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Background: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) may affect the male reproductive system as it uses angiotensin‐converting enzyme (ACE)2, which is expressed in testicular tissue, as an entry point into the cell. Few studies have evaluated the long‐term effects of mild coronavirus disease 2019 (COVID‐19) on testicular function, and insulin‐like factor 3 (INSL3) levels have not previously been assessed during acute SARS‐CoV‐2 infection. Objectives: The aim of the study was to assess the impact of acute SARS‐CoV‐2 infection on testicular function including INSL3 and the presence of SARS‐CoV‐2 RNA in semen in non‐hospitalised men with mild COVID‐19. Materials and methods: This longitudinal study included 36 non‐hospitalised SARS‐CoV‐2‐positive men (median age 29 years). Inclusion was within seven days following a positive SARS‐CoV‐2 reverse‐transcription polymerase chain reaction test. Reproductive hormone levels, semen parameters, and the presence of SARS‐CoV‐2 RNA in oropharyngeal and semen samples were assessed during acute SARS‐CoV‐2 infection (baseline) and at three‐ and six‐month follow‐up. Wilcoxon matched‐pair signed‐rank (two samples) test was used to assess time‐related alterations in reproductive hormone levels and semen parameters. Results: Lower plasma testosterone (T) (total and calculated free (c‐fT)) and higher luteinising hormone (LH) concentrations were observed during acute SARS‐CoV‐2 infection (baseline) compared to three‐ and six‐month follow‐up. Consequently, ratios of c‐fT/LH were lower at baseline compared to three‐ and six‐month follow‐up (p < 0.001 and p = 0.003, respectively). Concomitantly, lower INSL3 concentrations were observed at baseline compared to three‐month follow‐up (p = 0.01). The total number of motile spermatozoa was also lower at baseline compared to six‐month follow‐up (p = 0.02). The alterations were detected irrespective of whether the men had experienced SARS‐CoV‐2‐related fever episodes or not. No SARS‐CoV‐2 RNA was detected in semen at any time point. Discussion and conclusion: This study showed a reduction in testicular function, which was for the first time confirmed by INSL3, in men mildly affected by SARS‐CoV‐2 infection. The risk of transmission of SARS‐CoV‐2 RNA via semen seems to be low. Febrile episodes may impact testicular function, but a direct effect of SARS‐CoV‐2 cannot be excluded. [ABSTRACT FROM AUTHOR]

Context Nonprogressive premature thelarche (PT) is a self-limiting variant of early puberty, while idiopathic central precocious puberty (ICPP) is a disorder that causes progressive development of secondary sexual characteristics and often requires treatment. The diagnostic differentiation between these conditions is important but can be challenging since they often both initially present clinically with isolated breast development. Objective To describe relevant clinical variables in a large cohort of girls referred for early puberty, and to evaluate clinical and biochemical parameters to distinguish between girls with ICPP and PT. Methods This retrospective study included 1361 girls referred with signs of early puberty to a single, tertiary center from 2009 to 2019. We evaluated clinical presentation, medical history, growth velocity, bone age, hormonal serum concentrations, and gonadotropin-releasing hormone (GnRH) test results. Results Central precocious puberty was diagnosed in 11% (ICPP: n = 143, organic CPP: n = 11) girls, whereas 8% (n = 91 girls) presented with PT. Receiver operating characteristic (ROC) analysis showed several biochemical and anthropometric markers as potential parameters to differentiate between ICPP and PT; however, none were individually adequate. Principal component analysis (PCA)–derived clinical and hormone profiles could predict girls with ICPP from girls with PT with a specificity of 90% and sensitivity of 84%, outperforming any single marker. Conclusion Differentiation of girls with ICPP and PT can be supported by individual clinical and biochemical parameters. However, dimension reduction of clinical and hormonal profiles by PCA improved the diagnostic value, which in the future may support the diagnostic process as a supplement to the GnRH test in evaluation of pubertal disorders. [ABSTRACT FROM AUTHOR]

