IntroductionThe COVID-19 pandemic forced the Italian government to issue extremely restrictive measures on daily activities since 11 March 2020 (‘lockdown’), which may have influenced the metabolic control of type 1 diabetes mellitus (T1D). The aims of the study were to investigate continuous glucose monitoring (CGM) metrics in children and adults with T1D during lockdown and to identify their potentially related factors.Research design and methodsWe enrolled 130 consecutive patients with T1D (30 children (≤12 years), 24 teenagers (13–17 years), and 76 adults (≥18 years)) using either Dexcom or FreeStyle LibreCGM>70% during the study period, without hybrid closed-loop insulin pump. CGM metrics during the 20 days before and the 20 days after lockdown were calculated. By telephonic contact, we performed validated physical activity and perceived stress questionnaires.ResultsIn children, significantly lower glucose SD (SDglu) (p=0.029) and time below range (TBR)<54 mg/dL (TBR2) (p=0.029) were detected after lockdown. CGM metrics were comparable in teenagers before and during lockdown. After lockdown, adults improved significantly time in range (TIR) 70–180 mg/dL (p<0.001) and remaining metrics, except percent coefficient of variation and TBR2. In adults, considering the changes in SDglu and TIR occurred before and during lockdown, we identified a group with improved TIR and SDglu who performed more physical activity, one with improved glucose variability who was younger than the other patients, and one with worsened glucose variability who showed higher perceived stress than others.ConclusionIn patients with T1D during lockdown, CGM metrics mostly improved in children and adults, whereas it was unchanged in teenagers. In adults, age, physical activity, and perceived stress may be relevant contributing factors.

The term ‘differences of sex development’ (DSD) refers to a group of congenital conditions that are associated with atypical development of chromosomal, gonadal, or anatomical sex. Disorders of steroidogenesis comprise autosomal recessive conditions that affect adrenal and gonadal enzymes and are responsible for some conditions of 46,XX DSD where hyperandrogenism interferes with chromosomal and gonadal sex development. Congenital adrenal hyperplasias (CAHs) are disorders of steroidogenesis that mainly involve the adrenals (21-hydroxylase and 11-hydroxylase deficiencies) and sometimes the gonads (3-beta-hydroxysteroidodehydrogenase and P450-oxidoreductase); in contrast, aromatase deficiency mainly involves the steroidogenetic activity of the gonads. This review describes the main genetic, biochemical, and clinical features that apply to the abovementioned conditions. The activities of the steroidogenetic enzymes are modulated by post-translational modifications and cofactors, particularly electron-donating redox partners. The incidences of the rare forms of CAH vary with ethnicity and geography. The elucidation of the precise roles of these enzymes and cofactors has been significantly facilitated by the identification of the genetic bases of rare disorders of steroidogenesis. Understanding steroidogenesis is important to our comprehension of differences in sexual development and other processes that are related to human reproduction and fertility, particularly those that involve androgen excess as consequence of their impairment.

Sexual development is a complex mechanism activated by the hypothalamic-pituitary-gonadal axis. Over the last one hundred years there has been a decline in the age at puberty onset in industrialised countries. Some Italian studies showed an increase in diagnoses of Central Precocious Puberty (CPP) during the COVID-19 pandemic. It is thus supposed that in this period there was an increased impact of factors that can influence pubertal development. Our retrospective monocentric study aimed to confirm the existence of this phenomenon and analysed possible related factors. We retrospectively evaluated clinical, laboratory, radiological and ultrasound (US) data of 154 girls referred to our Tertiary Centre of Paediatric Endocrinology from January 2019 to April 2021 for different forms of Precocious Puberty. We subdivided the cases into subgroups according to the final diagnosis: CPP, Early Puberty (EP), isolated thelarche and isolated pubarche. The observation period was subdivided into: Period 1, before lockdown (1 January 2019 – 8 March 2020) and Period 2, lockdown and the following months (9 March 2020 – 30 April 2021). Period 2 was further divided into “restrictive lockdown period” (Period 2.1) (March 2020 – 14 June 2020, in which the schools were closed) and “less restrictive lockdown period” (Period 2.2) (15 June 2020 – 30 April 2021). We analysed data regarding the use of electronic devices before and during lockdown in a group of girls with CPP diagnosed in Period 2 and we compared the data with that of a control group. Our data show an increase in the number of new diagnoses of CPP during lockdown and in the following months, compared with the previous period. We also detected a higher use of PCs and smartphones in girls with CPP diagnosed in Period 2, compared with the control group. The percentage of the presence of endometrial rhyme detected during the pelvic ultrasound was higher in girls with CPP in Period 2, compared with the previous period. Based on our data we assume there was an environmental effect on pubertal timing that calls our attention to factors such as food, use of electronic devices and stress. We will need further studies to better understand this data.

Congenital adrenal hyperplasia includes autosomal recessive conditions that affect the adrenal cortex steroidogenic enzymes (cholesterol side-chain cleavage enzyme; 3β-hydroxysteroid dehydrogenase; 17α-hydroxylase/17,20 lyase; P450 oxidoreductase; 21-hydroxylase; and 11β-hydroxylase) and proteins (steroidogenic acute regulatory protein). These are located within the three major pathways of the steroidogenic apparatus involved in the production of mineralocorticoids, glucocorticoids, and androgens. Many countries have introduced newborn screening program (NSP) based on 17-OH-progesterone (17-OHP) immunoassays on dried blood spots, which enable faster diagnosis and treatment of the most severe forms of 21-hydroxylase deficiency (21-OHD). However, in several others, the use of this diagnostic tool has not yet been implemented and clinical diagnosis remains challenging, especially for males. Furthermore, less severe classic forms of 21-OHD and other rarer types of CAHs are not identified by NSP. The aim of this mini review is to highlight both the main clinical characteristics and therapeutic options of these conditions, which may be useful for a differential diagnosis in the neonatal period, while contributing to the biochemical evolution taking place in the steroidogenic field. Currently, chromatographic techniques coupled with tandem mass spectrometry are gaining attention due to an increase in the reliability of the test results of NPS for detecting 21-OHD. Furthermore, the possibility of identifying CAH patients that are not affected by 21-OHD but presenting elevated levels of 17-OHP by NSP and the opportunity to include the recently investigated 11-oxygenated androgens in the steroid profiles are promising tools for a more precise diagnosis and monitoring of some of these conditions.

Background: Classic criteria for a maturity-onset diabetes of the young (MODY) diagnosis are often unable to identify all subjects, and traditional Sanger sequencing, using a candidate gene approach, leads to a high prevalence of missed genetic diagnosis, classified as MODY-X. Next generation sequencing (NGS) panels provide a highly sensitive method even for rare forms. Methods: We investigated 28 pediatric subjects suspected for MODY-X, utilizing a 15-gene NGS panel for monogenic diabetes (MD). Results: NGS detected variants of uncertain significance (VUS), likely pathogenic or pathogenic for rarer subtypes of MODY, in six patients. We found variants in the wolframin gene (WFS1), traditionally not considered in MD genetic screening panels, in three patients; KCNJ11 gene mutation, typically responsible for neonatal diabetes and rarely causing isolated diabetes in adolescents; INS gene mutation; a variant in the HNF1B gene in a young male with diabetes on sulfonylurea treatment. Conclusion: In our cohort, the availability of an NGS panel for MD was determined for the correct identification of MD subtypes in six patients with MODY-X. Our study underlines how a precise diagnosis utilizing NGS may have an impact on the management of different forms of MODY and, thus, lead to a tailored treatment and enable genetic counselling of other family members.