Avril Mason

Impact of Inflammatory Bowel Disease on Pubertal Growth

Background: Puberty is thought to be commonly affected in adolescents with inflammatory bowel disease (IBD). Aims: To determine the impact of Crohn’s disease (CD) and ulcerative colitis (UC) on the pubertal growth spurt. Methods: Retrospective study of 30 boys with CD (CD-M), 11 girls with CD (CD-F), 14 boys with UC (UC-M) and 12 girls with UC (UC-F). Pubertal growth was assessed by calculating peak height velocity SDS (PHV SDS), height SDS at diagnosis (HtDiag) and height SDS at PHV (HtPHV) and age at PHV (AgePHV). Systemic markers of disease activity were also collected. Results: Altered parameters of pubertal growth were observed in the CD groups compared to the normal population: in the CD-M group, median HtDiag was –0.56 (p = 0.001) and median AgePHV was 14.45 years (p = 0.004), and in the CD-F group, median HtDiag was –1.14 (p = 0.007) and HtPHV was –0.79 (p = 0.039). Individually, 8/30 CD-M cases had one or more parameter affected: 2 boys had HtDiag <–2, 3 boys had HtPHV <–2, 2 boys had an AgePHV >2 years above population mean, and 2 boys had a PHV SDS <–2. In the whole group, AgePHV showed an association with erythrocyte sedimentation rate (r = 0.4; p = 0.005) and an inverse association with BMI (r = 0.4; p = 0.001). Conclusion: Disorders of pubertal growth are more likely to occur in CD and, particularly, in boys.

Growth in children receiving contemporary disease specific therapy for Crohn's disease

Introduction It is unclear whether recent therapeutic advances have improved the growth of children with Crohns disease (CD). Aim To assess the frequency of short stature and poor growth and their relationship to disease course and therapy in children with CD. What is already known on this topic Growth retardation may occur in children with Crohns disease (CD). Current therapy for CD in the UK is less likely than previously to involve the use of long-term glucocorticoids. What this study adds Despite advances in therapy, short stature and slow growth continue to be encountered in children with CD. There is a need for simple and consistent definitions of growth that can identify poor growth in children with chronic disease. Methods The anthropometric and treatment details of 116 children (68 male) with a mean (range) age at diagnosis of 10.8 years (4.9–15.5) and a mean age at maximum follow-up (MF) of 15.4 years (9.4–19.3) were studied retrospectively at diagnosis (T0), at 1 (T1), 2 (T2) and 3 years (T3) after diagnosis and at MF. Results At T0, mean height SD score (HtSDS) was −0.5 (−3.3 to 2.6) compared to a mid-parental HtSDS of 0.2 (−2.0 to 01.4) (p=0.002). At T1, T2, T3 and MF, mean HtSDS was −0.6 (−4.8 to 7.8), −0.6 (−2.9 to 2.2), −0.7 (−3.6 to 2.5) and −0.5 (−3.5 to 2.9), respectively. Mean Ht velocity (HV) SDS at T1, T2, T3 and MF was −1.4 (−7.4 to 7.4), −0.6 (−7.5 to 6.1), −0.1 (−6.6 to 7.6) and 0.6 (−4.8 to 7.8), respectively (p<0.05). In final models, HtSDS was associated negatively with the use of prednisolone (p=0.0001), azathioprine (p=0.0001), methotrexate (p=0.0001) and weight SDS (WtSDS) (p=0.0001). HVSDS was associated positively with age (p=0.0001) and WtSDS (p=0.01). ΔHtSDS was associated negatively with use of prednisolone (p<0.02). Conclusion Although current therapy for CD is associated with improved rate of growth for the first few years, a substantial proportion of children remain short. This study also highlights the need for consistency in describing growth in children with chronic diseases.