Context: Supraphysiological serum insulin-like growth factor-I (IGF-I) concentrations have been a matter of concern in children treated with GH because high IGF-I levels were associated with risk of later disease in former epidemiological studies. Objective: To determine whether a single IGF-I measurement reliably reflects lifetime IGF-I exposure we evaluated intraindividual longitudinal tracking of IGF-I and IGF-binding protein-3 (IGFBP-3) levels and we estimated cumulative lifetime exposure to IGF-I in healthy and GH-treated individuals. Methods: We included 6459 healthy participants (cross-sectional=5326; longitudinal=1133) aged 0-76 years (9963 serum samples) and 9 patients born small-for-gestational-age (SGA) with 238 serum samples during GH treatment. Intraindividual tracking of IGF-I and IGFBP-3 (SD score [SDS]) was determined by intraclass correlation coefficients (ICCs). Cumulative lifetime IGF-I exposure was estimated by area under the curve of the predicted SDS trajectory from 0 to 76 years. Results: For IGF-I (SDS), ICCs were 0.50 (95% CI, 0.47-0.53) for male and 0.53 (0.50-0.56) for female participants. Lifetime IGF-I exposure was significantly higher in female (mean 12 723±3691 SD) than in male participants (12 563±3393); P=0.02. In SGA children, treatment with GH increased the lifetime exposure to IGF-I from 9512±1889 to 11 271±1689, corresponding to an increase in lifetime IGF-I trajectory from -0.89 SD±0.57 to -0.35 SD±0.49. Conclusion: Because IGF-I and IGFBP-3 levels track throughout life, a single measurement reliably reflects lifetime exposure. GH therapy increased the lifetime exposure to IGF-I only slightly and it remained below the average lifetime exposure in the reference population. [ABSTRACT FROM AUTHOR]

Background: With the development of molecular high-throughput assays (i.e. next generation sequencing), the knowledge on the contribution of genetic and epigenetic alterations to the etiology of inherited endocrine disorders has massively expanded. However, the rapid implementation of these new molecular tools in the diagnostic settings makes the interpretation of diagnostic data increasingly complex.Main Body: This joint paper of the ENDO-ERN members aims to overview chances, challenges, limitations and relevance of comprehensive genetic diagnostic testing in rare endocrine conditions in order to achieve an early molecular diagnosis. This early diagnosis of a genetically based endocrine disorder contributes to a precise management and helps the patients and their families in their self-determined planning of life. Furthermore, the identification of a causative (epi)genetic alteration allows an accurate prognosis of recurrence risks for family planning as the basis of genetic counselling. Asymptomatic carriers of pathogenic variants can be identified, and prenatal testing might be offered, where appropriate.Conclusions: The decision on genetic testing in the diagnostic workup of endocrine disorders should be based on their appropriateness to reliably detect the disease-causing and -modifying mutation, their informational value, and cost-effectiveness. The future assessment of data from different omic approaches should be embedded in interdisciplinary discussions using all available clinical and molecular data. [ABSTRACT FROM AUTHOR]

Using measurements of circulating anti-Müllerian hormone (AMH) in diagnosing and managing reproductive disorders in pediatric patients requires thorough knowledge on normative values according to age and gender.We provide age- and sex-specific reference ranges for the Immunotech assay and conversion factors for theDSL andGeneration II assays.With this tool in hand, the pediatrician can use serum concentrations of AMH when determining the presence of testicular tissue in patients with bilaterally absent testes or more severe Disorders of Sex Development (DSD). Furthermore, AMH can be used as a marker of premature ovarian insufficiency (POI) in both Turner Syndrome patients and in girls with cancer after treatment with alkylating gonadotoxic agents. Lastly, its usefulness has been proposed in the diagnosis of polycystic ovarian syndrome (PCOS) and ovarian granulosa cell tumors and in the evaluation of patients with hypogonadotropic hypogonadism. [ABSTRACT FROM AUTHOR]

In the context of severe coronavirus disease 2019 (COVID-19) illness, we examined endogenous glucocorticoid concentrations, steroidogenic enzyme activity, and their correlation with inflammation and patient outcomes. This observational study included 125 hospitalized COVID-19 patients and 101 healthy individuals as a reference group. We utilized LC-MS to assess serum concentrations of 11-deoxycortisol, cortisol, and cortisone, as well as activities of steroidogenic enzymes (11β-hydroxylase and 11β-hydroxysteroid-dehydrogenase type 1). Cox proportional hazards regression analysis and competing risk analysis were employed to analyze associations between glucocorticoid concentrations and outcomes, adjusting for relevant factors. In patients with COVID-19, cortisol concentrations were higher and cortisone concentrations were lower compared to the reference group, while 11-deoxycortisol concentrations were similar. Steroidogenic enzyme activity favored cortisol production. Correlations between glucocorticoid concentrations and inflammatory markers were low. A doubling in concentrations cortisol, was associated with increased 90-day mortality and mechanical ventilation (HR: 2.40 95% CI: (1.03-5.59) , P = 0.042 and HR: 3.83 (1.19-12.31), P = 0.024). A doubling in concentrations of 11-deoxycortisol was also associated to mortality (HR: 1.32 (1.05-1.67), P = 0.018), whereas concentrations of cortisone were associated with mechanical ventilation (HR: 5.09 (1.49-17.40), P = 0.009). In conclusion, serum concentrations of glucocorticoid metabolites were altered in patients hospitalized with severe COVID-19, and steroidogenic enzyme activity resulting in the conversion of cortisone to biologically active cortisol was preserved, thus not favoring critical-illness-related corticosteroid insufficiency at the enzymatic level. Glucocorticoid release did not counterbalance the hyperinflammatory state in patients with severe COVID-19. High serum concentrations of 11-deoxycortisol and cortisol were associated with 90-day mortality, and high serum concentrations of cortisol and cortisone were associated with mechanical ventilation.

