Search for other papers by Orwa Dandash in
Google Scholar
PubMed
Search for other papers by James Allebone in
Google Scholar
PubMed
Search for other papers by Adam Mirabelli in
Google Scholar
PubMed
Search for other papers by Nicholas Russell in
Google Scholar
PubMed
Search for other papers by Mathis Grossmann in
Google Scholar
PubMed
Department of Florey Institute, University of Melbourne, Parkville, Victoria, Australia
Search for other papers by Andrea Gogos in
Google Scholar
PubMed
Search for other papers by Richard A Kanaan in
Google Scholar
PubMed
We investigated the effect of estradiol add-back therapy (EAT) on brain activation related to cognitive function and affect in addition to putative changes in gray and white matter volume in testosterone depleted participants with prostate cancer. We conducted a randomized controlled, double-blinded trial in which 40 patients received 0.9 mg of transdermal estradiol per day for 6 months or matched placebo. Anatomical MRI and three functional MRI (fMRI) scans were obtained for the emotion recognition task, verbal memory task, and visuospatial memory task. Activation in corresponding cognitive and affective brain networks was demonstrated for all tasks. Longitudinally, there was no difference in brain activation, reaction time, or accuracy in response to the fMRI tasks between the EAT group and placebo group at 6 months. In addition, there was no detectable change in whole-brain gray or white matter volume or in hippocampal volume between the two groups after 6 months. This study supports earlier findings that EAT does not improve verbal memory or affect and has no immediate effect on hippocampal volume in testosterone depleted patients with prostate cancer.
Search for other papers by Sonja Kunz in
Google Scholar
PubMed
Search for other papers by Xiao Wang in
Google Scholar
PubMed
Search for other papers by Uta Ferrari in
Google Scholar
PubMed
Search for other papers by Michael Drey in
Google Scholar
PubMed
Search for other papers by Marily Theodoropoulou in
Google Scholar
PubMed
Search for other papers by Katharina Schilbach in
Google Scholar
PubMed
Search for other papers by Martin Reincke in
Google Scholar
PubMed
KORA Study Centre, University Hospital of Augsburg, Augsburg, Augsburg, Germany
Search for other papers by Margit Heier in
Google Scholar
PubMed
German Centre for Cardiovascular Research (DZHK), Partner site Munich Heart Alliance, Munich, Germany
Search for other papers by Annette Peters in
Google Scholar
PubMed
German Heart Centre Munich, Technical University of Munich, Munich, Germany
Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
Search for other papers by Wolfgang Koenig in
Google Scholar
PubMed
German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany
Search for other papers by Tanja Zeller in
Google Scholar
PubMed
Search for other papers by Barbara Thorand in
Google Scholar
PubMed
Search for other papers by Martin Bidlingmaier in
Google Scholar
PubMed
Objective
Measurements utilizing commercially available sets of reagents for determination of steroid hormone profiles by liquid chromatography–tandem mass spectrometry (LC-MS/MS) have become increasingly important for routine laboratories. However, method-specific publications of reference intervals obtained from sufficiently large studies are often missing.
Methods
After validation of performance characteristics, a widely available kit for steroid analysis by LC-MS/MS was used to measure concentrations of 15 endogenous steroids (aldosterone, cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate, estradiol, testosterone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, 17-hydroxyprogesterone, 11-deoxycorticosterone, progesterone) in more than 500 blood samples from a population-based study. While randomly selected from a larger cohort, the samples equally represented both sexes and covered a wide range of adult age groups. Age- and sex-specific reference intervals were calculated, and correlation with BMI was assessed.
Results
Performance characteristics of the assay matched expectations for 9 of 15 steroids. For most of them, reference intervals obtained from our study population were comparable to those reported by others, with age and sex being the major determinants. A sex-specific correlation with BMI was found for seven steroids. We identified limitations regarding sensitivity of the method for quantification of progesterone in males and postmenopausal females. Concentrations of aldosterone, 21-deoxycortisol, estradiol, 11-deoxycorticosterone, and dihydrotestosterone could not be quantified in a large percentage of samples.
Conclusions
The reference intervals for nine steroids will support meaningful interpretation for steroid profiles as measured by a widely used kit for LC-MS/MS-based quantification. Laboratories using such kits must be aware of potential limitations in sensitivity for some steroids included in the profile.