Effect of Testosterone Therapy for Delayed Growth and Puberty in Boys with Inflammatory Bowel Disease

Background: Pubertal delay and growth retardation are common in children with inflammatory bowel disease (IBD). Aims: To assess pubertal status and growth in a group of boys with IBD undergoing testosterone therapy for pubertal induction. Methods: Retrospective study of height, weight and pubertal status in 8 boys with IBD before and after testosterone therapy. Height velocity (HV) over the 6 months before each assessment was converted to standard deviation score. Markers of disease activity and concomitant medication were recorded. Response was based on an advance in pubertal status and a greater than 50% increase in HV. Results: Eight boys with IBD, median age 14.8 years, had pubertal induction using either monthly injections of 50 mg Sustanon or daily 2.5/5 mg Andropatch. Seven boys showed an advance of pubertal status. Six boys had a greater than 50% increase in HV; median HV at T0 was 1.6 cm/year (0, 5) compared with 6.9 cm/year (1, 11.7) at T6 (p = 0.005). C-reactive protein during testosterone therapy had a significant association with HV at T6 (r = –0.786; p = 0.021). Conclusion: In most cases, testosterone therapy in boys with IBD and delayed growth and puberty is associated with an advance in pubertal status and an improvement in growth.

A Prospective Longitudinal Study of Growth and Pubertal Progress in Adolescents with Inflammatory Bowel Disease

Background: Puberty and growth may be affected in inflammatory bowel disease (IBD) but the extent is unclear. Methods: We performed a prospective study over 12 months in 63 adolescents (Crohns disease, CD, n = 45; ulcerative colitis/IBD unclassified, UC, n = 18) with a median age of 13.4 years (range 10-16.6). Assessment included anthropometry, biochemical markers of growth and puberty and an assessment of quality of life by IMPACT-III. Results: Compared to the normal population, boys with CD were shorter, with a median height SDS (HtSDS) of -0.13 (-2.52 to 1.58; p < 0.05). In addition, the study cohort had a lower median IGF-1 SDS of -0.29 (-4.53 to 2.96; p = 0.008) and a higher median IGFBP3 SDS of 0.45 (-3.15 to 2.55; p = 0.002). Over the study period, the median Ht velocity (HV) was 5 cm/year (0.2-8.7) and the change in HtSDS was 0.06 (-0.48 to 0.57). The median difference between the chronological and bone age was 0.3 years (-2.5 to 3.0) and pubertal examination was not delayed. In the whole group, the erythrocyte sedimentation rate (ESR) showed an inverse association with HV (r = -0.29; p = 0.025) and IGF-1:IGFBP3 (r = -0.34; p = 0.016). The score in the body image domain, IMPACT-III, was inversely associated with HtSDS (r = -0.31; p = 0.03). Conclusion: Despite no evidence of pubertal delay, adolescents with IBD display growth retardation which may be associated with raised ESR, adverse quality of life measures and an abnormality of IGF-1 bioavailability.

A critical appraisal of vertebral fracture assessment in paediatrics

PURPOSE There is a need to improve our understanding of the clinical utility of vertebral fracture assessment (VFA) in paediatrics and this requires a thorough evaluation of its readability, reproducibility, and accuracy for identifying VF. METHODS VFA was performed independently by two observers, in 165 children and adolescents with a median age of 13.4 years (range, 3.6, 18). In 20 of these subjects, VFA was compared to lateral vertebral morphometry assessment on lateral spine X-ray (LVM). RESULTS 1528 (84%) of the vertebrae were adequately visualised by both observers for VFA. Interobserver agreement in vertebral readability was 94% (kappa, 0.73 [95% CI, 0.68, 0.73]). 93% of the non-readable vertebrae were located between T6 and T9. Interobserver agreement per-vertebra for the presence of VF was 99% (kappa, 0.85 [95% CI, 0.79, 0.91]). Interobserver agreement per-subject was 91% (kappa, 0.78 [95% CI, 0.66, 0.87]). Per-vertebra agreement between LVM and VFA was 95% (kappa 0.79 [95% CI, 0.62, 0.92]) and per-subject agreement was 95% (kappa, 0.88 [95% CI, 0.58, 1.0]). Accepting LVM as the gold standard, VFA had a positive predictive value (PPV) of 90% and a negative predictive value (NPV) of 95% in per-vertebra analysis and a PPV of 100% and NPV of 93% in per-subject analysis. CONCLUSION VFA reaches an excellent level of agreement between observers and a high level of accuracy in identifying VF in a paediatric population. The readability of vertebrae at the mid thoracic region is suboptimal and interpretation at this level should be exercised with caution.

