Dosage of estradiol, bone and body composition in Turner syndrome: a 5-year randomized controlled clinical trial.

OBJECTIVE: Reduced bone mineral density (BMD) is seen in Turner syndrome (TS) with an increased risk of fractures, and body composition is characterized by increased body fat and decreased lean body mass. To evaluate the effect of two different doses of oral 17B-estradiol in young TS women on bone mineral density (BMD), biochemical markers of bone turnover and body composition with the hypothesis of a positive effect of the higher dose. DESIGN: A double-blind 5-year randomized controlled clinical trial. 20 young TS women participated. Inclusion criteria were diagnosis of TS, age 15-25 years and current treatment with 2 mg oral estradiol daily. METHODS: The low-dose (LD) group was administered 2 mg 17B-estradiol/day orally and placebo, the high-dose (HD) group was administered 2 + 2 mg 17B-estradiol/day orally. Main outcome measures were whole body and regional bone mineral density (BMD), lean body mass (LBM), fat mass (FM) measured yearly by DXA scan and resorptive and formative bone markers in serum. RESULTS: BMD, whole body and regional, increased over time with an attenuation toward the end of the study, and bone turnover markers decreased over time, both with no differences between the treatment groups (P = 0.2-0.9). LBM increased significantly more in the HD group (P = 0.02). FM remained stable in both groups. CONCLUSIONS: A steady increase in BMD over time in TS was found similar to healthy young women. The higher estrogen dose did not differentially affect BMD or bone markers. The positive effect on body composition may have long-ranging health benefits in TS.

Bone health in primary ovarian insufficiency.

The etiology of primary ovarian insufficiency (POI) may be genetic, autoimmune, or iatrogenic. Genetic conditions include 45,X, 46,XX and 46,XY POI, and POI associated with galactosemia and FMR premutations. Women with autoimmune polyglandular syndromes 1 and 2 may develop autoimmune POI, as may those who receive chemotherapy or radiotherapy. Hypogonadism in POI can result in reduced rates of bone mass accrual in adolescents and young women, and low bone density for age in older women. Measures to optimize bone density in women with POI include attention to lifestyle measures and hormone replacement. Resistance training and adequate calcium and vitamin D supplementation are essential, as is replacement of estrogen/progestin. Estrogen/progestin replacement may be problematic in women with estrogen-sensitive breast cancer who developed POI in the course of therapy for cancer. In these instances, bisphosphonates are an option. In particular, zoledronic acid has been used successfully in conjunction with chemotherapy, tamoxifen, and aromatase inhibitors.

Altered inorganic composition of dental enamel and dentin in primary teeth from girls with Turner syndrome.

In Turner syndrome (TS) one X-chromosome is missing or defective. The amelogenin gene, located on the X-chromosome, plays a key role during the formation of dental enamel. The aim of this study was to find support for the hypothesis that impaired expression of the X-chromosome influences mineral incorporation during amelogenesis and, indirectly, during dentinogenesis. Primary tooth enamel and dentin from girls with TS were analysed and compared with the enamel and dentin of primary teeth from healthy girls. Qualitative and quantitative changes in the composition of TS enamel were found, in addition to morphological differences. Higher frequencies of subsurface lesions and rod-free zones were seen in TS enamel using polarized light microscopy. Similarly, scanning electron microscopy showed that the enamel rods from TS teeth were of atypical sizes and directions. Using X-ray microanalysis, high levels of calcium and phosphorus, and low levels of carbon, were found in both TS enamel and dentin. Using microradiography, a lower degree of mineralization was found in TS enamel. Rule induction analysis was performed to identify characteristic element patterns for TS. Low values of carbon were the most critical attributes for the outcome TS. The conclusion was that impaired expression of the X-chromosome has an impact on dental hard tissue formation.

Disproportional geometry of the proximal femur in patients with Turner syndrome: a cross-sectional study.

OBJECTIVE: Patients with Turner syndrome (TS) have altered growth and increased risk of osteoporosis due to oestrogen deficiency and possibly a host of other factors. Thus, TS patients have a 4.9-fold increased risk of femoral neck fractures. Most patients are treated with oestrogen during puberty and adolescence to facilitate pubertal development and prevent secondary osteoporosis. The geometry of the hip is a predictor for hip fractures independent of bone mineral density (BMD). The purpose of the present study was to investigate the variation of the geometry of the hip in patients with TS in comparison with healthy controls. PATIENTS: The study population comprised 58 patients with TS (aged 22-67 years) and 60 age-matched healthy women (aged 21-65 years). MEASUREMENTS: Hip axis length (HAL), neck width (NW), neck shaft angle (NSA), and femoral head-radius (HR) on dual-energy X-ray absorptiometry (DXA) screen images. These parameters related to age of oestrogen supplementation, menarche, and duration of oestrogen exposure. RESULTS: Height was 146.6 +/- 6.9 cm and 167.1 +/- 6.2 cm (P < 0.1) and weight 57.4 +/- 13.9 kg and 62.3 +/- 8.3 kg (P < 0.001) in patients and controls, respectively. After adjustment for differences in height, HAL was not significantly different (9.4 +/- 0.5 vs. 9.5 +/- 0.5 cm; NS) in TS compared with controls while NW was significantly increased (3.5 +/- 0.4 cm vs. 3.3 +/- 0.2 cm, P < 0.001), NSA was similar (129 +/- 4 degrees vs. 130 +/- 4 degrees , NS), and HR was significantly decreased (4.1 +/- 0.4 vs. 4.5 +/- 0.3 cm, P < 0.001). The duration of oestrogen exposure was significantly shorter among TS, but did not correlate significantly with the geometrical parameters in either TS or controls. CONCLUSION: Our data demonstrates that hip geometry is disproportionate in TS compared with normal controls. The altered hip geometry, however, cannot explain the increased risk of hip fracture in TS.

