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We hypothesised that growth hormone (GH) deficiency (GHD) in children with attention deficit hyperactivity disorder (ADHD) is rare. This study aimed to determine any distinct clinical or biochemical parameters, including GH provocation testing, in children with ADHD on psychostimulants or idiopathic short stature (ISS). Retrospective cross-sectional study of children who had GH provocative testing between 1998 and 2013 at one tertiary paediatric endocrine centre. Clinical data included age, sex, anthropometry, pubertal staging, bone age, diagnostic code as per the European Society Paediatric Endocrinology (ESPE), GH provocation test results, thyroid function tests, serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) levels. Four hundred ninety-three subjects underwent GH provocation testing for investigation of short stature to exclude GHD during the study period. Fifty-one children had a diagnosis of ADHD. In the remaining children, the diagnosis was Idiopathic short stature (n=240), GHD +/− hypopituitarism (n=60), and 142 subjects had other causes of short stature. Children with ADHD were older, had higher height and weight SDS and were GH-sufficient. All 51 children with ADHD had a normal serum IGFBP-3, while 20 out of these 51 subjects had a low serum IGF-1. GHD in children with ADHD on psychostimulant medication is rare. GH testing in children with ADHD may not be necessary, particularly if serum IGFBP-3 is in the normal range. We suggest IGFBP-3 could be used as a surrogate marker of GH sufficiency in children with ADHD. However, this needs to be confirmed with a larger study group. [ABSTRACT FROM AUTHOR]

We describe a 4-year-old boy with developmental delay who was found to carry by clinical grade (CG) molecular cytogenetics (MCs) a chromosome Xq26 microduplication. The report prompted a referral of the patient for possible X-linked acrogigantism (X-LAG), a well-defined condition (MIM300942) due to chromosomal microduplication of a nearby region. The patient was evaluated clinically and investigated for endocrine abnormalities related to X-LAG and not only did he not have acrogigantism, but his growth parameters and other hormones were all normal. We then performed high definition MCs and the duplication copy number variant (CNV) was confirmed to precisely map outside the X-LAG critical region and definitely did not harbor the X-LAG candidate gene, GPR101. The patient's phenotype resembled that of other patients with Xq26 CNVs. The case is instructive for the need for high definition MCs when CG MCs' results are inconsistent with the patient's phenotype. It is also useful for further supporting the contention that GPR101 is the gene responsible for X-LAG.

X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2-3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management.

Type 1 diabetes (T1D) is well-recognised as a continuum heralded by the development of islet autoantibodies, progression to islet autoimmunity causing beta cell destruction, culminating in insulin deficiency and clinical disease. Abnormalities of glucose homeostasis are known to exist well before the onset of typical symptoms. Laboratory-based tests such as the oral glucose tolerance test (OGTT) and glycated haemoglobin (HbA1c) have been used to stage T1D and assess the risk of progression to clinical T1D. Continuous glucose monitoring (CGM) can detect early glycaemic abnormalities and can therefore be used to monitor for metabolic deterioration in pre-symptomatic, islet autoantibody positive, at-risk individuals. Early identification of these children can not only reduce the risk of presentation with diabetic ketoacidosis (DKA), but also determine eligibility for prevention trials, which aim to prevent or delay progression to clinical T1D. Here, we describe the current state with regard to the use of the OGTT, HbA1c, fructosamine and glycated albumin in pre-symptomatic T1D. Using illustrative cases, we present our clinical experience with the use of CGM, and advocate for an increased role of this diabetes technology, for monitoring metabolic deterioration and disease progression in children with pre-symptomatic T1D. [ABSTRACT FROM AUTHOR]

Aim: To compare HbA1c and clinical outcomes in adolescents and young adults with type 1 diabetes (T1D), with or without celiac disease (CD). Methods: Longitudinal data were extracted from ADDN, a prospective clinical diabetes registry. Inclusion criteria were T1D (with or without CD), ≥ 1 HbA1c measurement, age 16–25 years and diabetes duration ≥ 1 year at last measurement. Multivariable Generalised Estimated Equation models were used for longitudinal analysis of variables associated with HbA1c. Results: Across all measurements, those with coexisting T1D and CD had lower HbA1c when compared to those with T1D alone (8.5 ± 1.5% (69.4 ± 16.8 mmol/mol) vs. 8.7 ± 1.8% (71.4 ± 19.8 mmol/mol); p < 0.001); lower HbA1c was associated with shorter diabetes duration (B = − 0.06; 95% CI − 0.07 to − 0.05; p < 0.001), male sex (B = − 0.24; − 0.36 to − 0.11; p < 0.001), insulin pump therapy use (B = − 0.46; − 0.58 to − 0.34; p < 0.001), coexistence of T1D and CD (B = − 0.28; − 0.48 to − 0.07; p = 0.01), blood pressure (B = − 0.16; − 0.23 to − 0.09; p < 0.001) and body mass index (B = -− 0.03; − 0.02 to − 0.04; p = 0.01) in the normal range. At last measurement, 11.7% of the total population had a HbA1c < 7.0% (53.0 mmol/mol). Conclusions: Across all measurements, coexisting T1D and CD is associated with lower HbA1c when compared to T1D alone. However, HbA1c is above target in both groups. [ABSTRACT FROM AUTHOR]

