Growth during pubertal induction in girls with Turner Syndrome: a retrospective cohort analysis.

CONTEXT: Patients with Turner Syndrome often present with short stature and ovarian insufficiency. The optimal method of pubertal induction to maximize adult height (AH) is unknown. OBJECTIVE: To identify variables related to pubertal induction that are associated with growth and AH. DESIGN & SETTING: Retrospective cohort analysis of patients attending a specialized Turner Syndrome clinic at a quaternary children's hospital. PATIENTS: Patients with Turner Syndrome (n=107) who attended the clinic between 2015 and 2021. Of these, 51 received estradiol for pubertal induction. MAIN OUTCOME MEASURES: Change in height standard deviation score (ΔHeightSDS) during pubertal induction, and AH. METHODS: Age at pubertal induction, bone age delay, midparental height (MPH), growth hormone treatment, and karyotype were assessed as predictors of AH and ΔHeightSDS. Associations between karyotype and comorbidities were also assessed. RESULTS: AH was predicted by MPH (0.8cm/cm, P=0.0001) and bone age delay (-1.84 cm/year, P= 0.006). ΔHeightSDS was predicted by growth hormone dose (0.09 SDS/mg/m2/week; P=0.017), bone age delay (-1.37 SDS/year; P=0.003), and age at pubertal induction (0.44 SDS/year; P=0.001). There was an interaction between bone age delay and pubertal induction age (P=0.013), with the combination of younger age at pubertal induction and a less-delayed bone age associated with a lower ΔHeightSDS. Karyotype did not influence AH or ΔHeightSDS, but did affect rates of other comorbidities. CONCLUSIONS: Decisions around timing of pubertal induction in patients with Turner Syndrome should be tailored to the individual. The current approach to estrogen supplementation needs to be refined in order to facilitate pubertal induction in a physiological manner without compromising height.

Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes.

Vitamin D is synthesised in the skin through the action of UVB radiation (sunlight), and 25-hydroxy vitamin D (25OHD) measured in serum as a marker of vitamin D status. Several studies, mostly conducted in high latitudes, have shown an association between type 1 diabetes mellitus (T1DM) and low serum 25OHD. We conducted a case-control study to determine whether, in a sub-tropical environment with abundant sunlight (latitude 27.5°S), children with T1DM have lower serum vitamin D than children without diabetes. Fifty-six children with T1DM (14 newly diagnosed) and 46 unrelated control children participated in the study. Serum 25OHD, 1,25-dihydroxy vitamin D (1,25(OH)(2) D) and selected biochemical indices were measured. Vitamin D receptor (VDR) polymorphisms Taq1, Fok1, and Apa1 were genotyped. Fitzpatrick skin classification, self-reported daily hours of outdoor exposure, and mean UV index over the 35 d prior to blood collection were recorded. Serum 25OHD was lower in children with T1DM (n = 56) than in controls (n = 46) [mean (95%CI) = 78.7 (71.8-85.6) nmol/L vs. 91.4 (83.5-98.7) nmol/L, p = 0.02]. T1DM children had lower self-reported outdoor exposure and mean UV exposure, but no significant difference in distribution of VDR polymorphisms. 25OHD remained lower in children with T1DM after covariate adjustment. Children newly diagnosed with T1DM had lower 1,25(OH)(2) D [median (IQR) = 89 (68-122) pmol/L] than controls [121 (108-159) pmol/L, p = 0.03], or children with established diabetes [137 (113-153) pmol/L, p = 0.01]. Children with T1DM have lower 25OHD than controls, even in an environment of abundant sunlight. Whether low vitamin D is a risk factor or consequence of T1DM is unknown.

Klebsiella pneumoniae bacteraemia complicating rotavirus gastroenteritis in two infants with glucocorticoid deficiency.

Rotavirus gastroenteritis was complicated by Klebsiella Pneumoniae bacteraemia in two infants with glucocorticoid deficient conditions who were treated with 'stress dose' hydrocortisone during their illness. Delayed healing in the context of glucocorticoid administration combined with damage from rotavirus infection may result in increased risk of mucosal invasion by gastrointestinal bacteria and subsequent enteric gram-negative bacteraemia.

Glucose requirements to maintain euglycemia after moderate-intensity afternoon exercise in adolescents with type 1 diabetes are increased in a biphasic manner.

