{"title":"Levothyroxine: Conventional and Novel Drug Delivery Formulations.","authors":"Hanqing Liu, Wei Li, Wen Zhang, Shengrong Sun, Chuang Chen","doi":"10.1210/endrev/bnac030","DOIUrl":"https://doi.org/10.1210/endrev/bnac030","url":null,"abstract":"<p><p>Although levothyroxine is one of the most prescribed medications in the world, its bioavailability has been reported to be impaired by many factors, including interfering drugs or foods and concomitant diseases, and persistent hypothyroidism with a high dose of levothyroxine is thus elicited. Persistent hypothyroidism can also be induced by noninterchangeability between formulations and poor compliance. To address these issues some strategies have been developed. Novel formulations (liquid solutions and soft gel capsules) have been designed to eliminate malabsorption. Some other delivery routes (injections, suppositories, sprays, and sublingual and transdermal administrations) are aimed at circumventing different difficulties in dosing, such as thyroid emergencies and dysphagia. Moreover, nanomaterials have been used to develop delivery systems for the sustained release of levothyroxine to improve patient compliance and reduce costs. Some delivery systems encapsulating nanoparticles show promising release profiles. In this review, we first summarize the medical conditions that interfere with the bioavailability of oral levothyroxine and discuss the underlying mechanisms and treatments. The efficacy of liquid solutions and soft gel capsules are systematically evaluated. We further summarize the novel delivery routes for levothyroxine and their possible applications. Nanomaterials in the levothyroxine field are then discussed and compared based on their load and release profile. We hope the article provides novel insights into the drug delivery of levothyroxine.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 3","pages":"393-416"},"PeriodicalIF":20.3,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9913373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marian Schini, Tatiane Vilaca, Fatma Gossiel, Syazrah Salam, Richard Eastell
{"title":"Bone Turnover Markers: Basic Biology to Clinical Applications.","authors":"Marian Schini, Tatiane Vilaca, Fatma Gossiel, Syazrah Salam, Richard Eastell","doi":"10.1210/endrev/bnac031","DOIUrl":"https://doi.org/10.1210/endrev/bnac031","url":null,"abstract":"<p><p>Bone turnover markers (BTMs) are used widely, in both research and clinical practice. In the last 20 years, much experience has been gained in measurement and interpretation of these markers, which include commonly used bone formation markers (bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide); and commonly used resorption markers (serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen, and tartrate-resistant acid phosphatase type 5b). BTMs are usually measured by enzyme-linked immunosorbent assay or automated immunoassay. Sources contributing to BTM variability include uncontrollable factors (eg, age, gender, ethnicity) and controllable factors, particularly relating to collection conditions (eg, fasting/feeding state, and timing relative to circadian rhythms, menstrual cycling, and exercise). Pregnancy, season, drugs, and recent fracture(s) can also affect BTMs. BTMs correlate with other methods of assessing bone turnover, such as bone biopsies and radiotracer kinetics, and can usefully contribute to diagnosis and management of several diseases such as osteoporosis, osteomalacia, Paget's disease, fibrous dysplasia, hypophosphatasia, primary hyperparathyroidism, and chronic kidney disease-mineral bone disorder.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 3","pages":"417-473"},"PeriodicalIF":20.3,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9541586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brian P Cary, Xin Zhang, Jianjun Cao, Rachel M Johnson, Sarah J Piper, Elliot J Gerrard, Denise Wootten, Patrick M Sexton
{"title":"New Insights into the Structure and Function of Class B1 GPCRs.","authors":"Brian P Cary, Xin Zhang, Jianjun Cao, Rachel M Johnson, Sarah J Piper, Elliot J Gerrard, Denise Wootten, Patrick M Sexton","doi":"10.1210/endrev/bnac033","DOIUrl":"https://doi.org/10.1210/endrev/bnac033","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors. Class B1 GPCRs constitute a subfamily of 15 receptors that characteristically contain large extracellular domains (ECDs) and respond to long polypeptide hormones. Class B1 GPCRs are critical regulators of homeostasis, and, as such, many are important drug targets. While most transmembrane proteins, including GPCRs, are recalcitrant to crystallization, recent advances in cryo-electron microscopy (cryo-EM) have facilitated a rapid expansion of the structural understanding of membrane proteins. As a testament to this success, structures for all the class B1 receptors bound to G proteins have been determined by cryo-EM in the past 5 years. Further advances in cryo-EM have uncovered dynamics of these receptors, ligands, and signaling partners. Here, we examine the recent structural underpinnings of the class B1 GPCRs with an emphasis on structure-function relationships.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 3","pages":"492-517"},"PeriodicalIF":20.3,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9541594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael Nyberg, Dijana Terzic, Trine P Ludvigsen, Peter D Mark, Natasha B Michaelsen, Steen Z Abildstrøm, Mads Engelmann, A Mark Richards, Jens P Goetze
