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°vs. 130 ± 4°, 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.     

The relationship between reduced testosterone,stimulated growth hormone secretion and increased carotid intima‐media thickness in obese men

Objective Obesity is associated with reduced testosterone and growth hormone (GH). However, the interrelationship between these axes and their independent contributions to cardiovascular risk is unknown. The objectives of this study were to determine (1) the association between testosterone and GH in obesity, (2) whether excess adiposity mediates this association and (3) the relative contribution of reduced testosterone and GH to increased carotid intima‐media thickness (cIMT) in obesity. Design Fifty obese men were studied with GH‐releasing hormone–arginine testing, and morning free testosterone (FT) was measured by equilibrium dialysis. Metabolic, anthropometric and cardiovascular risk indices, including cIMT were measured. Twenty‐six normal weight men served as controls. Results Obese subjects demonstrated lower mean (±SEM) peak stimulated GH (5·9 ± 0·6 vs 36·4 ± 3·9 μg/l; P < 0·0001) and FT (0·41 ± 0·03 vs 0·56 ± 0·03 nmol/l; P = 0·0005) compared to controls. GH was significantly associated with FT (r = +0·44; P < 0·0001) and both were inversely related to visceral adipose tissue (VAT) (GH: r = ?0·65; P < 0·0001; FT: r = ?0·51; P < 0·0001). In multivariate regression analysis controlling for VAT, FT was no longer related to GH. Both GH and FT were associated with cIMT in univariate analysis. However, in multivariate modelling including traditional cardiovascular risk markers, GH (β = 0·003; P = 0·04) but not FT (P = 0·35) was associated with cIMT. Conclusions These results demonstrate a strong relationship between FT and GH in obesity and suggest that this relationship is more a function of excess adiposity rather than a direct relationship. While reduced FT and GH are both related to increased cIMT, the relationship with reduced GH remains significant controlling for reduced FT and traditional cardiovascular disease risk markers.     

Monocyte Chemoattractant Protein‐1 and Large Artery Structure and Function in Young Individuals: The African‐PREDICT Study

To better understand hypertension development, the authors determined whether monocyte chemoattractant protein‐1 (MCP‐1) is associated with arterial stiffness (pulse wave velocity [PWV]) and carotid intima‐media wall thickness (cIMT) in a young apparently healthy black and white population (N=403, aged 20–30 years). Carotid‐femoral PWV, central systolic blood pressure, and cIMT were measured, and MCP‐1, reactive oxygen species, inflammatory markers (interleukin 6, tumor necrosis factor α), and endothelial activation (intercellular adhesion molecule, vascular cell adhesion molecule) were determined from blood samples. Although carotid‐femoral PWV and cIMT were similar between blacks and whites, black men and women showed higher central systolic blood pressure, MCP‐1, and reactive oxygen species than whites (all P<.05). In addition, black women had higher brachial blood pressure and interleukin 6 (all P<.001). A consistent positive association only in black women between cIMT and MCP‐1 in multiple regression analyses was found (R²=0.151, β=0.248; P=.021). In this model, cIMT was also independently associated with vascular cell adhesion molecule (β=0.251; P=.022). The authors found elevated central systolic blood pressure and MCP‐1 in young blacks, where cIMT was independently associated with MCP‐1 in black women.     

Bone geometry and volumetric bone mineral density in girls with Turner syndrome of different pubertal stages

Objective An increased rate of fractures has been reported in patients with Turner syndrome (TS). We aimed to assess bone geometry and volumetric bone mineral density (vBMD) at the radius in girls with TS and to evaluate the relationships between bone parameters and fracture history. Methods and design Sixty‐seven girls with TS aged 6–19 years treated currently or in the past with growth hormone (GH) and/or oestrogens were examined using peripheral quantitative computed tomography. Results were compared to reference data. Results Cortical area and cortical thickness were low in all age groups (all P < 0·001). Height‐adjusted total bone area at the diaphysis was increased in prepubertal and postpubertal girls (mean Z‐score 1·0, P < 0·05 for both) and normal in the pubertal group (mean Z‐score 0·1). Cortical vBMD was decreased (mean age‐specific Z‐scores ?2·0, ?1·6 and ?1·0 for prepubertal, pubertal and postpubertal groups, respectively, P < 0·01 for all groups). Height‐ , age‐ and cortical thickness‐adjusted cortical vBMD was positively correlated to the duration of GH therapy (P = 0·012) and to oestrogen administration (P = 0·047). Girls with a history of fractures had lower total vBMD at the metaphysis compared to nonfractured TS girls (mean Z‐scores ?1·7 vs?0·9, P = 0·04). Conclusions There is a cortical bone deficit in girls with TS characterized by low cortical area, thin cortex and probably decreased cortical vBMD. Early commencement of GH therapy, as well as oestrogen replacement, is associated with higher cortical vBMD. Further studies should investigate the potential causality of this relation.     

