Accuracy of final height prediction and effect of growth-reductive therapy in 362 constitutionally tall children.

Height reduction by means of treatment with high doses of sex steroids in constitutionally tall stature (CTS) is a well known, though still controversial, therapy. The establishment of the effect of such therapy is dependent on the height prediction method applied. We evaluated the reliability of various prediction methods together with the subjective clinician's judgment in 143 untreated children (55 boys and 88 girls) with CTS and the effect of height-reductive therapy in 249 tall children (60 boys and 159 girls) treated with high doses of sex hormones (cases). For this purpose, we compared the predicted adult height with the attained height at a mean adult age of 25 yr and adjusted the therapeutic effect for differences in bone age (BA), chronological age (CA), and height prediction between untreated and treated children. At the time of the height prediction, controls were significantly shorter, had more advanced estimated BAs (except for the BA according to Greulich and Pyle in boys), had lower target heights, and had smaller adult height predictions compared with the CTS patients (P < 0.05). At the time of the follow-up, CTS patients were significantly taller than controls for both boys and girls (P < 0.02). In controls, a large variability was found for the errors of prediction of the various prediction methods and in relation to CA. The prediction according to Bailey and Pinneau systematically overestimated adult height in CTS children, whereas the other prediction methods (Tanner-Whitehouse prediction and index of potential height) systematically underestimated final height. The mean (SD) absolute errors of the prediction methods varied from 2.3 (1.8) to 5.3 (4.3) cm in boys and from 2.0 (1.9) to 3.7 (3.5) cm in girls. They were significantly negatively correlated with CA (r = [minus 0.27 to -0.65; P < 0.05), except for the Tanner-Whitehouse prediction in boys, indicating that height prognosis is more reliable with increasing CA. In addition, experienced clinicians gave accurate height predictions by evaluating the growth chart of the child while taking into account various clinical parameters, such as CA, BA, and pubertal stage. The effect of sex hormone therapy was assessed by means of multiple regression analysis while adjusting for differences in height prediction, CA, and BA at the start of therapy between treated and untreated children. The mean (SD) adjusted effect varied from -0.5 (2.4) to 0.3 (1.4) cm in boys and from -0.6 (2.1) to 2.4 (1.4) cm in girls. The adjusted height reduction was dependent on the BA at the time of start of sex hormone therapy and was more pronounced when treatment was started at a younger BA. In boys, the treatment effect was significantly negative at BAs exceeding 14-15 yr. After cessation of therapy, additional mean (SD) growth of 2.4 (1.2) and 2.7 (1.1) cm was observed for boys and girls, respectively. The mean (SD) BA according to Greulich and Pyle at that time was 17.1 (0.7) yr for boys and 15.2 (0.6) yr for girls. These data demonstrate that height prediction in children with CTS is inaccurate in boys, but clinically acceptable in girls. With increasing age, height prognosis became more accurate. Overall, the height-reducing effect of high doses of sex hormones in children with CTS was limited, especially in boys. However, a significant effect of treatment was observed when treatment was started at BAs less than 14-15 yr, depending on the method of BA assessment. In boys, treatment appeared to be contraindicated at BAs older than 14-15 yr, because androgen administration caused extra growth instead of growth inhibition. It is recommended that referral should take place early, preferably before puberty, for careful monitoring of growth and height prediction. Moreover, it is recommended not to discontinue therapy before complete closure of the epiphyses of the hand has occurred to avoid considerable posttreatment growth.

Long term sequelae of sex steroid treatment in the management of constitutionally tall stature.

AIM: To evaluate possible long term side effects of high doses of sex steroids in the management of constitutionally tall stature, with special attention to hypothalamic-gonadal function. METHODS: Sixty four tall adult men and 180 tall adult women, who received supraphysiological doses of sex hormones during puberty, were interviewed in a standardised way at a mean follow up period of 10 years after cessation of treatment. Sixty one untreated tall adult men and 94 untreated tall adult women served as controls. RESULTS: The majority of the subjects were satisfied with their decision regarding hormone treatment. Seventy seven per cent of the women and 78% of the men reported one or more side effects during treatment. Most side effects were mild. In women, only 3% stopped treatment because of an adverse event; in men, the reported side effects never stopped treatment. The frequency of reported side effects in women was higher during treatment with high doses of oestrogens than during oral contraceptive use, indicating a dose dependent relationship. Amenorrhoea of longer than six months after cessation of therapy was found in 5%. Menstrual cycle characteristics of previously treated women were comparable with controls. Malignancy was not reported. Information about a total of 127 pregnancies was obtained and revealed no distinct differences in details and outcome between previously treated women and men, and controls. CONCLUSIONS: At a mean follow up of 10 years there is no evidence that pharmacological doses of sex hormones have a long term effect on reproductive function. However, this period is still too short to draw definite conclusions.

[Immunologically mediated contact urticaria caused by foods in young children with constitutional eczema]. / Immunologisch bepaalde contacturticaria door voeding bij jonge kinderen met constitutioneel eczeem.

Fifty-two children with atopic dermatitis were investigated with the mixed-food radio-allergosorbent test (RAST) and the skin provocation test 'Skin Application Food Test' (SAFT). The mixed-food RAST is a commercially available test with multiple allergens on one disk. The disk contains 6 common food allergens: cow's milk, egg, peanut, soy, codfish and wheat. The SAFT is a system with which foods are applied to the skin in the state in which they are consumed. This test system is routinely used in our subdivision of Paediatric Dermatology in Sophia Children's Hospital. In some children, atopic dermatitis grew worse after a positive SAFT reaction. In 50% of the 38 children with food allergy a correlation was found between exacerbation/induction of atopic dermatitis and consumption or direct skin contact of foods to which the child was allergic. Due to direct skin contact of foods, atopic dermatitis can grow worse with sudden attacks of pruritus, especially on the hands and in the face. The SAFT imitates the naturally occurring symptoms, is child friendly and easy to perform. The mixed-food RAST can be used as a screening test to identify the children with atopic dermatitis and an atopic immune response to foods, so possibly food allergy. Further investigations of the sensitivity of the target organ (in atopic dermatitis: the skin) and the usefulness of the SAFT are then indicated.

Food immediate-contact hypersensitivity (FICH) and elimination diet in young children with atopic dermatitis. Preliminary results in 107 children.

In atopic dermatitis [AD], not only food consumption, but direct skin-contact too can provoke hypersensitivity reactions. We imitated food immediate-contact hypersensitivity [FICH] to cow's milk, egg, peanut or soy by a skin provocation test. This skin application food test [SAFT] was applied in 91 patients aged up to 5 years and suffering from AD, and in 16 healthy controls (all SAFT-negative). In the SAFT-positive patients (n = 61), FICH to egg was observed in 72%, to cow's milk in 47%, to peanut in 34% and soy in only 1 patient. SAFT and RAST scores correlated weakly. Nevertheless, many discrepancies between SAFT and RAST results were found. In 20 of the 61 (33%) patients with FICH, a flare-up in AD was noted at SAFT testing. Upon introducing dietary restrictions, AD improved impressively in 9 of 23 patients who could be followed up. FICH is an important symptom in children with AD and food allergy.

[The 'Phadiatop Paediatric': a useful in-vitro test on an atopic immune response in infants and young children]. / De 'Phadiatop Paediatric': een bruikbare in vitro-test op een atopische immuunrespons bij zuigelingen en kleuters.

The aim of this study was to evaluate a new test for IgE antibody screening in children--the Phadiatop Paediatric. The mixture of allergens in this test contains the food and inhalant allergens for infants and children most relevant. 180 sera were selected from samples submitted for routine diagnostic IgE antibody assay. 91% of these sera were from children less than 5 year old. Half the sera were positive in RASTs that were initially requested by the physicians and the highest RAST scores for each serum were equally distributed over the range RAST class 1-4. 20 control sera were from children 1-4 years old. Results of the Phadiatop Paediatric were compared with results of the combination 'Phadiatop + mixed-food-RAST'. 22% of the sera that were negative in all RASTs that were initially requested by the physicians were positive in both tests. This suggests that an IgE antibody response to food components or inhalants was underdiagnosed in these cases. Whereas 135 sera were found positive in the Phadiatop Paediatric, only 116 sera had a positive Phadiatop result and/or a result of the mixed-food-RAST that was RAST class 1 (greater than or equal to 0.35 PRU/ml) or higher. In 11 of 16 sera with RAST class 0/1 (0.18-0.35 PRU/ml) in the mixed-food-RAST specific IgE against individual food allergens with RAST class 1 or higher could be demonstrated. Results of Phadiatop and Phadiatop Paediatric were not only expressed as 'positive' or 'negative', but also as a serum:reference ratio. Clinical documentation was collected retrospectively from the written case reports of 171 children.(ABSTRACT TRUNCATED AT 250 WORDS)

IgE antibody screening in children. Evaluation of the Phadiatop Paediatric.

