Karl Olof Nilsson

Dose-Dependent Effect of Growth Hormone on Final Height in Children with Short Stature without Growth Hormone Deficiency

CONTEXT The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH). OBJECTIVE The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls. DESIGN AND SETTING A randomized, controlled, long-term multicenter trial was conducted in Sweden. INTERVENTION Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated. SUBJECTS A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population. MAIN OUTCOME MEASURES We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS. RESULTS After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations. CONCLUSION GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.

Gingival inflammation in diabetic children related to degree of metabolic control.

Earlier studies indicate that diabetic children are less resistant to periodontal disease than healthy children. As the degree of metabolic control of the diabetes ranges widely in a juvenile population, the susceptibility to gingival inflammation may vary. The aim of the present study was to compare the gingival status in diabetic children, subgrouped for control of the disease, with that in non-diabetic children. All comparisons were performed under controlled plaque conditions. 43 diabetic children took part in the study. The controls consisted of age- and sex-matched healthy children. The degree of gingival inflammation and the amount of bacterial plaque were assessed in terms of the Gingival Index and the Plaque Index, respectively. The Plaque Index scores constituted the basis for all comparisons of gingival status. The metabolic control of the diabetics was assessed from the amount of glycosylated hemoglobin fraction HbA1c. For children with the highest Plaque Index scores, diabetics showed statistically significantly higher Gingival Index scores. Only minor differences were seen in the other Plaque Index classes. The diabetic children with poor metabolic control showed a clear tendency towards higher Gingival Index scores than the non-diabetics, while no such tendency was seen between the diabetics with good metabolic control and the non-diabetics.

Prevalence of coeliac disease in Turner syndrome.

This study was undertaken to investigate the prevalence of coeliac disease in children and adolescents with Turner syndrome. Eighty‐seven children and adolescents with Turner syndrome were screened for IgA‐antiendomysium antibodies (EMA) and IgA‐antigliadin antibodies (AGA), 5% (4/87) being found to be EMA‐positive, and 15% (13/87) to have AGA levels above normal. Of the 10 patients who were either AGA‐ or EMA‐positive and further investigated with intestinal biopsy, four manifested villous atrophy (i.e. all three of the EMA‐positive patients, but only one of the seven AGA‐positive patients). The results suggest EMA‐positivity to be a good immunological marker for use in screening for coeliac disease, and such screening to be justified in patients with Turner syndrome. □Coeliac disease, IgA‐antiendomysium antibodies, IgA‐antigliadin antibodies, Turner syndrome

Growth in Infancy and Childhood in Girls with Turner's Syndrome

ABSTRACT. We describe spontaneous longitudinal growth in girls with Turners syndrome (TS), using the infancy‐childhood‐puberty (ICP) growth model. Lenght/height during the first 12 years of life was studied in 58 Swedish girls with TS. Their mean length at birth was 47.8 cm (SDS –1.4) and mean height at 12.0 years of age 127.3 cm (SDS –3.0). A clear age‐dependent subnormality was observed in the change in length‐height SDS (ΔSDS). Mean ΔSDS values at ages 0.0 to 0.5 and 3.0 to 6.0 years were normal. In contrast, the mean ΔSDS at ages 0.5 to 3.0 and 6.0 to 12.0 years were subnormal. The onset of the childhood growth component (normally located between 0.5 and 1.0 year of age) was, on the average, delayed by 0.28 year. This accounts for the subnormality of ΔSDS at 0.5 to 3.0 years of age. About 50% of the variation in height at 12.0 years of age, as determined by a multiple linear regression analysis, was significantly explained by length at 0.5 year of age, age at the onset of the childhood component, and ΔSDS at 6.0 to 12.0 years of age.