Significance Statement
Quantification of steroid hormones is a cornerstone for diagnosis of several diseases. Commonly used immunoassays have limitations in specificity. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) is a promising alternative, particularly if methods are harmonized across laboratories. The use of kits from commercial suppliers might support this. Clinical interpretation of steroid concentrations requires availability of appropriate reference intervals (RIs), but studies on RIs reported in the literature differ in preanalytical and analytical procedures. Here, we provide RIs for steroids measured by a widely available kit under preanalytical conditions mirroring common clinical practice. Such RIs might facilitate interpretation for those using the same method and comparable conditions in clinical routine.
Search for other papers by Enrique Pedernera in
Google Scholar
PubMed
Search for other papers by Flavia Morales-Vásquez in
Google Scholar
PubMed
Search for other papers by María J Gómora in
Google Scholar
PubMed
Search for other papers by Miguel A Almaraz in
Google Scholar
PubMed
Universidad La Salle, Posgrado de la Facultad de Ciencias Químicas, Ciudad de México, México
Search for other papers by Esteban Mena in
Google Scholar
PubMed
Search for other papers by Delia Pérez-Montiel in
Google Scholar
PubMed
Search for other papers by Elizabeth Rendon in
Google Scholar
PubMed
Search for other papers by Horacio López-Basave in
Google Scholar
PubMed
Search for other papers by Juan Maldonado-Cubas in
Google Scholar
PubMed
Search for other papers by Carmen Méndez in
Google Scholar
PubMed
The incidence of ovarian cancer has been epidemiologically related to female reproductive events and hormone replacement therapy after menopause. This highlights the importance of evaluating the role of sexual steroid hormones in ovarian cancer by the expression of enzymes related to steroid hormone biosynthesis in the tumor cells. This study was aimed to evaluate the presence of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), aromatase and estrogen receptor alpha (ERα) in the tumor cells and their association with the overall survival in 111 patients diagnosed with primary ovarian tumors. Positive immunoreactivity for 17β-HSD1 was observed in 74% of the tumors. In the same samples, aromatase and ERα revealed 66% and 47% positivity, respectively. No association was observed of 17β-HSD1 expression with the histological subtypes and clinical stages of the tumor. The overall survival of patients was improved in 17β-HSD1-positive group in Kaplan–Meier analysis (P = 0.028), and 17β-HSD1 expression had a protective effect from multivariate proportional regression evaluation (HR = 0.44; 95% CI 0.24–0.9; P = 0.040). The improved survival was observed in serous epithelial tumors but not in nonserous ovarian tumors. The expression of 17β-HSD1 in the cells of the serous epithelial ovarian tumors was associated with an improved overall survival, whereas aromatase and ERα were not related to a better survival. The evaluation of hazard risk factors demonstrated that age and clinical stage showed worse prognosis, and 17β-HSD1 expression displayed a protective effect with a better survival outcome in patients of epithelial ovarian tumors.
Search for other papers by Peiwen Wu in
Google Scholar
PubMed
Search for other papers by Dongjie He in
Google Scholar
PubMed
Search for other papers by Hao Chang in
Google Scholar
PubMed
Search for other papers by Xiaozhi Zhang in
Google Scholar
PubMed
Background
Updated epidemiological data of neuroendocrine tumors are currently lacking. Thus, we performed epidemiological and survival analyses on a large cohort of patients with neuroendocrine tumors and developed a new nomogram to predict survival.
Methods
This population-based study examined 112,256 patients with neuroendocrine tumors between 2000 and 2018 using data from the Surveillance, Epidemiology, and End Results program.
Results
The age-adjusted incidence per 100,000 persons of neuroendocrine tumors increased from 4.90 in 2000 to 8.19 in 2018 (annual percentage change, 3.40; 95% confidence interval, 3.13–3.67), with the most significant increases in grade 1, localized stage, and appendix neuroendocrine tumors. The age-adjusted mortality rate increased 3.1-fold from 2000 to 2018 (annual percentage change, 4.14; 95% confidence interval, 3.14–5.15). The 1-, 5-, and 10-year relative survival rates for all neuroendocrine tumors were 80.5%, 68.4%, and 63.5%, respectively. Multivariate analyses showed that male sex; older age; Black, American Indian, and Alaska Native populations; earlier year of diagnosis; lung neuroendocrine tumors; higher grades; and later stage were associated with a worse prognosis and that disease stage and grade were the most important risk factors for prognosis. Furthermore, we established a nomogram to predict the 3-, 5-, and 10-year survival rates, and its discrimination ability was better than that of the TNM classification.
