IGF-1 Assessment During Weekly Somatrogon Treatment in Pediatric Patients With GH Deficiency.

Context: In patients with GH deficiency (GHD) receiving GH treatment, IGF-1 concentrations are used by physicians to monitor treatment safety and efficacy and guide dosing decisions. Somatrogon is a long-acting GH approved as a once-weekly treatment for pediatric GHD. Somatrogon administration results in characteristic changes in the IGF-1 profile, with values measured at 96 hours postdose representing mean IGF-1 concentrations that best reflect overall somatrogon exposure.

Long-Acting Growth Hormone Therapy in Pediatric Growth Hormone Deficiency: A Consensus Statement.

Context: Several long-acting growth hormone (LAGH) therapies have recently become available, but guidance on their usage in children with growth hormone (GH) deficiency is limited.

Methods: International experts in pediatric endocrinology were invited to join a consensus group based on their expertise in treating children with daily GH and LAGH. The group comprised 11 experts from 10 countries across the world.

International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents.

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70-80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork.

International consensus on mitotane treatment in pediatric patients with adrenal cortical tumors: indications, therapy, and management of adverse effects.

Objective: Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects.

Methods: A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements.

Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement.

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time.

Challenges in the care of individuals with severe primary insulin-like growth factor-I deficiency (SPIGFD): an international, multi-stakeholder perspective.

Background: Severe primary insulin-like growth factor-I (IGF-I) deficiency (SPIGFD) is a rare growth disorder characterized by short stature (standard deviation score [SDS] ≤ 3.0), low circulating concentrations of IGF-I (SDS ≤ 3.0), and normal or elevated concentrations of growth hormone (GH).

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

Context: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy.

Objective: To evaluate safety and efficacy of intranasal carbetocin in PWS.

The Efficacy, Safety, and Pharmacology of a Ghrelin O-Acyltransferase Inhibitor for the Treatment of Prader-Willi Syndrome.

Context: Acylated ghrelin (AG) stimulates appetite and is elevated compared to its unacylated (UAG) counterpart in Prader-Willi syndrome (PWS). GLWL-01 is a selective, reversible inhibitor of ghrelin O-acyltransferase (GOAT), the enzyme that converts UAG into AG.

Objective: This work aimed to assess the efficacy, pharmacokinetics, pharmacodynamics, and safety of GLWL-01 in the treatment of PWS patients.

Insulin-like Growth Factor 1, but Not Insulin-Like Growth Factor-Binding Protein 3, Predicts Central Precocious Puberty in Girls 6-8 Years Old: A Retrospective Study.

Background: Central precocious puberty (CPP) in females is characterized by thelarche before 8 years of age. Evidence of reproductive axis activation confirms the diagnosis (basal serum luteinizing hormone (LH) ≥0.3 IU/L or LH-releasing hormone (LHRH)-stimulated LH ≥5 IU/L).

Gene expression signatures predict response to therapy with growth hormone.

Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD (n = 71) and TS patients (n = 43) were recruited to study response to r-hGH over 5 years.

Clinical Outcomes and Complications of Pituitary Blastoma.

Context: Pituitary blastoma is a rare, dysontogenetic hypophyseal tumor of infancy first described in 2008, strongly suggestive of DICER1 syndrome.

Objective: This work aims to describe genetic alterations, clinical courses, outcomes, and complications in all known pituitary blastoma cases.

Design And Setting: A multi-institutional case series is presented from tertiary pediatric oncology centers.

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.

Safety Outcomes During Pediatric GH Therapy: Final Results From the Prospective GeNeSIS Observational Program.

Context: Safety concerns have been raised regarding premature mortality, diabetes, neoplasia, and cerebrovascular disease in association with GH therapy.

Objective: To assess incidence of key safety outcomes.

Design: Prospective, multinational, observational study (1999 to 2015).

Growth hormone treatment of Canadian children: results from the GeNeSIS phase IV prospective observational study.

Background: Country-specific data on outcomes of treatment with recombinant human growth hormone are lacking. We present such data for children treated with growth hormone in Canada.

Methods: We describe characteristics and outcomes of 850 children (mean age at baseline 8.

Chitayat-Hall and Schaaf-Yang syndromes:a common aetiology: expanding the phenotype of -related disorders.

Background: Chitayat-Hall syndrome, initially described in 1990, is a rare condition characterised by distal arthrogryposis, intellectual disability, dysmorphic features and hypopituitarism, in particular growth hormone deficiency. The genetic aetiology has not been identified.

Methods And Results: We identified three unrelated families with a total of six affected patients with the clinical manifestations of Chitayat-Hall syndrome.

Genetic variations at the human growth hormone receptor (GHR) gene locus are associated with idiopathic short stature.

GH plays an essential role in the growing child by binding to the growth hormone receptor (GHR) on target cells and regulating multiple growth promoting and metabolic effects. Mutations in the GHR gene coding regions result in GH insensitivity (dwarfism) due to a dysfunctional receptor protein. However, children with idiopathic short stature (ISS) show growth impairment without GH or GHR defects.

Safety Outcomes and Near-Adult Height Gain of Growth Hormone-Treated Children with SHOX Deficiency: Data from an Observational Study and a Clinical Trial.

Background/aims: To assess auxological and safety data for growth hormone (GH)-treated children with SHOX deficiency.

Methods: Data were examined for GH-treated SHOX-deficient children (n = 521) from the observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS). For patients with near-adult height information, GeNeSIS results (n = 90) were compared with a clinical trial (n = 28) of SHOX-deficient patients.

Timing of Hormone Withdrawal in Children Undergoing 131I Whole-Body Scans for Thyroid Cancer.

Background: Little objective pediatric data exist to guide the optimal time needed to achieve thyroid-stimulating hormone (TSH) levels ≥30 μIU/mL prior to performing 131I or 123I whole-body scan (WBS) imaging in children with thyroid cancer in the post-thyroidectomy period or after hormone discontinuation.

Methods: Retrospective study of patients aged 5-19 years who underwent WBS. Patient data collection included type and duration of withdrawal (liothyronine [L-T3], levothyroxine [L-T4], or post-thyroidectomy status without hormonal replacement) and TSH measured prior to WBS (level and timing).

Characterization of facial phenotypes of children with congenital hypopituitarism and their parents: a matched case-control study.

Congenital Hypopituitarism (CH) has traditionally been associated with specific facial phenotypes subsumed under the term midface retrusion, based on cephalometric studies. In this study, we used a systematic anthropometric approach to facial morphology in 37 individuals with CH and their parents, primarily of French Canadian ancestry, and compared them to a control group of 78 French Canadian patients with well-controlled type 1 diabetes and their parents. We were able to demonstrate clear morphological differences, which were more prevalent in the affected group than in the control group.