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W J de Waal

Publications and source records attributed to W J de Waal.

11 recordsLinked to original sources

[Hormonal therapy of constitutionally tall children].

Children of constitutionally tall stature may experience serious problems related to their height. Treatment with high dose sex steroids may be considered in order to limit final adult height. Prediction of adult height plays a central part in the management of children of tall stature. Various aspects of height prediction in children of tall stature are discussed. The height reducing effect varies between studies from 2 to 10 cm. Recently, in a large Dutch study the mean effects of therapy were 0.7 and 2.4 cm for boys and girls respectively. The effect depended on the bone age at start of treatment. Beyond a critical bone age of about 14 years treatment had no effect. Minimal age for intervention is 9.5-10 year for boys and 9.0-9.5 year for girls. Recommended treatment for boys is 250 mg testosterone esters i.m. per week and for girls ethinyloestradiol orally 200 micrograms per day in combination with medroxyprogesterone or dydrogesterone (both 5-10 mg per day) during the first 12-14 days of the cycle. Treatment has to be continued until complete closure of the epiphyses. While side effects during hormonal therapy are frequent, they are mostly temporary and mild and seldom lead to cessation of therapy. So far there have been no indications of adverse effects on, for instance, gonadal function.

Administration, Oral↗

A new model to predict final height in constitutionally tall children.

In order to develop new height prediction models for children with constitutionally tall stature, 55 such boys and 88 girls were recalled for measurement of adult final height (FH). Data on height (H), age (CA), and target height (TH) were collected from the hospital charts and radiographs of the left hand and wrist were retrieved and used for bone age (BA) determination [BA according to the methods of Greulich and Pyle (BAGP) and Tanner and Whitehouse (BARUS)]. Standard multiple regression techniques were used to develop prediction equations for FH. In addition to test the validity of the new equations, FH was measured in a second group of constitutionally tall children (n = 32) and compared with the predicted FH according to our models. In addition, a comparison was made with other prediction methods. Mean (SD) FH was 196.0 (4.9) cm in boys and 180.5 (3.8) cm in girls. The ultimate regression equation was FH (cm) = 216.07 + 0.75 x H + 0.25 x TH -11.09 BAGP + 0.74 x (CA x BAGP) for boys and FH = 161.42 + 0.73 x H + 0.15 x TH - 8.41 x CA -8.83 x BARUS -2.45 x M + 0.55 x (CA x BARUS) for girls. The models showed satisfying accuracy: the mean (SD) errors were -1.4(3.2) cm for boys and -0.5(3.1) cm for girls with corresponding mean (SD) absolute errors of 2.7 (2.2) cm and 2.0 (2.4) cm, respectively. Compared with the current prediction methods, the new models were quite promising. Their clinical validity has to be ascertained in larger groups of tall children.

Adult↗

Self-concept before and after two years of growth hormone treatment in intrauterine growth-retarded children.

The objective of this study was to assess self-concept in children with short stature after intrauterine growth retardation (IUGR), before and after 2 years of growth hormone (hGH) treatment. We assessed 25 children before treatment, and 40 children after a 2-year treatment period. Seventeen of the 25 children of whom we had pretreatment data, were reassessed after 2 years of hGH treatment. All children had a birth length below the 3rd percentile, and did not show catch-up growth (current height < P3). We compared the self-concept measures (Self-Perception Profile for Children; SPPC) of the IUGR group with similar measures of a Dutch school sample. Four of the six SPPC mean scale scores of the IUGR group prior to treatment were significantly lower than mean scores of the school sample. Mean-scale scores of the group children, assessed after 2 years of hGH treatment, did not differ significantly from those of the school sample. In the group of 17 children who were assessed before as well as after 2 years of treatment, the mean scale scores of 'social acceptance' and 'general self-worth' were significantly higher at the second assessment (t = -5.93, p < 0.001 and t = -4.36, p < 0.001, respectively). From the present study we can hypothesize that short stature after IUGR and a low self-concept are related.

Child↗

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.

Adolescent↗

High dose testosterone therapy for reduction of final height in constitutionally tall boys: does it influence testicular function in adulthood?

