Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
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Department of Paediatric Endocrinology, Astrid Lindgren Children Hospital, Karolinska University Hospital, Stockholm, Sweden
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Department of Pediatric Endocrinology, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France
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Consensus Conference on Intersex organized by the Lawson Wilkins Pediatric Endocrine Society & the European Society for Paediatric Endocrinology . Consensus statement on management of intersex disorders. International Consensus Conference on Intersex
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Japan Endocrine Society
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European Society for Pediatric Endocrinology
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European Society of Endocrinology
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Wellcome-MRC Institute of Metabolic Science, University of Cambridge & Addenbrooke’s Hospital, Cambridge Biomedical Campus, Cambridge, UK
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Brazilian Society of Endocrinology and Metabolism
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Endocrine Society of Australia
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Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, UK
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Pituitary Society
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members: Endocrine Society, European Society of Endocrinology, Pituitary Society, Society for Endocrinology, European Society for Paediatric Endocrinology, Endocrine Society of Australia, Brazilian Endocrine Society, and Japan Endocrine Society, and is
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Sphingosine-1-phosphate lyase (SGPL1) insufficiency syndrome (SPLIS) is an autosomal recessive multi-system disorder, which mainly incorporates steroid-resistant nephrotic syndrome and primary adrenal insufficiency. Other variable endocrine manifestations are described. In this study, we aimed to comprehensively annotate the endocrinopathies associated with pathogenic SGPL1 variants and assess for genotype–phenotype correlations by retrospectively reviewing the reports of endocrine disease within our patient cohort and all published cases in the wider literature up to February 2022. Glucocorticoid insufficiency in early childhood is the most common endocrine manifestation affecting 64% of the 50 patients reported with SPLIS, and a third of these individuals have additional mineralocorticoid deficiency. While most individuals also have nephrotic syndrome, SGPL1 variants also account for isolated adrenal insufficiency at presentation. Primary gonadal insufficiency, manifesting with microphallus and cryptorchidism, is reported in less than one-third of affected boys, all with concomitant adrenal disease. Mild primary hypothyroidism affects approximately a third of patients. There is paucity of data on the impact of SGPL1 deficiency on growth, and pubertal development, limited by the early and high mortality rate (approximately 50%). There is no clear genotype–phenotype correlation overall in the syndrome, with variable disease penetrance within individual kindreds. However, with regards to endocrine phenotype, the most prevalent disease variant p.R222Q (affecting 22%) is most consistently associated with isolated glucocorticoid deficiency. To conclude, SPLIS is associated with significant multiple endocrine disorders. While endocrinopathy in the syndrome generally presents in infancy, late-onset disease also occurs. Screening for these is therefore warranted both at diagnosis and through follow-up.
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diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop . Journal of Clinical
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Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
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was designed pertaining to the content of vitamin D supplementation policies, practices, infant health care and socioeconomic factors and policy implementation strategies. The questions were based on expert opinion (from paediatric endocrinology and
Department of Endocrinology, St James’s Hospital, Dublin, Ireland
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Department of Endocrinology, University of Manchester, Manchester, UK
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Department of Paediatric Endocrinology & Diabetes, Newcastle-upon-Tyne Hospitals, Newcastle upon Tyne, UK
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Endocrine Research Group, Institute of Genetic Medicine, University of Newcastle-upon-Tyne, Newcastle upon Tyne, UK
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We present herein our 20-year experience of pubertal induction in apubertal older (median age 56 years; range 38.4–69.5) men with congenital hypogonadotrophic hypogonadism (n = 7) using a simple fixed-dose and fixed-interval intramuscular testosterone that we originally pioneered in relation to achieving virilisation of natal female transgender men. This regime was effective and well tolerated, resulting in complete virilisation by around 1 year after treatment initiation. No physical or psychological adverse effects were encountered in this group of potentially vulnerable individuals. There were no abnormal excursions of laboratory parameters and extended follow-up beyond the first year of treatment revealed remarkable improvements in bone density. We highlight advantages to both patients and physicians of this regime in testosterone-naïve older men with congenital hypogonadism and discourage the over-rigid application to such patients of treatment algorithms derived from paediatric practice in relation to the evaluation and management in younger teenagers with delayed puberty of uncertain cause.
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
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John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
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John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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Glucocorticoids (GCs) reduce inflammation and preserve muscle function in boys with Duchenne muscular dystrophy (DMD) but cause pubertal delay. Pubertal induction with testosterone is recommended but longer-term outcome is unknown.
Objective
To assess hypothalamic–pituitary–gonadal axis, muscle volume and function 5 years after pubertal induction.
Methods
A prospective observational follow-up of a clinical study was conducted. 15 GC-treated males with DMD were treated with incremental testosterone for 2 years (end of regimen +2 years) then evaluated at +2.5 years and +5 years (final follow-up ~3 years after last injection). Data collected included testicular volume (TV), gonadotrophin, testosterone, inhibin B, muscle function, and limb muscle MRI.
