About

Sally Radovick, MS, MD, is a Professor of Pediatrics and the Director of the Clinical and Translational Research Institute at the University of Arizona. She specializes in pediatric diabetes, growth, development, and pubertal disorders in children. Dr. Radovick has conducted biomedical research and mentored over 75 graduate students, postdoctoral fellows, and early career faculty for 30 years, receiving NIH funding as a mentor for numerous mentees. Her research focuses on the regulation of the gonadotropin-releasing hormone (GnRH) gene, which plays a central role in controlling the onset of puberty. She was the first to generate GnRH-expressing neuronal cell lines and map the cellular regulation of this gene in vitro. Her work includes developing genetically modified mouse models to elucidate mechanisms of GnRH secretion regulation in response to neuroendocrine stimulation and sex steroid feedback, with recent studies implicating kisspeptin in pubertal onset, reproductive cycling, and its potential link to obesity and reproductive dysfunction. Additionally, her research characterizes transcription factors essential for pituitary development, providing insights into growth, metabolism, and reproductive health. Dr. Radovick's long-term NIH-supported studies include epidemiologic research on the metabolic effects of premature birth and investigations into the genetics of short stature, pubertal development, and reproductive health.

Research topics

• Internal medicine
• Endocrinology
• Medicine
• Gynecology
• Oncology
• Biology

Selected publications

• Data from: Kisspeptin made in the preoptic area is required for normal estradiol-induced LH surges and optimal fertility in females.

  DRYAD · 2026-04-30

  datasetOpen access

  Ovulation is triggered by a surge in luteinizing hormone (LH) secretion from the pituitary. The LH surge is itself driven by a surge in GnRH release induced by estrogen positive feedback action in the hypothalamus. While ERα-expressing kisspeptin (Kiss1) neurons in the preoptic area (in mice, the rostral periventricular region of the third ventricle [RP3V]) are proposed to mediate this estrogen positive feedback event, the functional necessity of RP3V-derived kisspeptin for the LH surge has not been directly tested. Here we leveraged Cre/lox technology and the known high co-expression of tyrosine hydroxylase (TH) with Kiss1 in only the RP3V region to generate novel transgenic mice with selective knockout (KO) of the Kiss1 gene in just RP3V neurons (Kiss1RP3V KO mice). In situ hybridization confirmed a significant 70% reduction in cells expressing Kiss1 in the RP3V region, but not in the arcuate nucleus, along with no change in RP3V Th expression. Kiss1RP3V KO females exhibited normal pubertal timing and estrous cycles. However, functional interrogation of the ability of Kiss1RP3V KO females to generate an estradiol-induced LH surge demonstrated markedly blunted LH surges and reduced occurrence of surges, in line with the partial Kiss1RP3V knockout in this group. Correspondingly, fertility assessment revealed significant subfertility, including fewer and smaller litters. This subfertility is consistent with the observed impaired LH surges, though the downstream ovarian mechanism(s) underlying the smaller litters still needs to be determined. These findings provide direct causal evidence that RP3V-derived kisspeptin is essential for normal LH surge magnitude and optimal fertility.

  PublisherDOI

• Kisspeptin made in the preoptic area is required for normal estradiol-induced LH surges and optimal fertility in females

  Endocrinology · 2026-04-30

  articleOpen access

  Ovulation is triggered by a surge in luteinizing hormone (LH) secretion from the pituitary. The LH surge is itself driven by a surge in gonadotropin-releasing hormone release induced by estrogen positive feedback action in the hypothalamus. While ERα-expressing kisspeptin (Kiss1) neurons in the preoptic area (in mice, the rostral periventricular region of the third ventricle [RP3V]) are proposed to mediate this estrogen positive feedback event, the functional necessity of RP3V-derived kisspeptin for the LH surge has not been directly tested. Here we leveraged Cre/lox technology and the known high co-expression of tyrosine hydroxylase (TH) with Kiss1 in only the RP3V region to generate novel transgenic mice with selective knockout (KO) of the Kiss1 gene in just RP3V neurons (Kiss1RP3V KO mice). In situ hybridization confirmed a significant 70% reduction in cells expressing Kiss1 in the RP3V region, but not in the arcuate nucleus, along with no change in RP3V Th expression. Kiss1RP3V KO females exhibited normal pubertal timing and estrous cycles. However, functional interrogation of the ability of Kiss1RP3V KO females to generate an estradiol-induced LH surge demonstrated markedly blunted LH surges and reduced occurrence of surges, in line with the partial Kiss1RP3V knockout in this group. Correspondingly, fertility assessment revealed significant subfertility, including fewer and smaller litters. This subfertility is consistent with the observed impaired LH surges, though the downstream ovarian mechanism(s) underlying the smaller litters still needs to be determined. These findings provide direct causal evidence that RP3V-derived kisspeptin is essential for normal LH surge magnitude and optimal fertility.

