B10 - Blood pressure central obesity and insulin sensitivity in early childhood - associated with adrenal function birthweight and early growth - 01/07/2001

B number: 
Principal applicant name: 
Prof David Dunger (University of Cambridge, UK)
Title of project: 
Blood pressure, central obesity and insulin sensitivity in early childhood - associated with adrenal function, birthweight and early growth
Proposal summary: 

At UCLH we run a nationally used service for investigation of adrenal disease based on urine steroid analysis. We frequently get referred samples from children with early pubertal development which we attribute to adrenarche. From epidemiological studies we have conducted in collaboration with Professor Baker in Southampton we have examined changes in adrenal function in 9 year old children in Salisbury. In 24 hour urine collections both adrenal androgen and cortisol metabolites were quantified. Urinary androgen excretion was higher in children who had been light at birth. A 1 kg decrease in birthweight was associated with a 40% increase in androgen excretion. In contrast the relationship with urinary cortisol excretion was U-shaped with higher outputs at the extremes of birthweight. Birthweight was associated with metabolite output independent of current weight, gender and gestational age at birth, indicating that the HPA function was related to fetal growth rather than prematurity. A reduced birth size has also been associated with cardiovascular disease risk and insulin-dependent diabetes. High blood pressure and cardiac hypertrophy may be the consequence of the hyperactive adrenal secreting both cortisol and adrenal androgens from early puberty.

In children with asthma at 8 years of age there is absence of adrenal androgen output. This leads to a reduction in growth rate such that asthmatic children at this stage are shorter than their peers. As they go into puberty they catch-up on the lost height. Loss of adrenal androgens is a feature of many sytemic illnesses (severe burns, HIV and AIDS) and may be linked with states of immune suppression. Children with diabetes would be another group worth investigating.

In keeping with the objectives of the ALSPAC study these children would be worth studying in the same way with the aim of clarifying:

* Adrenal function in relation to birth weight

* Adrenal function in relation to parental adrenal function

* Adrenal function in asthmatic children

In addition to examining the balance of adrenal androgens and cortisol the urine data can be examined to establish whether changes would be due to increased circulating levels or due to changes in the degradative process for cortisol through it's metabolism to inactive cortisone. Thus metabolites of cortisol and cortisone will be examined along with the excretion rates of the free hormones themselves.

24 hour urine samples would be desirable from the children and their parents in order to assess cortisol and adrenal androgen productions.

Date proposal received: 
Sunday, 1 July, 2001
Date proposal approved: 
Sunday, 1 July, 2001
Biological Samples, Cardiovascular , Endocrine, Obesity, Weight, Blood Pressure
Primary keyword: