Biological basis of child health 12: the endocrine system and common childhood endocrinopathies.

This article, the 12th in a series on the biological basis of child health, focuses on the endocrine system. This system works alongside the nervous system to regulate the functioning of the human body using chemical mediators called hormones. It is composed of several glands secreting a wide range of hormones that act on target cells in organs and tissues. Various functions of the human body are controlled by the endocrine system, including growth, puberty, metabolism and bone health. This article explores the anatomy and pathophysiology of the endocrine system, the effects of hormonal excesses or deficiencies on the body, and the presentation and management of endocrinopathies commonly seen in children.

Urinary conjugated α-tocopheronolactone--a biomarker of oxidative stress in children with type 1 diabetes.

Increased oxidative stress has been implicated in both the onset and the progression of diabetes mellitus and its complications. The development of easy to measure biomarkers of oxidative stress would, therefore, help in determining in a prospective manner the impact of glycemic control on oxidative stress and macrovascular disease in patients with diabetes. We report the development and validation of a novel method to directly measure the urinary concentrations of the conjugated metabolites of vitamin E (α-tocopherol) and investigate whether the oxidized metabolite α-tocopheronolactone (α-TL) could be used as a biomarker of oxidative stress in children with type 1 diabetes. A novel method using liquid chromatography-tandem mass spectrometry was developed and used to measure directly and rapidly the urinary concentrations of the glucuronidated and sulfated metabolites of α-tocopherol in 32 young patients with type 1 diabetes and age-matched controls. The mean concentrations of the glucuronidated and sulfated conjugates of α-TL were all highly significantly increased in the children with type 1 diabetes (p<0.001). The results suggest that the measurement of the urinary concentrations of α-TL conjugates may provide a useful biomarker of oxidative stress in diabetes and possibly in other clinical conditions in which oxidative stress has been implicated.

The growth hormone receptor gene deleted for exon three (GHRd3) polymorphism is associated with birth and placental weight.

CONTEXT: Human growth hormone receptor (GHR) transcripts have two isoforms, full-length (GHRfl) or exon 3 deleted (GHRd3). An association of these isoforms has been found with small for gestational age (SGA) infants but does not influence adult height. The role of this polymorphism in the birth size spectrum in the general population is unclear. OBJECTIVE: To determine the association of maternal and infants GHR exon 3 polymorphism with antenatal growth, birth size and early postnatal growth in two large, normal white European birth cohorts. STUDY DESIGN: Pregnant women from white European families were recruited by the University College London Foetal Growth Study (n = 774) and the Moore normal pregnancy cohort (n = 274). GHR variants, wild-type (fl) and deleted for exon 3 (d3) were analysed using multiplex PCR. RESULTS: There was a significant underrepresentation of infants wild-type fl/fl (36%) and overrepresentation of d3/d3 (14%) genotypes in the SGA infants within the cohorts (χ(2) = 11·2, P = 0·003, df = 2). Fl/fl was overrepresented in large for gestational age (LGA) infants (χ(2) = 6·1, P = 0·047, df = 2). There was a significant association of infants GHR isoforms with placental weight (P < 0·001) and birth weight standard deviation scores (P = 0·04) with the fl/fl genotype associated with a larger placental and birth weight. In multiple regression analysis, the GHR isoform type, maternal booking weight and parity influenced placental weight (R(2) = ·35; P < 0·001, df = 7). The GHR isoform type was not related to antenatal anthropometric measurements or growth in infancy. CONCLUSION: These data suggest that the GHR isoforms are associated with placental and birth weight.

Effects of current size, postnatal growth, and birth size on blood pressure in early childhood.

OBJECTIVE: In a prospective study, we investigated the impact of early growth on blood pressure at 3 years of age. METHODS: We measured systolic blood pressure (SBP) and diastolic blood pressure (DBP) for 590 children 3 years of age and related measurements to current size and size at birth, 6 months, 1 year, and 2 years of age. RESULTS: SBP was related positively to weight at 3 and 2 years and, after adjustment for current size, negatively to weight at birth and 6 months but not at 1 or 2 years. No effect was observed for DBP. A family history of hypertension was associated with higher maternal blood pressure, greater weight, and gestational hypertension (P = .05). Mothers with a history of gestational hypertension had higher SBP and DBP values (P < .001). In multivariate linear regression analyses, SBP was influenced positively by weight at 3 years and family history of hypertension and negatively by weight at 6 months. None of the factors was associated with DBP. CONCLUSIONS: For 3-year-old children, current weight was a determinant of SBP and postnatal growth to 6 months of age was more predictive than birth weight. A family history of hypertension is important in determining maternal blood pressure. These observations suggest a window in which postnatal growth might be modified.

Management of altered hydrocortisone pharmacokinetics in a boy with congenital adrenal hyperplasia using a continuous subcutaneous hydrocortisone infusion.

BACKGROUND: Conventional hydrocortisone dosing schedules do not mimic the normal circadian rhythm of cortisol, making it difficult to optimize treatment in congenital adrenal hyperplasia (CAH). CASE DETAILS: We report a 14.5-year-old boy with CAH who had reduced bioavailability [42% (normal 80% orally and 100% by im route)] and increased clearance [half-life 50 min (normal range, 70-100 min)] of oral doses of hydrocortisone leading to ambient serum 17-hydroxyprogesterone concentrations of 400 nmol/liter (14.5 ng/ml) and androstenedione concentrations of 24.9 nmol/liter (7.1 ng/ml). INTERVENTION: Using a continuous but variable sc hydrocortisone infusion via an insulin pump, rapid control of his CAH was attained with a normal cortisol circadian profile. Average daily hydrocortisone dose was 17.4-18.6 mg/m(2), which produces on average 24-h serum cortisol and 17-hydroxyprogesterone concentrations of 316 nmol/liter (115 ng/ml) and 4.3 nmol/liter (1.4 ng/ml), respectively. Therapy has been maintained over 4 yr with suppression of normal adrenal androgen production and normal progression through puberty. CONCLUSIONS: Continuous sc infusion of hydrocortisone may prove a valuable adjunct to therapy for CAH, particularly in patients requiring high doses of oral hydrocortisone and in those with abnormal hydrocortisone pharmacokinetics.