Endocrines最新文献

{"title":"Parathyroid Carcinoma: Update on Pathogenesis and Therapy","authors":"F. Marini, F. Giusti, Gaia Palmini, C. Aurilia, Simone Donati, M. Brandi","doi":"10.3390/endocrines4010018","DOIUrl":"https://doi.org/10.3390/endocrines4010018","url":null,"abstract":"Parathyroid carcinoma (PC) is a very rare endocrine cancer with aggressive behavior, a high metastatic potential, and a poor prognosis. Surgical resection of affected gland(s) and other involved structures is the elective therapy. Pre-operative and intra-operative differential diagnosis with benign parathyroid adenoma remains a challenge. The lack of a clear pre-operative diagnosis does not allow one, in many cases, to choose the correct surgical approach to malignant PC, increasing persistence, the recurrence rate, and the risk of metastases. An initial wrong diagnosis of parathyroid adenoma, with a minimally invasive parathyroidectomy, is associated with over 50% occurrence of metastases after surgery. Genetic testing could help in identifying patients at risk of congenital PC (i.e., CDC73 gene) and in driving the choice of neck surgery extension. Targeted effective treatments, other than surgery, for advanced and metastatic PC are needed. The pathogenesis of malignant parathyroid carcinogenesis is still largely unknown. In the last few years, advanced molecular techniques allowed researchers to identify various genetic abnormalities and epigenetic features characterizing PC, which could be crucial for selecting molecular targets and developing novel targeted therapeutic agents. We reviewed current findings in PC genetics, epigenetics, and proteomics and state-of-the-art therapies.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47410624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of COVID-19 Regulations on Adherence to Recombinant Human Growth Hormone Therapy: Evidence from Real-World Data","authors":"P. van Dommelen, R. Baños, L. Arnaud, Q. Le Masne, E. Koledova","doi":"10.3390/endocrines4010017","DOIUrl":"https://doi.org/10.3390/endocrines4010017","url":null,"abstract":"Worldwide regulations during COVID-19 positively and negatively impacted self-management in paediatric patients with chronic medical conditions. We investigated the impact of regulations on adherence to recombinant human growth hormone (r-hGH) therapy in paediatric patients with growth disorders, using real-world adherence data extracted March 2019–February 2020 (before COVID-19) and March 2020–February 2021 (during COVID-19) from the easypod™ connect ecosystem. Data from three measures of regulations were analysed: stringency index (SI), school closure and stay-at-home. The mean SI, and the proportion of days with required school closure or stay-at-home during COVID-19 were categorised as high versus medium/low based on the 75th percentile. Adherence was categorised as optimal (≥85%) versus suboptimal (<85%). Adherence data were available for 8915 patients before and 7606 patients during COVID-19. A high SI (mean ≥68) and a high proportion of required school closure (≥88%) resulted in an increase in the proportion of optimal adherence during COVID-19 versus pre-COVID-19 (p < 0.001). Stay-at-home requirements showed no statistically significant effect (p = 0.13). Stringent COVID-19 regulations resulted in improved adherence to r-hGH therapy in patients with growth disorders, supported by connected digital health technologies. Insights into patient behavior during this time are useful to understand potential influences and strategies to improve long-term adherence to r-hGH.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42359374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Krebs Cycle Intermediates on the Endocrine System and Immune System: A Comparison","authors":"B. Arneth","doi":"10.3390/endocrines4010016","DOIUrl":"https://doi.org/10.3390/endocrines4010016","url":null,"abstract":"Introduction: The Krebs cycle is an important set of reactions that synthesize different molecules and substances that affect various organs. The objective of this paper was to compare the effects of Krebs cycle intermediates on the endocrine system and the immune system. Methods and Materials: The articles used in this paper were obtained from a systematic search of PsycINFO, PubMed, Web of Science, CINAHL, and primary databases. The search terms were “Krebs cycle,” “intermediates,” “endocrine system,” “tricarboxylic acid,” “citric acid cycle,” and “immune system,” and Boolean operators (AND/OR) were used to combine terms. Results: A review of the selected studies showed that Krebs cycle intermediates influence