Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries, which GH dosage to use and which age to start puberty induction are issues of debate. This study shows final height (FH) in 60 girls with Turner syndrome treated in a randomized dose-response trial, combining GH treatment with low dose estrogens at a relatively young age.Girls were randomly assigned to group A (4 IU/m 2 ⅐d; ϳ0.045 mg/kg/d), group B (first year, 4 IU/m 2 ⅐d; thereafter 6 IU/m 2 ⅐d), or group C (first year, 4 IU/m 2 ⅐d; second year, 6 IU/m 2 ⅐d; thereafter, 8 IU/m 2 ⅐d). After a minimum of 4 yr of GH treatment, at a mean age of 12.7 ؎ 0.7 yr, low dose micronized 17␤-estradiol was given orally. After a mean duration of GH treatment of 8.6 ؎ 1.9 yr, FH was reached at a mean age of 15.8 ؎ 0.9 yr. FH, expressed in centimeters or SD score, was 157.6 ؎ 6.5 or ؊1.6 ؎ 1.0 in group A, 162.9 ؎ 6.1 or ؊0.7 ؎ 1.0 in group B, and 163.6 ؎ 6.0 or -0.6 ؎ 1.0 in group C. The difference in FH in centimeters, corrected for height SD score and age at start of treatment, was significant between groups A and B [regression coefficient, 4.1; 95% confidence interval (CI), 1.4, 6.9; P < 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3, 7.7; P < 0.001), but not between groups B and C (coefficient, 0.9; 95% CI, ؊1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH SD score, more than ؊2). After starting estrogen treatment, the decrease in height velocity (HV) changed significantly to a stable HV, without affecting bone maturation (change in bone age/change in chronological age). The following variables contributed significantly to predicting FH SD score: GH dose, height SD score (ref. normal girls), chronological age at start of treatment, and HV in the first year of GH treatment. GH treatment was well tolerated.In conclusion, GH treatment leads to a normalization of FH in most girls, even when puberty is induced at a normal pubertal age. The optimal GH dosage depends on height and age at the start of treatment and first year HV. (2), subnormal levels of GH and IGF-I have been reported (3, 4). It has been postulated that a diminished sensitivity for growth factors might explain their growth retardation (5, 6). Nevertheless, GH treatment in a supraphysiological dosage has been shown to accelerate growth (4, 7). Another clinical feature in most girls with TS is the absence of spontaneous pubertal development, for which estrogen substitution is necessary. Although GH treatment for short stature in TS is now an accepted treatment in many countries, reports on final height are inconsistent (8,9), and which dosage to use and which age to start puberty induction are issues of debate.Previously, we have demonstrated that long-term GH treatment in TS leads to normalization of height (4, 10). This study shows final height (FH) results in 60 girls with TS treated in a randomized dose-response trial comparing 3 dosage schedules. In addition, we show the effect of low dose estrogen treatment begun at a relatively ...

Androgen insensitivity syndrome encompasses a wide range of phenotypes, which are caused by numerous different mutations in the AR gene. Detailed information on the genotype/phenotype relationship in androgen insensitivity syndrome is important for sex assignment, treatment of androgen insensitivity syndrome patients, genetic counseling of their families, and insight into the functional domains of the AR. The commonly accepted concept of dependence on fetal androgens of the development of Wolffian ducts was studied in complete androgen insensitivity syndrome (CAIS) patients. In a nationwide survey in The Netherlands, all cases (n = 49) with the presumptive diagnosis androgen insensitivity syndrome known to pediatric endocrinologists and clinical geneticists were studied. After studying the clinical phenotype, mutation analysis and functional analysis of mutant receptors were performed using genital skin fibroblasts and in vitro expression studies. Here we report the findings in families with multiple affected cases. Fifty-nine percent of androgen insensitivity syndrome patients had other affected relatives. A total of 17 families were studied, seven families with CAIS (18 patients), nine families with partial androgen insensitivity (24 patients), and one family with female prepubertal phenotypes (two patients). No phenotypic variation was observed in families with CAIS. However, phenotypic variation was observed in one-third of families with partial androgen insensitivity resulting in different sex of rearing and differences in requirement of reconstructive surgery. Intrafamilial phenotypic variation was observed for mutations R846H, M771I, and deletion of amino acid N682. Four newly identified mutations were found. Follow-up in families with different AR gene mutations provided information on residual androgen action in vivo and the development of the prepubertal and adult phenotype. Patients with a functional complete defective AR had some pubic hair, Tanner stage P2, and vestigial Wolffian duct derivatives despite absence of AR expression. Vaginal length was functional in most but not all CAIS patients. The minimal incidence of androgen insensitivity syndrome in The Netherlands, based on patients with molecular proof of the diagnosis is 1:99,000. Phenotypic variation was absent in families with CAIS, but distinct phenotypic variation was observed relatively frequent in families with partial androgen insensitivity. Molecular observations suggest that phenotypic variation had different etiologies among these families. Sex assignment of patients with partial androgen insensitivity cannot be based on a specific identified AR gene mutation because distinct phenotypic variation in partial androgen insensitivity families is relatively frequent. In genetic counseling of partial androgen insensitivity families, this frequent occurrence of variable expression resulting in differences in sex of rearing and/or requirement of reconstructive surgery is important information. During puberty or normal dose androgen therapy, n...

In children with differentiated thyroid cancer, treatment should consist of total thyroidectomy, followed by a modified radical neck dissection (when indicated) and iodine-131 ablation treatment. This aggressive approach seems to be justified because of the high incidence of nodal involvement and the low complication and recurrence rate after surgery.

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The deficit between target height and final height highlights the reduction of adult height in the majority of male and female childhood ALL survivors who had received prophylactic cranial irradiation, in particular in those who were diagnosed at a younger age. This reduction would have been masked if patients FH was only compared with standard methods. RAH might be a sensitive predictor for growth hormone deficiency as these results suggest that radiation-induced growth hormone deficiency in these patients is the rule rather than the exception.