Differential Methylation of CYP11B1 in Girls with High DHEAS Levels and Correlation with 11-Oxyandrogen Levels: A Pilot Study.

Introduction: Premature adrenarche in girls is defined biochemically by an increase in adrenal androgen (DHEAS) levels above the age-specific reference range before age 8 years. Recently, increased levels of 11-oxyandrogens have also been reported in girls with premature adrenarche. Epigenetic modifications, specifically CpG methylation, may affect gene expression and/or activity of steroidogenic enzymes during developmental changes in adrenal androgen secretion.

Adult Height Following Prepubertal Treatment With Antiandrogen, Aromatase Inhibitor, and Reduced Hydrocortisone in CAH.

Context: Height outcome in patients with classic congenital adrenal hyperplasia (CAH) is suboptimal due to glucocorticoid and androgen excess.

Methods: In an open, randomized, controlled trial, children with classic CAH were randomized to receive a combination regimen of antiandrogen, aromatase inhibitor, reduced hydrocortisone, and fludrocortisone prior to puberty or standard therapy (hydrocortisone, fludrocortisone). Females continued on antiandrogen during puberty.

MBX 2109, a Once-Weekly Parathyroid Hormone Replacement Therapy Prodrug: Phase 1, First-in-Human, Randomized Trial.

Introduction: Hypoparathyroidism denotes parathyroid hormone (PTH) deficiency and impaired mineral metabolism. MBX 2109, a novel prodrug yielding a biologically active PTH peptide agonist (PTH[1-32], extended by a fatty acylated Lys33), is being developed as a long-acting, once-weekly PTH replacement therapy. Here, we report the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of MBX 2109 in healthy volunteers.

Longitudinal Evaluation of Reproductive Endocrine Function in Men With ACTH-Dependent Cushing Syndrome.

Context: Hypogonadism may be caused by Cushing syndrome (CS) and may intensify its adverse consequences.

Objective: This work aimed to determine the frequency of male hypogonadism before and after curative surgery for CS, and its cause.

Methods: Post hoc analyses of prospective cohort studies were conducted at a clinical research center.

Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal Hyperplasia.

Background: Adrenal insufficiency in patients with classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) is treated with glucocorticoid replacement therapy. Control of adrenal-derived androgen excess usually requires supraphysiologic glucocorticoid dosing, which predisposes patients to glucocorticoid-related complications. Crinecerfont, an oral corticotropin-releasing factor type 1 receptor antagonist, lowered androstenedione levels in phase 2 trials involving patients with CAH.

Differential methylation pattern in pubertal girls associated with biochemical premature adrenarche.

Biochemical premature adrenarche is defined by elevated serum DHEAS [≥40 μg/dL] before age 8 y in girls. This condition is receiving more attention due to its association with obesity, hyperinsulinemia, dyslipidemia, and polycystic ovary syndrome. Nevertheless, the link between early androgen excess and these risk factors remains unknown.

High DHEAS in girls and metabolic features throughout pubertal maturation.

Context: An association between premature adrenarche and metabolic syndrome at presentation has been described. Our aim was to assess whether the presence of high dehydroepiandrosterone sulphate (DHEAS [HD]) at the adrenarche determines the risk of metabolic syndrome during puberty, taking into account body mass index (BMI) and birth weight.

Design: Prospective observational.

Genome-Wide Association Study and Polygenic Risk Scores of Serum DHEAS Levels in a Chilean Children Cohort.

Context: Adrenarche reflects the developmental growth of the adrenal zona reticularis, which produces increasing adrenal androgen secretion (eg, dehydroepiandrosterone [DHEA]/dehydroepiandrosterone sulfate [DHEAS]) from approximately age 5 to 15 years.

Objective: We hypothesized that the study of the genetic determinants associated with variations in serum DHEAS during adrenarche might detect genetic variants influencing the rate or timing of this process.

Methods: Genome-wide genotyping was performed in participants of the Chilean pediatric Growth and Obesity Chilean Cohort Study (GOCS) cohort (n = 788).