how the endocrine system regulates and controls body processes, including energy uptake. Moreover, these intermediates have both direct and indirect effects on immune function, memory, and activation. Discussion: An understanding of the effects of Krebs cycle intermediates on endocrine and immune processes will provide valuable insights for the development of new therapies. Additionally, this knowledge is a basis for exploring the pathogenesis of the complications related to endocrine system function and for evaluating the immune system response to pathogens. Conclusions: The evidence gathered in this review shows that Krebs cycle intermediates have significant effects on immune and endocrine processes. However, further human and in vivo studies are required to generate additional evidence for the underlying pathways and to identify the potential strategies for targeting these mechanisms to manage specific disorders.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46901429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the Molecular and Hormonal Regulation of Complications of X-Linked Hypophosphatemia","authors":"Supriya Jagga, Shreya Venkat, Melissa Sorsby, E. Liu","doi":"10.3390/endocrines4010014","DOIUrl":"https://doi.org/10.3390/endocrines4010014","url":null,"abstract":"X-linked hypophosphatemia (XLH) is characterized by mutations in the PHEX gene, leading to elevated serum levels of FGF23, decreased production of 1,25 dihydroxyvitamin D3 (1,25D), and hypophosphatemia. Those affected with XLH manifest impaired growth and skeletal and dentoalveolar mineralization as well as increased mineralization of the tendon–bone attachment site (enthesopathy), all of which lead to decreased quality of life. Many molecular and murine studies have detailed the role of mineral ions and hormones in regulating complications of XLH, including how they modulate growth and growth plate maturation, bone mineralization and structure, osteocyte-mediated mineral matrix resorption and canalicular organization, and enthesopathy development. While these studies have provided insight into the molecular underpinnings of these skeletal processes, current therapies available for XLH do not fully prevent or treat these complications. Therefore, further investigations are needed to determine the molecular pathophysiology underlying the complications of XLH.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43130969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Adult Height in Patients with Non-Permanent Idiopathic GH Deficiency","authors":"A. Murianni, A. Lussu, C. Guzzetti, A. Ibba, Letizia Casula, M. Salerno, M. Cappa, S. Loche","doi":"10.3390/endocrines4010015","DOIUrl":"https://doi.org/10.3390/endocrines4010015","url":null,"abstract":"Background: Several studies have evaluated the role of IGF-1 in the diagnosis of growth hormone deficiency (GHD). According to a recent study, an IGF-1 concentration of a −1.5 standard deviation score (SDS) appeared to be the best cut-off for distinguishing between children with GHD and normal children. This value should always be interpreted in conjunction with other clinical and biochemical parameters for the diagnosis of GHD, since both stimulation tests and IGF-1 assays have poor diagnostic accuracy by themselves. Our study was designed to evaluate the adult height (AH) in children with short stature and baseline IGF-1 concentration ≤ −1.5 SDS. Design: This retrospective analysis included 52 children and adolescents evaluated over the last 30 years for short stature and/or deceleration of the growth rate who underwent diagnostic procedures to evaluate a possible GHD. Only the patients who had baseline IGF-1 values ≤−1.5 SDS at the time of the first test were included in the study. Patients with genetic/organic GHD or underlying diseases were not included. Method: The case group consisted of 24 patients (13 boys and 11 girls) with non-permanent, idiopathic, and isolated GHD (peak GH < 10 μg/L after two provocative tests with arginine (Arg), insulin tolerance test (ITT), and clonidine (Clo), or <20 μg/L after GHRH + Arginine (GHRH+Arg); normal MRI; normal GH; and/or normal IGF-1 concentrations at near-AH). These patients were treated with GH (25–35 μg/kg/die) until near-AH. The control group consisted of 28 patients (23 boys and 5 girls) with idiopathic short stature (ISS, normal peak GH after provocative testing, no evidence of other causes for their shortness). Both groups had basal IGF-1 ≤−1.5 SDS. Results: AH and height gain in both groups were comparable. In the group of cases, mean IGF-1 SDS at the time of diagnosis was significantly lower than the levels found at the time of retesting. Conclusions: In this study, both treated patients with idiopathic GHD and untreated patients with ISS reached similar near-AHs (within target height) and showed similar increases in SDS for their height. Thus, the efficacy of treatment with rhGH in these patients may be questionable. This could be due to the fact that children with ISS are frequently misdiagnosed with GHD.