Ankylosing spondylitis in a patient with Turner syndrome: a case report.

Turner's syndrome (TS) is a chromosomal disorder where phenotypic females have either a missing chromosome (45 X0) or a structural aberration of one of the chromosomes. It is possible for TS to accompany such autoimmune diseases as thyroid diseases, inflammatory intestinal diseases, diabetes mellitus, psoriatic arthritis and juvenile rheumatoid arthritis. Herein, we present an unusual case with Ankylosing spondylitis (AS) and autoimmune thyroiditis associated with TS. We suggest that the possibility that TS patients may also develop such other diseases as AS apart from the already known accompanying autoimmune diseases should not be ruled out when monitoring TS patients.

[Identification of sex chromosome markers using fluorescence in situ hybridization (FISH)]. / Identificación de cromosomas sexuales marcadores mediante hibridación in situ con fluorescencia (FISH).

From 6 to 15% of the patients with Turner syndrome have a mosaic karyotype, i.e. a 45,X cell line and another with a small sex chromosome marker of undetermined origin which may be a ring or a centric fragment. It is important to establish whether this marker chromosome derives from a Y chromosome as this implies that the patient has a high risk of developing gonadoblastoma. The objective of the present paper was to identify the origin of small sex chromosome markers using fluorescence in situ hybridization (FISH). Eight patients were studied; seven had a Turner phenotype and one had a short stature with ambiguous genitalia. In all cases karyotype in peripheral lymphocytes showed mosaicism, with one cell line that had a sex chromosome marker, and in three cases, the mosaicism was corroborated in fibroblast cultures. Biotin labeled DNA probes with complementary centromeric alpha-satellite sequences of chromosomes X and Y were used in the FISH technique. In seven patients the chromosome marker came from the X chromosome as established with the X chromosome alpha-satellite probe. In the patient with ambiguous genitalia, the marker did derive from the Y chromosome. We conclude that the FISH technique proved to be useful to establish the origin of sex chromosome markers in our laboratory.

X-chromosome effects on female brain: a magnetic resonance imaging study of Turner's syndrome.

Many neuropsychiatric disorders differ between the sexes in incidence, symptoms, and age at onset. To investigate the effects of X-chromosome aneuploidy and of sex steroid deficiency during childhood on brain structure and function, we used neuropsychological tests and quantitative magnetic resonance imaging (MRI) to study the brains of eighteen women with Turner's syndrome (TS) and nineteen healthy control women of similar age. Nine TS subjects had mosaic 45,X karyotypes, and 9 had non-mosaic 45,X. The TS group had significantly lower scores than the controls for all the Wechsler adult intelligence scale tests, except verbal comprehension and reading level. The greatest difference was in visuospatial construction (mean 90 [SD12] vs 118 [13], p < 0.0001). The TS subjects also had a greater discrepancy than controls between verbal and performance intelligence quotients (9 [8] vs -5 [9], p < 0.001). We found that TS subjects had significantly smaller values than controls in MRI-measured volumes of hippocampus, caudate, lenticular, and thalamic nuclei, and parieto-occipital brain matter, on both sides. Women with mosaic TS had values between the full TS and control groups for cerebral hemisphere and lenticular and thalamic nuclei volume and for verbal ability. Within the mosaic TS group, visuospatial ability was significantly correlated with the percentage of lymphocytes that had the 45,X karyotype. Hippocampal volume and memory test scores were significantly lower in mosaic and non-mosaic 45,X TS subjects than in controls. We postulate that in human beings the X chromosome plays an important part in the development and ageing of grey matter in striatum, diencephalon, and cerebral hemispheres.

The incidence of Turner's syndrome in Ibadan, Nigeria.

A study of 22 769 consecutive live births in a Nigerian hospital has revealed the incidence of Turner's syndrome to be 1 in 2745 live females. Shortness of stature and neck, low posterior hair line, broad chest with widely spaced rudimentary nipples, congenital lymphoedema, redundant lax neck skin and hypoplastic nails were the most common clinical features. Birth weight was above 2.5 kg in only five of the fourteen cases in which this measurement was taken. Associated renal and cardiovascular anomalies occurred in 87.5 and 45% of the cases respectively. While neither parental age nor the birth rank of the patients were contributory factors in the causation of the syndrome, ingestion of traditional medicinal concoctions during the pregnancy which appeared to have played a role in four out of the sixteen cases requires further studies.

A neuropathological and neuropsychological study of Turner's syndrome.

A neuropathological study was made in 2 women with Turner's syndrome. Neuropsychological investigation in one of them correlated with what has previously been found in Turner's syndrome as well as with the localization of the most pronounced neuropathological aberration which was of atherosclerotic nature, most pronounced in the right temporo-parietal area. These findings as well as the findings of acidophile hypoplasia of the pituitary gland are discussed.