Objective: To describe the natural history of inhibin B throughout life according to sex, age, and pubertal development., Methods: Based on serum samples from 2707 healthy controls aged 0 to 80 years, sex- and age-specific reference ranges of inhibin B concentrations were constructed. Concentrations were evaluated according to pubertal development and use of oral contraceptives (OCs). Also, measurements from 42 patients with Klinefelter syndrome were included., Results: In both sexes, inhibin B concentrations were high during minipuberty, decreased in childhood, and increased significantly from Tanner stages B1 to B3 (peak: B4) in females and from G1 to G3 (peak: G3) in males. Despite variations in menstruating females, inhibin B concentrations remained relatively constant after puberty, until becoming unmeasurable at menopause. Despite a modest decrease, the inhibin B concentration in males remained relatively high from puberty onwards. At any age, males had highest concentrations. Inhibin B standard deviation (SD) scores were lower in OC-users (median SD score = -0.88) than in non-users (SD score = 0.35), p < 0.001. In patients with Klinefelter syndrome, inhibin B concentrations spanned the reference range until around 15 years of age, where they decreased to subnormal or unmeasurable levels., Conclusion: Valuable sex- and age-specific reference data for inhibin B concentrations were provided. In OC-users, decreased concentrations of inhibin B underlined the ovaries as the only place of inhibin B production. In patients with Klinefelter syndrome, the decline in inhibin B concentrations at puberty underlined the shift in regulation of inhibin B production at pubertal onset., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Adult patients with Klinefelter syndrome (KS) are characterized by a highly variable phenotype, including tall stature, obesity, and hypergonadotropic hypogonadism, as well as an increased risk of developing insulin resistance, metabolic syndrome, and osteoporosis. Most adults need testosterone replacement therapy (TRT), whereas the use of TRT during puberty has been debated. In this retrospective, observational study, reproductive hormones and whole-body dual-energy x-ray absorptiometry-derived body composition and bone mineral content were standardized to age-related standard deviation scores in 62 patients with KS aged 5.9-20.6 years. Serum concentrations of total testosterone and inhibin B were low, whereas luteinizing hormone and follicle-stimulating hormone were high in patients before TRT. Despite normal body mass index, body fat percentage and the ratio between android fat percentage and gynoid fat percentage were significantly higher in the entire group irrespective of treatment status. In patients evaluated before and during TRT, a tendency toward a more beneficial body composition with a significant reduction in the ratio between android fat percentage and gynoid fat percentage during TRT was found. Bone mineral content (BMC) did not differ from the reference, but BMC corrected for bone area was significantly lower when compared to the reference. This study confirms that patients with KS have an unfavorable body composition and an impaired bone mineral status already during childhood and adolescence. Systematic studies are needed to evaluate whether TRT during puberty will improve these parameters.

Introduction: Failure to thrive, defined as insufficient weight gain according to age, is a well-known condition among infants and toddlers. The aim of the study was to investigate the prevalence of diagnosed failure to thrive and possible comorbidity in hospitalised 0-2 year-old children in the County of Copenhagen., Material and Methods: It resulted from inquiries sent to all paediatric departments in Denmark that the most frequently used ICD-10 diagnoses for failure to thrive were R62.8, E64.9, and E34.3. Data concerning patients with these three diagnoses hospitalised in two paediatric departments in the County of Copenhagen during a two-year period were drawn from the Patient Registry System. The following parameters were registered: sex, age, diagnoses, hospitalizations, and address., Results: Among referred children below the age of two years, 173 or 4% were diagnosed with failure to thrive. Girls were in excess, the ratio girls-boys being 107:66. More than half, 60% were below one year of age, 40% were below six months of age. We found equal distribution of index children from municipalities with low and high incomes. The diagnosis R62.8 was found in 170 patients, of whom 155 had the diagnosis as either main diagnosis or side diagnosis. Out of these 155 patients 46% had additional somatic diagnosis, whereas 5% had child psychiatric comorbidity., Discussion: Failure to thrive was diagnosed in 4% of hospitalised children under two years of age. Nearly half of the children diagnosed with failure to thrive had a comorbid somatic diagnosis, whereas only a few was diagnosed with psychiatric or social disturbances.