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48148726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deleting Cellular Retinoic-Acid-Binding Protein-1 (Crabp1) Gene Causes Adult-Onset Primary Hypothyroidism in Mice","authors":"Fatimah Najjar, Jennifer Nhieu, Chin-Wen Wei, L. Milbauer, Lynn Burmeister, D. Seelig, Li-Na Wei","doi":"10.3390/endocrines4010013","DOIUrl":"https://doi.org/10.3390/endocrines4010013","url":null,"abstract":"Adult-onset primary hypothyroidism is commonly caused by iatrogenic or autoimmune mechanisms; whether other factors might also contribute to adult hypothyroidism is unclear. Cellular Retinoic-Acid-Binding Protein 1 (CRABP1) is a mediator for Non-canonical signalling of all-trans retinoic acid (atRA). CRABP1 Knockout (CKO) mice develop and reproduce normally but begin to exhibit primary hypothyroidism in adults (~3 months old) including increased body weight, decreased body temperature, reduced plasma levels of triiodothyronine and thyroxine, and elevated levels of thyroid-stimulating hormone. Histopathological and gene expression studies reveal significant thyroid gland morphological abnormalities and altered expression of genes involved in thyroid hormone synthesis, transport, and metabolism in the CKO thyroid gland at ~6 months old. These significantly affected genes in CKO mice are also found to be genetically altered in human patients with hypothyroidism which could result in a loss of function, supporting the clinical relevance of CKO mice in humans with hypothyroidism. This study identifies, for the first time, an important role for CRABP1 in maintaining the health of the thyroid gland in adults and reports that CKO mice may provide an experimental animal model for studying the mechanisms underlying the development of adult hypothyroidism in humans.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69823079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does Testosterone Salvage PDE5i Non-Responders? A Scoping Review","authors":"M. Pignanelli, N. Stern, G. Brock","doi":"10.3390/endocrines4010011","DOIUrl":"https://doi.org/10.3390/endocrines4010011","url":null,"abstract":"Erectile physiology, in order to function normally, requires the complex coordination of endocrine, neurocognitive, neuromuscular and vascular mechanisms. Testosterone (T) influences male sexuality as well as penile erections at multiple levels, including a direct influence on the nitric oxide synthase (NOS)/cGMP/phosphodiesterase 5 pathway in the penis. However, the precise role of testosterone replacement (TRT) to “salvage” men with mixed ED failing phosphdiesterase-5 inhibitors (PDE5i) remains unclear. We conducted a scoping review identifying the rationale for TRT in ED failing PDE5i, and we critically discuss clinical trials that have examined TRT in the setting of PDE5i use. Overall, TRT replacement appears to be well tolerated and may enhance the response to PDE5i and quality of life, particularly for men with mixed ED, and particularly among men with very low levels of testosterone. However, most of the available literature examines concurrent TRT alone or simultaneous TRT + PDE5i usage, without necessarily selecting for PDE5i failure cases. The present studies are limited to heterogenous studies with small sample sizes, without an exact predominant etiologic factor causing ED. Furthermore, studies showing the most benefit are non-placebo-controlled trials; however, the correction of more profound hypogonadism may lead to an improved response to PDE5i. Stronger conclusions would require properly selected patient populations and larger placebo-controlled RCTs.