Gabriele Haeusler

Spontaneous growth in turner syndrome: Evidence for a minor pubertal growth spurt

Spontaneous growth of 141 untreated girls with Turner syndrome was analysed. Of the patients 25% were born prematurely; their weight and height were normal when compared to prematurely born healthy infants. However, birth weight and height was significantly retarded in Turner patients born at term. A curve for height and growth velocity for the age range 0–16 years was constructed with a sensitive statistical method. By use of a mathematical model equations were created for calculating z-scores and the related percentiles for the height of individual patients at given age. median height of 18 untreated patients at 18 years was 143.8 cm. Analysis of growth velocity revealed a minor but significant growth spurt at the age of 12.5 years. This growth spurt was also detectable in patients without signs of spontaneous puberty and occurred later in patients with 45,X0 karyotype. Bone age progression was linear up to the age of 7.5 years and decelerated thereafter.

Estrogen Receptor-Alpha and Estrogen Receptor-Beta Are Present in the Human Growth Plate in Childhood and Adolescence, in Identical Distribution

Objective: To localize estrogen receptor-α (ER-α) and estrogen receptor-β (ER-β) within the growth plate and adjacent bony tissue of children in the prepubertal and pubertal age period. Methods: Tissue was taken during orthopedic surgery (epiphysiodesis) for correction of congenital or traumatic leg length difference in 2 prepubertal females and 2 adolescent males. Immunohistochemistry was performed on paraffin-embedded or cryostat sections by using commercially available rabbit polyclonal antibodies for ER-α and ER-β. Results: Both ER-α and ER-β were detected within the growth plate in all sections investigated. Immunostaining was restricted to hypertrophic chondrocytes. In the bony tissue adjacent to the growth plate, osteoblasts stained positive for both ER-α and ER-β, whereas osteocytes and osteoclasts were negative. Staining with ER-α was mainly nuclear but some cells also showed cytoplasmic signals, while ER-β staining was predominantly cytoplasmic, only few nuclei stained positive. There was no difference in the local distribution of both ERs between tissue from prepubertal and pubertal patients. Conclusion: Our findings indicate that the hypertrophic chondrocyte is the main target cell for estrogen action within the growth plate. The presence of ER in prepubertal children suggests that estrogens play a role in skeletal maturation under physiological conditions also in this age-group.

Growth Hormone Therapy in Patients with Turner Syndrome

This article summarizes the published data on final height after growth-promoting therapy in Turner syndrome. Using growth hormone (GH) doses ranging between 0.5 and 1.2 IU/kg/week, final height after therapy is improved by 1.5–9.3 cm [final height after therapy vs. projected adult height (PAH)] within various studies. There is no obvious GH dose-response relationship, but a better estimated benefit from therapy seems to result in those studies that combined even rather low GH doses with the anabolic steroid oxandrolone. It is not possible to retrospectively define an optimal treatment regime out of the various published data due to different GH doses, age and dosage of estrogen replacement therapy and the variable methods for calculating the benefit from therapy. It seems to be essential to start estrogens at a safe bone age (> 13 years) in very low doses. Higher GH doses (up to 2.0 IU/kg/week) led to a better growth response during the first years of therapy but data on final height are still to be awaited.

Growth hormone treatment in Turner's syndrome: short and long-term effects on metabolic parameters

objective The effect of GH administration on various metabolic parameters and on growth and bone age development was studied in patients with Turners syndrome

Treatment of patients with Ullrich-Turner syndrome with conventional doses of growth hormone and the combination with testosterone or oxandrolone: effect on growth, IGF-I and IGFBP-3 concentrations.