Thyroid autoantibodies, Turner's syndrome and growth hormone therapy

The prevalence of thyroid autoantibodies, i.e. thyroglobulin antibodies and antibodies to thyroid peroxidase, was analyzed in 89 girls, aged 3‐16 years (mean age 10 years), with Turners syndrome. The analyses were performed before the start of growth‐promoting treatment and during a follow‐up period of 1‐5 years. The patients were divided into four groups according to karyotype as follows: group 1, 45, X (n= 63); group 2 with structural abnormalities of the X chromosome (n= 4); group 3 with mosaicism but no structural abnormalities of the X chromosome (n = 10); and group 4, with isochromosome X of the long arm (n = 12): 199 healthy girls aged 12 years, served as controls. Thyroid autoantibodies were demonstrated in 46 of 89 (52%) patients with Turners syndrome compared with 34 of 199 (17%) age‐matched control girls (p < 0.001), thus confirming the relationship between thyroid abnormalities and Turners syndrome. There was also an increase in the prevalence of thyroid antibodies with age. Simultaneous presence of both autoantibodies was significantly more frequent in group 1 (45, X) and group 4 (isochromosome X of the long arm) than in group 3 (mosaicism) (p= 0.04 and p < 0.002, respectively) and significantly more frequent in group 4 than in group 1 (p < 0.05). During 12‐60 months of growth‐promoting treatment, no increase in the prevalence of thyroid antibodies was observed. The findings demonstrate the importance of continuous monitoring of thyroid function in girls with Turners syndrome.

Final height after combined growth hormone and GnRH analogue treatment in adopted girls with early puberty

Background: Girls adopted from developing countries often have early or precocious puberty, requiring treatment with gonadotrophin‐releasing hormone (GnRH) analogues. During such treatment, decreased growth velocity is frequent. Aim: To study whether the addition of growth hormone (GH) to GnRH analogue treatment improves final height in girls with early or precocious puberty. Methods: Forty‐six girls with early or precocious puberty (age ± 9.5y) adopted from developing countries were randomized for treatment for 2–4 y with GnRH analogue, or with a combination of GH and GnRH analogue. Results: During treatment, the mean growth velocity in the GH/GnRH analogue group was significantly higher compared to the control group. Combined GH/GnRH analogue treatment resulted in a higher final height: 158.9 cm compared to 155.8 cm in the GnRH analogue‐treated group. Three out of 24 girls (13%) in the combined group and nine of the 22 girls (41%) treated with GnRH analogue alone attained a final height below –2 standard deviation scores (SDS).

Effect of growth hormone (GH) during puberty in GH-deficient children : preliminary results from an ongoing randomized trial with different dose regimens

Albertsson Wikland K, Alm F, Aronsson S, Gustafsson J, Hagenas L, Hager A, Ivarsson S, Kristrom B, Marcus C, Moe11 C, Nilsson KO, RitzCn M, Tuvemo T, Westgren U, Westphal 0, Aman J. Effect of growth hormone (GH) during puberty in GH‐deficient children: preliminary results from an ongoing randomized trial with different dose regimens. Acta Pxdiatr 1999; Suppl 428:80‐4. Stockholm. ISSN 0803‐5326

Nonislet Pancreatic Autoantibodies in Sibship With Permanent Neonatal Insulin-Dependent Diabetes Mellitus

Neonatal insulin-dependent diabetes mellitus (IDDM) occurs rarely. A sibship of two HLA-Dw3/4-positive boys who developed IDDM within the 1st wk of life is described. Although the HLA-D region genotype would be consistent with IDDM associated with islet autoimmunity, islet cell antibodies were negative, but both boys exhibited the presence of a novel autoantibody that reacted specifically with a conspicuous, yet unidentified, determinant in the interstitial tissue among the acinar cells. The possible relationship between this acinar nonislet autoantibody and permanent neonatal diabetes remains to be established.

Munchausen syndrome by proxy: an unexpected cause of severe chronic diarrhoea in a child

Carlson J, Fernlund P, Ivarsson S‐A, Jakobsson I, Neiderud J, Nilsson KO, Svensson M, Swanstein U. Munchausen syndrome by proxy: an unexpected cause of severe chronic diarrhoea in a child. Acta Pædiatr 1994;83:119–21. Stockholm. ISSN 0803–5253

NEONATAL MENINGITIS CAUSED BY SALMONELLA THOMPSON

A case of neonatal meningitis caused by Salmonella Thompson is presented. In spite of adequate antibiotic treatment during 1 month a relapse occurred and treatment had to be continued for 3 months. The final outcome was very favourable and at the age of 2 years the patient appeared quite normal. During the course of the disease the immunoglobulin levels and the Widal test were followed. Evidence of an antibody deficiency syndrome explaining the patients relapse could not be demonstrated.