  PublisherOA PDFDOI

• Biomarkers of GH deficiency identified in untreated and GH-treated Pit-1 mutant mice

  Frontiers in Endocrinology · 2025-04-30 · 1 citations

  articleOpen accessSenior author

  Background: Growth Hormone Deficiency (GHD) is marked by insufficient growth hormone (GH) production, leading to disruptions in growth and metabolism. Its diagnosis is challenging due to the lack of sensitive, specific tests. To address this, we used a novel mouse model with a POU1F1 (Pit-1) gene mutation (K216E). This study aimed to identify metabolic biomarkers of GHD and assess their responsiveness to GH therapy, alongside pathway analysis to uncover disrupted metabolic pathways. Methods: mouse model was validated for GHD through assessments of GH production, growth, and body composition. Metabolomic profiling was conducted to identify biomarkers, while pathway analysis examined disrupted metabolic pathways and their response to GH treatment. This approach aimed to improve understanding of GHD's metabolic impact and potential therapeutic strategies. Results: mouse confirmed GHD, as evidenced by reduced GH production and altered body composition. Metabolomic profiling identified three distinct biomarker groups associated with GHD: (1) GHD Biomarkers, found exclusively in GH-deficient mutant mice but absent in WT controls; (2) GH Treatment Responsive Biomarkers, which were altered in GH-deficient mutant mice (GHD) and further modulated following GH treatment, reflecting a response specific to the GHD condition and its treatment, but not observed in WT mice; and (3) GH Treatment-Specific Responsive Biomarkers, observed exclusively in the GHD condition after GH therapy. Pathway analysis revealed significant disruptions in purine metabolism, amino acid metabolism, and protein synthesis, with notable sex-specific differences. Male mice exhibited imbalances in taurine and hypotaurine metabolism, while female mice showed disruptions in tyrosine metabolism and mitochondrial function, highlighting sex-dependent metabolic responses to GHD and GH therapy. Conclusion: mouse model offers a robust platform for exploring GHD's molecular mechanisms. The identification of distinct, sex-specific metabolic biomarkers provides insights into GHD-related metabolic disruptions and supports personalized management strategies. These findings establish a framework for leveraging metabolic biomarkers to enhance the diagnosis and monitoring of GHD, with promising applications for future human studies and therapeutic strategies.

  PublisherOA PDFDOI

• A novel variant in an intron splicing enhancer associated with familial growth hormone deficiency

  Hormone Research in Paediatrics · 2025-03-08

  articleOpen access1st authorCorresponding

  INTRODUCTION: Variants in the intron splicing enhancer (ISE) of intron 3 in the GH1 gene are implicated in the etiology of isolated growth hormone deficiency type 2 (type II IGHD). METHODS: Exome sequencing was performed to screen variants that co-segregated with IGHD in an extended family with type II IGHD. The causality of the candidate variant was assessed using bioinformatic tools and previous in vitro studies. RESULTS: Exome sequencing identified a rare intronic variant (NM_000515.5, c.291+34 G>A) in the second XGGG repeat of ISE in intron 3 of GH1, which occurred de novo in the mother with IGHD and was passed onto her two affected children. The variant was previously shown in vitro to cause exon 3 skipping in 50% of the mRNAs and was predicted to create a new binding site for exonic splicing enhancer binding proteins (SR proteins). CONCLUSION: Our familial case reiterates the importance of intronic variants in the splicing enhancer region as a cause of IGHD. Consideration should be given to sequencing the splicing enhancer region in intron 3 of GH1 for patients who undergo genetic testing for growth hormone deficiency.