Therapy with PTH 1-34 or calcitriol and calcium in diverse etiologies of hypoparathyroidism over 27 years at a single tertiary care center.

Objective: Hypoparathyroidism has heterogeneous genetic and acquired etiologies with a broad spectrum of severity. Herein we describe the clinical outcomes of the largest cohort of hypoparathyroid patients reported to date, who were followed over 27-years.

Design: Pooled analysis of current and past studies describing the differential responses to PTH 1-34 injections vs conventional therapy among the varied hypoPT etiologies.

Height Gain and Safety Outcomes in Growth Hormone-Treated Children with Idiopathic Short Stature: Experience from a Prospective Observational Study.

Background/objectives: Growth hormone (GH) treatment of idiopathic short stature (ISS) received US Food and Drug Administration approval in 2003. We assessed height gain and safety in 2,450 children with ISS treated with GH in US clinical practice.

Methods: Short-term height gain, near-adult height (NAH), and safety outcomes were investigated using Genetics and Neuroendocrinology of Short Stature International Study data.

Long-Term Parathyroid Hormone 1-34 Replacement Therapy in Children with Hypoparathyroidism.

Objective: To determine whether multiple daily injections of parathyroid hormone (PTH) 1-34 are safe and effective as long-term therapy for children with hypoparathyroidism.

Study Design: Linear growth, bone accrual, renal function, and mineral homeostasis were studied in a long-term observational study of PTH 1-34 injection therapy in 14 children.

Methods: Subjects were 14 children with hypoparathyroidism attributable to autoimmune polyglandular syndrome type 1 (N = 5, ages 7-12 years) or calcium receptor mutation (N = 9, ages 7-16 years).

Effect of Antiandrogen, Aromatase Inhibitor, and Gonadotropin-releasing Hormone Analog on Adult Height in Familial Male Precocious Puberty.

Objective: Antiandrogen, aromatase inhibitor, and gonadotropin-releasing hormone analog (GnRHa) treatment normalizes growth rate and bone maturation and increases predicted adult height (AH) in boys with familial male-limited precocious puberty (FMPP). To evaluate the effect of long-term antiandrogen, aromatase inhibitor, and GnRHa on AH, boys with FMPP who were treated were followed to AH.

Study Design: Twenty-eight boys with FMPP, referred to the National Institutes of Health, were started on antiandrogen and aromatase inhibitor at 4.

In Vivo and In Vitro Characterization of Basal Insulin Peglispro: A Novel Insulin Analog.

The aim of this research was to characterize the in vivo and in vitro properties of basal insulin peglispro (BIL), a new basal insulin, wherein insulin lispro was derivatized through the covalent and site-specific attachment of a 20-kDa polyethylene-glycol (PEG; specifically, methoxy-terminated) moiety to lysine B28. Addition of the PEG moiety increased the hydrodynamic size of the insulin lispro molecule. Studies show there is a prolonged duration of action and a reduction in clearance.

Radiological Features in Patients with Short Stature Homeobox-Containing (SHOX) Gene Deficiency and Turner Syndrome before and after 2 Years of GH Treatment.

Background/aims: The short stature homeobox-containing (SHOX) gene is one of many genes that regulate longitudinal growth. The SHOX deficiency (SHOX-D) phenotype, caused by intragenic or regulatory region defects, ranges from normal stature to mesomelic skeletal dysplasia. We investigated differences in radiological anomalies between patients with SHOX-D and Turner syndrome (TS) and the effect of 2 years of growth hormone (GH) treatment on these anomalies.

Effects of pump versus twice-daily injection delivery of synthetic parathyroid hormone 1-34 in children with severe congenital hypoparathyroidism.

Objective: To compare the response with synthetic human parathyroid hormone (PTH) 1-34 delivered by twice-daily injection vs insulin pump in children with severe congenital hypoparathyroidism due to calcium receptor mutation or autoimmune polyglandular syndrome type 1.

