A Prospective Study of Lipids in Adult Women With Turner Syndrome.

Context: Turner syndrome (TS) is a rare genetic syndrome with an increased mortality, mainly attributed to cardiovascular disease. Objective: This work aimed to investigate and correlate the lipid profile in adult women with TS to clinical characteristics. Methods: A 12-year prospective cohort study, including 4 study visits, was conducted at a specialist hospital. A total of 102 women with TS qualified for inclusion. Excluding missing variables and participants lost to follow-up, 86 women (mean age 38.1 years; range, 18.4-62.1 years) were included in this study. Fifty-three women completed the study. Repeated-measurement analysis was performed, using total cholesterol (Total-C), low-density lipoprotein (LDL), triglycerides (TGs), and high-density lipoprotein (HDL) as outcome variables and age, karyotype, body mass index (BMI), treatment with statins, antidiabetics, and hormone replacement therapy as explanatory variables. Principal component analysis (PCA) and partial least squares (PLS) analysis were performed at the first study visit. Results: Hyperlipidemia was present in 30% of the TS cohort. Total-C increased with age (0.12 mmol/L/y; P = .016). LDL (P = .08), TGs (P = .14), and HDL (P = .24) were not associated with age. BMI significantly increased total-C (0.19 mmol/L/kg/m2; P = .006), LDL (0.63 mmol/L/kg/m2; P < .001), and TGs (0.80 mmol/L/kg/m2; P < .001) and decreased HDL (-0.59 mmol/L/kg/m2; P < .001). PCA and PLS analysis found correlations between weight and BMI and total-C, LDL, and TGs. Conclusion: Hyperlipidemia is more prevalent in adult women with TS across adulthood compared to the background population. Total-C, LDL, TGs, and HDL were significantly associated with BMI characterizing the atherogenic profile in adult women with TS.

The Changing Face of Turner Syndrome.

Turner syndrome (TS) is a condition in females missing the second sex chromosome (45,X) or parts thereof. It is considered a rare genetic condition and is associated with a wide range of clinical stigmata, such as short stature, ovarian dysgenesis, delayed puberty and infertility, congenital malformations, endocrine disorders, including a range of autoimmune conditions and type 2 diabetes, and neurocognitive deficits. Morbidity and mortality are clearly increased compared with the general population and the average age at diagnosis is quite delayed. During recent years it has become clear that a multidisciplinary approach is necessary toward the patient with TS. A number of clinical advances has been implemented, and these are reviewed. Our understanding of the genomic architecture of TS is advancing rapidly, and these latest developments are reviewed and discussed. Several candidate genes, genomic pathways and mechanisms, including an altered transcriptome and epigenome, are also presented.

Prostate Cancer Detection Rate of Manually Operated and Robot-assisted In-bore Magnetic Resonance Imaging Targeted Biopsy.

Background: The diagnostic efficacy regarding prostate cancer (PC) detection by manually operated in-bore magnetic resonance imaging (MRI) targeted prostate biopsy (MO-MRGB) versus robot-assisted in-bore MRI targeted prostate biopsy (RA-MRGB) is lacking evidence. Objective: We hypothesized that the detection rates (DRs) for PC of MO-MRGB and RA-MRGB were similar and aimed to compare these. Design setting and participants: We prospectively included all patients who received in-bore MRI targeted prostate biopsy (MRGB) of the prostate in the Central Denmark Region from August 2014 to February 2020. From August 2014, MO-MRGB was used, and from March 2018, RA-MRGB was preferred. Referral to in-bore MRGB was based on multiparametric MRI (mpMRI). Outcome measurements and statistical analysis: We compared PC DRs of MO-MRGB and RA-MRGB with Pearson's chi-square test. We made three binary regression models and calculated the risk difference (RD) of PC between the in-bore MRGB systems. Results and limitations: A total of 3107 patients were referred to mpMRI, and 884 (28%) patients went on to receive in-bore MRGB. The MO-MRGB and RA-MRGB systems were used in 505 (57%) and 379 (43%) patients, respectively. Taking clinically relevant covariates into account, we found no statistically significant difference in PC DRs between MO-MRGB and RA-MRGB (72% vs 73%, RD 1%, 95% confidence interval -4% to 7%, p = 0.6). The main limitation was a shift in population characteristics. Conclusions: We did not see evidence of an effect on the DR or the RD for PC when we compared MO-MRGB with RA-MRGB. Cost effectiveness should be considered carefully when choosing the MRGB system. Patient summary: We compared two magnetic resonance imaging guided prostate tissue sampling systems regarding prostate cancer (PC) detection. One system was manually operated, and the other system was robot assisted. Comparing the systems, we found no evidence of a difference in their ability to detect PC.