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• Editorial: Insights in pediatric endocrinology: 2024

  Frontiers in Endocrinology · 2025-08-28

  editorialOpen accessSenior author

  This research topic included three papers on puberty related issues. A review by Bangalore Krishna and Garibaldi discusses assays currently used for assessment of pubertal hormones and the limitations of these assays.1 The review emphasizes the importance of using highly sensitive assays when relying on a single early morning basal luteinizing hormone (LH) level to diagnose central precocious puberty (CPP), and the importance of confirming this with a repeat, early morning sample. The authors point out that while pubertal levels of basal LH are diagnostic of CPP, undetectable LH levels do not exclude onset of central puberty, and that such results may occur in 20-35% of girls and about 5% of boys in early puberty. They point out that high dose biotin supplements can interfere with results of gonadal steroid assays, and should be discontinued if results do not make clinical sense. Finally, they point out that girls with CPP may not always demonstrate a stimulated LH level following leuprolide administration of > 5 IU/L; however, the majority will achieve peak estradiol levels of > 50 pg/mL about 20-24 hours after leuprolide, consistent with pubertal activation. In contrast, boys with CPP do demonstrate peak LH levels of > 5 IU/L and 20-24 hour testosterone levels are less important. Further, Li et al, report on the possible contribution of perfluorinated endocrine disrupters to the increased risk of CPP in girls noted during the COVID-19 pandemic.2 Using metabolomics and enrichment analysis, they demonstrate an increase in levels of three perfluorinated compounds in girls with CPP compared to prepubertal controls and involvement of multiple pathways in the CPP process. They conclude that perfluorinated compounds may promote CPP in girls by interfering with pathways that impact the hypothalamic-pituitary-gonadal axis, and urge additional research on environmental endocrine disrupters. Finally, Ebo et al. report on the validity and reliability of self-staging of puberty, particularly in the context of the use of this strategy during televisits, using data gathered during the COVID-19 pandemic.3 A kappa value of ≥ 0.60 was used to indicate significant agreement of ratings of breast and pubic hair staging in girls, and testicular size and pubic hair staging in boys as assessed by the patient and the physician. The highest kappa values were evident in girls at the extremes of pubertal staging (stages 1 and 5), while for boys, the highest values were noted for Tanner stages 1 and 2 of puberty. Self-staging appears to work well in distinguishing between presence or absence of puberty, while being less useful in characterizing specific pubertal stages. In addition to televisits, these findings have important implications for the use of self-staging in research studies. Zhu et al. examine associations of the inflammatory marker, high sensitivity C-reactive protein (hs-CRP), with sex steroid levels in prepubertal and pubertal children, and report inverse associations of hs-CRP with testosterone in pubertal boys and with estradiol in pubertal girls.4 In contrast, hs-CRP levels were positively associated with estradiol in prepubertal and pubertal boys, and with testosterone in prepubertal girls. BMI was associated positively and sex hormone binding globulin (SHBG) negatively with hs-CRP levels, consistent with higher BMI being associated with higher insulin and lower SHBG levels and greater metabolic risk. The study demonstrates that many factors regulate inflammatory and metabolic risk in youth. Marin et al. discuss the use of MRI in pediatric endocrinology for conditions such as growth hormone deficiency, short stature and CPP, and report on the large proportion of normal scans (67%), the high prevalence of incidentalomas (17%), and that 86% of repeat scans were unnecessary based on established protocols.5 They recommend developing guidelines for scanning to optimize yield, reduce costs and minimize distress to patients and caregivers. Giannopoulou et al. report on the impact of aromatase inhibitor therapy (letrozole) in a family with aromatase excess syndrome and demonstrate prevention of gynecomastia and improved adult height when letrozole therapy is initiated early, and improved physical strength and libido when this is started in adult life.6 Thus, aromatase inhibitors may be considered a therapeutic strategy in patients with aromatase excess syndrome. The research topic includes two papers on Prader Willi syndrome. The paper by Wędrychowicz and others explores the prevalence of central adrenal insufficiency (CAI) in children with Prader Willi syndrome using the low dose ACTH stimulation test, the glucagon stimulation test or both.7 Overall, only 1 of 46 children demonstrated convincing evidence of CAI, suggesting a low prevalence. The authors recommend against routine screening for CAI, and that the diagnosis should be confirmed with two tests to avoid unnecessary treatment with hydrocortisone. The second paper is a review of the condition by Madeo et al. and describes endocrine conditions in relation to specific genetic etiology of Prader Willi syndrome.8 Wang et al. discuss data from a meta-analysis and systemic review of burosomab treatment in children with X-linked hypophosphatemia. The study includes data from eight cohort studies and two randomized controlled trials and concludes that burosumab has excellent therapeutic efficacy in treating this condition.9 Januś et al. present a retrospective analysis of the histopathology underlying the ultrasound findings in benign, borderline, and malignant thyroid nodules in 47 children at a single tertiary thyroid center in Poland. Each type of thyroid nodule is characterized in detailed pathological terms, along with sonographic findings. The reader immediately notes the descriptive overlap in ultrasound findings among the different tumor types, leading the authors to conclude that ultrasonography is insufficient for accurate risk stratification, thereby necessitating fine-needle aspiration biopsy (FNAB) in children.10 An increase in the prevalence of autoimmune diseases during the COVID-19 pandemic has been reported in several studies, while others have not found an association. Hampering these studies was the lack of pre-pandemic control data. Hence, Herczeg and colleagues, in a retrospective analysis, determined the prevalence of thyroid autoimmunity (TA) for the 10 years prior to the pandemic and during the pandemic in a cohort of 1,361 children and young adults with type 1 diabetes (T1D).11 The increase in the prevalence of anti-thyroid autoantibodies in children with T1D was detected during the pre-pandemic years but not during the COVID-19 pandemic. Interestingly, 28.5% of children with anti-thyroid autoantibodies had clinically relevant thyroid-stimulating hormone (TSH) abnormalities (most commonly subclinical hypothyroidism) and/or were prescribed thyroid medication. They conclude that although there was a rise in the prevalence of thyroid autoimmunity among T1D children over the past decade, there was no association with the increase in the development of the disease with COVID-19. Type 1 diabetes is characterized by the destruction of pancreatic beta cells, which leads to insulin deficiency and significantly reduced levels of the exocrine pancreatic enzymes amylase, lipase, and trypsin. Bruggeman and colleagues