Aim: To determine low‐density lipoprotein cholesterol (LDL‐C) screening frequency and levels, and factors associated with elevated LDL‐C, in Australasian youth with type 1 diabetes (T1D). Methods: Data were extracted from the Australasian Diabetes Data Network (ADDN), a prospective clinical quality registry, on all T1D healthcare visits attended by young people aged 16–25 years (with T1D duration of >1 year) between January 2011 and December 2020. The primary outcomes were elevated LDL‐C > 2.6 mmol/L (100 mg/dL) and threshold for treatment: >3.4 mmol/L (130 mg/dL), according to consensus guidelines. Multivariable Generalised Estimated Equations (GEE) were used to examine factors associated with elevated LDL‐C across all visits. Results: A cohort of 6338 young people (52.6% men) were identified, of whom 1603 (25.3%) had ≥1 LDL‐C measurement documented. At last measurement, mean age, age at T1D diagnosis and T1D duration were 18.3 ± 2.4, 8.8 ± 4.5 and 8.9 ± 4.8 years, respectively. LDL‐C was elevated in 737 (46.0%) and at the treatment threshold in 250 (15.6%). In multivariable GEE elevated LDL‐C continuously was associated with older age (OR = 0.07; 0.01–0.13, p = 0.02), female sex (OR = 0.31; 0.18–0.43; p < 0.001), higher HbA1c (OR = 0.04; 0.01–0.08; p = 0.01) and having an elevated BMI (OR = 0.17, 0.06–0.39, p < 0.001). Conclusions: LDL‐C screening and levels are suboptimal in this cohort, increasing future cardiovascular complication risk. There is an urgent need to understand how healthcare services can support improved screening and management of dyslipidaemia in this population. [ABSTRACT FROM AUTHOR]

Aim: Hypertension increases complication risk in type 1 diabetes (T1D). We examined blood pressure (BP) in adolescents and young adults with T1D from the Australasian Diabetes Data Network, a prospective clinical diabetes registry in Australia and New Zealand. Methods: This was a longitudinal study of prospectively collected registry data. Inclusion criteria: T1D (duration ≥ 1 year) and age 16–25 years at last visit (2011–2020). Hypertension was defined as (on ≥ 3 occasions) systolic BP and/or diastolic BP > 95th percentile for age < 18 years, and systolic BP > 130 and/or diastolic BP > 80 mmHg for age ≥ 18 years. Multivariable Generalised Estimating Equations were used to examine demographic and clinical factors associated with BP in the hypertensive range across all visits. Results: Data from 6338 young people (male 52.6%) attending 24 participating centres across 36,655 T1D healthcare visits were included; 2812 (44.4%) had BP recorded at last visit. Across all visits, 19.4% of youth aged < 18 years and 21.7% of those aged ≥ 18 years met criteria for hypertension. In both age groups, BP in the hypertensive range was associated with male sex, injection (vs. pump) therapy, higher HbA1c, and higher body mass index. Conclusions: There is a high proportion of adolescents and young adults reported with BP persistently in hypertensive ranges. Findings flag the additive contribution of hypertension to the well-established body of evidence indicating a need to review healthcare models for adolescents and young adults with T1D. [ABSTRACT FROM AUTHOR]

Background: Competing challenges in adolescence and young adulthood can distract from optimal type 1 diabetes (T1D) self‐management, and increase risks of premature morbidity and mortality. There are limited data mapping the glycemic control of people with T1D in this age group, across Australasia. Research Design and Methods: Clinical data were extracted from the Australasian Diabetes Data Network, a prospective clinical diabetes registry. Inclusion criteria were individuals with T1D aged 16–25 years at their last recorded T1D healthcare visit (from 1st January 2011 to 31st December 2020), with T1D duration of at least 1 year. Data were stratified by two last recorded T1D healthcare visit ranges, while generalized estimated equation (GEE) modeling was used to examine factors associated with HbA1c across visits during the 10 year period. Results: Data from 6329 young people (52.6% male) attending 24 diabetes centers across Australasia were included. At the last visit within the most recent 5 years, mean ± SD age was 18.5 ± 2.3 years, T1D duration was 8.8 ± 4.7 years and HbA1c was 8.8 ± 1.8% (72.2 ± 19.9 mmol/mol); only 12.3% had an HbA1c below the international target of <7.0% (53 mmol/mol). Across all T1D healthcare visits, in GEE modeling, higher HbA1c was associated with female sex (B = 0.20; 95% CI 0.12 to 0.29, p < 0.001), longer T1D duration (B = 0.04, 0.03 to 0.05, p < 0.001). Lower HbA1c was associated with attendance at a pediatric T1D healthcare setting (B = −0.33, −0.45 to −0.21, p < 0.001) and use of CSII versus BD/MDI therapy (B = −0.49, −0.59 to 0.40, p < 0.001). Conclusions: This Australasian study demonstrates widespread and persistent sub‐optimal glycemic control in young people with T1D, highlighting the urgent need to better understand how healthcare services can support improved glycemic control in this population. [ABSTRACT FROM AUTHOR]