Hearing impairment and vestibular function in patients with a pathogenic splice variant in the LHX3 gene.

Background: LHX3 is a gene encoding a LIM-homeodomain transcription factor important for the fetal development of several organs, such as the pituitary gland, spinal motor neurons and the inner ear. Pathogenic and likely pathogenic variants in the LHX3 gene are infrequent and result in a rare syndrome known as combined pituitary hormone deficiency-3, CPHD3.

Methods: We have studied hearing and vestibular functions in a group of eight individuals, aged 8-36 years, all of whom were homozygous for a specific variant in the LHX3 gene at chromosome 9q34.

Availability, Usage, and Preferences of Estradiol and Progestogen Preparations for Puberty Induction from a Multicentral Perspective.

Introduction: Natural oestrogen administration as oral or transdermal 17β-estradiol is recommended for pubertal induction in girls with hypogonadism. However, suitable low-dose formulations are not consistently available globally. This questionnaire study aimed to identify the current availability of oestrogen and progesterone preparations worldwide.

Normalization of puberty and adult height in girls with Turner syndrome: results of the Swedish Growth Hormone trials initiating transition into adulthood.

Objective: To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH). However, age at diagnosis will limit treatment possibilities.

Methods: National multicenter investigator-initiated studies (TNR 87-052-01 and TNR 88-072) in girls with TS, age 3-16 years at GH start during year 1987-1998, with AH in 2003-2011.

A systematic review of hormone treatment for children with gender dysphoria and recommendations for research.

Aim: The aim of this systematic review was to assess the effects on psychosocial and mental health, cognition, body composition, and metabolic markers of hormone treatment in children with gender dysphoria.

Methods: Systematic review essentially follows PRISMA. We searched PubMed, EMBASE and thirteen other databases until 9 November 2021 for English-language studies of hormone therapy in children with gender dysphoria.

Safety and Effectiveness of Recombinant Human Growth Hormone in Children with Turner Syndrome: Data from the PATRO Children Study.

Introduction: PATRO Children is an international, observational, postmarketing surveillance study for a biosimilar recombinant human growth hormone (rhGH; somatropin, Omnitrope®; Sandoz), approved by the European Medicines Agency in 2006. We report safety and effectiveness data for patients with Turner syndrome (TS).

Methods: The study population included infants, children, and adolescents with TS who received Omnitrope® treatment according to standard clinical practice.

Ten years with biosimilar rhGH in clinical practice in Sweden - experience from the prospective PATRO children and adult studies.

Background: In 2007, Omnitrope® was the first biosimilar recombinant human growth hormone (rhGH) to be approved in Sweden for treatment in adults and children. Over 10 years' safety and effectiveness data for biosimilar rhGH can now be presented.

Methods: PATRO Children and PATRO Adults are multicenter, longitudinal, observational, post-marketing surveillance studies.

Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective.

The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports.

Optimal Pubertal Induction in Girls with Turner Syndrome Using Either Oral or Transdermal Estradiol: A Proposed Modern Strategy.

Background: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17β-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease.

Estradiol matrix patches for pubertal induction: stability of cut pieces at different temperatures.

Objective: Transdermal estradiol patches are primarily designed for adult women. No low-dose patches are licensed for pubertal induction in hypogonadal girls. Low doses can be achieved by cutting a matrix patch into smaller pieces.

GH Dose Reduction Maintains Normal Prepubertal Height Velocity After Initial Catch-Up Growth in Short Children.

Context: GH responsiveness guides GH dosing during the catch-up growth (CUG) period; however, little is known regarding GH dosing during the prepubertal maintenance treatment period.

Objective: To evaluate whether SD score (SDS) channel parallel growth with normal height velocity can be maintained after CUG by reducing the GH dose by 50% in children receiving doses individualized according to estimated GH responsiveness during the catch-up period.

Design And Settings: Prepubertal children (n = 98; 72 boys) receiving GH during CUG (GH deficient, n = 33; non-GH deficient, n = 65), were randomized after 2 to 3 years to either a 50% reduced individualized dose (GHRID; n = 27; 20 boys) or unchanged individualized dose (GHUID; n = 38; 27 boys).

Broad variability in pharmacokinetics of GH following rhGH injections in children.

Objective: Daily subcutaneous self-injection of GH is used worldwide to treat short stature in childhood; longitudinal data on the impact of this regimen on GH-uptake are lacking.

