The Proportion of Diploid 46,XX Cells Increases with Time in Women with Turner Syndrome-A 10-Year Follow-Up Study

In the normal population, loss of one of the sex chromosomes leading to monosomy (45,X) is a part of the aging process. In Turner syndrome (TS), the classic karyotype 45,X is found in up to 50% at birth, and others have a second cell line; mosaicism. The aim was to study if the chromosomal pattern in TS women changes over time. Fluorescence in situ hybridization was performed on buccal smear cells obtained twice, 10 years apart, from 42 women with TS aged 26-66 years (mean +/- standard deviation: 42.0 +/- 11.6). DNA probes specific for chromosomes X (DXZ1) and Y (DYZ3) were used and >100 cells were analyzed/patient. Nineteen women had monosomy (45,X) (<10% 46,XX), nine had 45,X/46,XX mosaicism, and 14 had iso, ring, or a marker chromosome at baseline. At 10 years, the percentage of diploid cells had increased in 29 of 42 women (69%), with an average increase of 5.7 +/- 13.0%. There was a positive correlation between age and % change in diploid 46,XX or 46,XY cells (r=0.38, p=0.023). This new finding might have relevance for the life expectancy in TS

Aortic growth rates in a Swedish cohort of women with Turner syndrome

Background: Aortic dilation, cardiac malformations and hypertension are known risk factors for aortic dissection in Turner syndrome (TS). In the current guidelines, rapid growth of the aorta has been added as a risk marker. This study aimed to estimate the growth of the ascending aorta over time, to identify risk factors of aortic growth, and to describe aortic complications in TS. Methods: A transthoracic echocardiogram was performed at least twice in 101 women with TS, mean age 28 years, with a mean follow-up of 8.3 ± 3.4 (range 1–17) years. The investigator was blinded to the clinical status. Logistic regression analysis was used to identify risk factors of aortic growth. Results: The prevalence of ascending aortic dilation (ASI >20 mm/m2) was 26 % and the mean ascending aortic diameter was 27.0 ± 4.8 mm at baseline. Significant aortic growth was found at sinus of Valsalva 1.08 (±2.11) mm, sinotubular junction 1.07 (±2.23) mm, and the ascending aorta 2.32 (±2.93) mm, p < 0.001. The mean ascending aortic growth rate was 0.25 (±0.35) mm/year, and higher compared to the general female population, 0.12 (±0.05) mm/year, p < 0.0001. No risk factors for aortic growth (bicuspid aortic valve, coarctatio, hypertension or karyotype) other than body weight could be identified, Odds ratio 1.05 (95 % CI 1.00–1.09), p = 0.029. Eight women had an aortic event of whom all had bicuspid aortic valves. Conclusions: The growth rate of the ascending aorta in TS was increased compared to the general female population. Congenital cardiovascular malformations were not predictive of aortic growth

Hypothyroidism Is Common in Turner Syndrome: Results of a Five-Year Follow-Up

Turner syndrome (TS) is caused by a sex chromosome aberration. The aim was to study the prevalence and incidence of thyroid disease in adults with TS. Women with TS (n = 91; mean age, 37.7 +/- 11 yr) were compared with an age-matched female random population sample (n = 228). At baseline, 15 (16%) TS women were treated for hypothyroidism, and elevated serum TSH was found in another eight (9%). As a result, hypothyroidism was more common in women with TS (25%) than in controls (2%; P < 0.0001). Serum free T-4 was lower (P = 0.02), and serum TSH was higher (P < 0.0001) in TS women than in age-matched controls. Of all TS women with hypothyroidism, 10 (43%) had an elevated thyroid peroxidase antibody titer vs. 15 (22%) of those without hypothyroidism (P < 0.05), evenly distributed between the karyotype 45, X and mosaicism. A high body mass index, but not a family history or blood lipids, was associated with hypothyroidism in TS. After the 5-yr follow-up, an additional 11 (16%) developed hypothyroidism, of whom four (36%) had elevated thyroid peroxidase. Altogether, 34 (37%) TS women had hypothyroidism after the 5-yr follow-up. Autoimmune hypothyroidism was common, with an annual incidence of 3.2% in TS. Thyroid function should be checked regularly in TS