Adolescents with congenital adrenal hyperplasia because of 21-hydroxylase deficiency have vascular dysfunction

Context Patients with congenital adrenal hyperplasia (CAH) because of 21‐hydroxylase deficiency have multiple vascular risk factors. Young adults with CAH have increased intima media thickness, but there have been no studies of vascular function and structure in children with CAH. Objective To establish whether children with CAH have reduced vascular function and increased carotid intima media thickness (cIMT) when compared to healthy and obese children. Design and Patients Cross‐sectional study of 14 patients (14·8 years ± 3·2, seven boys) with CAH secondary to 21‐hydroxylase deficiency compared to 28 obese and 53 healthy controls. Measurements All subjects had assessment of endothelial function flow‐mediated dilatation, (FMD), smooth muscle function glyceryl tri‐nitrate dilatation (GTN) and cIMT. Anthropometric data, resting blood pressure and biochemical variables were also measured. Results Congenital adrenal hyperplasia subjects had significantly reduced FMD (4·5 ± 3·0%vs 7·5 ± 5·2%; P = 0·04) and GTN (17·2 ± 1·6%vs 28·4 ± 8·4%; P < 0·001) when compared to controls and the impairment was comparable to the obese cohort. There was no significant difference in cIMT between groups. CAH subjects had increased homoeostasis model of assessment‐insulin resistance [HOMA‐IR 2·5 (0·2–2·9) vs 1·8 (0·5–4·2); P = 0·04], waist‐to‐height ratio (0·47 ± 0·05 vs 0·44 ± 0·04; P = 0·02) and higher systolic blood pressure Z score (0·29 ± 0·9 vs?0·24 ± 0·64, P = 0·01) compared to healthy controls but not when compared to obese controls. Conclusions Subjects with CAH have evidence of vascular dysfunction by adolescence.     

The Metabolic syndrome is associated with subclinical atherosclerosis independent of insulin resistance: the Guangzhou Biobank Cohort Study‐CVD

Objective We examined whether the association of the metabolic syndrome (MetS) and subclinical atherosclerosis is independent of insulin resistance in a Chinese community sample with no history of type 2 diabetes. Methods Five hundred and ninety‐six men and 526 women from a substudy of the Guangzhou Biobank Cohort Study (GBCS‐CVD) had carotid intimal‐medial thickness (IMT) measured by B‐mode ultrasonography, and brachial‐ankle pulse wave velocity (PWV) and ankle‐brachial systolic blood pressure index (ABI) measured simultaneously by a noninvasive automatic waveform analyser. Results Fourteen percentage had MetS as defined by the International Diabetes Federation. Obesity indices, systolic and diastolic blood pressure and pulse pressure, lipids, fasting and postload glucose and insulin, homeostatic model assessment of insulin resistance, glycosylated haemoglobin A1c, leptin, high‐sensitivity C‐reactive protein, IMT and PWV increased and high‐density lipoprotein‐cholesterol, adiponectin and ABI decreased significantly with increasing number of MetS components after adjusting for age and sex (P for trend from 0·004 to <0·001). After adjusting for traditional cardiovascular risk factors and insulin resistance, the odds ratios [OR (95% CI)] of thicker IMT (≥1·0 mm), higher PWV (≥14·0 m/s) and low ABI (≤1·0) for MetS were significantly increased [2.28 (1.19?4.38), 2.17 (1.36?3.46) and 1.72 (1.14?2.59), respectively, all P < 0.01] but were lower than the adjusted OR for those with three or more MetS components. Conclusion MetS was associated with subclinical atherosclerosis independent of insulin resistance. The presence of increasing number of MetS risk factors appeared to be more important than the diagnosis of MetS in predicting subclinical atherosclerosis. Early screening for MetS risk factors might identify those at greater cardiovascular risk.     