Study Design: Children and young adults aged 7-20 years with congenital hypoparathyroidism (N = 12) were randomized to receive PTH 1-34, delivered either by twice-daily subcutaneous injection or insulin pump for 13 weeks, followed by crossover to the opposite delivery method. The principal outcome measures were serum and urine calcium levels.

Effects of low-dose estrogen replacement during childhood on pubertal development and gonadotropin concentrations in patients with Turner syndrome: results of a randomized, double-blind, placebo-controlled clinical trial.

Context: The optimal approach to estrogen replacement in girls with Turner syndrome has not been determined.

Objective: The aim of the study was to assess the effects of an individualized regimen of low-dose ethinyl estradiol (EE2) during childhood from as early as age 5, followed by a pubertal induction regimen starting after age 12 and escalating to full replacement over 4 years.

Design: This study was a prospective, randomized, double-blind, placebo-controlled clinical trial.

Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with idiopathic isolated GH deficiency.

Objective: We assessed the characteristics of children initially diagnosed with idiopathic isolated GH deficiency (IGHD) who later developed additional (multiple) pituitary hormone deficiencies (MPHD).

Design: Data were analyzed for 5805 pediatric patients with idiopathic IGHD, who were GH-naïve at baseline and GH-treated in the multinational, observational Genetics and Neuroendocrinology of Short Stature International Study.

Methods: Development of MPHD was assessed from investigator diagnoses, adverse events, and concomitant medications.

GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: results of a multicenter trial.

Context: Growth impairment in short stature homeobox-containing gene (SHOX) deficiency and Turner syndrome share a similar etiology. Because of the established effect of GH treatment on height in patients with Turner syndrome, we hypothesized that GH therapy would also stimulate growth in patients with SHOX deficiency.

Objective: Our objectives were to evaluate long-term efficacy of GH treatment in short patients with SHOX deficiency and to compare the effect on final (adult) height (FH) in patients with SHOX deficiency and Turner syndrome.

Associations between pituitary imaging abnormalities and clinical and biochemical phenotypes in children with congenital growth hormone deficiency: data from an international observational study.

Background/aims: Magnetic resonance imaging (MRI) is used to investigate the etiology of growth hormone deficiency (GHD). This study examined relationships between MRI findings and clinical/hormonal phenotypes in children with GHD in the observational Genetics and Neuroendocrinology of Short Stature International Study, GeNeSIS.

Methods: Clinical presentation, hormonal status and first-year GH response were compared between patients with pituitary imaging abnormalities (n = 1,071), patients with mutations in genes involved in pituitary development/GH secretion (n = 120) and patients with idiopathic GHD (n = 7,039).

Prospective safety surveillance of GH-deficient adults: comparison of GH-treated vs untreated patients.

Context: In clinical practice, the safety profile of GH replacement therapy for GH-deficient adults compared with no replacement therapy is unknown.

Objective: The objective of this study was to compare adverse events (AEs) in GH-deficient adults who were GH-treated with those in GH-deficient adults who did not receive GH replacement.

Design And Setting: This was a prospective observational study in the setting of US clinical practices.

Synthetic human parathyroid hormone 1-34 replacement therapy: a randomized crossover trial comparing pump versus injections in the treatment of chronic hypoparathyroidism.

Context: Vitamin D therapy for hypoparathyroidism does not restore PTH-dependent renal calcium reabsorption, which can lead to renal damage. An alternative approach, PTH 1-34 administered twice daily, provides acceptable long-term treatment but is associated with nonphysiological serum calcium fluctuation.

Objective: Our objective was to compare continuous PTH 1-34 delivery, by insulin pump, with twice-daily delivery.

Growth hormone plus childhood low-dose estrogen in Turner's syndrome.

Background: Short stature and ovarian failure are characteristic features of Turner's syndrome. Although recombinant human growth hormone is commonly used to treat the short stature associated with this syndrome, a randomized, placebo-controlled trial is needed to document whether such treatment increases adult height. Furthermore, it is not known whether childhood estrogen replacement combined with growth hormone therapy provides additional benefit.