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43852692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presentation and Diagnosis of Pediatric X-Linked Hypophosphatemia","authors":"K. Ikegawa, Y. Hasegawa","doi":"10.3390/endocrines4010012","DOIUrl":"https://doi.org/10.3390/endocrines4010012","url":null,"abstract":"X-linked hypophosphatemia (XLH) is a rare type of hereditary hypophosphatemic rickets. Patients with XLH have various symptoms that lower their QOL as defined by HAQ, RAPID3, SF36-PCS, and SF36-MCS in adult patients and SF-10 and PDCOI in pediatric patients. Early diagnosis and treatment are needed to reduce the burden, but the condition is often diagnosed late in childhood. The present review aims to summarize the symptoms, radiological and biological characteristics, and long-term prognosis of pediatric XLH. Typical symptoms of XLH are lower leg deformities (age six months or later), growth impairment (first year of life or later), and delayed gross motor development with progressive lower limb deformities (second year of life or later). Other symptoms include dental abscess, bone pain, hearing impairment, and Chiari type 1 malformation. Critical, radiological findings of rickets are metaphyseal widening, cupping, and fraying, which tend to occur in the load-bearing bones. The Rickets Severity Score, validated for XLH, is useful for assessing the severity of rickets. The biochemical features of XLH include elevated FGF23, hypophosphatemia, low 1,25(OH)2D, and elevated urine phosphate. Renal phosphate wasting can be assessed using the tubular maximum reabsorption of phosphate per glomerular filtration rate (TmP/GFR), which yields low values in patients with XLH. XLH should be diagnosed early because the multisystem symptoms often worsen over time. The present review aims to help physicians diagnose XLH at an early stage.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47708190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Possible Outcomes of Poor Adherence to Conventional Treatment in Patients with X-Linked Hypophosphatemic Rickets/Osteomalacia","authors":"Hiroaki Zukeran, K. Ikegawa, C. Numakura, Y. Hasegawa","doi":"10.3390/endocrines4010010","DOIUrl":"https://doi.org/10.3390/endocrines4010010","url":null,"abstract":"X-linked hypophosphatemic rickets/osteomalacia is an inherited disease caused by the loss of function in PHEX. Elevated plasma FGF23 in patients with XLH leads to hypophosphatemia. The conventional treatment for XLH, consisting of oral phosphate and active vitamin D, is often poorly adhered to for various reasons, such as the requirement to take multiple daily doses of phosphate. Burosumab, an anti-FGF23 antibody, is a new drug that directly targets the mechanism underlying XLH. We report herein three adult patients with poor adherence to the conventional treatment. In Patient 1, adherence was poor throughout childhood and adolescence. The treatment of Patients 2 and 3 became insufficient after adolescence. All of the patients suffered from gait disturbance caused by pain, fractures, and lower extremity deformities early in life. We prescribed burosumab for the latter two patients, and their symptoms, which were unaffected by resuming conventional treatment, dramatically improved with burosumab. Maintaining adherence to the conventional treatment is crucial but challenging for patients with XLH. Starting burosumab therapy from childhood or adolescence in pediatric patients with poor adherence may help prevent the early onset of complications.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47812302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Features of Transient Growth Hormone Deficiency","authors":"Yuki Sakai, K. Ikegawa, Kazuhiro Shimura, Y. Hasegawa","doi":"10.3390/endocrines4010009","DOIUrl":"https://doi.org/10.3390/endocrines4010009","url":null,"abstract":"Background: Most patients with idiopathic growth hormone deficiency (iGHD) in childhood have normal GH stimulation test results in adulthood. The present study aimed to investigate the characteristics and possible etiology of transient iGHD. Methods: Patients with childhood-onset iGHD who completed their GH treatment between March 2010 and March 2021 were retrospectively studied. Patients with a clear history of child abuse or constitutional delay of growth and puberty were excluded. Ten patients with a diagnosis of iGHD based on a decreased growth rate and growth hormone stimulation test findings at the time of onset were included. Retesting demonstrated that these patients had a normal GH level. Results: Five patients had insufficient weight gain (BMI SD score < −1.0 at the start of treatment or a decrease in BMI SD score > 1.0 from one year before treatment to the start of treatment). The other five patients had no remarkable clinical features. One patient had decreased height velocity at the same time as their sibling. Conclusion: Insufficient pre-treatment weight gain or a familial cluster of cases may be related to low GH peaks of GHST, leading to a diagnosis of transient GHD.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49113327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}