Relation between age and carotid artery intima‐medial thickness: a systematic review

Carotid artery intima‐medial thickness (cIMT) represents a popular measure of atherosclerosis and is predictive of future cardiovascular and cerebrovascular events. Although older age is associated with a higher cIMT, little is known about whether this increase in cIMT follows a linear relationship with age or it is affected under influence of cardiovascular diseases (CVD) or CVD risk factors. We hypothesize that the relationship between cIMT and age is nonlinear and is affected by CVD or risk factors. A systematic review of studies that examined cIMT in the general population and human populations free from CVD/risk factors was undertaken. The literature search was conducted in PubMed, Scopus, and Web of Science. Seventeen studies with 32 unique study populations, involving 10,124 healthy individuals free from CVD risk factors, were included. Furthermore, 58 studies with 115 unique study populations were included, involving 65,774 individuals from the general population (with and without CVD risk factors). A strong positive association was evident between age and cIMT in the healthy population, demonstrating a gradual, linear increase in cIMT that did not differ between age decades (r = 0.91, P < 0.001). Although populations with individuals with CVD demonstrated a higher cIMT compared to populations free of CVD, a linear relation between age and cIMT was also present in this population. Our data suggest that cIMT is strongly and linearly related to age. This linear relationship was not affected by CVD or risk factors.     

Relationships between vascular resistance and energy deficiency, nutritional status and oxidative stress in oestrogen deficient physically active women

Objective Oestrogen deficiency contributes to altered cardiovascular function in premenopausal amenorrheic physically active women. We investigated whether other energy deficiency‐associated factors might also be associated with altered cardiovascular function in these women. Design A prospective observational study was completed at a research facility at the University of Toronto. Participants Thirty‐two healthy premenopausal women (18–35 years old) were studied; 9 sedentary and ovulatory; 14 physically active and ovulatory; and 8 physically active and amenorrheic. Measurements We measured calf vascular resistance, resting heart rate, dietary energy intake, resting energy expenditure and serum measures of homocysteine, high‐sensitivity C‐reactive protein, oxidized low‐density lipoproteins, total T₃, ghrelin, leptin and insulin. Results Groups were similar (P > 0·05) in age (25·1 ± 0·8 years; mean ± SEM), weight (57·3 ± 1·1 kg), and BMI (21·4 ± 0·3 kg/m²). Resting vascular resistance and ghrelin were highest (P < 0·05, main effect), and total T₃ and energy expenditure adjusted for fat free mass lowest (P < 0·05, main effect) in oestrogen deficient women. Using pooled data for stepwise multiple regression modelling: ghrelin and resting energy expenditure adjusted for fat free mass were associated with resting vascular resistance (R² = 0·398, P = 0·018); adjusted dietary energy intake was associated with peak‐ischaemic vascular resistance (R² = 0·231, P = 0·015). Adjusted resting energy expenditure (r = 0·624, P < 0·001) and total T₃ correlated (r = 0·427, P = 0·019) with resting heart rate. Homocysteine, high‐sensitivity C‐reactive protein and oxidized low‐density lipoproteins were similar (P > 0·05, main effect) among the groups, and were unrelated to cardiovascular measures. Conclusion Altered resting vascular resistance in premenopausal oestrogen deficient physically active amenorrheic women is not associated with vascular inflammation or oxidative stress, but rather with parameters that reflect metabolic allostasis and dietary intake, suggesting a potential role for chronic energy deficiency in vascular regulation.     

Carotid integrated backscatter analysis in patients with subclinical hypothyroidism

Objective The aim of the present study was to determine whether integrated backscatter (IBS) analysis combined with conventional ultrasonography could differentiate the tissue characteristics of carotid artery intimal hyperplasia in patients with subclinical hypothyroidism (SH). Methods Forty‐one patients with SH, as judged by elevated serum TSH levels and free thyroid hormones within the normal range, and 31 sex‐ and age‐matched euthyroid volunteers underwent two‐dimensional conventional ultrasonography and IBS analysis of the carotid wall. Carotid intima–media thickness (IMT) and corrected IBS (C‐IBS), an index of arterial wall degeneration and fibrosis, were evaluated. Results Mean IMT as well C‐IBS values were higher in SH than in controls (P < 0·0001 for both), whereas the carotid diameter was not significantly different between the two groups. The distribution of C‐IBS values in each group showed that regions with higher C‐IBS values were found more frequently in SH patients than in control subjects. The percentage of regions that could be considered as fibromatous (C‐IBS value from –18 to –21 dB) was 28% in SH and 9% in euthyroid subjects (P < 0·0001). In the SH group, C‐IBS values were significantly and positively associated with plasma TSH (r = 0·32, P < 0·05 and r = 0·59, P < 0·0001, respectively) and with both total cholesterol (r = 0·46, P = 0·01) and low density lipoprotein (LDL)‐cholesterol (r = 0·55, P = 0·001). Conclusions Carotid IMT in subclinically hypothyroid patients is higher than that in euthyroid controls. This is characterized by increased IBS values, which are related to the collagen content of the arterial wall. The severity of this remodelling process seems to be related to TSH and cholesterol levels.     

