Mechanisms in endocrinology: Metabolic syndrome through the female life cycle

The normal function of the female reproductive system is closely linked to energy homeostasis with the ultimate scope of fertility and human race perpetuation through the centuries. During a woman's lifetime there are normal events such as puberty, pregnancy and menopause which are related to alterations in energy homeostasis and gonadal steroids levels followed by increase of body fat and insulin resistance, important components of metabolic syndrome (MetS). Pathological conditions such as premature adrenarche, polycystic ovary syndrome and gestational diabetes also present with shifts in gonadal steroid levels and reduced insulin sensitivity. The aim of this review is to discuss these conditions, both normal and pathological, analyzing the changes or abnormalities in ovarian function that coexist with metabolic abnormalities which resemble MetS in relationship with environmental, genetic and epigenetic factors

Hypokalemia: A clinical update

Hypokalemia is a common electrolyte disturbance, especially in hospitalized patients. It can have various causes, including endocrine ones. Sometimes, hypokalemia requires urgent medical attention. The aim of this review is to present updated information regarding: (1) the definition and prevalence of hypokalemia, (2) the physiology of potassium homeostasis, (3) the various causes leading to hypokalemia, (4) the diagnostic steps for the assessment of hypokalemia and (5) the appropriate treatment of hypokalemia depending on the cause. Practical algorithms for the optimal diagnostic, treatment and follow-up strategy are presented, while an individualized approach is emphasized

A General Mechanistic Model for Admixture Histories of Hybrid Populations

Admixed populations have been used for inferring migrations, detecting natural selection, and finding disease genes. These applications often use a simple statistical model of admixture rather than a modeling perspective that incorporates a more realistic history of the admixture process. Here, we develop a general model of admixture that mechanistically accounts for complex historical admixture processes. We consider two source populations contributing to the ancestry of a hybrid population, potentially with variable contributions across generations. For a random individual in the hybrid population at a given point in time, we study the fraction of genetic admixture originating from a specific one of the source populations by computing its moments as functions of time and of introgression parameters. We show that very different admixture processes can produce identical mean admixture proportions, but that such processes produce different values for the variance of the admixture proportion. When introgression parameters from each source population are constant over time, the long-term limit of the expectation of the admixture proportion depends only on the ratio of the introgression parameters. The variance of admixture decreases quickly over time after the source populations stop contributing to the hybrid population, but remains substantial when the contributions are ongoing. Our approach will facilitate the understanding of admixture mechanisms, illustrating how the moments of the distribution of admixture proportions can be informative about the historical admixture processes contributing to the genetic diversity of hybrid populations

Adrenocortical incidentalomas and bone: from molecular insights to clinical perspectives

Adrenal incidentalomas constitute a common clinical problem with an overall prevalence of around 2–3%, but are more common with advancing age being present in 10% of those aged 70 years. The majority of these lesions are benign adrenocortical adenomas (80%), characterized in 10–40% of the cases by autonomous cortisol hypersecretion, and in 1–10% by aldosterone hypersecretion. Several observational studies have shown that autonomous cortisol and aldosterone hypersecretion are more prevalent than expected in patients with osteopenia and osteoporosis: these patients have accelerated bone loss and an increased incidence of vertebral fractures. In contrast to glucocorticoid action, the effects of aldosterone on bone are less well understood. Recent data, demonstrating a concomitant co-secretion of glucocorticoid metabolites in patients with primary aldosteronism, could explain some of the metabolic abnormalities seen in patients with aldosterone hypersecretion. In clinical practice, patients with unexplained osteoporosis, particularly when associated with other features such as impaired glucose tolerance or hypertension, should be investigated for the possible presence of autonomous cortisol or aldosterone secretion due to an adrenal adenoma. Randomized intervention studies are needed, however, to investigate the optimum interventions for osteoporosis and other co-morbidities in these patients

Inferring Geographic Coordinates of Origin for Europeans Using Small Panels of Ancestry Informative Markers

Recent large-scale studies of European populations have demonstrated the existence of population genetic structure within Europe and the potential to accurately infer individual ancestry when information from hundreds of thousands of genetic markers is used. In fact, when genomewide genetic variation of European populations is projected down to a two-dimensional Principal Components Analysis plot, a surprising correlation with actual geographic coordinates of self-reported ancestry has been reported. This substructure can hamper the search of susceptibility genes for common complex disorders leading to spurious correlations. The identification of genetic markers that can correct for population stratification becomes therefore of paramount importance. Analyzing 1,200 individuals from 11 populations genotyped for more than 500,000 SNPs (Population Reference Sample), we present a systematic exploration of the extent to which geographic coordinates of origin within Europe can be predicted, with small panels of SNPs. Markers are selected to correlate with the top principal components of the dataset, as we have previously demonstrated. Performing thorough cross-validation experiments we show that it is indeed possible to predict individual ancestry within Europe down to a few hundred kilometers from actual individual origin, using information from carefully selected panels of 500 or 1,000 SNPs. Furthermore, we show that these panels can be used to correctly assign the HapMap Phase 3 European populations to their geographic origin. The SNPs that we propose can prove extremely useful in a variety of different settings, such as stratification correction or genetic ancestry testing, and the study of the history of European populations

Adrenocortical incidentalomas and bone: from molecular insights to clinical perspectives.

The original version of this article unfortunately contained a mistake in Figure 1. There is a typo in the word "osteoclastogenesis" and the word "activity" is missing in the same entity. It should be "osteoclastogenesis" instead of "osteoclestogenesis"

MECHANISMS IN ENDOCRINOLOGY: Metabolic syndrome through the female life cycle

The normal function of the female reproductive system is closely linked to energy homeostasis with the ultimate scope of fertility and human race perpetuation through the centuries. During a woman's lifetime there are normal events such as puberty, pregnancy and menopause which are related to alterations in energy homeostasis and gonadal steroids levels followed by increase of body fat and insulin resistance, important components of metabolic syndrome (MetS). Pathological conditions such as premature adrenarche, polycystic ovary syndrome and gestational diabetes also present with shifts in gonadal steroid levels and reduced insulin sensitivity. The aim of this review is to discuss these conditions, both normal and pathological, analyzing the changes or abnormalities in ovarian function that coexist with metabolic abnormalities which resemble MetS in relationship with environmental, genetic and epigenetic factors

Genetic Association Signal Near NTN4 in Tourette Syndrome

Tourette syndrome (TS) is a neurodevelopmental disorder with a complex genetic etiology. Through an international collaboration, we genotyped 42 single nucleotide polymorphisms (p \u3c 10(-3)) from the recent TS genomewide association study (GWAS) in 609 independent cases and 610 ancestry-matched controls. Only rs2060546 on chromosome 12q22 (p = 3.3 x 10 (-4)) remained significant after Bonferroni correction. Meta-analysis with the original GWAS yielded the strongest association to date (p = 5.8 x 10 (7)). Although its functional significance is unclear, rs2060546 lies closest to NTN4, an axon guidance molecule expressed in developing striatum. Risk score analysis significantly predicted case-control status (p - 0.042), suggesting that many of these variants are true TS risk alleles