aimed to determine whether the recently approved immunotherapies—anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF)—resulted in changes in these three exocrine pancreatic enzymes that could serve as biomarkers to delineate response to treatment.12 Although the number of patients was small, there were interesting findings noted among responders to therapy (n=4-6), placebo "responders" (n=2), treated non-responders (n=16), and placebo non-responders (n=10). Responders were defined as having at least 60% of baseline area under the curve (AUC) C-peptide levels after a 2-hour mixed meal tolerance test (MMTT) at two years post-treatment. Baseline levels of lipase and trypsin were lower, although not significantly, but improved to 115% of baseline in responders to immunotherapy six months after treatment. Non-responders and placebo subjects experienced a decline in lipase and trypsin to 80-90% of baseline during this time period. There were no differences in amylase levels between groups at baseline or six months after treatment. These preliminary findings suggest that lipase and trypsin may serve as biomarkers for response to immunotherapy in type 1 diabetes. As the authors note, further studies with larger participant numbers are needed to address this question. In a review, Tas and colleagues explore whether metabolic dysfunction-associated steatotic liver disease (MASLD) may explain the increased risk of cardiovascular disease (CVD) in individuals with Type 1 Diabetes (T1D).13 The review manuscript focuses on observational studies, cohort studies, and meta-analyses that investigate the prevalence of MASLD in T1D populations and its association with CVD. Furthermore, the manuscript examines the physiological mechanisms that link MASLD and CVD, including hepatic insulin resistance, systemic inflammation, and atherogenic dyslipidemia, to assess the independent contribution of MASLD to cardiovascular risk in T1D patients. The literature suggests that chronic inflammation and atherogenic lipid profiles associated with MASLD elevate the risk of CVD and recommends routine assessments of liver dysfunction in the care of patients with T1D to mitigate the risk of cardiovascular complications. Chimatapu et al. report retrospective data from a group of 42 adolescent males followed at a single center who tested sufficient on the initial growth hormone stimulation test but continued to present with short stature or growth failure.14 Interestingly, 59% tested deficient upon reevaluation and were started on rhGH therapy, exhibiting an excellent response. The adult height was reported for half of the patients treated with rhGH who reached adult height, which was comparable to results reported for those with IGHD. The authors emphasize the importance of re-evaluating children who show ongoing evidence of inadequate growth despite previously normal growth hormone stimulation testing. They recommend longitudinal monitoring and retesting for patients who continue to experience growth failure and may benefit from rhGH therapy. The authors hypothesize that the evolving growth hormone deficiency (EGHD) is due to 'progressive decline or insufficient production of growth hormone (GH), especially during the period of pubertal development.' In a case report of a 14-year-old male with insulinoma and primary hyperparathyroidism, a novel heterozygous mutation in MEN1 is reported and characterized.15 The mutation is also found in the proband's father, who exhibited only hyperparathyroidism in adulthood, suggesting that family members may present variations in clinical phenotypes. The grandparents and the father's siblings were unwilling to undergo genetic testing, opting only for screening of blood glucose, calcium, phosphate, and PTH, all of which were normal. No additional pathologic involvement of the pituitary gland, adrenal glands, or lungs was found in the proband. This manuscript underscores the importance of genetic testing in patients with MEN1 and their family members. Rett syndrome (RTT) is an X-linked progressive neurodevelopmental disorder primarily affecting girls and is the second most common cause of genetic intellectual disability. RTT results in neurological regression between 6 and 18 months of age and is associated with varying degrees of neurological impairment. Recent data indicate that the endocrine system is frequently involved in RTT patients, including disorders of growth, bone health, the thyroid, pubertal onset, and weight abnormalities. However, systematic data on endocrinopathies in patients with RTT are limited. Pepe and colleagues' systematic review manuscript aims to analyze the prevalence and types of endocrine comorbidities in the RTT population to facilitate early diagnosis and appropriate endocrinological management.16 Out of the 1090 studies screened, 22 met the inclusion criteria. The main endocrinopathies reported were malnutrition, bone abnormalities, and delayed puberty onset. The authors conclude that endocrinopathies are not uncommon in RTT patients and recommend screening and monitoring for endocrinopathies. Digital health technologies are becoming an integral part of enhancing patient care and the management of chronic conditions. These technological advances can lead to increased adherence, a cost-effective healthcare system, and improved medication self-management. To assess the willingness of 22 healthcare providers to integrate the connected rhGH injection pen into their clinical practice, participatory workshops were conducted in Rome, Italy, and Seoul, Korea—two diverse healthcare ecosystems.17 This qualitative study explored current attitudes toward the digitalization of rhGH therapy through panel discussions, analyzed healthcare providers' perceptions regarding the potential acceptance of the connected device compared to other non-connected alternatives (e.g., pen and paper adherence diaries), and assessed factors affecting their intent to use and integrate digital health solutions that support rhGH therapy in clinical practice. The authors conclude that understanding the nuances of these perspectives is essential for developing strategies to address the challenges and capitalize on the opportunities presented by the ongoing digital transformation in healthcare. Although healthcare providers recognize the potential of digital health solutions to enhance patient engagement and, consequently, clinical outcomes, the participatory workshops highlighted several aspects of how this digital transformation is influencing treatment options and the necessity for digital literacy for successful implementation.17 Finally, a manuscript by Zucchini and colleagues in the Study Group on Diabetes of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED) is based on a systematic review of available scientific evidence and a Delphi consensus methodology, aiming to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia.18 The objective of these recommendations is to improve the timely recognition and prevention of hypoglycemic episodes and to apply the correct treatment, especially for patients using continuous glucose monitoring (CGM) or advanced hybrid closed-loop systems. Practical flow charts are included to aid clinical decision-making, which will be very helpful for clinicians, especially when caring for patients using CGM and other advanced technologies. Importantly, the authors explore the concept of 'fear of hypoglycemia' (FoH), nasal glucagon use, and educational support to fully address the needs of the Italian community.