OBJECTIVE: We have studied the effect of treatment with high doses of androgens during puberty on testicular function in adult men with constitutionally tall stature, taking into account confounding factors interfering with sperm quality, since existing published data do not include whether testicular function is impaired by such treatment. DESIGN: Historical cohort study. PATIENTS: Forty-three previously androgen treated tall men (cases) and 30 non-treated tall men (controls). MEASUREMENTS: Physical examination, semen analysis and plasma levels of LH, FSH, testosterone (T), sex hormone binding globulin (SHBG) and inhibin. RESULTS: Sperm quality and testis volume were comparable between cases and controls. Mean sperm concentration was 66.4 x 10(6)/ml in cases and 66.2 x 10(6)/ml in controls. A left-sided varicocele was found in 45% of the cases and 37% of the controls. In cases we observed a significant effect of the age at start of androgen therapy on sperm motility (regr. coeff. (SE): 4.92 (2.41)%, P = 0.048). In addition, testicular size at start of therapy had a significant effect on sperm concentration (regr. coeff. (SE): 5.57 (1.54) x 10(6)/ml, P = 0.0012) and on total sperm count (regr. coeff. (SE): 43.1 (7.73) x 10(6), P = 0.0001). Plasma levels of T, SHBG and inhibin were not statistically different between the groups. Cases had significantly higher FSH levels (mean (SD) 3.3 (2.2) vs 2.1 (0.8) IU/I, P = 0.004) and significantly lower LH levels (mean (SD) 2.3 (0.9) vs 3.1 (1.4) IU/I, P = 0.019). We found a significant effect of age at start of therapy on plasma FSH level in the treated men (regr. coeff. (SE): -0.73 (0.18) IU/I, P = 0.0003). CONCLUSIONS: Treatment with high doses of androgens for reduction of final height in constitutionally tall stature has no long-term side-effect on sperm quality, testicular volume or plasma testosterone levels. However, treated men had significantly higher plasma levels of FSH compared with controls. The meaning of this difference remains to be established. Varicocele was present in 42% of the adult tall men.

Adult↗

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.

Adult↗

Endogenous and stimulated GH secretion, urinary GH excretion, and plasma IGF-I and IGF-II levels in prepubertal children with short stature after intrauterine growth retardation. The Dutch Working Group on Growth Hormone.

OBJECTIVE: The pathophysiological mechanisms underlying the failure of catch up-growth in children with short stature after intrauterine growth retardation (IUGR) remain obscure. Since GH secretion disturbances might play a role in the growth retardation of these children we have investigated various aspects of the GH/IGF axis. DESIGN: Cross-sectional study in one group of patients. PATIENTS: Forty prepubertal children (15 girls/25 boys; mean age (range) 7.5 years (3.4-10.8)) with short stature (height below the third centile) after IUGR, defined as a birth length below the third centile for gestational age, were studied. MEASUREMENTS: GH secretion was determined by a 24-hour plasma GH profile (sampling every 20 minutes) and, on a separate occasion, by a standard arginine provocation test (ATT). Plasma IGF-I and IGF-II levels were measured at the start of the GH profile. Urine was collected to measure urinary GH levels. Plasma and urinary GH were determined by double antibody RIA. IGF-I and IGF-II were determined by specific RIA after acid chromatography. The 24-hour GH profiles were analysed using Pulsar. RESULTS: Endogenous GH secretion was similar for boys and girls. Boys had significantly lower mean GH levels compared to healthy controls. Forty per cent of the children met our criteria for a normal 24-hour GH profile (group A; n = 16) and 60% (n = 24) did not. We subdivided these 24 children into two groups: group B (n = 14) (children with either mean GH levels less than controls but with at least one spontaneous GH peak above 20 mU/l and children with normal mean GH levels but with no GH peak above 20 mU/l (subnormal 24-hour GH profile)) and group C (n = 10) (children with mean GH levels less than controls and no GH peak above 20 mU/l (low 24-hour GH profile)). The GH secretory abnormalities were due to a decrease in pulse amplitude, not in pulse frequency. Mean (SD) maximal GH response during ATT was 22.3 (12.1) mU/l. Nineteen children (47.5%) had a maximal GH value < 20 mU/l. Moderate, but significant, correlations were found between several 24-hour GH profile characteristics and the maximal GH response during ATT (r = 0.31-0.35; P < 0.05). Mean (SD) overnight urinary GH excretion was 3.8 (2.1) and 4.4 (3.5) microU/night for boys and girls, respectively. Compared to healthy schoolchildren, overnight urinary GH was lower in boys, but not in girls. Mean (SD) IGF-I and IGF-II SDS levels for chronological age were -0.88 (1.40) and -0.64 (1.48), respectively. Plasma IGF-I and IGF-II levels were significantly reduced compared to controls. Height SDSCA or height velocity SDSCA did not correlate with either spontaneous or stimulated GH secretion, urinary GH excretion or plasma IGF-I or IGF-II levels. CONCLUSIONS: Our study indicates that 50-60% of children with short stature after intrauterine growth retardation have 24-hour GH profile abnormalities and/or subnormal responses to arginine provocation, while mean plasma IGF-I and IGF-II levels are significantly reduced, indicating GH insufficiency. Urinary GH excretion is lower in boys, but not in girls. The precise mechanism of the failure to catch up growth needs further elucidation. It seems justified to start clinical trials in order to investigate whether treatment with exogenous GH might be beneficial for these children.

Arginine↗