M G Shaikh

Vitamin D and its effects on glucose homeostasis, cardiovascular function and immune function.

In recent years there has been increasing interest in the non-skeletal effects of vitamin D. It has been suggested that vitamin D deficiency may influence the development of diabetes, cardiovascular dysfunction and autoimmune diseases. This review focuses on the current knowledge of the effects of vitamin D and its deficiency on cardiovascular function, glucose homeostasis and immune function, with a particular focus on children. Although, there is good evidence to show that there is an association between vitamin D deficiency and an abnormality of the above systems, there is little evidence to show that vitamin D supplementation leads to an improvement in function, especially in childhood.

Growth hormone deficiency during young adulthood and the benefits of growth hormone replacement

Until quite recently, the management of children with growth hormone deficiency (GHD) had focussed on the use of recombinant human GH (rhGH) therapy to normalise final adult height. However, research over the past two decades that has demonstrated deficits in bone health and cardiac function, as well as impaired quality of life in adults with childhood-onset GHD (CO-GHD), has questioned this practice. Some of these studies suggested that there may be short-term benefits of rhGH in certain group of adolescents with GHD during transition, although the impact of GHD and replacement during the transition period has not been adequately investigated and its long-term benefits remain unclear. GH therapy remains expensive and well-designed long-term studies are needed to determine the cost effectiveness and clinical benefit of ongoing rhGH during transition and further into adulthood. In the absence of compelling data to justify widespread continuation of rhGH into adult life, there are several questions related to its use that remain unanswered. This paper reviews the effects of growth hormone deficiency on bone health, cardiovascular function, metabolic profile and quality of life during transition and young adulthood.

MRI-based abnormalities in young adults at risk of adverse bone health due to childhood-onset metabolic & endocrine conditions

Traditional methods of bone densitometry may not provide a comprehensive assessment of bone health. We aimed to assess bone micro‐architecture and bone marrow adiposity (BMA) by MRI in adults with osteogenesis imperfecta (OI) and endocrinopathy including GH deficiency and/or hypogonadism.

The measurement of urinary gonadotropins for assessment and management of pubertal disorder

OBJECTIVE: Measurement of urinary LH (uLH) and FSH (uFSH) may facilitate non-invasive pubertal assessment but there is a need for further validation by studying children and adolescents with disorders of puberty. DESIGN: 65 cases (Male: 25) with a median age of 12 years (2.9–18.1) supplied at least one non-timed urine sample for uLH and uFSH measurement by immunoassay and corrected for creatinine excretion. 25 cases were receiving GnRH-agonist (GnRH-a) at the time of sample collection. In 41 cases, urine samples were collected prior to a LHRH test and in 12 cases matched serum samples for basal LH (sLH) and FSH (sFSH) were also available. RESULTS: There was a significant correlation between sLH and uLH:uCr (r=0.82; p-value <0.001) and sFSH and uFSH:uCr (r=0.93; p-value <0.001). Based on receiver operator characteristics analysis, a uLH:uCr value of 0.05 IU/mmol as a cut-off would detect a LH peak >5U I/L with a sensitivity of 86% and a specificity of 72% with a positive predictive value of 93%. In pubertal boys (6) and girls (22) with a sLH peak >5UI/L, median uLH:uCr was 0.27 IU/mmol (0.27–0.28) and 0.17 IU/mmol (0.09–0.43), respectively. The median uFSH:uCr was 0.51 IU/mmol (0.41–0.60) for boys and 1.1 IU/mmol (0.21–2.44) for girls. In the 25 cases on GnRH-a, the median uLH:uCr for boys and girls was 0.02 IU/mmol (0.01–0.02) and 0.02 IU/mmol (0.004–0.07), respectively, and the median uFSH:uCr was 0.07 IU/mmol (0.05–0.09) and 0.27 IU/mmol (0.09–0.54), respectively. CONCLUSION: Urinary gonadotrophins reflect serum gonadotrophin concentration and may represent a reliable non-invasive method of assessing pubertal progress.

Longitudinal changes in bone parameters in young girls with anorexia nervosa

BACKGROUND Anorexia nervosa (AN) during childhood and adolescence has been reported to adversely affect bone health, but few studies have investigated longitudinal changes. METHOD DXA-derived bone parameters and body composition were retrospectively assessed in 111 young girls with AN with a median age of 15.4 years (10.9, 19.8). In 68 (61%) vertebral fracture assessment (VFA) was performed and in 31 (28%), a follow-up DXA was performed. Correlations with growth, changes in body composition and effects of illness duration and menstruation were examined. Size adjusted DXA standard deviation scores were calculated for total body (TB) less head bone mineral content (TBLH-BMC) and lumbar spine bone mineral apparent density (LS-BMAD). RESULTS Mean (range) bone area (BA) for height centile was 27.1 (0-97), and mean lean mass for height centile was 28.8 (0-95) at baseline. Mean (range) LS BMAD was -1.0 (-2.6, 0.8) SDS at first and - 1.2 (-3.0, -0.2) at second DXA (p = 0.023). On follow up, lean mass for height increased from 27th centile (0, 75) to 40th centile (0, 70) (p = 0.006), and fat mass for height increased from 55 g/cm to 67 g/cm (11.3, 124.2) (p < 0.001). Duration of illness was the only negative predictor of LS BMAD (p < 0.0001). Change in height SDS was the only positive predictor of change in TBLH-BMC (r = 0.384, p = 0.037), and change in LS BMAD (r-0.934, p < 0.0001). Of 68 patients who had VFA, 4 (5.9%) had a mild vertebral fracture. CONCLUSION Bones are smaller and less dense in childhood/adolescent AN compared to healthy adolescents. Although there are significant gains in lean mass and fat mass, over time, BMAD SDS decreases slightly. Improvement in BMAD SDS is related to improvement in height SDS.