Conclusions
The incidence, prevalence, and mortality rate of neuroendocrine tumors continued to increase over the last two decades. Additionally, the nomogram could accurately quantify the risk of death in patients with neuroendocrine tumors and had good clinical practicability.
Search for other papers by Margarida Brito in
Google Scholar
PubMed
Search for other papers by Susana Prazeres in
Google Scholar
PubMed
Search for other papers by Marta Malheiros in
Google Scholar
PubMed
Background
Fulvestrant resembles estradiol in its structure. Reports have been published concerning fulvestrant measured as estradiol by the immunoassays. This may induce falsely elevated estradiol results and wrongly impact medical decisions. Our aim was to confirm the interference of fulvestrant on estradiol concentration and test a method to identify the false results.
Methods
Four serum samples with low estradiol levels were spiked with fulvestrant at various concentrations. Estradiol was then measured directly on serum (Dir), after a 1:5 dilution (Dil), and a ratio Dil/Dir was estimated. On the second part of the study, estradiol results (Dir, Dil and ratio Dil/Dir) from 14 women treated with fulvestrant were analysed, as well as from 14 patients not under this treatment.
Results
The addition of exogenous fulvestrant to the serum samples induced a gradual rise on estradiol concentration with a mean ratio for the Dil/Dir samples of 2.1 ± 0.4 (range 1.7–2.9). Patients on fulvestrant treatment experienced a mean ratio for the Dil/Dir estradiol sample of 2.4 ± 0.4 (range 1.6–3.0). In the control group, a mean estradiol ratio Dil/Dir of 1.1 ± 0.1 was observed (range 0.8–1.3). No correlation between the number of days after fulvestrant injection and estradiol result (r = 0.531) was observed.
Conclusion
Our study confirmed the interference of fulvestrant in the estradiol measurement by immunoassay. When fulvestrant was present, the estradiol ratio for Dil/Dir sample was about 2. In the control group, the ratio was around 1. The estradiol Dil/Dir ratio is a simple tool which can be used to identify fulvestrant false immunoassay estradiol results.
Leeds Institute for Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, UK
Search for other papers by Nikolaos Kyriakakis in
Google Scholar
PubMed
Search for other papers by Marilena Giannoudi in
Google Scholar
PubMed
Search for other papers by Satish S Kumar in
Google Scholar
PubMed
Leeds Institute for Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, UK
Search for other papers by Khyatisha Seejore in
Google Scholar
PubMed
Search for other papers by Georgios K Dimitriadis in
Google Scholar
PubMed
Search for other papers by Harpal Randeva in
Google Scholar
PubMed
Leeds Institute of Medical Research, University of Leeds, UK
Search for other papers by Adam Glaser in
Google Scholar
PubMed
Search for other papers by Michelle Kwok-Williams in
Google Scholar
PubMed
Search for other papers by Georgina Gerrard in
Google Scholar
PubMed
Search for other papers by Carmel Loughrey in
Google Scholar
PubMed
Search for other papers by Ahmed Al-Qaissi in
Google Scholar
PubMed
Search for other papers by Ramzi Ajjan in
Google Scholar
PubMed
Search for other papers by Julie Lynch in
Google Scholar
PubMed
Leeds Institute for Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, UK
Search for other papers by Robert D Murray in
Google Scholar
PubMed
Background
Survivors of childhood brain tumours (SCBT) and teenage and young adult cancer survivors have an adverse cardiovascular risk profile, which translates into an increased vascular mortality. Data on cardiovascular risk profiles in SCBT are limited, and furthermore, there are no data in adult-onset (AO) brain tumours.
Patients and
methods: Fasting lipids, glucose, insulin, 24-h blood pressure (BP), and body composition were measured in 36 brain tumour survivors (20 AO; 16 childhood-onset (CO)) and 36 age- and gender-matched controls.
Results
Compared with controls, patients had elevated total cholesterol (5.3 ± 1.1 vs 4.6 ± 1.0 mmol/L, P = 0.007), LDL-C (3.1 ± 0.8 vs 2.7 ± 0.9 mmol/L, P = 0.011), insulin (13.4 ± 13.1 vs 7.6 ± 3.3 miu/L, P = 0.014), and increased insulin resistance (homeostatic model assessment for insulin resistance (HOMA-IR) 2.90 ± 2.84 vs 1.66 ± 0.73, P = 0.016). Patients showed adverse body composition, with increased total body fat mass (FM) (24.0 ± 12.2 vs 15.7 ± 6.6 kg, P < 0.001) and truncal FM (13.0 ± 6.7 vs 8.2 ± 3.7 kg, P < 0.001).