Cardiovascular and renal effects of growth hormone*

OBJECTIVE With the advent of recombinant human GH (rhGH), it has become possible in controlled clinical studies to explore the effects of GH replacement in adults with GH deficiency. The objective of this study was to determine cardiovascular and renal effects of GH replacement in adults with GH deficiency. PATIENTS We studied ten patients (one woman and nine men), mean age 47 years, with GH deficiency. DESIGN The patients were given s.c. rhGH (Humatrope, Ell Lilly) 0·5 U/kg/week or placebo in a 6-month double blind cross-over study. Cardiac and renal function was measured before drug administration (baseline), before cross-over (i.e. after 6 months), and before termination of drug administration (after another 6 months). Analysis of variance was used to compare measurements during GH replacement with baseline and placebo measurements. One patient was excluded because of atrial fibrillation. MEASUREMENTS Main outcome measures were glomerular filtration rate and Doppler-echocardiographic estimates of cardiac function and structure. Computerized exercise electrocardiogram, spirometry, and blood samples for analyses of plasma hormones were also obtained. RESULTS Left ventricular function was maintained during GH replacement. However, left ventricular mass increased from 211 to 249 g (P<0·05) mainly due to increased left ventricular dimension since wall thicknesses did not increase. The left atrium increased from 38 to 41 mm (P<0·05), possibly because stroke volume increased from 92 to 118 ml (P<0·0001) and cardiac output increased from 5·29 to 7·58 l/min (P<0·05). Total peripheral resistance decreased from 18·9 to 12·4 mmHg min/l (P<0·05), and diastolic blood pressure from 79 to 72 mmHg (P<0·05). Heart rate at rest increased from 58 to 70 beats/min. Systolic blood pressure at rest was unchanged, as was systolic blood pressure during dynamic exercise. GH replacement did not cause ST-abnormalities. Serum creatinine decreased from 91·4 to 85·3 μmol/l (P<0·05) and glomerular filtration rate increased from 89·6 to 99·8 ml/min (P<0·01). CONCLUSIONS Thus, GH replacement has favourable cardiovascular and renal effects including increase of stroke volume and glomerular filtration rate with reduction of peripheral resistance.     

Insulin-like growth factor-1 deficiency determines increased intima-media thickness at common carotid arteries in adult patients with growth hormone deficiency

objective To investigate the role of IGF‐1 on intima–media thickness (IMT) at common carotid arteries by Doppler ultrasonography. subjects Thirty‐nine patients (17 women, 22 men, aged 25–70 years) with severe GH deficiency (GHD), 19 with normal and 20 with low IGF‐1 levels, and 39 sex‐, age‐ and body mass index (BMI)‐matched healthy controls. results Patients with GHD showed abnormalities in lipid profile, and increased fibrinogen levels, mean IMT (0·88 ± 0·26 vs. 0·69 ± 0·14 mm, P < 0·001), and systolic and diastolic peak velocity (P < 0·001) compared to controls. Eight patients (18%) and one control (2·1%, P = 0·04) had well‐defined plaques. In controls, but not in patients with GHD, mean carotid IMT was correlated with age (r = 0·78, P < 0·001). In both controls (r = ?0·82; P < 0·0001) and patients with GHD (r = ?0·84, P < 0·0001), serum IGF‐1 levels were inversely correlated with mean IMT at common carotid arteries. At the stepwise multiple regression, the variables most significantly related to IMT in GH‐deficient patients were total cholesterol levels (t = 5·2, P < 0·001), followed by disease duration (t = 2·4, P = 0·02), while in controls the variables most significantly related to IMT were IGF‐1 levels (t = ?9·9, P < 0·001), followed by low density lipoprotein (LDL)‐cholesterol levels (t = ?2·3, P = 0·02). Compared to patients with normal IGF‐1 levels, those with low IGF‐1 levels had lower high density lipoprotein (HDL)‐cholesterol levels (1·0 ± 0·2 vs. 1·3 ± 0·2 mmol/l, P = 0·0002), and higher glucose (54·3 ± 6·1 vs. 48·9 ± 5·9 mmol/l, P = 0·008), insulin (25·2 ± 6·8 vs. 18·8 ± 6·0 mUl/l, P = 0·004), total cholesterol (7·1 ± 1·1 vs. 4·9 ± 0·6 mmol/l, P < 0·0001), total/HDL‐cholesterol ratio (7·2 ± 1·8 vs. 3·9 ± 0·7, P < 0·0001), fibrinogen levels (319·8 ± 56·9 vs. 241·8 ± 53·0 mg/dl, P < 0·0001) and mean IMT at common carotid arteries (1·05 ± 0·25 vs. 0·69 ± 0·07 mm, P < 0·0001). Atherosclerotic plaques were found only in GH‐deficient patients with low IGF‐1 levels. conclusions GH‐deficient patients have alterations in lipid profile with an increase in the total/HDL‐cholesterol ratio, which is an index of increased cardiovascular risk, but only patients with IGF‐1 deficiency have increased IMT.     