Morbidity and mortality after childbirth in women with Turner karyotype

Do women with Turner karyotype have increased mortality and morbidity in the years after childbirth? No mortality occurred during pregnancy and follow-up in women with Turner karyotype, but a higher rate of circulatory and endocrine diseases and a high risk of aortic aneurysm were confirmed. Pregnancies in women with Turner karyotype are high-risk pregnancies with an increased risk of maternal mortality from aortic dissection and morbidity from hypertensive disorders. A retrospective Swedish population-based registry study of 124 women with Turner karyotype born between 1957 and 1987 and who gave birth between 1973 and 2010. Women with Turner karyotype without childbirth (n 378) were selected as controls. A second control group consisted of women from the Swedish Medical Birth Register (MBR) (n 1230) matched for maternal age, number of children and year of birth of the first child. Women with Turner karyotype were identified in the Swedish Genetic Turner Register. Data were obtained by using the unique personal identification number with cross linkage to the Swedish MBR, the Cause of Death Register, the National Patient Register and the Swedish Cancer Register. Hazard ratio (HR) with 95 confidence interval (CI) was used in the analysis of morbidity. No mortality occurred in women with Turner karyotype and childbirth. Diseases of the circulatory system occurred more often in women with Turner syndrome under the age of 40 years compared with the MBR control group (HR 4.59; 95 CI 2.757.66) but was similar at or above the age of 40 years. Morbidity from circulatory diseases was increased before pregnancy (HR 3.83; 95 CI 1.0214.43) and during pregnancy or within 1 year after (HR 5.78; 95 CI 1.9417.24), but was similar after 1 or more years after delivery (HR 1.91; 95 CI 0.744.96). Aortic aneurysm occurred in 11/502 (2.2) women with Turner karyotype and in three women (2.4) during pregnancy. The long-term follow-up showed that aortic dissection was a common cause of death in young women with Turner karyotype without childbirth. A thorough cardiac evaluation before pregnancy in women with Turner karyotype is of utmost importance. Although this was a population-based registry study performed over a period of more than 20 years, a much longer follow-up and larger series are needed to assess rare events. The study also lacks information on phenotype and mode of conception in women with Turner karyotype. Women who gave birth probably represent a selection of healthier women with Turner karyotype. The high risk of aortic aneurysm in young women with Turner karyotype is in agreement with the literature. No conflicts of interest exist. The study has been supported by grants from the Gothenburg Medical Society, the Medical Care executive Board of the Region Vstra Gtaland, grants from the ALF agreement at the Sahlgrenska University Hospital, the Hjalmar Svensson foundation, the Swedish Board of Health and Welfare, the Swedish Heart Lung Foundation and the Swedish Council for Working Life and Social Research. None

Elevated liver enzymes in Turner syndrome during a 5‐year follow‐up study

Objectives To study the prevalence and incidence of elevated liver enzymes and their relationship with body weight, metabolic factors and other diseases in Turner syndrome (TS). Design Five-year follow-up. Patients Women with TS (n = 218, mean age 33 +/- 13, range 16-71 years) from outpatient clinics at university hospitals in Sweden. Measurements Fasting blood samples for aspartate (AST) and alanine aminotransferase (ALT), bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transferase (GT), viral hepatitis serology and hepatic auto-antibodies, vitamin B12, blood glucose, lipids and hormones. Results Seventy-nine subjects (36%) had one or more liver enzyme levels higher than the reference level, the most prevalent being GT. Karyotype 45,X was present in 51% of all TS women and in 48% of those with elevated liver enzymes. Body weight, body mass index (BMI), total cholesterol, triglycerides, and apolipoproteins A and B at start were higher in TS women with elevated liver enzymes than in TS women with normal levels. At 5 years, AST, ALT and GT were increased and another 23% of patients had developed elevated liver enzymes, that is, 59% in total (36% + 23%), while in 6%, the elevated liver enzymes had been normalized and all 6% also had lowered cholesterol levels. Multivariate analysis showed that GT was correlated with total cholesterol; P = 0.0032 at start and P = 0.0005 at 5 years, independently of other factors. Liver biopsy in six TS women showed one cholangitis, one hepatitis C, two steatosis and two normal biopsies. Withdrawal of oestrogen substitution did not influence the liver enzymes. Conclusions Pathological liver enzymes were common in TS women, with a prevalence of 36% at 33 years of age, an annual incidence over 5 years of 3.4%. There was no relation to karyotype, alcohol, viral hepatitis, E-2 or autoimmunity, but a connection with total serum cholesterol