Results
Participants were 18.7 years (s.d. 1.6) at the final follow-up and had been on GC for 11.2 years (s.d. 2.2). Testosterone levels were similar at +2.5 years (8.6 nmol/L (s.d. 3.4) and 5 years (11.0 nmol/L (s.d. 6.1). TV increased from 2.8 mL (s.d. 0.9) at +2 years to 7.1 mL (s.d. 1.8) then 10.6 mL (s.d. 3.5) at +2.5 years and +5.0 years (P < 0.001). Inhibin B levels increased from 55.6 pg/mL (s.d. 47.0) at baseline to 158.2 pg/mL (s.d.87.6), P =0.004 at 5 years but remained lower than reference values (mean 305 pg/mL). Muscle contractile bulk decreased.
Interpretation
Pubertal induction with testosterone in DMD is associated with HPG axis activation and ongoing increases in inhibin B, TV, and testosterone concentrations. Some patients have normal levels which is promising regarding future fertility. Given the beneficial impact of testosterone on bone health, muscle, and well-being, monitoring testosterone levels in this population and supplementation of sub-optimal levels is important.
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Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
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Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden
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Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan Italy
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Department of Medicine, Haukeland University Hospital, Bergen, Norway
Department of Medicine, Karolinska Institutet, Stockholm, Sweden
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Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
Developmental Endocrinology Research Group, University of Glasgow, Glasgow, United Kingdom
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–2020) and supported by ENDO-ERN (European Reference Network on Rare Endocrine Conditions), European Society of Endocrinology (ESE) and European Society for Paediatric Endocrinology (ESPE) and is open to all centres across the world. Following a discussion
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Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy
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Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy
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Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy
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Objective
This retrospective study aimed to evaluate children observed for suspected precocious puberty in five Italian centers of Pediatric Endocrinology during the first wave of coronavirus disease 2019 pandemic (March–September 2020), compared to subjects observed in the same period of the previous year.
Design
The study population (490 children) was divided according to the year of observation and final diagnosis: transient thelarche, non-progressive precocious puberty, central precocious puberty (CPP), or early puberty.
Results
Between March and September 2020, 338 subjects were referred for suspected precocious puberty, compared to 152 subjects in the same period of 2019 (+122%). The increase was observed in girls (328 subjects in 2020 vs 140 in 2019, P < 0.05), especially during the second half of the period considered (92 girls from March to May vs 236 girls from June to September); while no difference was observed in boys (10 subjects in 2020 vs 12 in 2019). The percentage of girls with confirmed CPP was higher in 2020, compared to 2019 (135/328 girls (41%) vs 37/140 (26%), P < 0.01). Anthropometric and hormonal parameters in 2019 and 2020 CPP girls were not different; 2020 CPP girls showed more prolonged use of electronic devices and a more sedentary lifestyle both before and during the pandemic, compared to the rest of the 2020 population.
Conclusions
The present findings corroborate the recently reported association between the complex lifestyle changes related to the lockdown and a higher incidence of CPP in Italian girls.
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Background
Hypogonadism is a key feature of Prader–Willi syndrome (PWS) but clear strategies for hormone replacement are lacking.
Objective
To evaluate the gonadal status and outcome in patients attending a Scottish PWS clinic from 1991 to 2019.
Methods
In 93 (35F:56M) patients, median follow-up 11.2 years, gonadal and pubertal status were assessed clinically. Pelvic ultrasound findings and basal/stimulated gonadotrophins were compared with age-matched controls.
Results
Females:of 22 patients aged > 11, 9 had reached B4–5, while 5 were still at B2–3, and 6 remained prepubertal. Eight patients experienced menarche aged 9.8–21.4 years, none with a normal cycle. Uterine length and ovarian volumes were normal but uterine configuration remained immature, with low follicular counts. Gonadotrophins were unremarkable, serum oestradiol 129 (70–520) pmol/L. Only 5 patients received oestrogen replacement. Males:fifty-four (96%) patients were cryptorchid (9 unilateral). Weekly hCG injections resulted in unilateral/bilateral descent in 2/1 of 25 patients. Of 37 boys aged > 11, 14 (9 with failed/untreated bilateral cryptorchidism) failed to progress beyond G1, 15 arrested at G2–3 (testes 3–10 mL), and 8 reached G4–5. Gonadotrophins were unremarkable except in boys at G2–5 in whom FSH was elevated: 12.3/27.3 vs 3.25/6.26 U/L in controls (P < 0.001). In males aged > 13, testosterone was 3.1 (0.5–8.4) nmol/L. Androgen therapy, given from 13.5 to 29.2 years, was stopped in 4/24 patients owing to behavioural problems.
Conclusion
Despite invariable hypogonadism, few females and only half the males with PWS in this study received hormone replacement. Double-blind placebo-controlled crossover trials of sex steroids are required to address unproven behavioural concerns.