Partial growth hormone deficiency is associated with an adverse cardiovascular risk profile and increased carotid intima‐medial thickness

Objective To quantify the relative prevalence of surrogate markers of vascular risk in adults with partial GH deficiency (GH insufficiency, GHI). Context Hypopituitary adults with untreated GH deficiency (GHD) have an excess vascular mortality and demonstrate clustering of adverse vascular risk factors. The vascular risk profile of GHI adults has yet to be comprehensively studied. Design A cross‐sectional case controlled study. Patients Thirty GHD adults, 24 GHI, and 30 age‐ and sex‐matched controls. GHI adults were defined biochemically using two GH stimulation tests (peak GH 3–7 μg/l). Measurements Serum lipids and apolipoproteins, plasminogen activator inhibitor type‐I (PAI‐I), C‐reactive protein (CRP), lipoprotein (a) [Lp(a)], fibrinogen, blood pressure and carotid intima‐medial thickness (IMT). Results IGF‐I levels of GHI adults were lower than controls (373 ± 123 vs 295 ± 104 μg/l; P < 0·001). Total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C) and triglycerides (TG) values were consistently between those of, but not significantly different from, GHD and control subjects. GHI adults showed significantly elevated PAI‐I levels [80 (13–98) vs 50·5 (3–98) ng/ml; P = 0·01], although no there were differences in CRP, Lp(a), and fibrinogen levels compared with control subjects. No differences in systolic or diastolic blood pressure were shown between study groups. In parallel with the increased vascular risk profile of GH‐insufficient adults, carotid IMT was significantly increased (0·503 ± 0·08 vs 0·578 ± 0·130 mm; P = 0·02). TC, LDL‐C, Waist‐Hip Ratio (WHR), truncal fat mass, and IMT correlated with IGF‐I levels and GH status. TG, K_ITT, and PAI‐I additionally correlated with GH status, but not with IGF‐I levels. Conclusion GHI adults are at elevated vascular risk, reflected by adverse surrogate markers and increased carotid IMT. The surrogate risk marker profile parallels GHD adults, but is less divergent from that observed in healthy individuals. No data are yet available as to whether these anomalies will be reflected in an increased vascular mortality in GHI adults.     

The Relationship Between Flow‐Mediated Dilatation of the Brachial Artery and Intima‐Media Thickness of the Carotid Artery to Framingham Risk Scores in Older African Americans

The objective of this study was to investigate the relationship of flow‐mediated dilatation and intima‐media thickness (IMT) with coronary risk in African Americans (AAs). Endothelial dysfunction and IMT of carotid arteries are considered early steps in atherosclerotic disease process and have been used as surrogate markers of subclinical atherosclerosis. Data were collected on 106 AAs with a mean age of 64.0±6.6 years. Carotid artery IMT was measured with B‐mode ultrasonography, as was brachial artery diameter at rest, during reactive hyperemia, and after nitroglycerin. Percent change in flow‐mediated dilatation (%FMD) was defined as 100×(diameter during reactive hyperemia – resting diameter)/resting diameter. Percent change in nitroglycerin‐mediated dilatation (%NMD) was defined as 100×(diameter with nitroglycerin‐resting diameter)/resting diameter. The Framingham 10‐year risk score (FRS) was calculated for each patient using the National Cholesterol Education Program (NCEP) risk score calculator and participants were categorized into 3 groups with FRS as <10%, 10% to 20%, and >20%. Thirty‐eight participants had risk scores <10%, 26 had 10% to 20%, and 42 >20%. There was a significant inverse relation between %FMD and FRS (P<.0001) and between %NMD and FRS (P<.001). IMT was not statistically different among the risk groups. Endothelial dysfunction assessed by FMD significantly correlates inversely with FRS in AAs. FMD, an index of arterial compliance, appears to be a sensitive and reliable index of cardiovascular disease.     

