We previously described a biphasic dose-response curve for ethinyl estradiol on short term growth in patients with Turner's syndrome. To investigate whether there is a similar phenomenon in boys, we measured the 3-week ulnar growth velocity (TUG) after administration of different doses of estradiol to five prepubertal or early pubertal boys. Basal TUG was determined initially. Subsequently, the boys received a 4-day iv infusion of estradiol at each of three doses (4, 20, and 90 micrograms/day) given double blind in a randomized sequence. TUG was determined before and after each infusion and was allowed to return to baseline before giving the second and third infusions. Mean TUG increased from 0.45 +/- 0.11 (+/- SEM) to 1.38 +/- 0.51 mm/3 weeks after the 4 micrograms/day infusion (P less than 0.05), from 0.49 +/- 0.11 to 1.0 +/- 0.4 mm/3 weeks after the 20 micrograms/day infusion (P = NS), and from 0.46 +/- 0.1 to 0.84 +/- 0.12 mm/3 weeks after the 90 micrograms/day infusion (P = NS). The mean serum estradiol level was 10 +/- 2.3 pg/ml during the 4 micrograms/day infusion, 16 +/- 2.3 pg/ml during the 20 micrograms/day infusion, and 96 +/- 12 pg/ml during the 90 micrograms/day infusion. Mean serum somatomedin-C levels were significantly higher only after the 20 and 90 micrograms/day estradiol infusions. We conclude that low dose estrogen can stimulate ulnar growth in boys and may play a role in the male pubertal growth spurt.

The normal ranges for GH responses to GH-releasing hormone (GHRH) have previously been defined for adult men and women. To determine whether the GHRH responses of normal children differ from those of adults and whether children with GH deficiency (GHD) and children who are growing below the first percentile but are otherwise normal (ISS) have GH responses comparable to those of normal children, we studied 90 normal children, 46 girls and 44 boys, with heights between the 10th and 95th percentiles for age, at different pubertal stages. Their responses were compared to those of 24 children with ISS and 32 children with GHD and to values previously measured in young adult men and women. Girls were grouped by Tanner breast stages and boys by testicular volumes. Plasma somatomedin-C, estradiol or testosterone, and bone age were measured in all children. All received a 1 microgram/kg iv bolus dose of GHRH-(1-44)NH2, and GH responses were measured during a 2-h sampling period. Incremental serum GH responses in girls did not change throughout pubertal development and were similar to those of adult women. The responses in boys at midpuberty were somewhat lower (P less than 0.05) than those in either prepubertal boys or adult men. ISS children had mean GH responses [23 +/- 4 (+/- SE) ng/ml] similar to those of normal children. GHD children had significantly lower mean GH responses (11 +/- 3.7 ng/ml) than normal prepubertal children (35 +/- 4.0 ng/ml; P less than 0.01), but the responses of 17 of the 32 GHD children overlapped with the normal range. GH responses to GHRH were not correlated with bone age, weight, height, SmC levels, or estradiol or testosterone concentrations. These results indicate that GH responses to GHRH testing are relatively constant throughout puberty and young adulthood, that ISS children respond normally to GHRH, and that the GHRH test is not a reliable discriminator between individual normal and GHD children.

The immune response to intradermal or intramuscular hepatitis B vaccine in 18 children with insulin dependent diabetes mellitus (IDDM) compared with 24 healthy children was studied. Patients were divided into responders, hyporesponders, and non-responders according to their antihepatitis B serum concentrations after hepatitis B vaccination. We also studied HLA class II antigen distribution and did delayed type hypersensitivity (DTH) tests on children with IDDM and controls.No diVerence in the immune response (antihepatitis B surface antigen antibody titres) was found with intramuscular administration, whereas with intradermal administration a statistically lower immune response (p < 0.001) was observed in children with IDDM v controls. This hyporesponsiveness cannot be attributed to HLA class II antigen distribution because their frequency was the same in both groups of children with IDDM.It is suggested that the poor immune response to intradermal hepatitis B vaccine may be due to impaired macrophage activity resulting in failure of antigen presentation, which may be of importance in the immune dysfunction in children with IDDM. This hypothesis is suggested by a significantly lower score on a DTH test to a battery of antigens in the IDDM group when compared with controls. It is therefore suggested that when the hepatitis B vaccination is oVered to children with IDDM it may be preferable to give it intramuscularly. (Arch Dis Child 1998;78:54-57)

This study suggests that celiac disease can be associated with Turner syndrome and even responsible for a failure of growth hormone therapy. Therefore we propose to perform in Turner syndrome patients antiendomysium antibody determination as a screening followed by intestinal biopsy in positive cases. This would be advisable at least before starting growth hormone treatment.