ESE audit on management of Adult Growth Hormone Deficiency in clinical practice.

Guidelines recommend adults with pituitary disease in whom GH therapy is contemplated, to be tested for GH deficiency (AGHD); however, clinical practice is not uniform. AIMS: 1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD. DESIGN: On-line survey in endocrine centres throughout Europe. PATIENTS AND METHODS: Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018. RESULTS: Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved. CONCLUSION: Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.

Natural History of Hypertension in Turner Syndrome During a 12-Year Pragmatic Interventional Study.

Turner syndrome is caused by complete or partial X monosomy in some or all cells. Cardiovascular complications are dominant, including increased blood pressure (BP), leading to early-onset hypertension. The aim is to describe the debut, development, and treatment of hypertension in Turner syndrome during a 12-year pragmatic interventional study to help identify risk factors associated with hypertension. One hundred and two women (aged 38±11 years, range: 18-62 years) with Turner syndrome verified by karyotyping (45, X: n=58 [57%]) were included consecutively. Ambulatory BPs were recorded over 24 hours with oscillometric measurements every 20 minutes. Antihypertensive treatment was recommended if the BP was above 135/85 mm Hg during the daytime. Overall, systolic BP, diastolic BP, and pulse pressure increased during the study, while heart rate decreased. The number of patients treated with antihypertensive medicine increased from 29 (28.71%) at baseline to 34 (53.13%) at the end of study. Twenty-four-hour systolic BP and 24-hour pulse pressure increased significantly with age, while 24-hour heart rate decreased with age, and diastolic BP was insignificantly affected by age. Antihypertensive treatment lowered systolic BP (24-hour: -5 mm Hg), diastolic BP (24-hour: -5 mm Hg), and diminished the pulse pressure (24-hour: -6 mm Hg) but did not affect nighttime systolic BP. Antihypertensive treatment did not affect heart rate. Our study showed that both systolic and diastolic BP increases significantly in women with Turner syndrome resulting in an increased risk of cardiovascular comorbidities. This increment should be considered of multifactorial origin with many contributing factors which is supported by our results.

Polymorphisms in the CTSH gene may influence the progression of diabetic retinopathy: a candidate-gene study in the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987).

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) is increasing globally, and as a consequence, more patients are affected by microvascular complications such as diabetic retinopathy (DR). The aim of this study was to elucidate possible associations between diabetes-related single-nucleotide polymorphisms (SNP) and the development of DR. METHODS: Three hundred and thirty-nine patients with T1DM from the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987) went through an ophthalmic examination in 1995; 185 of these were reexamined in 2011. The development of DR was assessed by comparison of overall DR level between baseline and follow-up in the worst eye at baseline. Patients were graded on a modified version of the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and 20 SNPs were genotyped in 130 of the 185 patients. RESULTS: We found the CTSH/rs3825932 variant (C > T) was associated with reduced risk of progression to proliferative diabetic retinopathy (PDR) (OR [95 % CI] = 0.20 [0.07-0.56], p = 2.4 × 10(-3), padjust = 0.048) and ERBB3/rs2292239 variant (G > T) associated with increased risk of two-step progression (OR [95 % CI] = 2.76 [1.31-5.80], p = 7.5 × 10(-3), padjust = 0.15). The associations were independent of other known risk factors, such as HbA1c, sex, and diastolic blood pressure. CONCLUSION: In conclusion, CTSH/rs3825932 and ERBB3/rs2292239 SNPs were associated with reduced risk of progression to PDR and two-step progression of DR on the ETDRS scale accordingly. The variant CTSH remained statistically significant after adjusting for multiple testing. Our results suggest an overlap between genetic variants that confer risk of T1DM and progression of DR.