With 200 sera from children, results of the Phadiatop Paediatric test were compared with results of the combination "Phadiatop + mixed-food-RAST". The Phadiatop Paediatric test was found to be efficient for IgE antibody screening in young children, when the results of this test were not solely given as "positive" or "negative", but also as "sample/reference-ratio". Clinical documentation could be obtained retrospectively for 171 children and revealed that 99% of the children with atopic disease were found positive in the Phadiatop Paediatric, 17% of the children who were considered non-atopic on clinical grounds, were positive both in the Phadiatop Paediatric and in the combination "Phadiatop + mixed-food-RAST". It is concluded that an atopic immune response is not always associated with current symptoms.

Immediate contact reactions to cow's milk and egg in atopic children.

Forty children (0-5 years old), presented with immediate contact urticaria, rash and often atopic dermatitis (n = 34). Redness or urticaria around the mouth appearing after consuming cow's milk or egg, were the major complaints in all. These symptoms suggested a food-induced immediate contact reaction, which can be immune-mediated or irritative. To reinduce this reaction, a skin provocation test, called SAFT, was performed. SAFT stands for Skin Application Food Test. This test is based on direct skin contact, during a maximum of 30 min with food in its 'ordinary consumptive state'. The SAFT can be regarded as a 'physiological' provocation patch test. If positive, contact urticaria develops most often within a few minutes. The results of SAFT and IgE RAST correlated significantly well. Total IgE values were not informative. The rapid onset of the SAFT reaction, induced by proteins, supported by RAST results, strongly indicates an immune-mediated mechanism. In 52% of the 34 patients with atopic dermatitis, dermatitis was exacerbated following food-to-skin contact. Immune-mediated contact reactions to foods play an important role in (dermal) food allergy.

Psychological impact of continuous subcutaneous insulin infusion pump therapy in non-selected newly diagnosed insulin dependent (type 1) diabetic children: evaluation after two years of therapy.

Thirty type 1 (insulin dependent) diabetic children were treated from diagnosis onwards in a random order (using a table of random permutations) with either continuous subcutaneous insulin infusion pump therapy (CSII), or with conventional injection therapy (CT). After two years of therapy psychosocial measurements were obtained of fifteen CSII children (8 boys, 7 girls; mean age: 12+/-4 years) and thirteen CT children (6 boys, 7 girls; mean age: 10+/-4 years) and their parents. Two families of the CT group refused to participate. The examination consisted of six tests (for the children: junior dutch personality test, WISC-R intelligence test, family relation test, diabetes questionnaire; for the parents: family interaction scale and assessment of acceptance scale). Parents (and pediatricians) rated CSII children higher on compliance and better on metabolic control. Acceptance of diabetes, physical and psychological condition was rated equally by parents and doctors. Except for the diabetes questionnaire, the children of the two groups scored not significantly different. The CSII group expressed significantly less physical complaints and physical restrictions. CSII children showed a tendency to score higher on recalcitrance compared with CT children. How adequate this coping of CSII children may be, is discussed.

Continuous subcutaneous insulin infusion (CSII) versus conventional injection therapy in newly diagnosed diabetic children: two-year follow-up of a randomized, prospective trial.

The effect of continuous subcutaneous insulin infusion (CSII), begun at diagnosis, on blood glucose control and endogenous insulin production was studied in a group of consecutively referred newly diagnosed diabetic children. In a random order, 15 children started CSII (age 9.5 +/- 4.2 (+/- SD) years) and 15 conventional injection therapy (age 7.0 +/- 3.6 years). For 2 years HbA1 and urinary C-peptide were measured monthly, C-peptide responses to glucagon 6-monthly, and insulin antibodies every 3 months. None of the patients requested change of therapy during the study period, but at 28 months 1 adolescent girl changed to injection therapy from CSII. Severe hypoglycaemia was observed once in each group, but ketoacidosis only once, in the injection therapy group. From 2 months after diagnosis onwards the CSII group had significantly lower HbA1 levels. Urinary and plasma C-peptide levels did not differ between the two groups and similar insulin doses were used throughout the study. At the end of the 2 years of therapy, the CSII group had significantly lower insulin antibody levels. The observations suggest that CSII is well accepted in newly diagnosed children and improves metabolic control, but does not prolong endogenous insulin production.