{"title":"A State of Natriuretic Peptide Deficiency.","authors":"Michael Nyberg, Dijana Terzic, Trine P Ludvigsen, Peter D Mark, Natasha B Michaelsen, Steen Z Abildstrøm, Mads Engelmann, A Mark Richards, Jens P Goetze","doi":"10.1210/endrev/bnac029","DOIUrl":"https://doi.org/10.1210/endrev/bnac029","url":null,"abstract":"<p><p>Measurement of natriuretic peptides (NPs) has proven its clinical value as biomarker, especially in the context of heart failure (HF). In contrast, a state of partial NP deficiency appears integral to several conditions in which lower NP concentrations in plasma presage overt cardiometabolic disease. Here, obesity and type 2 diabetes have attracted considerable attention. Other factors-including age, sex, race, genetics, and diurnal regulation-affect the NP \"armory\" and may leave some individuals more prone to development of cardiovascular disease. The molecular maturation of NPs has also proven complex, with highly variable O-glycosylation within the biosynthetic precursors. The relevance of this regulatory step in post-translational propeptide maturation has recently become recognized in biomarker measurement/interpretation and cardiovascular pathophysiology. An important proportion of people appear to have reduced effective net NP bioactivity in terms of receptor activation and physiological effects. The state of NP deficiency both entails a potential for further biomarker development and could also offer novel pharmacological possibilities. Alleviating the state of NP deficiency before development of overt cardiometabolic disease in selected patients could be a future path for improving precision medicine.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 3","pages":"379-392"},"PeriodicalIF":20.3,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John Richard Apps, Hermann Lothar Muller, Todd Cameron Hankinson, Torunn Ingrid Yock, Juan Pedro Martinez-Barbera
{"title":"Contemporary Biological Insights and Clinical Management of Craniopharyngioma.","authors":"John Richard Apps, Hermann Lothar Muller, Todd Cameron Hankinson, Torunn Ingrid Yock, Juan Pedro Martinez-Barbera","doi":"10.1210/endrev/bnac035","DOIUrl":"10.1210/endrev/bnac035","url":null,"abstract":"<p><p>Craniopharyngiomas (CPs) are clinically aggressive tumors because of their invasive behavior and recalcitrant tendency to recur after therapy. There are 2 types based on their distinct histology and molecular features: the papillary craniopharyngioma (PCP), which is associated with BRAF-V600E mutations and the adamantinomatous craniopharyngioma (ACP), characterized by mutations in CTNNB1 (encoding β-catenin). Patients with craniopharyngioma show symptoms linked to the location of the tumor close to the optic pathways, hypothalamus, and pituitary gland, such as increased intracranial pressure, endocrine deficiencies, and visual defects. Treatment is not specific and mostly noncurative, and frequently includes surgery, which may achieve gross total or partial resection, followed by radiotherapy. In cystic tumors, frequent drainage is often required and intracystic instillation of drugs has been used to help manage cyst refilling. More recently targeted therapies have been used, particularly in PCP, but also now in ACP and clinical trials are underway or in development. Although patient survival is high, the consequences of the tumor and its treatment can lead to severe comorbidities resulting in poor quality of life, in particular for those patients who bear tumors with hypothalamic involvement. Accordingly, in these patients at risk for the development of a hypothalamic syndrome, hypothalamus-sparing treatment strategies such as limited resection followed by irradiation are recommended. In this review, we provide an update on various aspects of CP, with emphasis on recent advances in the understanding of tumor pathogenesis, clinical consequences, management, and therapies.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 3","pages":"518-538"},"PeriodicalIF":20.3,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adam Ramzy, Paul J Belmonte, Mitchell J S Braam, Shogo Ida, Emily M Wilts, Megan K Levings, Alireza Rezania, Timothy J Kieffer
{"title":"A Century-long Journey From the Discovery of Insulin to the Implantation of Stem Cell-derived Islets.","authors":"Adam Ramzy, Paul J Belmonte, Mitchell J S Braam, Shogo Ida, Emily M Wilts, Megan K Levings, Alireza Rezania, Timothy J Kieffer","doi":"10.1210/endrev/bnac021","DOIUrl":"https://doi.org/10.1210/endrev/bnac021","url":null,"abstract":"<p><p>For the past century, insulin injections have saved millions of lives, but glycemic instability is still a persistent challenge for people with diabetes, leading to tremendous morbidity and premature mortality. Research in the field of islet transplantation has demonstrated that replacing insulin-producing β cells can restore euglycemia comparable to individuals without diabetes. However, a short supply of cadaveric islet donors, the technically challenging process of isolating islets, and the requirement for chronic immune suppression have impeded widespread clinical adoption. Rather than relying on cadaveric cells, pluripotent stem cells could serve as a virtually unlimited supply of insulin-producing β cells. Protocols have been developed that mimic the normal in vivo development of the human pancreas to generate pancreatic progenitor cells in vitro. Ongoing investigations have yielded progressively more mature β-like cells in vitro that produce insulin but do not yet fully mimic healthy mature β cells. Alongside development of differentiation protocols, other work has provided insight into potential implantation sites for stem cell-derived islet cells including the subcutaneous space, portal vein, and omentum. To optimize implanted cell survival and function, development of immune modulation therapies is ongoing, including selection of immunomodulatory medications and genetic modification of implanted cells to evade immune responses. Further, macroencapsulation or microencapsulation devices could be used to contain and/or immunoprotect implanted cells from the immune response including by using 3-dimensional bioprinting to facilitate the process. Remarkably, ongoing clinical trials have now yielded the first patient relying on differentiated stem cells rather than syringes as their insulin replacement therapy.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 2","pages":"222-253"},"PeriodicalIF":20.3,"publicationDate":"2023-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9145671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mirela-Diana Ilie, Alexandre Vasiljevic, Philippe Bertolino, Gérald Raverot