Impaired body balance, fine motor function and hearing in women with Turner syndrome

Objective Fractures are related to falling. Turner syndrome (TS) is associated with hypogonadism, osteoporosis and fractures and has been considered as a syndrome of early ageing. The aim was to study whether fine motor function (FM) and body balance (BB) were impaired and related to genotype, fractures, metabolic variables and hearing. Design Cross‐sectional study. Patients TS women, n = 75, mean age 30 years (range 16–59) and treated with oestrogen hormone replacement therapy (HRT) at the out‐patient clinic, Sahlgrenska University Hospital, Göteborg, Sweden, and 31 healthy controls, mean age 37 years (range 24–63). Measurements Six FM and eight BB tests with open and closed eyes, respectively, were done. Bone mineral density was estimated with Dual energy X‐ray Absorptiometry. Presence/absence of fractures was noted, blood samples were taken and audiometry was done in the TS women. Results TS women had poorer FM (27·4 ± 6·0 vs. 32·8 ± 2·2; P < 0·0001) and BB (28·0 ± 8·1 vs. 34·7 ± 2·4; P < 0·0001) than controls. FM was poorer in TS women with hearing aids compared to those without (P < 0·05). FM and BB were negatively correlated with age, waist : hip ratio and positively correlated with hearing, and bone mineral density, and BB was negatively correlated with physical activity in TS women. BB correlated negatively with age in controls. FM, BB and hearing function were poorer in 45,X, nonmosaics, than in 45,X/46,XX, mosaics. Conclusions FM and BB were poorer in adult TS women on HRT than in controls. Higher age, hearing impairment, osteoporosis, abdominal obesity, a sedentary lifestyle and the TS per se were strong determinants, and mosaicism mitigated both fine motor function and BB in TS.     

Haemoglobin A1c is associated with carotid intima-media thickness in a Chinese population

Background The association between haemoglobin A1c (HbA1c) levels and subclinical atherosclerosis in carotid arteries in Chinese populations is unknown. Aim, design and methods The objective of this study was to investigate this relationship and evaluate the ability of HbA1c levels to predict carotid atherosclerosis in a Chinese population. This was a cross‐sectional study, which included 541 subjects without known diabetes (Taiwan Lifestyle Study). About 67 (9·2%) subjects were newly diagnosed with diabetes during the study. Carotid intima–media thickness (IMT) and the presence of carotid plaques were determined using ultrasonography. Results The HbA1c level in all subjects was positively correlated with carotid IMT (β = 0·018, P = 0·03) after being adjusted for age, gender, smoking, low‐density lipoprotein cholesterol level, hypertension and body mass index. HbA1c level was higher in subjects with plaques in carotid arteries (P = 0·01). There was a positive and linear relationship between HbA1c levels and the probability of having plaques, thickened carotid IMT or both (P for all comparisons, <0·05). The ability of HbA1c levels to predict thickened carotid IMT or the presence of plaques was only modest {the optimal cutoff of HbA1c level [5·7%] was determined from the receiver operating characteristic (ROC) curve (sensitivity = 67%, specificity = 61%) and the area under the ROC curve [0·666]}. Conclusions Thus, HbA1c level is associated with subclinical atherosclerosis in carotid arteries in a Chinese population. The relationship is linear without an inflection point. However, HbA1c criterion is not a useful marker for the identification of subclinical atherosclerosis.     

The effect of oxandrolone on body proportions and body composition in growth hormone‐treated girls with Turner syndrome