[Is juvenile seborrheic dermatitis a candidiasis? Studies of a possible link with microbial infections]. / Is juveniele seborrhoïsche dermatitis een candidide? Onderzoek naar mogelijk verband met microbiële infecties.

Infantile seborrheic dermatitis (ISD), a disease occurring in the first months of life, is an erythematosquamous skin disease of unknown origin. This article presents results of microbial studies in 20 patients with ISD. Isolation of candida in a high percentage may indicate a primary role of this micro-organism in the etiology of this disease. It is striking that this disease often starts after disturbing the microbial colonization of the intestinal tract. Often ISD develops during the transition of breastfeeding to humanized cow milk.

Long-acting somatostatin analogue (Sandostatin) reduces late night insulinopenic ketogenesis in diabetic teenagers.

Ten diabetic teenagers were admitted into our hospital for two nights, separated by one week. In a double-blind cross-over randomized study they received either 50 micrograms of the new long-acting somatostatin analogue Sandostatin sc or placebo. All patients were between 12 and 16 years of age, C-peptide negative with a duration of diabetes of at least four years. They had either conventional therapy or insulin pump therapy. Insulin doses and diets were kept unchanged. Blood samples were taken half hourly from 17.00 h until 09.30 h the next morning from an indwelling venous catheter. Hormonal and metabolic profiles on the two nights were evaluated by means of a distribution free time sequential co-movement analysis and by the paired Wilcoxon's signed rank test. After Sandostatin was given at 22.00 h, GH levels were significantly suppressed during 4 h. During that period blood glucose was slightly but significantly lower than after placebo. The free-insulin profiles from both nights were very comparable. Co-movement analysis showed a significant correlation between glucose and free insulin variations with a 30-min backward shift of the glucose curve. However, after Sandostatin administration this relation was lost in the period between 22.00 and 07.00 h, indicating a different effect of insulin on glucose levels during the nights Sandostatin was given. Early morning glucose rises were associated with free insulin levels below 20 mU/l. This association was not altered during the Sandostatin nights. Glucagon was not suppressed by Sandostatin except at 120 min after injection, and remained unchanged during the rest of the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Normalization of glucose homeostasis by a long-acting somatostatin analog SMS 201-995 in a newborn with nesidioblastosis.

A female child was admitted to the hospital few days after birth with severe hypoglycemia and convulsive episodes. Plasma insulin levels were elevated and oral and intravenous administration of glucose were unable to keep blood glucose above 2 mmol/l limit. Intravenous infusion of a long acting somatostatin analog, SMS 201-995, at a dosage gradually increasing from 2 to 50 micrograms/24 hr, was accompanied by a dramatic fall in circulating insulin levels. Normality of glucose homeostasis was restored and convulsive spells ceased. Fasting blood glucose levels stabilized between 3.4 and 4.7 mmol/l. No rebound phenomenon was observed during short term interruptions of the SMS 201-995 infusion. A subtotal pancreatectomy was performed during SMS treatment, and the diagnosis of nesidioblastosis was confirmed by immunocytologic and electron-microscopic studies. It is concluded that this new potent and long acting somatostatin derivative may be useful in the management of hyperinsulinism in the neonate.

Prediction of type 1 diabetes mellitus--a report on three cases.

In three children (patients 1, 2 and 3) insulin-dependency was predicted 28, 32 and 4 months, respectively before the disease became clinically manifest, by the finding of islet cell antibodies at that time. These retrospective findings support the evidence for a long pre-diabetic phase in childhood diabetes, marked by the presence of islet cell antibodies, as well as the linkage of HLA-antigens to the susceptibility to this disease. The possibility of detecting pre-diabetic states in children before the endogenous insulin secretion decreases to the point of producing clinical symptoms support efforts by basic scientists to develop techniques for immunological intervention early in the course of the disease.