After stratification by timing of onset, CO survivors showed significantly increased LDL-C, insulin, and HOMA-IR compared with controls. Body composition was characterized by the increased total body and truncal FM. Truncal fat mass was increased by 84.1% compared with controls. AO survivors showed similar adverse cardiovascular risk profiles, with increased total cholesterol and HOMA-IR. Truncal FM was increased by 41.0% compared with matched controls (P = 0.029). No difference in mean 24-h BP was noted between patients and controls irrespective of the timing of cancer diagnosis.
Conclusion
The phenotype of both CO and AO brain tumour survivors is characterized by an adverse metabolic profile and body composition, putatively placing long-term survivors at increased risk of vascular morbidity and mortality.
Search for other papers by Ruth Percik in
Google Scholar
PubMed
Search for other papers by Sherwin Criseno in
Google Scholar
PubMed
Search for other papers by Safwaan Adam in
Google Scholar
PubMed
Search for other papers by Kate Young in
Google Scholar
PubMed
Royal Marsden Hospital, London, UK
Search for other papers by Daniel L Morganstein in
Google Scholar
PubMed
Checkpoint inhibitors are now widely used in the management of many cancers. Endocrine toxicity is amongst the most common side effects. These endocrinopathies differ from most other immune-related toxicities in frequently being irreversible and rarely requiring cessation of checkpoint inhibitor therapy. This review considers an approach to the presentation and diagnosis of endocrinopathies, compared to classical endocrine diagnosis, suggesting improvements to classification and treatment based on fundamental endocrine principles. These will help to align management with other similar endocrine conditions and standardise the diagnosis and reporting of endocrine toxicity of checkpoint inhibitors to improve both endocrine and oncological care. In particular, the importance of considering any inflammatory phase (such as painful thyroiditis or hypophysitis resulting in the pituitary enlargement), from the endocrine consequences (transient hyperthyroidism followed by hypothyroidism, pan-hypopituitarism or isolated adrenocorticotrophic hormone deficiency), is highlighted. It is also important to consider the potential confounder of exogenous corticosteroids in adrenal suppression.
Search for other papers by Kaili Yang in
Google Scholar
PubMed
Search for other papers by Jiarui Li in
Google Scholar
PubMed
Search for other papers by Yuejuan Cheng in
Google Scholar
PubMed
Search for other papers by Chunmei Bai in
Google Scholar
PubMed
Background
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogenous malignancies that require well-designed trials to develop effective management strategies. This cross-sectional study aimed to illustrate the current landscape of clinical trials in GEP-NENs to provide insights for future research.
Materials and methods
We reviewed all clinical trials registered on ClinicalTrials.gov between 1 January 2000 and 31 December 2021 with GEP-NEN in the ‘condition or disease’ field.
Results
We included 206 eligible trials. Most trials enrolled less than 50 patients (59.8%) and were sponsored by institutions other than government or industry (67.0%). Most trials were conducted in high-income countries (86.6%) and countries located in Europe (30.1%) or Northern America (29.6%). The overall result reporting rates of GEP-NEN trials was 41.4%, and the median time from primary completion to result reporting was 101 months. Characteristics that improved the reporting of results included larger sample size, tumor differentiation specification for inclusion, progression-free survival as primary endpoint, industry sponsorship, and multicenter or multinational participation (all P < 0.05). Compared with trials registered between 2000 and 2011 (n = 28), trials registered between 2012 and 2021 (n = 178) were more likely to specify the Ki-67 index for inclusion (68.0% vs 35.7%, P = 0.002) and to be conducted outside Europe or Northern America (16.4% vs 3.7%, P = 0.02), while the sample size and the sponsorship did not change significantly.
Conclusions
Novel management options have been explored for GEP-NENs with more specific inclusion criteria during the past two decades. More efforts are needed to promote international collaborations in clinical trials and enhance timely result dissemination.