Objective Untreated girls with Turner syndrome (TS) have short stature, relatively broad shoulders, a broad pelvis, short legs, a high fat mass and low muscle mass. Our objective was to assess the effect of the weak androgen oxandrolone (Ox) on body proportions and composition in growth hormone (GH)‐treated girls with TS. Design/Patients 133 patients were included in a randomized, placebo‐controlled, double‐blind study. Methods Patients were treated with GH (1·33 mg/m² per day) from baseline, combined with placebo (Pl) or Ox in a low (0·03 mg/kg per day) or previously conventional (0·06 mg/kg per day) dose from the age of eight, and oestrogens from the age of twelve. Sitting height, biacromial and biiliacal distances compared with height (i.e. shape values), BMI, waist circumference, sum of 4 skinfolds (sum4skin) and upper arm muscle area (UAMA) SD scores (SDS) were assessed half‐yearly. Results Compared with GH + Pl, adult shape values on GH + Ox tended to be higher for sitting height (Ox 0·03, P = 0·2; Ox 0·06, P = 0·02) and biacromial distance (Ox 0·03, P = 0·2; Ox 0·06, P = 0·07) and lower for biiliacal distance (Ox 0·03, P = 0·004; Ox 0·06, P = 0·08). Sum4skin SDS tended to decrease more (Ox 0·03, P = 0·2; Ox 0·06, P = 0·005) while UAMA SDS increased more (Ox 0·03, P < 0·001; Ox 0·06, P < 0·001) than on GH + Pl. The increase in BMI and waist circumference SDS was comparable between the dosage groups. Conclusions In GH‐treated girls with TS, Ox 0·06 increases sitting height and tends to increase biacromial distance and decrease biiliacal distance, while Ox 0·03 significantly decreases biiliacal distance compared with height. Furthermore, Ox 0·06 reduces subcutaneous fat mass, and both Ox dosages increase muscle mass.     

Health status in women with Turner syndrome: a questionnaire study on health status,education, work participation and aspects of sexual functioning

Context Turner syndrome (TS) is a complex medical condition with specific cognitive and psychosocial characteristics and frequent medical morbidity. Few studies have investigated the influence this has on health status, education and ability to work. Objective To explore health status, level of education, work participation, medical conditions, physical activity, satisfaction with life and aspects of sexual functioning in adult TS women and compare with a matched control group. Design A questionnaire was sent to 168 adult women with TS >18 years registered in a database of Frambu Resource Centre for Rare Disorders and The TS Association in Norway. We assessed health status with Short Form 36, education with Norwegian Standard Classification of Education, and employment with The General Nordic Questionnaire. Life satisfaction was measured with LiSat‐9, and questions on psychological strain during life phases were included. Results Eighty women with TS (34·0 ± 11·7 years) and 214 controls (32·9 ± 10·6) responded. The TS group reported significantly more health problems and impaired health status in the two subscales “physical functioning” and “general health” (P < 0·001). Level of education and work participation was similar among TS and controls. TS moved away from their parents’ home later than controls (20·4 ± 4·0 vs. 18·7 ± 2·1, P = 0·001). Age at sexual debut differed significantly (21·2 ± 4·3 vs. 17·3 ± 2·4 years, P < 0·001). Conclusion TS attains the same level of education and level of employment as controls, they report more frequent occurrence of medical conditions, but scored lower on only two subscales in the SF‐36. Despite considerable medical morbidity, TS seem to cope well with life.     

Asymmetric dimethylarginine as a risk factor for cardiovascular disease in Japanese patients with type 2 diabetes mellitus

Aims Although asymmetric dimethylarginine (ADMA) is known to be involved in the developing process of cardiovascular diseases (CVD), little is known about the effects of ADMA on atherosclerosis in Asian patients with diabetes , who have the racial feature of lower body mass index (BMI) and decreased capacity of insulin secretion and sensitivity. Methods We employed 55 Japanese patients with type 2 diabetes mellitus (mean age, 64·2 years; 56% men) in a 6‐month‐longitudinal study and 450 patients (mean age, 62·7 years; 56% men) in a cross‐sectional study and examined the association of serum ADMA with atherosclerosis parameters [intima‐media thickness (IMT) and brachial‐ankle pulse wave velocity (baPWV)] as well as with the presence of CVD. Results In the longitudinal study, multiple regression analysis showed that basal serum ADMA level had a significantly positive association with changes in IMT (β = 0·35, P = 0·03) independently of age, duration of diabetes, BMI, blood pressure, low‐density lipoprotein and high‐density lipoprotein (LDL and HDL) cholesterol, HbA_1c, and renal function. In the cross‐sectional study, the serum ADMA level was significantly and positively associated with the presence of CVD (odds ratio = 7·22, 95% confidence interval 1·29–40·40, P = 0·02, by logistic analysis) and with baPWV (β = 0·14, P < 0·01, by multiple regression analysis). In contrast, serum symmetric dimethylarginine level, a structural isomer of ADMA, was associated neither with parameters for atherosclerosis nor with the presence of CVD in both studies. Conclusions Serum ADMA is a predictor of atherosclerosis and associated with the presence of CVD in Japanese patients with type 2 diabetes mellitus.     