{"title":"Biological and Therapeutic Implications of the Tumor Microenvironment in Pituitary Adenomas.","authors":"Mirela-Diana Ilie, Alexandre Vasiljevic, Philippe Bertolino, Gérald Raverot","doi":"10.1210/endrev/bnac024","DOIUrl":"https://doi.org/10.1210/endrev/bnac024","url":null,"abstract":"<p><p>Pituitary adenomas (PAs) are neoplasms derived from the endocrine cells of the anterior pituitary gland. Most frequently, they are benign tumors, but may sometimes display an aggressive course, and in some cases metastasize. Their biology, including their wide range of behavior, is only partly understood. In terms of therapeutic targeting, most PAs are easily treated with available medical treatments, surgery, and sometimes radiotherapy. Nevertheless, gonadotroph adenomas lack medical therapeutic options, and treatment of aggressive PAs and pituitary carcinomas remains challenging. Here, we present an overview of the implications of the tumor microenvironment in PAs, reviewing its composition and function, as well as published cases that have been treated thus far using tumor microenvironment-targeting therapies. Additionally, we discuss emerging views, such as the concept of nonangiogenic tumors, and present perspectives regarding treatments that may represent future potential therapeutic options. Tumor-infiltrating lymphocytes, tumor-associated macrophages, folliculostellate cells, tumor-associated fibroblasts, angiogenesis, as well as the extracellular matrix and its remodeling, all have complex roles in the biology of PAs. They have been linked to hormone production/secretion, size, invasion, proliferation, progression/recurrence, and treatment response in PAs. From a therapeutic perspective, immune-checkpoint inhibitors and bevacizumab have already shown a degree of efficacy in aggressive PAs and pituitary carcinomas, and the use of numerous other tumor microenvironment-targeting therapies can be foreseen. In conclusion, similar to other cancers, understanding the tumor microenvironment improves our understanding of PA biology beyond genetics and epigenetics, and constitutes an important tool for developing future therapies.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 2","pages":"297-311"},"PeriodicalIF":20.3,"publicationDate":"2023-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9521257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rodrigo A Toledo, Camilo Jimenez, Gustavo Armaiz-Pena, Carlota Arenillas, Jaume Capdevila, Patricia L M Dahia
{"title":"Hypoxia-Inducible Factor 2 Alpha (HIF2α) Inhibitors: Targeting Genetically Driven Tumor Hypoxia.","authors":"Rodrigo A Toledo, Camilo Jimenez, Gustavo Armaiz-Pena, Carlota Arenillas, Jaume Capdevila, Patricia L M Dahia","doi":"10.1210/endrev/bnac025","DOIUrl":"https://doi.org/10.1210/endrev/bnac025","url":null,"abstract":"<p><p>Tumors driven by deficiency of the VHL gene product, which is involved in degradation of the hypoxia-inducible factor subunit 2 alpha (HIF2α), are natural candidates for targeted inhibition of this pathway. Belzutifan, a highly specific and well-tolerated HIF2α inhibitor, recently received FDA approval for the treatment of nonmetastatic renal cell carcinomas, pancreatic neuroendocrine tumors, and central nervous system hemangioblastomas from patients with von Hippel-Lindau disease, who carry VHL germline mutations. Such approval is a milestone in oncology; however, the full potential, and limitations, of HIF2α inhibition in the clinic are just starting to be explored. Here we briefly recapitulate the molecular rationale for HIF2α blockade in tumors and review available preclinical and clinical data, elaborating on mutations that might be particularly sensitive to this approach. We also outline some emerging mechanisms of intrinsic and acquired resistance to HIF2α inhibitors, including acquired mutations of the gatekeeper pocket of HIF2α and its interacting partner ARNT. Lastly, we propose that the high efficacy of belzutifan observed in tumors with genetically driven hypoxia caused by VHL mutations suggests that a focus on other mutations that similarly lead to HIF2α stabilization, such as those occurring in neuroendocrine tumors with disruptions in the tricarboxylic acid cycle (SDHA/B/C/D, FH, MDH2, IDH2), HIF hydroxylases (EGLN/PHDs), and the HIF2α-encoding gene, EPAS1, are warranted.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 2","pages":"312-322"},"PeriodicalIF":20.3,"publicationDate":"2023-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9882714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: \"The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty\".","authors":"","doi":"10.1210/endrev/bnac036","DOIUrl":"https://doi.org/10.1210/endrev/bnac036","url":null,"abstract":"","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"44 2","pages":"355"},"PeriodicalIF":20.3,"publicationDate":"2023-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9524546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}