  PublisherOA PDFDOI

• Corrigendum: Biomarkers of GH deficiency identified in untreated and GH-treated Pit-1 mutant mice

  Frontiers in Endocrinology · 2025-08-07

  erratumOpen accessSenior author

  Corrigendum on: Al-Samerria S, Xu H, Diaz-Rubio ME, Phelan J, Su C, Ma K, Newen A, Li K, Yamada S, Negron AL, Wondisford F and Radovick S (2025) Biomarkers of GH deficiency identified in untreated and GH-treated Pit-1 mutant mice. Front. Endocrinol. 16:1539797. doi: 10.3389/fendo.2025.1539797 In the published article, there was an error in Figure 5 as published. Figure 5 was incorrect and mistakenly showed the same content as Figure 6, rather than the correct figure. The corrected Figure 5 The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

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• Targeting negative phosphorylation to activate AMPK

  Endocrine Connections · 2025-07-01 · 1 citations

  articleOpen access

  AMPK is a master regulator of metabolism and is highly conserved and ubiquitously expressed. Activation of AMPK stimulates the catabolic pathway (glucose utilization and β-oxidation) and inhibits the anabolic pathway (gluconeogenesis, protein synthesis, and lipogenesis), leading to improvement of cellular energy status. However, the mechanisms of maintaining low cellular AMPK activity are not fully understood. We and other investigators showed that activated PKA in the glucagon-cAMP signaling pathway and insulin-activated AKT both can directly phosphorylate AMPKα1/2 at S496/491 to inhibit AMPK activity. In the current study, we found that activation of AMPK by an activator, AICAR, led to elevated and prolonged phosphorylation of AMPKα1/2 at S496/S491, reflecting a feedback inhibition of AMPK activity. In an in vitro assay, functional AMPKα1β1γ1 or AMPKα2β1γ1 can phosphorylate AMPKα1 at S496 or AMPKα2 at S491, respectively. We designed and successfully screened a new AMPKα2-targeting peptide to activate AMPK through competitively blocking the negative phosphorylation, resulting in suppression of gluconeogenic gene expression and promotion of mitochondrial fission in hepatocytes.

  PublisherDOI

• Consensus and controversies about diagnosing GH deficiency: a Delphi survey by the GH research society

