Potential for Optimization of Growth Hormone Treatment in Children with Growth Hormone Deficiency, Small for Gestational Age, and Turner Syndrome in Germany: Data from the PATRO® Children Study.

Introduction: Growth hormone (GH) treatment in children with growth hormone deficiency (GHD), short children born small for gestational age (SGA), and Turner syndrome (TS) is well established. However, a variety of parameters are still under discussion to achieve optimal growth results and efficiency of GH use in real-world treatment.

Methods: German GH-treatment naïve patients of the PATRO Children database were grouped according to their start of treatment into groups of 3 years from 2007 to 2018.

Cross-sectional analysis: clinical presentation of children with persistently low ALP levels.

Objectives: Low activity of serum alkaline phosphatase (ALP) is a hallmark of hypophosphatasia (HPP), but low readings of ALP are not always recognized in clinical routine. Understanding the clinical presentations associated with low ALP may contribute to a timelier diagnosis of HPP.

Methods: Data from paediatric patients with low ALP, excluding patients in intensive care and with oncological/haematological disorders, were analysed.

Increased Insulin Concentrations During Growth Hormone Treatment in Girls With Turner Syndrome Are Ameliorated by Hormone Replacement Therapy.

Objective: Turner syndrome (TS) is characterized by complete or partial loss of one sex chromosome and is commonly associated with short stature, metabolic changes (such as central obesity, abnormal glucose tolerance and high triglycerides) and premature ovarian insufficiency (POI). Primary management of TS during childhood and adolescence comprises treatment with human growth hormone (hGH) and, in cases with early loss of ovarian function, hormone replacement therapy (HRT). Given that metabolic parameters are altered when HRT is applied during menopause, we analyzed whether metabolic changes might be positively or negatively affected within 10 years after HRT and/or hGH in girls with TS.

Safety and Effectiveness of Omnitrope®, a Biosimilar Recombinant Human Growth Hormone: More Than 10 Years' Experience from the PATRO Children Study.

Introduction: Omnitrope® was approved as a biosimilar recombinant human growth hormone (rhGH) in 2006.

Objective: The purpose of this work was to evaluate the long-term safety and effectiveness of Omnitrope® in PATRO Children - an ongoing, international, longitudinal, non-interventional study in children who require rhGH treatment.

Methods: The study population includes infants, children, and adolescents receiving Omnitrope®.

Diabetes screening in overweight and obese children and adolescents: choosing the right test.

Unlabelled: Type 2 diabetes can occur without any symptoms, and health problems associated with the disease are serious. Screening tests allowing an early diagnosis are desirable. However, optimal screening tests for diabetes in obese youth are discussed controversially.

Low association between fasting and OGTT stimulated glucose levels with HbA1c in overweight children and adolescents.

Background: Diabetes and prediabetes are defined based on different methods such as fasting glucose, glucose at 2-hour in oral glucose tolerance test (OGTT), and glycated hemoglobin A1c (HbA1c). These parameters probably describe different deteriorations in glucose metabolism limiting the exchange between each other in definitions of diabetes.

Objective: To investigate the relationship between OGTT and HbA1c in overweight and obese children and adolescents living in Germany.

Acceptance of a reusable self-injection device for recombinant human growth hormone: final data from a questionnaire-based, cross-sectional, international, multicenter, observational study in pediatric patients.

Background: A questionnaire-based survey was conducted to assess attitudes toward a reusable self-injection system (SurePal™) among pediatric patients with growth disturbances who were prescribed treatment with Omnitrope(®) within routine clinical practice.

Methods: This was a multicenter, observational study, incorporated into the noninterventional PAtients TReated with Omnitrope(®) (PATRO) Children study. Included subjects, or their caregivers, completed a questionnaire on the following five main areas: attractiveness of SurePal™, training received, using the device, the low drug wastage system, and experience versus other devices used previously (pretreated patients).

Acceptability of the reusable SurePal™ self-injection device for Omnitrope(®) among pediatric patients: results from a questionnaire-based, cross-sectional, multicenter observational study.

Background: SurePal™ is a reusable self-injection system that has been developed to support daily administration of Omnitrope(®) (Sandoz, Kundl, Austria). A questionnaire-based cross-sectional survey was conducted to evaluate acceptability of, and preference for, SurePal™ in pediatric patients who were prescribed treatment with Omnitrope(®) within routine clinical care.