Search for other papers by Hélène Singeisen in
Google Scholar
PubMed
Search for other papers by Mariko Melanie Renzulli in
Google Scholar
PubMed
Search for other papers by Vojtech Pavlicek in
Google Scholar
PubMed
Search for other papers by Pascal Probst in
Google Scholar
PubMed
Search for other papers by Fabian Hauswirth in
Google Scholar
PubMed
Search for other papers by Markus K Muller in
Google Scholar
PubMed
Search for other papers by Magdalene Adamczyk in
Google Scholar
PubMed
Search for other papers by Achim Weber in
Google Scholar
PubMed
Search for other papers by Reto Martin Kaderli in
Google Scholar
PubMed
Search for other papers by Pietro Renzulli in
Google Scholar
PubMed
Objective
Multiple endocrine neoplasia type 4 (MEN4) is caused by a CDKN1B germline mutation first described in 2006. Its estimated prevalence is less than one per million. The aim of this study was to define the disease characteristics.
Methods
A systematic review was performed according to the PRISMA 2020 criteria. A literature search from January 2006 to August 2022 was done using MEDLINE® and Web of ScienceTM.
Results
Forty-eight symptomatic patients fulfilled the pre-defined eligibility criteria. Twenty-eight different CDKN1B variants, mostly missense (21/48, 44%) and frameshift mutations (17/48, 35%), were reported. The majority of patients were women (36/48, 75%). Men became symptomatic at a median age of 32.5 years (range 10–68, mean 33.7 ± 23), whereas the same event was recorded for women at a median age of 49.5 years (range 5–76, mean 44.8 ± 19.9) (P = 0.25). The most frequently affected endocrine organ was the parathyroid gland (36/48, 75%; uniglandular disease 31/36, 86%), followed by the pituitary gland (21/48, 44%; hormone-secreting 16/21, 76%), the endocrine pancreas (7/48, 15%), and the thyroid gland (4/48, 8%). Tumors of the adrenal glands and thymus were found in three and two patients, respectively. The presenting first endocrine pathology concerned the parathyroid (27/48, 56%) and the pituitary gland (11/48, 23%). There were one (27/48, 56%), two (13/48, 27%), three (3/48, 6%), or four (5/48, 10%) syn- or metachronously affected endocrine organs in a single patient, respectively.
Conclusion
MEN4 is an extremely rare disease, which most frequently affects women around 50 years of age. Primary hyperparathyroidism as a uniglandular disease is the leading pathology.
Faculty of Medicine Division 2, Internal Medicine Endocrinology, Leiden University Medical Centre, Leiden, The Netherlands
Search for other papers by E K White in
Google Scholar
PubMed
Search for other papers by I V Wagner in
Google Scholar
PubMed
Faculty of Medicine Division 2, Internal Medicine Endocrinology, Leiden University Medical Centre, Leiden, The Netherlands
Search for other papers by C van Beuzekom in
Google Scholar
PubMed
Search for other papers by V Iotova in
Google Scholar
PubMed
Department of Paediatrics, UMHAT ‘Sveta Marina’ Varna, Medical University of Varna, Varna, Bulgaria
Search for other papers by S F Ahmed in
Google Scholar
PubMed
Search for other papers by O Hiort in
Google Scholar
PubMed
Search for other papers by A M Pereira in
Google Scholar
PubMed
In 2017, the European Commission installed 24 European Reference Networks (ERNs) for different categories of rare and complex conditions to facilitate cross-border health care via virtual case consultations in a secure Clinical Patient Management System (CPMS). The ERN for rare endocrine conditions (Endo-ERN) previously reviewed the CPMS, in which they detailed the difficulties physicians encountered with the system and proposed solutions to these that should enable the system to be used to a greater extent. This paper will further the endeavor of the first by performing a critical evaluation of the CPMS, assessing how these suggested improvements have been implemented, and if these have affected the usage of the system. The evaluation involves an assessment of CPMS usage statistics since its conception that takes into consideration the technical updates and the external factors that may have affected these, including data from a review survey following a training workshop for our new healthcare providers (HCPs) added in January 2022. It appears that the improvements made to the system since the first review, in particular the implementation of the Operational Helpdesk, have had a positive effect in increasing CPMS membership; however, the regular usage of the system continues to fluctuate. Several suggestions are made on how to further facilitate the use of CPMS by our members both individually and network-wide, by integrating CPMS activities with other network initiatives and further integrating these into national health care systems as well as looking for ways to measure patient satisfaction from the CPMS discussions outcomes.