  Pituitary · 2025-05-07 · 6 citations

  reviewOpen access
  PublisherOA PDFDOI

• Editorial: What’s new in endocrinology? volume II

  Frontiers in Endocrinology · 2025-02-17

  editorialOpen access

  The prevalence of obesity and type 2 diabetes mellitus (T2DM) have grown alarmingly across the world during the last few decades and have become major challenges for public health. Both conditions present due to hormonal disturbances, and it has become increasingly clear that these result from dietary changes caused by a transformation in our food environment. Anjom-Shoae et al. review recent evidence examining the acute and long-term effects of high protein diets and comparing the effects of diets high in either animal or plant proteins (2). It is well established that high protein diets can have beneficial effects on body weight and glycaemic control, at least over a short timeframe, related to their effects on satiety, gastric emptying times and gut hormone release. Diets high in either animal or plant proteins had these beneficial effects on body weight and glycaemic control over shorter periods; in comparison, longer-term studies, greater than 12 months, indicated that diets high in plant proteins had either neutral or beneficial effects, whereas diets high in animal protein exerted adverse effects. The latter observations are consistent with several prospective epidemiological studies of large populations that have all shown that diets high in animal proteins are associated with an increased risk of obesity and T2DM. The reasons for the differential long-term effects of animal and plant proteins are not clear, but could be due to differences in amino acid composition, glycaemic load and/or the higher insulinotropic effects of animal proteins, with the insulin then promoting fat deposition and inhibiting fat oxidation. More studies are needed to understand the effects of different proteins on the gastrointestinal and other mechanisms involved in food intake and glycaemic control.With the prevalence of T2DM continuing to grow, the marked differences in its presentation and progression present challenges for the management of patients. Groups working with the Risk Assessment and Progression of Diabetes (RHAPSODY) consortium have used an unsupervised, "bottom-up", multimodal, multivariate strategy to analyze multi-omic data obtained from two European cohorts of patients with T2DM in order to better characterize the complexity of the molecular interactions that underlie this heterogeneity among patients (3). By measuring 180 circulating lipids and 1195 proteins, they identified two subgroups of patients who differed in terms of insulin sensitivity and secretion, and glycemic deterioration,. and identified various groups of biomarkers, most notably those involved in immune processes, that were associated with these distinct subgroups of patients. These biomarkers will provide valuable targets for future studies examining causal pathways for disease progression.Proinflammatory cytokines have been implicated in the pancreatic -cell failure that underlies both type 1 diabetes mellitus (T1DM) and T2DM. Understanding the molecular mechanisms in this process can lead to the discovery of biomarkers that may assist in monitoring disease progression and to new targets for therapeutic interventions. A novel cytokine mediated effect on -cell RNA turnover is reported by Ghjiasi et al (4). Another very international collaboration used human and rodent -cell models to reveal a novel cytokine mediated effect on -cell RNA turnover. These investigators found that cytokines decreased the activity of nonsense-mediated RNA decay (NMD), which normally functions to eliminate premature termination containing mRNAs, and thus could disturb the balance between anti-and pro-apoptotic transcripts. These findings open up new avenues of research into the various components of the NMD machinery as potential biomarkers or therapeutic targets.The regulation of reproductive function is intimately controlled in relation to metabolic status. Recent advances in our understanding of the pathways involved is reviewed by Rodríguez-Vázquez et al, with a focus on the impact of metabolism on pubertal development and fertility (5). They describe the pivotal role played by the hypothalamus in integrating central neuronal signals with hormonal signals, wherein peripheral metabolic hormones such as leptin, insulin, and ghrelin act on Kiss1 and GnRH neurons to regulate pubertal development according to metabolic status. In addition, it has emerged that many cellular sensors also play a direct role in this integration, including energy sensors such as AMPK, mTOR and SIRT1, as well as several lipid sensing pathways, including fatty acid receptors, fatty acid transport proteins, and nuclear receptors. Nuclear receptors such as peroxisome proliferator-activated receptors are differentially expressed in specific hypothalamic neurons, and when fatty acids are bound, these are then translocated to the nucleus where they can activate or repress gene transcription. In addition, both bile acids (BA), which are synthesised in the liver, and secondary BA, which are formed after transformation by the gut microbiota, interact with the G protein coupled-receptor, TGR5, in the hypothalamus. A complex framework for the integral regulation of whole-body metabolism and reproductive function is described, which should enable further functional connectivity mapping of the hypothalamic neuronal and glial cells involved.Cushing's syndrome (CS) is a classical, but relatively rare, endocrine disease that is due to hypercortisolism and is treated by surgical excision of the causal adrenal or pituitary lesion. Despite successful treatment a large proportion of patients in remission suffer from persistent fatigue, muscle weakness and sarcopenia. Recent evidence has increasingly implicated microRNAs (miRNAs) in skeletal muscle regulation and Seco-Cervera et al. conducted a pilot study screening for circulating miRNAs that could be potential biomarkers of sarcopenia in a group of patients with CS in sustained biochemical remission (6). In a pilot study, confirmed in a second validation cohort, they found that miR-28-5p was upregulated in CS patients with sarcopenia as compared to those without. Prior evidence indicates that miR-28-5p is a muscle-specific miRNA that is involved in myoblast proliferation, differentiation and regeneration suggesting that there may be a functional link to the persistent sarcopenia. These preliminary findings suggest that miR-28-5p may be a promising candidate circulating biomarker to indicate the risk of persistent sarcopenia in treated CS patients despite normalised cortisol levels, who may then benefit from adapted exercise programs to improve their quality of life and prevent future falls. More generally it may also indicate a fertile area of future investigations as a potential therapeutic target for age-related sarcopenia and various pathological, muscle wasting conditions. Two manuscripts in this collection describe updated guidelines for the diagnosis and management of rickets and multiple endocrine neoplasia (MEN), two other classical endocrinopathies, particularly in light of advances in molecular medicine. Rickets is a heterogeneous group of skeletal diseases resulting from impaired mineralisation of growing bones due to nutritional or hereditary disturbances in calcium and phosphate homeostasis. On behalf of the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology, Baroncelli et al. present practical guidance on the diagnosis, treatment, and management of patients with rickets (7). Extensive guidelines, including algorithms, are provided to ensure early differential diagnosis of nutritional and genetic forms of rickets according to biochemical findings and clinical and radiological examinations. Specific recommendations for the multidisciplinary treatment programs of each distinct form of rickets are also provided, including for rare, hereditary forms of the disease.Multiple endocrine neoplasia (MEN) is a group of diseases characterised by multiple tumours occurring within endocrine tissues of an individual. Since the first form, MEN1, was reported 70 years ago three further forms, MEN2, MEN3 and MEN4 have subsequently been described. These syndromes were initially characterised according to their clinical phenotype and their underlying genetic causes were subsequently discovered. Romanet et al review recent advances in the genetics, diagnosis and screening for the various forms of MEN (8). MENs are rare hereditary diseases that are transmitted in an autosomal dominant manner and not all cases fit within the classical MEN subgroups. Romanet et al. describe guidelines for MEN diagnosis along with challenges and pitfalls of different sequencing strategies that can be applied. They (1) emphasise the strategy for management of index cases and presymptomatic genetic screening and counselling for relatives; (2) describe advances in strategies for unravelling gene-disease relationships including the value of using induced pluripotent stem cells to generate patient-derived spheroids, tumoroids and organoids for investigating the pathophysiology and potential drug responses; and (3) highlight the need for national or regional large cohort studies to better understand these rare diseases.Melatonin a classical hormone that is produced by the pineal gland, an outgrowth of the posterodorsal thalamus, is secreted predominantly at night, with a primary endocrine role in maintaining the circadian rhythm throughout the body. Less well known is that most melatonin is produced by extrapineal tissues, and Reiter et al (9) give an update on the potential functions of this second source of melatonin. They estimate that less than 5% of the melatonin in the body is produced in the pineal gland, whereas the vast majority of melatonin is produced in multiple tissues throughout the body and is not linked to dark/light cycles or secreted into the circulation, but acts locally, primarily in an autocrine, and possibly also paracrine, manner. This extrapineal melatonin appears to be produced in the mitochondria, where it has roles in scavenging free radicals, re-dox homeostasis and anti-inflammation, and may therefore be important for maintaining general health and countering pathology.The final article in the Research Topic does not relate to advances in endocrine science or practice but describes an emerging challenge regarding how endocrinology is reported. At Frontiers in Endocrinology, we have witnessed an exponential rise in the submission of manuscripts that are derivative, or primarily redundant and otherwise of low-quality. This phenomenon has been exacerbated by manuscripts that do not report novel findings or new data, but report analyses of huge amounts of data that can now be found within large publicly-available databases. Additionally, there has been considerable growth in redundant bibliometric reviews and fraudulent manuscripts, many produced by "papermills". Such manuscripts have been witnessed across most medical specialties and are of limited value to our or other readers. In a commentary, we document how this has affected Frontiers in Endocrinology, and we outline some of the measures that we have taken to reduce their frequency and prevent them from overwhelming the literature (10).Technological advances continue to provide endocrinologists with ever more powerful tools that continue to reveal new understanding and opportunities for novel treatments, even for the most well characterized endocrine conditions. The challenges faced by endocrinologists also continue to evolve as populations increasingly age and modern lifestyles increase the burden of metabolic disorders. This collection of articles reflects a variety of these challenges and the dynamic nature of modern endocrinology.