Amelioration of cardiovascular risk factors with partial biochemical control of acromegaly

Objective Complete remission of acromegaly is associated with favourable changes in cardiovascular risk parameters. We evaluated the effects of suboptimal therapy on haemodynamic, metabolic, inflammatory and coagulation cardiovascular risk indices. Design and methods Eighteen acromegalic patients on somatostatin analogues, with incomplete biochemical control, were evaluated at diagnosis and 6 months after treatment and compared to 15 healthy age‐ and body mass index (BMI)‐matched controls. Measurements of blood pressure, GH, IGF‐I, glucose, insulin, glycated haemoglobin (HbA1c), lipids, apolipoprotein A1 (apoA1), apoB, high‐sensitivity C‐reactive protein (hs‐CRP), fibrinogen, plasminogen activator inhibitor 1 (PAI‐1), tissue plasminogen activator (tPA) and circulating thrombomodulin were performed in all study participants, followed by an oral glucose tolerance test (OGTT). Insulin sensitivity (IS) was expressed by the Matsuda index (OGTT_ISI). Results Partial control of acromegaly resulted in a significant reduction in systolic and diastolic blood pressure, glucose, insulin, HbA1c, total (T‐C) and low density lipoprotein cholesterol (LDL‐C) and triglyceride levels, and a significant increase in apoA1, high density lipoprotein cholesterol (HDL‐C) and OGTT_ISI compared to pretreatment levels. Plasma fibrinogen and PAI‐1 levels fell significantly [respectively (mean ± SEM), 11·04 ± 0·41 vs. 10·12 ± 0·34 µmol/l, P = 0·003 and 9·6 ± 1·97 vs. 6·55 ± 1·89 µg/l, P < 0·001]. However, a marked reduction in tPA [median (IQR) 5·1 (2·5–15) vs. 3·4 (2·4–8·6) µg/l, P = 0·031] and an increase in hs‐CRP [median (IQR) 0·05 (0·03–0·11) vs. 0·1 (0·06–0·23) mg/l, P < 0·001] were also noted. On treatment, acromegalic patients were comparable to controls, except for OGTT_ISI, lipoprotein(a) [Lp(a)], fibrinogen and tPA and HDL‐C levels. Thrombomodulin and apoB levels were not affected by treatment. Conclusions Partial control in disease activity following somatostatin analogues results in significant improvement in a considerable number of cardiovascular risk markers in acromegaly.     

Uterus and ovaries in girls and young women with Turner syndrome evaluated by ultrasound and magnetic resonance imaging

Objective To determine uterine and ovarian size in Turner syndrome (TS) and to compare uterine and ovarian size evaluated by transabdominal ultrasound (US) and magnetic resonance imaging (MRI) in girls with TS and two groups of controls. Design A cross‐sectional study. Patients Forty‐one girls with TS (17·0 ± 3·3 years, range 11·2–24·9 years), 50 healthy age‐matched controls (16·9 ± 3·2 years, range 12·5–25·0 years) and 107 Tanner‐stage‐matched controls (15·0 ± 3·2 years, range 10·1–24·2). Measurements Uterine and ovarian volume by US and MRI. Results Ovaries were detected in 37% in TS by US and in 55% in TS by MRI (P = 0·1). Total ovarian volume was lower in TS compared to both groups of controls (TS vs C‐US: median 1·1 ml (range 0·1–29·3) vs 11·52 ml (1·9–77·9), P = 0·001, TS vs C‐MRI: 1·0 ml (0·1–34·2) vs 13·2 ml (2·4–30·1), P < 0·0005). Mean difference in total ovarian volume measured by MRI and US in patients with TS was 2·3 ± 3·8 ml (P = 0·01). Mean uterine volume by MRI was lower in TS compared to controls (29·5 ± 25·1 vs 54·3 ± 23·3 ml, P < 0·0005). Uterine volume by US was lower in TS at Tanner stage B5 compared to controls (TS vs C: 33·6 ± 18·2 vs 50·2 ± 18·0 ml, P = 0·007). Conclusions A larger ovarian volume was detected by MRI in TS compared to US. This finding is important with the advancements of performing ovarian biopsies for cryopreservation and later reimplantation. Mean uterine volumes by MRI and US in fully matured TS were lower compared to controls despite appropriate hormonal replacement therapy in TS.