Turner syndrome–issues to consider for transition to adulthood

BACKGROUND Turner syndrome (TS) is associated with a spectrum of health problems across the age span, which requires particular attention during the transition period in these adolescents. AREAS OF AGREEMENT The majority of girls with TS require oestrogen replacement from puberty onwards, which is important for adequate feminization, uterine development and maintenance of bone health. There is a lifetime increased risk from autoimmune conditions like hypothyroidism, coeliac disease, hearing loss and aortic dilatation with the potential to lead to aortic dissection. A systematic and holistic approach to provision of health care in TS is needed. AREAS OF CONTROVERSY Several unanswered questions remain, including the choice of hormone replacement therapy in the young person with TS and in adulthood; the optimal mode of cardiovascular assessment; the best management and assessment prior to and during pregnancy. AREAS TIMELY FOR DEVELOPING RESEARCH The optimal model of care and transition to adult services in TS requires attention. Further research is needed in relation to cardiovascular risk assessment, pregnancy management and hormone replacement therapy in TS.

Urinary gonadotrophins: a useful non-invasive marker of activation of the hypothalamic pituitary-gonadal axis.

BackgroundNon-invasive screening investigations are rarely used for assessing the activation and progression of the hypothalamic-pituitary gonadal axis through puberty. This study aimed to establish a normal range for urinary gonadotrophins in children progressing through puberty.MethodsUrine samples were collected from 161 healthy school children (76 boys, 85 girls) aged 4–19 yrs. Height and weight were converted to standard deviation score. Pubertal status, classified by Tanner staging, was determined by self-assessment. Urinary gonadotrophins were measured by chemiluminescent microparticle immunoassay. Results were grouped according to pubertal status (pre-pubertal or pubertal).ResultsOf the 161 children, 50 were pre-pubertal (28 boys; 22 girls) and 111 were pubertal (48 boys; 63 girls). Overall, urinary gonadotrophins concentrations increased with pubertal maturation. All pre-pubertal children had a low urinary LH:Creatinine ratio. LH:Creatinine ratios were significantly higher in pubertal compared to pre-pubertal boys (p<0.001). In girls, FSH:Creatinine ratios were significantly higher in the pubertal group (p = 0.006). However, LH:FSH ratios were a more consistent discriminant between pre-pubertal and pubertal states in both sexes (Boys 0.45 pubertal vs 0.1 pre-pubertal; girls 0.23 pubertal vs 0.06 pre-pubertal).ConclusionUrinary gonadotrophins analyses could be used as non-invasive integrated measurement of pubertal status which reflects clinical/physical status.

Permanent congenital hypothyroidism with blood spot thyroid stimulating hormone <10 mU/L

Background The UK recommended lower threshold for neonatal blood spot thyroid stimulating hormone (TSH) screening for congenital hypothyroidism (CHT) is 10.0 mU/L. Some laboratories use lower thresholds. This will lead to referral of mildly or unaffected infants but some will require thyroxine therapy. Methods Laboratory referrals with a first or repeat capillary TSH between 8.0 and <10.0 mU/L were identified (January 2004 to March 2014). The outcome of these cases was examined. Results 26 infants had one or more blood spot TSH values between 8.0 and 9.99 mU/L; 65% had transient elevated neonatal TSH while one is awaiting diagnostic challenge. The remaining eight (31%) have permanent CHT; three with dyshormonogenesis, two with thyroid ectopia and the others met the criteria for definite CHT. Two out of three with dyshormonogenesis presented with decompensated hypothyroidism. Conclusions Infants with permanent and occasionally severe CHT may have a screening TSH below the UK recommended lower cut-off.

Undetectable salivary testosterone in young women with premature ovarian failure

Background  The extent of androgen deficiency in young women with premature ovarian failure (POF) is unclear.

Sexual precocity in a 4 year old boy

Caution men treated with testosterone gel to wear clothing when in close contact with children