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• Editorial

  Current Opinion in Pediatrics · 2024-07-03

  editorial1st authorCorresponding

  Rutgers Robert Wood Johnson Medical School Camden: Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA Correspondence to Sally Radovick, MD, Rutgers Robert Wood Johnson Medical School Camden: Rutgers Robert Wood, Johnson Medical School, New Brunswick, NJ, USA. E-mail: [email protected]

  PublisherDOI

Recent grants

• NIH Grant R29HD030040

  NIH · $551k · 1997

• NIH Grant R01HD068777

  NIH · $2.4M · 2020

• TRANSFER: 5U01HD086838-03 Genetic Diagnosis of Childhood Growth Disorders

  NIH · $694k · 2017–2023

• NIH Grant K24DK002914

  NIH · $420k · 2006

• NIH Grant U01HD066432

  NIH · $1.6M · 2016

Frequent coauthors

• Fredric E. Wondisford

  Rutgers, The State University of New Jersey

  161 shared

• Andrew Wolfe

  University of Alberta

  103 shared

• Ivana Rabbone

  Azienda Unità Sanitaria Locale Della Romagna

  98 shared

• Gianluca Tamaro

  IRCCS Materno Infantile Burlo Garofolo

  98 shared

• Gianluca Tornese

  IRCCS Materno Infantile Burlo Garofolo

  70 shared

• Lars Sävendahl

  Monash University

  60 shared

• Christopher J. Romero

  Hospital Militar Central

  59 shared

• Tadej Battelino

  54 shared