Methods: This multicenter, observational study was incorporated into the ongoing non-interventional PATRO (PAtients TReated with Omnitrope(®)) Children study.

Treatment of central precocious puberty and early puberty with GnRH analog in girls with Williams-Beuren syndrome.

Objective: Little has been published on treatment of precocious puberty in girls with Williams-Beuren syndrome (WBS), a condition occurring frequently in this group. We analyzed our own data on growth/age at menarche of now adult female patients with WBS being diagnosed with central precocious puberty or early puberty. Data of patients treated with gonadotropin-releasing hormone (GnRH) analog (n=13) were compared with those not treated (control group, n=11).

Hormonal 'minipuberty' influences the somatic development of boys but not of girls up to the age of 6 years.

Objective: Hormonal 'minipuberty' refers to a transient sex-specific surge of LH, FSH, testosterone (T) and estradiol (E2) in the first few months of life. We hypothesized a potential long-term effect of this hormonal surge on somatic parameters in the following years and therefore designed this longitudinal study.

Design: A hierarchical multiple regression analysis was used to analyse the potential influence of hormone concentrations during minipuberty on anthropometric measurements conducted in the first 6 years of life.

Clinical and metabolic findings in a 6-year-old boy with a Leydig cell tumour.

Aim: To analyse the urinary steroid metabolome in a boy who had true precocious puberty after a Leydig cell tumour.

Method: Case report and detailed description of clinical and metabolic findings in a 7-year-old-boy with a Leydig cell tumour.

Results:   Before surgery, the urinary steroid metabolome showed an activation of an alternative route to gonadal androgens independent of dehydroepiandrosterone (DHEA).

No significantly increased frequency of the inversion polymorphism at the WBS-critical region 7q11.23 in German parents of patients with Williams-Beuren syndrome as compared to a population control.

Background: Typical Williams-Beuren syndrome (WBS) is commonly caused by a ~1.5 Mb - ~1.8 Mb heterozygous deletion of contiguous genes at chromosome region 7q11.

Orbital compression syndrome in sickle cell crisis.

This article is about a 9-year-old boy with known homozygous sickle cell disease who developed unilateral exophthalmia and eyelid swelling during a sickle cell crisis. The symptoms were due to a vaso-occlusive event in the orbital bones,known as orbital compression syndrome, which is a rare complication of sickle cell disease.

A large-scale mutation search reveals genetic heterogeneity in 3M syndrome.

The 3M syndrome is a rare autosomal recessive disorder recently ascribed to mutations in the CUL7 gene and characterized by severe pre- and postnatal growth retardation. Studying a series of 33 novel cases of 3M syndrome, we have identified deleterious CUL7 mutations in 23/33 patients, including 19 novel mutations and one paternal isodisomy of chromosome 6 encompassing a CUL7 mutation. Lack of mutations in 10/33 cases and exclusion of the CUL7 locus on chromosome 6p21.

Sex hormone testosterone affects language organization in the infant brain.

Using a phonological discrimination paradigm, we show that the brain responses of 4-week-old infants systematically vary as a function of biological sex and testosterone level. Females who are generally low on testosterone demonstrated a clear phonological discrimination effect with a bilateral distribution. In male infants this effect systematically varied as a function of testosterone level.

Endocrine evaluation after endoscopic third ventriculostomy (ETV) in children.

Objective: Endoscopic third ventriculostomy (ETV) is a standard procedure for the treatment of obstructive hydrocephalus in children. Main part of the procedure is the perforation of the third ventricle floor (tuber cinereum). This structure is part of the hypothalamic-pituitary neuronal network of cerebral endocrine regulation.

Initially elevated TSH and congenital central hypothyroidism due to a homozygous mutation of the TSH beta subunit gene: case report and review of the literature.

Congenital central hypothyroidism (CCH) is a rare disease which can be caused by mutations in the gene for the thyrotropin (TSH) beta subunit ( TSHB). The diagnosis is usually delayed because the TSH serum levels in these patients are not elevated leading to a negative result in the neonatal TSH screening. Herein, we report a 2-year-old girl with CCH due to a mutation in the TSHB gene, in whom the unusual finding of an initially elevated TSH level complicated the diagnostic workup.

Long-term GnRH agonist treatment for female central precocious puberty does not impair reproductive function.

Depot gonadotropin releasing hormone (GnRH) agonist (GnRHa) therapy is the treatment of choice for patients with central precocious puberty (CPP). It is still unclear whether long-term exposure to GnRHa is associated with impaired reproductive function in adulthood. The present study was performed on 46 women, former CPP patients, 12.

Three novel point mutations of the CYP21 gene detected in classical forms of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Congenital adrenal hyperplasia (CAH) [OMIM 201 910] is a group of autosomal recessive disorders most commonly due to 21-hydroxylase deficiency and presenting with a wide range of clinical manifestations. A limited number of inactivating pseudogene-derived mutations account for the majority of 21-hydroxylase gene ( CYP21) mutations, additional rare mutations can be found in single families and small populations. We found three novel CYP21 mutations in CAH patients suffering from the classical form of the disease, of which one is a frameshift mutation (1353-1354insA) leading to a premature termination codon (K277K, Q228A.

Absence of exercise-induced leptin suppression associated with insufficient epinephrine reserve in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Objective: Patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency suffer from glucocorticoid and mineralocorticoid deficiency. They have insufficient epinephrine reserves and increased basal leptin levels and are often insulin resistant. In healthy subjects, an inhibitory effect of acute catecholamine elevation on the leptin plasma concentrations has been reported.

Prevalence of autoantibodies associated with thyroid and celiac disease in Ullrich-Turner syndrome in relation to adult height after growth hormone treatment.

A prospective, multicenter study of patients with Ullrich-Turner syndrome (UTS) was conducted to estimate the prevalence of autoantibodies to tissue transglutaminase (tTg), thyroid stimulating hormone receptor (TSH-R), thyroglobulin (TG) and thyroid peroxidase (TPO) in relation to adult height after long-term growth hormone (GH) treatment. Out of 347 near-adult (> 16 years) patients with UTS from 96 German centers, whose longitudinal growth was documented within the Pharmacia International Growth Study (KIGS), 188 returned for a standardized follow-up visit at a median chronological age of 18.7 (16.

[Calcinosis cutis in Albright hereditary osteodystrophy: pseudohypoparathyroidism type Ia].

Albright hereditary osteodystrophy (AHO) is characterized by a symptom complex including short stature, brachymetacarpia, obesity, round facies, cutaneous osteomas, and mental retardation. AHO is caused by mutations in the GNAS-gene localized on chromosome 20 encoding for Gsalpha protein, a signal transducer of endocrine pathways. Therefore, AHO is often associated with endocrinopathy such as pseudohypoparathyroidism or hypothyroidism.

Sigmoid diverticulitis in patients with Williams-Beuren syndrome: relatively high prevalence and high complication rate in young adults with the syndrome.

In a retrospective survey of 128 adults with Williams-Beuren syndrome (age range 18-62 years) sigmoid diverticulitis was reported in 10 patients (2 f, 8 m). The diagnosis of diverticulitis had been made between the ages of 17.1 and 39.

Differences in infantile growth patterns in Turner syndrome girls with and without spontaneous puberty.

Objective: The role of prepubertal estrogen in child growth was modeled using Turner's syndrome, comparing growth patterns of girls who later did or did not enter puberty spontaneously. The hypothesis was that TS patients with normal prepubertal estrogen levels would have a different growth pattern from those with subnormal estrogen levels.

Study Design: Growth data from 78 full-term patients with Turner's syndrome were collected retrospectively.

Thirteen novel mutations in the NR0B1 (DAX1) gene as cause of adrenal hypoplasia congenita.

X-linked adrenal hypoplasia congenita (AHC) is a rare developmental disorder associated with primary adrenal insufficiency and combined primary and secondary male hypogonadism. It is caused by deletions or mutations of the NR0B1 (DAX1) gene encoding DAX1, an atypical orphan member of the nuclear receptor superfamily. The continuous molecular genetic analysis of male patients with primary adrenal insufficiency revealed 13 novel mutations within the coding region of the NR0B1 gene which are predicted to inactivate the DAX1 function.