Diagnosis and testing for growth hormone deficiency across the ages: a global view of the accuracy, caveats, and cut-offs for diagnosis

Growth hormone deficiency (GHD) is a clinical syndrome that can manifest either as isolated or associated with additional pituitary hormone deficie ncies. Although diminished height velocity and short stature are useful and important clin ical markers to consider testing for GHD in children, the signs and symptoms of GHD are not always so apparent in adults. Quality of life and metabolic health are often impac ted in patients with GHD; thus, making an accurate diagnosis is important so that appropr iate growth hormone (GH) replacement therapy can be offered to these patients. Scree ning and testing for GHD require sound clinical judgment that follows after obtaining a complete medical history of patients with a hypothalamic–pituitary disorder and a thorough physical examination with specific features for each period of life, while targeted bioche mical testing and imaging are required to confirm the diagnosis. Random measurements of se rum GH levels are not recommended to screen for GHD (except in neonates) as endog enous GH secretion is episodic and pulsatile throughout the lifespan. One or more GH stimulation tests may be required, but existing methods of testing might be inaccurat e, difficult to perform, and can be imprecise. Furthermore, there are multiple caveats when interpreting test results including individual patient factors, differences in peak GH cut -offs (by age and test), testing time points, and heterogeneity of GH and insulin-like g rowth factor 1 assays. In this article, we provide a global overview of the accuracy and cut-o ffs for diagnosis of GHD in children and adults and discuss the caveats in conducting and i nterpreting these tests

A Normative Model of Serum Inhibin B in Young Males

RTM is supported by a Wellcome Trust Intermediate Clinical Fellowship (Grant No: 098522).Inhibin B has been identified as a potential marker of Sertoli cell function in males. The aim of this study is to produce a normative model of serum inhibin B in males from birth to seventeen years. We used a well-defined search strategy to identify studies containing data that can contribute to a larger approximation of the healthy population. We combined data from four published studies (n = 709) and derived an internally validated model with high goodness-of-fit and normally distributed residuals. Our results show that inhibin B increases following birth to a post-natal peak of 270 pg/mL (IQR 210–335 pg/mL) and then decreases during childhood followed by a rise at around 8 years, peaking at a mean 305 pg/mL (IQR 240–445 pg/mL) at around age 17. Following this peak there is a slow decline to the standard mature adult normal range of 170 pg/mL (IQR 125–215 pg/mL). This normative model suggests that 35% of the variation in Inhibin B levels in young males is due to age alone, provides an age-specific reference range for inhibin B in the young healthy male population, and will be a powerful tool in evaluating the potential of inhibin B as a marker of Sertoli cell function in pre-pubertal boys.Publisher PDFPeer reviewe

A Validated Age-Related Normative Model for Male Total Testosterone Shows Increasing Variance but No Decline after Age 40 Years

The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men. We show that total testosterone peaks [mean (2.5-97.5 percentile)] at 15.4 (7.2-31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5-97.5 percentile)] to 13.0 (6.6-25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism.Publisher PDFPeer reviewe

Microbial networks for biomonitoring

Environmental DNA contains information on the species interaction networks that support ecosystem functions and services. Next‐Generation Biomonitoring proposes the use of this data to reconstruct ecological networks in real‐time and then compute network‐level properties to assess ecosystem change. We investigated the relevance of this proposal by assessing: (1) the replicability of DNA‐based networks in the absence of ecosystem change; and, (2) the benefits and shortcomings of community‐ and network‐level properties for monitoring change. We selected crop‐associated microbial networks as a case study since they support disease regulation services in agroecosystems and analyzed their response to change in agricultural practice between organic and conventional systems. Using two statistical methods of network inference, we showed that network‐level properties, especially β‐properties, could detect change. Moreover, consensus networks revealed robust signals of interactions between the most abundant species, that differed between agricultural systems. These findings complemented those obtained with community‐level data, that showed, in particular, a greater microbial diversity in the organic system. The limitations of network‐level data included (i) the very high variability of network replicates within each system; (ii) the low number of network replicates per system, due to the large number of samples needed to build each network; and, (iii) the difficulty in interpreting links of inferred networks. Tools and frameworks developed over the last decade to infer and compare microbial networks are therefore relevant to biomonitoring, provided that the DNA metabarcoding datasets are large enough to build many network replicates and progress is made to increase network replicability and interpretation.Biosurveillance Next-Gen des changements dans la structure et le fonctionnement des écosystèmesInitiative d'excellence de l'Université de BordeauxCEnter of the study of Biodiversity in Amazoni