Thirty-nine girls with Ullrich-Turner syndrome (UTS) (median age 9.5 years) were treated with growth hormone (GH) with either 12 or 18 IU/m2 per week for 12 months followed by combination therapy with either oxandrolone (Ox) (0.0625 mg/kg/day po) or low-dose testosterone (T) (5 mg im every 2 weeks). Growth velocity improved significantly after 12 IU/m2 per week (6.4±1.7 cm/year vs 4.0±1.3 cm/year, x±SD,P<0.001) and 18 IU/m2 per week of GH (6.5±1.3 cm/year vs 4.5±1.4 cm/year,P<0.001). Ox, but not T was effective in maintaining growth velocity during the 2nd year of therapy (6.9±1.3 vs 5.3±1.5 cm/year). Basal insulin-like growth factor-I (IGF-I) concentrations were in the lower normal range and increased significantly in patients treated with 18 IU/m2 per week (357±180 ng/ml vs 160±84 ng/ml) and 12 IU/m2 per week (273±121 ng/ml vs 140±77 ng/ml). IGF-I concentrations increased further after addition of Ox (533±124 ng/ml,P<0.001) or T (458±158,P<0.05). IGFBP-3 concentrations were in the upper normal range before therapy and increased only moderately in both GH dosage groups. However, IGF binding protein-3 (IGFBP-3) concentrations were not affected by additional Ox or T treatment.Conclusions1. Conventional GH doses are effective in increasing growth velocity in UTS, especially, when combined with Ox. This additive effect is not evident when GH is combined with low dose T. 2. Changes in growth velocity are accompanied by an increase of the IGF-I/IGFBP-3 ratio. 3. Ox obviously acts by increasing IGF-I levels independent of the GH status.

Short- and Long-Term (Final Height) Growth Responses to Growth Hormone (GH) Therapy in Patients with Turner Syndrome: Correlation of Growth Response to Stimulated GH Levels, Spontaneous GH Secretion, and Karyotype

In 41 girls with Turner syndrome, the growth hormone (GH) peak values during stimulation tests and parameters of spontaneous nocturnal GH secretion were studied and compared with respect to different karyotypes, short-term growth response to GH therapy, and final height. 22.0% of the girls tested had a subnormal (peak < 11 ng/ml) and 9.7% a pathological (< 7 ng/ml) GH response. The spontaneous GH secretion showed a good correlation with the data of the provocation tests, providing no further information regarding GH capacity. Short-term growth response to GH treatment could not be predicted by any of the investigated parameters. Although patients with isochromosomes had frequent subnormal GH tests, their growth response to GH treatment after 1 year was comparable to that of girls with XO karyotype and mosaicism. In 18 patients who had reached final height, the height gain during treatment (calculated as final height minus projected adult height) was not different among patients with normal, subnormal, or pathological GH tests. In contrast, final height minus projected adult height in 4 girls with isochromosomes was 15.7 +/- 5.1 versus 7.6 +/- 3.3 cm in 14 patients with other karyotypes (p < 0.01). These girls had a more pronounced bone age delay (3.3 +/- 0.3 vs. 1.8 +/- 1.2 years) at the start of therapy and thus a better growth potential. We conclude that short- and long-term growth responses to GH treatment in Turner syndrome could not be predicted by GH testing. Patients with isochromosomes might represent a subpopulation which is more frequently GH deficient and shows a marked bone age delay.

Hypoplasia of the corpus callosum and growth hormone deficiency in a boy with the XXXXY syndrome

Sirs, We report on new radiological and endocrine findings in a 3.6-year-old boy with the XXXXY syndrome. He demonstrated the typical clinical signs reviewed by Terheggen et al. (1973), which are retarded psychomotor development, brachycephaly, dysmorphic ears, hypoplasia of genitalia, clinodactyly, valgus deformity of the knees and minor malformation of inner organs (mild pulmonary stenosis, unilateral kidney hypoplasia). In addition, speech development was severely retarded, as described by Sheridan et al. (1990), height was below the 3rd percentile, and bone age retarded (1.8 “years”). MRI of the brain was performed by T1weighted, single-echo imaging in the saggital and coronal planes and by TZweighted sequence in the axial plane. We found hypoplasia of the corpus callosum which was quantified by means of reduced thickness and length and reduced corpus callosum/ brain ratio when compared to an agematched, healthy control (Fig. 1). Additional focal hypoplasia involved the posterior body and the rostrum of the corpus callosum (arrows); the ventricular system was enlarged due to a marked atrophy of the cerebral cortex. Because of bilateral undescended testes, orchidopexy was done and a biopsy of the