CONTEXT: Exercise increases the risk of hypoglycemia in type 1 diabetes. OBJECTIVE: This study aimed to investigate how the amount of glucose required to prevent an exercise-mediated fall in glucose level changes over time in adolescents with type 1 diabetes. SETTING: The study took place at a tertiary pediatric referral center. DESIGN, PARTICIPANTS, AND INTERVENTION: Nine adolescents with type 1 diabetes mellitus (five males, four females, aged 16 +/- 1.8 yr, diabetes duration 8.2 +/- 4.1 yr, hemoglobin A1c 7.8 +/- 0.8%, mean +/- SD) were subjected on two different occasions to a rest or 45 min of exercise at 95% of their lactate threshold. Insulin was administered iv at a rate based on their usual insulin dose, with similar plasma insulin levels for both studies (82.1 +/- 19.0, exercise vs. 82.7 +/- 16.4 pmol/liter, rest). Glucose was infused to maintain euglycemia for 18 h. MAIN OUTCOME MEASURES: Glucose infusion rates required to maintain euglcycemia and levels of counterregulatory hormones were compared between rest and exercise study nights. RESULTS: Glucose infusion rates to maintain stable glucose levels were elevated during and shortly after exercise, compared with the rest study, and again from 7-11 h after exercise. Counterregulatory hormone levels were similar between exercise and rest studies except for peaks in the immediate postexercise period (epinephrine, norepinephrine, GH, and cortisol peaks: 375.6 +/- 146.9 pmol/liter, 5.59 +/- 0.73 nmol/liter, 71.9 +/- 14.8 mIU/liter, and 558 +/- 69 nmol/liter, respectively). CONCLUSIONS: The biphasic increase in glucose requirements to maintain euglycemia after exercise suggests a unique pattern of early and delayed risk for nocturnal hypoglycemia after afternoon exercise.

Neonatal complete generalized glucocorticoid resistance and growth hormone deficiency caused by a novel homozygous mutation in Helix 12 of the ligand binding domain of the glucocorticoid receptor gene (NR3C1).

CONTEXT: Glucocorticoid resistance is a rare genetic condition characterized by reduced sensitivity to cortisol signaling and subsequent hyperactivation of the hypothalamic-pituitary-adrenal axis. OBJECTIVE: The objective was to confirm the diagnosis of glucocorticoid resistance in the patient, to determine the degree of suppression of cortisol and ACTH levels in response to dexamethasone, and to determine the underlying genetic abnormality and functional consequences of the mutation. PATIENT AND METHODS: The patient presented on the first day of life with profound hypoglycemia. Initial cortisol levels were appropriately elevated; however, the patient was found to have persistently elevated levels of both cortisol and ACTH. The baby developed a tanned appearance and severe hypertension and fatigued easily with feeding. Serial oral dexamethasone suppression tests were performed with doses escalating from 0.125 mg to 12 mg dexamethasone given at 2300 h. Sequencing of the glucocorticoid receptor gene was performed along with functional studies of the glucocorticoid receptor. GH secretion was assessed with an arginine glucagon stimulation test. RESULTS: Cortisol and ACTH levels did not suppress with doses of up to 12 mg dexamethasone. A 2-bp deletion was found at amino acid position 773 of the glucocorticoid receptor ligand binding domain. A complete lack of dexamethasone binding and in vitro biological effect was demonstrated. GH stimulation testing was consistent with GH deficiency. CONCLUSION: The homozygous mutation in the ligand-binding domain of the glucocorticoid receptor gene resulted in a functionally inactive glucocorticoid receptor and apparent complete glucocorticoid resistance with biochemical GH deficiency.

Increase in type 2 diabetes in children and adolescents in Western Australia.

OBJECTIVES: To document diagnosis rates of type 2 diabetes mellitus in children and adolescents in Western Australia over the past 12 years, the clinical characteristics of these patients and any comorbidities. DESIGN: Review of a prospectively recorded diabetes database. SETTING: Tertiary paediatric referral centre (the only such centre in WA). PATIENTS: All children and adolescents aged < 17 years diagnosed with type 2 diabetes between 1990 and 2002 and managed by Princess Margaret Hospital Diabetes Unit. MAIN OUTCOME MEASURES: Anthropometric and demographic data; glycohaemoglobin (HbA(1c)) level; blood pressure; lipid levels; presence of acanthosis nigricans. RESULTS: 43 patients (15 males and 28 females) were diagnosed with type 2 diabetes. Age (SD) at diagnosis was 13.6 (1.8) years. The rate of diagnosis has been progressively increasing (average annual increase in the unadjusted overall rates of type 2 diabetes was 27%). Twenty-three patients (53%) were of Indigenous origin and 18 (42%) resided in rural areas. The mean (SD) HbA(1c) level at diagnosis was 10.0% (3.2%). Seventy-two per cent of patients had acanthosis nigricans, 59% had hypertension, and 24% had hyperlipidaemia. CONCLUSIONS: There has been an increase in the diagnosis rate of type 2 diabetes in children and adolescents in WA. Comorbidities are frequent.