Biomarkers in congenital adrenal hyperplasia.

Monitoring of hormone replacement therapy represents a major challenge in the management of congenital adrenal hyperplasia (CAH). In the absence of clear guidance and standardised monitoring strategies, there is no consensus among clinicians regarding the relevance of various biochemical markers used in practice, leading to wide variability in their application and interpretation. In this review, we summarise the published evidence on biochemical monitoring of CAH. We discuss temporal variations of the most commonly measured biomarkers throughout the day, the interrelationship between different biomarkers, as well as their relationship with different glucocorticoid and mineralocorticoid treatment regimens and clinical outcomes. Our review highlights significant heterogeneity across studies in both aims and methodology. However, we identified key messages for the management of patients with CAH. The approach to hormone replacement therapy should be individualised, based on the individual hormonal profile throughout the day in relation to medication. There are limitations to using 17-hydroxyprogesterone, androstenedione and testosterone, and the role of additional biomarkers such 11-oxygenated androgens which are more disease specific should be further established. Noninvasive monitoring via salivary and urinary steroid measurements is becoming increasingly available and should be considered, especially in the management of children with CAH. Additionally, this review indicates the need for large scale longitudinal studies analysing the interrelation between different monitoring strategies used in clinical practice and health outcomes in children and adults with CAH.

National service evaluation of the quality of care for children and young people with congenital adrenal hyperplasia in the United Kingdom: survey responses from patients and clinicians.

INTRODUCTION: Quantifying differences in service provision for children and young people (CYP) living with Congenital Adrenal Hyperplasia (CAH) across the United Kingdom. METHODS: A national service evaluation using online questionnaires circulated to patients and clinicians from secondary and tertiary UK centres managing CYP with CAH, and via the "Living with CAH" support group mailing list. RESULTS: Total of 195 responses relating to patients aged 0-20 years attending 33 clinics (43 patients, 152 carers), as well as 34 clinicians from 18 trusts working across the 33 clinics. Only 12% of clinicians were 'completely satisfied' with the service provided, compared to 68% of carers and 76% of patients. Whilst 94% of clinicians reported providing formal training to families with CAH, over 80% of both patients and carers reported not attending what they considered formal training. Appetite for further training was higher in carers (86%) than patients (55%), although further 'unsure' responses suggested formal training sessions would likely be well attended. Access to psychological services was difficult for 44% of clinicians. Biochemical monitoring of treatment was broadly in keeping with international guidelines, with 67% of clinicians reporting regular use of dried blood spots, and 12% regular urinary steroid metabolites. CONCLUSION: While there is overall good satisfaction with care provision among patients and carers with CAH in the UK, extra resources addressing the psychological and educational needs about the disease and its management would benefit patients and carers. Improved access to allied health professionals and psychologists will help support families and improve patient outcomes.

Blood Pressure in Children with Congenital Adrenal Hyperplasia Due To 21-Hydroxylase Deficiency.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) leads to impaired glucocorticoid and mineralocorticoid synthesis with excess production of androgens. Replication of the normal circadian cortisol secretion is challenging and supraphysiological doses of glucocorticoids are often required. Most patients experience transient episodes of hyper- and hypocortisolaemia during the day leading to adverse metabolic outcomes such as insulin resistance, visceral adiposity and cardiovascular morbidity, including hypertension. These health problems are commonly diagnosed in adolescence and adulthood. Herein, we review the published data on the variation in blood pressure in CAH due to 21OHD and the interrelation with disease and treatment factors.

Big data and the NHS - we have the -technology, but we need patient and professional engagement.

The potential promise of 'big data' in the NHS has not been overhyped. However, cyber security and linkage attacks remain ongoing concerns, and previously damaging projects, such as care.data and the Royal Free's collaboration with google DeepMind, have raised concern among patient groups. We must use technology itself to minimise these risks, while publicising the good news stories and the positive case for using patient data in research. '#Datasaveslives' is a national campaign, launched by the Farr Institute in 2014, that aims to spread the importance of our duty to share patient data for the benefits of health outcomes. 2018 is an incredibly important year for the future of data sharing. We urge our colleagues to join the campaign by sharing stories online with #Datasaveslives to promote how learning from patient data helps improve healthcare for us all.

Using primary care data for health research in England - an overview.

In contrast to secondary care, where handwritten records remain widespread, electronic patient records have long been a key feature of UK general practice. By 1996, 96% of general practices were computerised and now almost every primary care consultation in the UK is recorded on a computerised clinical system. Consequently, we now have a vast repository of patient health data that spans decades, which could be used to address a range of important research questions. Unfortunately, accessing primary care data for health researchers can be a burdensome, confusing and time-consuming process. Understanding the way in which primary care data are recorded and 'coded' is not intuitive to those unfamiliar with general practice. The requirements of information governance mean that some data, or data presented in particular ways, are not available at all. This review provides a practical overview of the types of data recorded in primary care, the bodies responsible for them and how they can be accessed.

Diagnostic accuracy of bone turnover markers as a screening tool for aseptic loosening after total hip arthroplasty.

Aseptic loosening is the most common cause of prosthesis failure after total hip arthroplasty (THA). We measured serum cross-linked carboxyterminal telopeptide of type I collagen (ICTP), tartrate-resistant acid phosphatase 5b (TRAP5b), dickkopf-1 (dkk-1) and sclerostin; and urinary α isomer of C-terminal cross-linked telopeptide of type I collagen (αCTX-I) to investigate their potential diagnostic value detecting aseptic loosening after THA. Biomarkers were measured in 24 subjects with aseptic loosening of THA versus 26 control subjects without loosening after THA. Serum ICTP in the loose group (7.04 ng/mL) was higher than controls (5.15 ng/mL), (p = 0.0007). ROC analysis demonstrated that a serum ICTP >5.5 ng/L had a sensitivity of 91% and specificity of 69% for detecting aseptic loosening (area under ROC curve = 0.77, p = 0.0001), resulting in a positive predictive value (PPV) of 73% and a negative predictive value (NPV) of 90%. Serum TRAP5b in the aseptic loosening group (4.17U/L) was higher than controls (3.44 U/L), (p = 0.03). A serum TRAP5b >2.46 U/L had sensitivity of 100% and a specificity of 31% to detect aseptic loosening (AUC 0.67, p = 0.031), resulting in a PPV of 57% and a NPV of 100%. Serum dkk-1, serum sclerostin and urinary αCTX-I were not elevated in subjects with aseptic loosening (p>0.05). Serum ICTP and TRAP5b show potential utility as screening biomarkers for excluding aseptic loosening, because of their ability to discriminate individuals without disease. Our finding of elevated ICTP, generated by the action of matrix metalloproteinases, suggests a role for this group of endopeptidases in aseptic loosening.