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Final height, body proportions, pubertal growth and body mass index were studied retrospectively in 142 survivors of acute lymphoblastic leukaemia (ALL). Treatment consisted of combination chemotherapy and cranial irradiation (18 or 24 Gy). Significant standing height loss and disproportion, with a relatively short back, was seen in both radiation dose groups. Girls were more severely affected than boys. Pubertal growth was adversely affected, with a reduction in peak height velocity in both sexes. Puberty occurred early in girls but at the normal time in boys. Nearly half the group were obese at final height, with no significant difference in incidence between the sexes. The relative roles of cranial irradiation and chemotherapy in the disturbance of growth, puberty and body composition observed in survivors of childhood ALL remain unclear. The aetiology is almost certainly multifactorial, with radiation‐induced growth hormone insufficiency, early puberty, steroids and chemotherapy all having a role.

SummaryObjectives Corticosteroids are known to cause adrenal suppression. The aim of this study was to assess clinical factors affecting responses to a low dose short synacthen test (LDSST) in asthmatic children using corticosteroids. Design Patients were recruited from secondary care paediatric asthma populations within the UK. Patients Asthmatic children (5-18 years), receiving corticosteroids, underwent a LDSST (n = 525). Measurements Demographics and corticosteroid doses were tested for association with baseline and peak (stimulated) cortisol concentrations. Results Baseline cortisol was significantly associated with age (log baseline increased 0Á04 nM per year of age, P < 0Á0001), but not with gender or corticosteroid dose. Peak cortisol was significantly associated with total corticosteroid cumulative dose (decreased 0Á73 nM per 200 mcg/day, P < 0Á001) but not with age, gender inhaled/intranasal corticosteroid cumulative dose or number of courses of rescue corticosteroids. Biochemically impaired response (peak cortisol ≤500 nM) occurred in 37Á0% (161/435) overall, including children using GINA low (200-500 mcg/day beclomethasone-CFC equivalent 32%, n = 60), medium (501-1000 mcg/day (33%, n = 57) and high (>1000 mcg/day 40%, n = 13) doses of inhaled corticosteroid (ICS) similarly, and 36Á6% of those using fluticasone ICS ≥500 mcg/day (71/194). Impaired response was more frequent in patients on regular oral corticosteroids (66%, n = 27, P < 0Á001). Conclusion Children with asthma can develop biochemical adrenal suppression at similar frequencies for all ICS preparations and doses. The clinical consequence of biochemical suppression needs further study.

Purpose:To determine the effect of cranial irradiation (18 Gy and 24 Gy) on pubertal growth in young adult survivors of childhood acute lymphoblastic leukemia (ALL).Patients and Methods: Final height (FH) and pubertal growth were retrospectively examined in 142 young adult survivors of childhood ALL. All were in first remission and had received either 18 or 24 Gy of cranial irradiation. Eighty-four children (48 girls) were treated with 24 Gy and 58 (35 girls) with 18 Gy. None had received either testicular or spinal irradiation. Timing and duration of puberty were studied in 110 patients.Results: Significant reduction in height standard deviation score (SDS) from diagnosis to FH was seen in both sexes and in both dose groups. In girls, in both dose groups, mean age at peak height velocity (PHV) and A CUTE LYMPHOBLASTIC leukemia (ALL) is the most common childhood malignancy, with an incidence of 3.5 per 100,000. Survival rates for children with ALL have improved enormously over the last 20 years, such that 70% of children can now expect to be longterm survivors with current therapy.', 2 Since 1970, this has in part been achieved by the introduction of treatment directed at the CNS, with a combination of cranial irradiation and intrathecal methotrexate. 3 Until 1980, the dose of cranial irradiation given was 24 Gy (usually administered in 15 fractions over 3 weeks). This was reduced to 18 Gy (administered in 10 fractions over 2 weeks) in 1981 in an attempt to reduce the morbidity seen with the higher dose. It is well recognized that higher doses of cranial irradiation (21 to 24 Gy) can cause significant loss in standing height.4 -6 At lower doses, the effects on growth and, more importantly, on final height have been less clear. 68 Early and precocious puberty in girls have also been reported after both doses of cranial irradiation.Disproportion at final height after treatment for ALL in childhood was recently reported by our group. This suggests that at least in some children, much if not all of the height loss is due to a reduction in sitting height."' In this study, we examined the effect of both 18 Gy and 24 Gy of cranial irradiation on growth and the timing and duration of puberty. PATIENTS AND METHODSYoung adult survivors of childhood ALL were identified from three regional pediatric oncology/hematology centers. All had received combination chemotherapy and cranial irradiation as CNS prophylaxis. All were in first remission, and none had received either mean age at menarche occurred significantly earlier than in the normal population. In boys, there was a normal timing of PHV. The amplitude of PHV was significantly reduced in both sexes and in both dose groups. Parameters of pubertal duration (PHV to menarche, PHV to FH, and menarche to FH) were not significantly different from normal population values.Conclusion: In conclusion, puberty occurred early in girls, but not in boys. Amplitude of PHV was reduced in both sexes, with no reduction in the duration of puberty. It is likely that disturbances of both ti...