Design: Children with/without GH-deficiency participating in clinical trials were followed prospectively (≤8 times). Blood was sampled pre-GH-injection (dose GH/GH μg/kg) and either every 30 min thereafter for 24 h (Experimental-setting; 59 GH-curves/15 children); or every 2 h thereafter for 16 h (Clinical-setting; 429 GH-curves/117 children).

Using a spontaneous profile rather than stimulation test makes the KIGS idiopathic growth hormone deficiency model more accessible for clinicians.

Aim: Children treated with a growth hormone (GH) for idiopathic growth hormone deficiency (IGHD) may be monitored with the first-year prediction model from the Pfizer International Growth Database (KIGS) using auxology, age, GH dose and the maximum GH concentration from a stimulation test (GH stim). We tested the hypothesis that using a 12-hour spontaneous profile (GH 12h) would be as accurate.

Methods: We studied 98 prepubertal Swedish children (78 boys) aged 2-12 years enrolled in KIGS.

Clinical and Immunological Characteristics of Autoimmune Addison Disease: A Nationwide Swedish Multicenter Study.

Context: Studies of the clinical and immunological features of autoimmune Addison disease (AAD) are needed to understand the disease burden and increased mortality.

Objective: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles, and cardiovascular risk factors.

Design, Setting, And Participants: A cross-sectional, population-based study that included 660 AAD patients from the Swedish Addison Registry (2008-2014).

Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics.

Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment.

Design And Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (ISS) or born small for gestational age (SGA).

Participants: The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010).

Marginally low birthweight increases the risk of underweight and short stature at three and a half years of age.

Aim: Little is known about the long-term health of marginally low birthweight (LBW) children. This study characterised growth among infants weighing 2000 g-2500 g and explored the prevalence and predictors of sustained growth restriction.

Method: This prospective observational trial followed the weight and height of 281 Swedish marginally LBW children from birth to 3.

Growth hormone (GH) dose-dependent IGF-I response relates to pubertal height gain.

Background: Responsiveness to GH treatment can be estimated by both growth and ∆IGF-I. The primary aim of the present study was to investigate if mimicking the physiological increase during puberty in GH secretion, by using a higher GH dose could lead to pubertal IGFs in short children with low GH secretion. The secondary aim was to explore the relationship between IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 ratio and gain in height.

Sex Steroid Replacement Therapy in Female Hypogonadism from Childhood to Young Adulthood.

The overall goal of pubertal sex hormone replacement therapy (HRT) in girls is not only about development of secondary sexual characteristics, but also to establish an adult endocrine and metabolic milieu, as well as adult cognitive function. Estradiol (E2) is the first choice for HRT compared to ethinyl estradiol (EE2). E2 is the most potent endogenous estrogen in the circulation, with established levels during spontaneous puberty.

Growth Hormone Treatment Improves Cognitive Function in Short Children with Growth Hormone Deficiency.

Background/aims: We investigated the association between cognition and growth hormone (GH) status and GH treatment in short prepubertal children with broadly ranging GH secretion.

Methods: A total of 99 children (age 3-11 years), 41 with GH deficiency (GHD) and 58 with idiopathic short stature (ISS), were randomized to a fixed dose (43 µg/kg/day) or a prediction model-guided individualized dose (17-100 µg/kg/day) and followed up for 24 months. In a longitudinal and mixed within- and between-subjects study, we examined clinical effect size changes, measured by Cohen's d, in full-scale IQ (FSIQ) and secondary IQ indices.

Growth hormone dose-dependent pubertal growth: a randomized trial in short children with low growth hormone secretion.

Background/aims: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i.e.

IGF-1 and growth response to adult height in a randomized GH treatment trial in short non-GH-deficient children.

Context: GH treatment significantly increased adult height (AH) in a dose-dependent manner in short non-GH-deficient children in a randomized, controlled, clinical trial; the mean gain in height SD score (heightSDS) was 1.3 (range 0-3), compared with 0.2 in the untreated group.

Comparison of body surface area versus weight-based growth hormone dosing for girls with Turner syndrome.

Background/aims: Growth Hormone (GH) dosage in childhood is adjusted for body size, but there is no consensus whether body weight (BW) or body surface area (BSA) should be used. We aimed at comparing the biological effect and cost-effectiveness of GH treatment dosed per m2 BSA in comparison with dosing per kg BW in girls with Turner syndrome (TS).

Methods: Serum IGF-I, GH dose, and adult height gain (AHG) from girls participating in two Dutch and five Swedish studies on the efficacy of GH were analyzed, and the cumulative GH dose and costs were calculated for both dose adjustment methods.