proper development of the scotal\r\nsac. The patient will need monitoring, in order to identify the development of hypergonadic\r\nhypogonadism, which characterizes such patients in later life. This case underlines the\r\nimportance of comprehensively investigating any patient with even minor genitalia anomalies.

Background. Craniopharyngiomas are benign but locally invasive tumours of the sellar region that arise from ectopic embryonic remnants of Rathke's pouch, affecting both children (adamantinomatous type -aCP) and adults (papillary type -pCP) and associated with significant morbidity. Objective. To study the clinical presentation of CRF as well as the posttreatment evolution of craniopharyngioma in children versus adults in a large mixed cohort. Material and methods. We performed a retrospective review of CRF patients evaluated in the National Institute of Endocrinology in Bucharest between 1990 and 2016. Results. A total of 107 patients (72 adults, 35 children) with a mean follow-up of 6.2 years were included. The presenting symptoms were mostly headache, visual impairment, symptoms of hypopituitarism, diabetes insipidus. Some symptoms or hormonal abnormalities were significantly more prevalent in the children group (p<0.05): nausea/ vomiting (47.8% vs 16.7%), photophobia (21.7% vs 5.6%), diabetes insipidus(28.5% vs 8.3%), GH deficiency (68.8% vs 17.1%). Impaired visual acuity (67.6%of cases) or visual fields (71.4%) were more frequent in adults compared to children (44.1%; 51.6%). The tumor dimensions were similar in both groups (3.05± 1.05 cm in children; 2.7± 1.07 cm in adults). Massive suprasellar extension reaching the third ventricle was frequently present in all cases. All cases underwent surgery but only a minority of those not cured received postoperative adjuvant radiotherapy. Frequent postoperative complications were: aggravation of the endocrine deficit (>80% of cases in both groups needed chronic replacement therapy), central diabetes insipidus (68.2% children, 34.3% of adults). Conclusions. Despite similar tumor dimensions and extension compared to adults, craniopharyngioma in children is more frequently associated with signs of intracranial pressure. The results and complications of treatment are similar in adults and children