No studies to date have evaluated the relationship between exercise and microvascular function in youth with type 1 diabetes mellitus (T1DM). Twenty-nine complication free children and adolescents with T1DM were assessed for skin microvascular reactivity, aerobic fitness (VO2peak) and physical activity. VO2peak but not physical activity was significantly and independently associated with maximal hyperemia of the skin microcirculation (p < .01). No significant associations were found between venoarte-riolar reflex (VAR) vasoconstriction and VO2peak or physical activity. Aerobic fitness may be an important indicator or mediator of effective microvascular endothelial function in youth with T1DM.

Hyperthyrotropinaemia, in which normal levels of T4 occur in association with raised TSH, is picked up on neonatal screening. The outcome of children with persistent hyperthyrotropinaemia is uncertain. The study objective was to evaluate the outcome of children with the persistent form of hyperthyrotropinaemia. We carried out a retrospective analysis on children who attended one institution over the last 20 years with this diagnosis. Eight children were diagnosed with hyperthyrotropinaemia lasting more than 3 months in total. Four had a transient form lasting between 3 and 18 months in total. Three continue to have persistently raised TSH at 5, 9 and 17 years, respectively. One patient became biochemically hypothyroid at 1 year of age requiring treatment with replacement thyroxine. All of our group had normal growth and development. We recommend that thyroid function monitoring should continue in all children with hyperthyrotropinaemia until the thyroid function tests have normalised.

Context and objective Growth hormone insensitivity (GHI) in children is characterized by short stature, functional IGF-I deficiency and normal or elevated serum GH concentrations. The clinical and genetic etiology of GHI is expanding. We undertook genetic characterization of short stature patients referred with suspected GHI and features which overlapped with known GH-IGF-I axis defects. Design and methods Between 2008 and 2020, our center received 149 GHI referrals for genetic testing. Genetic analysis utilized a combination of candidate gene sequencing (CGS), whole exome sequencing (WES), array comparative genomic hybridization (aCGH) and a targeted whole genome short stature gene panel. Results Genetic diagnoses were identified in 80/149 subjects (54%) with 45/80 (56%) having known GH-IGF-I axis defects (GHR n=40, IGFALS n=4, IGFIR n=1). The remaining 35/80 (44%) had diagnoses of 3M syndrome (n=10) (OBSL1 n=7, CUL7 n=2 and CCDC8 n=1), Noonan syndrome (n=4) (PTPN11 n=2, SOS1 n=1 and SOS2 n=1), Silver-Russell syndrome (n=2) (Loss of methylation on chromosome 11p15 and uniparental disomy for chromosome 7), Class 3-5 copy number variations (n=10) and disorders not previously associated with GHI (n=9) (Barth syndrome, Autoimmune lymphoproliferative syndrome, Microcephalic osteodysplastic primordial dwarfism Type II, Achondroplasia, Glycogen storage disease Type IXb, Lysinuric protein intolerance, Multiminicore Disease, MACS syndrome and Bloom syndrome). Conclusion We report the wide range of diagnoses in 149 patients referred with suspected GHI, which emphasizes the need to recognize GHI as a spectrum of clinical entities in undiagnosed short stature patients. Detailed clinical and genetic assessment may identify a diagnosis and inform clinical management.

Abstract:Introduction: