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First-trimester prenatal treatment with glucocorticoid (GC) dexamethasone (DEX) in pregnancies at risk for classic congenital adrenal hyperplasia (CAH) is associated with ethical dilemmas. Though effective in reducing virilisation in girls with CAH, it entails exposure to high doses of GC in fetuses that do not benefit from the treatment. The current paper provides an update on the literature on outcomes of prenatal DEX treatment in CAH cases and unaffected subjects. Long-term follow-up research is still needed to determine treatment safety. In addition, advances in early prenatal diagnostics for CAH and sex-typing as well as studies assessing dosing effects of DEX may avoid unnecessary treatment and improve treatment safety.

The measurement of vitamin D metabolites aids in assessing vitamin D status and in diagnosing disorders of calcium homeostasis. Most laboratories measure total 25-hydroxyvitamin D (25(OH)D), while others have taken the extra effort to measure 25(OH)D₂ and 25(OH)D₃ separately and additional metabolites such as 1,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D. The aim of this review is to provide an updated overview of the main markers of vitamin D metabolism, define the intended measurands, and discuss the advantages and disadvantages of the two most widely used assays, automated assays and liquid chromatography–tandem mass spectrometry (LC-MS/MS). Whether using the easy and fast automated assays or the more complex LC-MS/MS, one should know the pitfalls of the used technique in order to interpret the measurements. In conclusion, automated assays are unable to accurately measure 25(OH)D in all patient groups, including persons using D₂. In these cases, an LC-MS/MS method, when appropriately developed and standardized, produces a more reliable measurement.

The etiology, presentation and mortality of patients with primary adrenal insufficiency (PAI) in developing countries may differ from economically developed nations. However, information in this regard is scanty. The aim of this study was to determine the etiology and compare the clinical characteristics and mortality in infectious and autoimmune causes of PAI in Indian patients. All eligible (n = 89) patients (ages 15–83 years) diagnosed with PAI between 2006 and 2019 were studied. Patients were followed for a median duration of 5.9 (range 0.1–15.7) years. Eighty-six subjects underwent an abdominal computerized tomography scan or ultrasonography, and adrenal biopsy was performed in 60 patients. The most frequent etiologies of PAI were adrenal histoplasmosis (AH, 45%), adrenal tuberculosis (AT, 15%), autoimmunity (AI, 25%) and primary lymphoma (6%). Forty-two percent of patients presented with an acute adrenal crisis. AH and AT could not be differentiated on the basis of clinical features, except for a greater frequency of hepatomegaly–splenomegaly and type 2 diabetes mellitus (63% vs 15%, P < 0.01) in the former. Patients with an autoimmune etiology had a higher frequency of 21-hydroxylase antibodies (41% vs 3%) and autoimmune thyroid disease (46% vs 5%) vs those with infectious etiologies. Mortality was significantly higher in AH (45%) compared with AT (8%) or AI (5%) (P = 0.001). Causes of death included adrenal crises, progressive AH and unexplained acute events occurring at home. In conclusion, infections, especially AH, were the most frequent cause of PAI in north India. Despite appropriate therapy, AH had very high mortality as compared with AT and AI.

Diabetes is a complex metabolic disease. In recent years, diabetes and its chronic complications have become a health hotspot of global concern. It is very important to find promising therapeutic targets and directions. Ferroptosis is a new type of programmed cell death that is different from cell necrosis, apoptosis, and autophagy. Ferroptosis is mainly characterized by iron-dependent lipid peroxidation. With the reduction of the anti-oxidative capacity of cells, the accumulated reactive lipid oxygen species will cause oxidative cell death and lead to ferroptosis at lethal levels. Recent studies have shown that ferroptosis plays an important regulatory role in the initiation and development of diabetes, as well as various complications of diabetes. In this review, we will summarize new findings related to ferroptosis and diabetic complications and propose ferroptosis as a potential target for treating diabetic complications.

Oxidative stress plays an important role in the pathophysiology of gestational diabetes mellitus (GDM). We investigated the relationship between NADPH oxidase p22^phox subunit (CYBA) C242T (rs4673) and myeloperoxidase (MPO) G-463A (rs2333227) genetic variants and GDM in 719 patients with GDM and 1205 control women. Clinical, metabolic, and oxidative stress parameters were analyzed. We found that frequencies of the A allele (15.6% vs 12.3%) and GA + AA genotype (28.5% vs 23.2%) of the MPO G-463A variation were significantly higher in patients with GDM than in the control women (OR = 1.318, 95% CI: 1.068–1.625, P = 0.010 for the dominant model; OR = 1.999, 95% CI: 1.040–3.843, P = 0.034 for the recessive model; OR = 1.320, 95% CI: 1.095–1.591, P = 0.004 for the allele model). Genotype GA + AA remained a significant predictor of GDM in a logistic regression model including age and BMI at delivery (OR = 1.282, 95% CI: 1.037‒1.583, P = 0.021). Furthermore, the ‒463A allele was associated with higher TG and the 242T allele was related to higher pre-pregnancy BMI and oxidative stress index in all subjects (P < 0.05). The 242T allele was also associated with higher homeostatic model assessment of insulin resistance but lower serum total antioxidant capacity in patients with GDM (P < 0.05). We conclude that the MPO G-463A, but not the CYBA C242T, genetic variation is associated with an increased risk of GDM in Chinese women. These two genetic polymorphisms may be linked to obesity, dyslipidemia, insulin resistance, and oxidative stress.

The 3rd International Workshop on Klinefelter Syndrome, Trisomy X, and 47,XYY syndrome was held in Leiden, the Netherlands, on September 12–14, 2022.

Here, we review new data presented at the workshop and discuss scientific and clinical trajectories. We focus on shortcomings in knowledge and therefore point out future areas for research.

We focus on the genetics and genomics of supernumerary sex chromosome syndromes with new data being presented. Most knowledge centre specifically on Klinefelter syndrome, where aspects on testosterone deficiency and the relation to bone, muscle and fat were discussed, as was infertility and the treatment thereof. Both trisomy X and 47,XYY syndrome are frequently affected by infertility.

Transitioning of males with Klinefelter syndrome was addressed, as this seemingly simple process in practise is often difficult.

It is now realized that neurocognitive changes are pervasive in all supernumerary sex chromosome syndromes, which were extensively discussed. New intervention projects were also described, and exciting new data concerning these were presented.

Advocacy organizations were present, describing the enormous burden carried by parents when having to explain their child’s specific syndrome to most professionals whenever in contact with health care and education systems. It was also pointed out that most countries do not have health care systems that diagnose patients with supernumerary sex chromosome syndromes, thus pinpointing a clear deficiency in the current genetic testing and care models.

At the end of the workshop, a roadmap towards the development of new international clinical care guidelines for Klinefelter syndrome was decided.