Recent guidelines for diagnostic and therapeutic management of accidentally detected adrenal tumours (incidentaloma) in adults.

At the end of 2023, the European Journal of Endocrinology published the latest guidelines of the European Society of Endocrinology (ESE) on the management of accidentally detected adrenal tumours (incidentalomas) in adults. Comparing them with the previous version of the ESE recommendations from 2016, a tendency towards far-reaching individualisation of the therapeutic and diagnostic approach in patients with adrenal incidentaloma can be seen - it is reflected by changes in the initial assessment of the malignancy of the lesion, in the scope of the proposed hormonal assessment, and qualification for surgery. The latest version of the guidelines includes 9 completely new recommendations, and 5 more recommendations have been significantly changed. Among the most important changes, the introduction of the term "mild autonomous cortisol secretion" (MACS) instead of the previously used term "autonomous cortisol secretion (ACS)" along with more precise recommendations regarding its management should be emphasised. An important novelty is also the modification of the criteria for benign adrenal adenoma, which does not require further imaging observation - due to the results of recent clinical studies, the authors have removed the criteria of size below 4 cm from the definition. Among others, the guidelines also encourage more proactive surgical treatment of indeterminate adrenal incidentaloma in people < 40 years of age and pregnant women. The authors of the recommendations repeatedly accentuate the importance of a multidisciplinary approach in making decisions regarding further management of patients with an unspecified adrenal tumour. Despite a few significant differences compared to the previous version of guidelines, the authors emphasise the presence of gaps in the current scientific evidence, which would not allow for the formulation of more unambiguous recommendations. The need to optimise ordered diagnostic tests, which generate additional socio-economic burdens without negative impact on patients' health, is also an important aspect of the latest guidelines.

Inositols and female reproduction disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)-Women's Endocrinology.

PURPOSE: To provide the latest scientific knowledge on the efficacy of inositols for improving reproductive disorders in women with and without polycystic ovary syndrome (PCOS) and to reach a consensus on their potential use through a Delphi-like process. METHODS: A panel of 17 endocrinologists and 1 gynecologist discussed 4 key domains: menses irregularity and anovulation, fertility, pregnancy outcomes, and neonatal outcomes. RESULTS: A total of eight consensus statements were drafted. Myo-inositol (Myo) supplementation can be used to improve menses irregularities and anovulation in PCOS. Myo supplementation can be used in subfertile women with or without PCOS to reduce the dose of r-FSH for ovarian stimulation during IVF, but it should not be used to increase the clinical pregnancy rate or live birth rate. Myo supplementation can be used in the primary prevention of gestational diabetes mellitus (GDM), but should not be used to improve pregnancy outcomes in women with GDM. Myo can be preconceptionally added to folic acid in women with a previous neural tube defects (NTD)-complicated pregnancy to reduce the risk of NTDs in newborns. Myo can be used during pregnancy to reduce the risk of macrosomia and neonatal hypoglycemia in mothers at risk of GDM. CONCLUSION: This consensus statement provides recommendations aimed at guiding healthcare practitioners in the use of inositols for the treatment or prevention of female reproductive disorders. More evidence-based data are needed to definitively establish the usefulness of Myo, the appropriate dosage, and to support the use of D-chiro-inositol (DCI) or a definitive Myo/DCI ratio.

Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline.

BACKGROUND: Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. OBJECTIVE: To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. METHODS: A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. RESULTS: The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D-containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. CONCLUSION: The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.

[When should a patient with obesity be referred to endocrinology? Current indications for bariatric surgery]. / ¿Cuándo derivar a endocrinología el paciente con obesidad? Indicaciones actuales de la cirugía bariátrica.

Bariatric surgery (BS) has been shown to be effective and efficient, but only 1% of selected patients will ever receive it. Compared to medical treatment of obesity, BS has demonstrated greater long-term sustained weight loss, a reduction in both total and cardiovascular (CV) mortality, improvement or remission of CV risk factors and other comorbidities associated with obesity, as well as improved mobility and quality of life. BS presents similar risks to other abdominal surgeries, with obesity as an added risk factor. However, mortality after this type of surgery is less than 1%, being in specialised centres even lower than 0.3%, with a morbidity of less than 7%. The most commonly performed surgical procedures at present are vertical gastrectomy and Roux---Y gastric bypass, preferably by laparoscopic approach.

Standardized Reproductive Endocrinology and Infertility Consultation for Pediatric and Adolescent Oncology Patients.

Purpose: To investigate the role of formal reproductive endocrinology and infertility (REI) consultation in fertility preservation counseling in a pediatric/adolescent oncology patient population. Methods: Retrospective chart review was performed at an academic adult hospital from 2021 to 2022. Pre- and postpubertal patients admitted to the pediatric/adolescent oncology service with cancer diagnoses and imminent gonadotoxic chemotherapy plans were included. Baseline characteristics were collected, including patient age, sex, race, language, insurance, and cancer diagnosis. Primary outcomes were formal REI consultation and fertility preservation election. Results: Nineteen of 58 eligible patients received a formal REI consultation. Patients were more likely to elect fertility preservation if they received a consult. Females were more likely to receive a consult than males and more likely to elect fertility preservation. Patients of age ≥16 years were more likely to receive consultation than younger patients. However, all patients of age <16 years who received a consult elected fertility preservation. There was no difference in consultation based on race, language, or insurance. Thirteen of 19 patients who received an REI consultation elected fertility preservation. Ten of 11 female elections were ovarian suppression, an unproven method of fertility preservation. The two male elections were semen cryopreservation. Conclusion: Underutilization of formal REI consults and a relative lack of proven fertility preservation elections may shed light on a need for increased fertility preservation awareness among young oncology patients and the providers who care for them. A streamlined process that automates formal REI consultation for all eligible patients may maximize the potential for comprehensive counseling and improve patient participation in fertility preservation.

Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes.

Improvement of glucose levels into the normal range can occur in some people living with diabetes, either spontaneously or after medical interventions, and in some cases can persist after withdrawal of glucose-lowering pharmacotherapy. Such sustained improvement may now be occurring more often due to newer forms of treatment. However, terminology for describing this process and objective measures for defining it are not well established, and the long-term risks versus benefits of its attainment are not well understood. To update prior discussions of this issue, an international expert group was convened by the American Diabetes Association to propose nomenclature and principles for data collection and analysis, with the goal of establishing a base of information to support future clinical guidance. This group proposed "remission" as the most appropriate descriptive term, and HbA1c < 6.5% (48 mmol/mol) measured at least 3 months after cessation of glucose-lowering pharmacotherapy as the usual diagnostic criterion. The group also made suggestions for active observation of individuals experiencing a remission and discussed further questions and unmet needs regarding predictors and outcomes of remission.

Consensus report: Definition and interpretation of remission in type 2 diabetes.

Improvement of glucose levels into the normal range can occur in some people living with diabetes, either spontaneously or after medical interventions, and in some cases can persist after withdrawal of glucose-lowering pharmacotherapy. Such sustained improvement may now be occurring more often due to newer forms of treatment. However, terminology for describing this process and objective measures for defining it are not well established, and the long-term risks versus benefits of its attainment are not well understood. To update prior discussions of this issue, an international expert group was convened by the American Diabetes Association to propose nomenclature and principles for data collection and analysis, with the goal of establishing a base of information to support future clinical guidance. This group proposed "remission" as the most appropriate descriptive term, and HbA1c <6.5% (48 mmol/mol) measured at least 3 months after cessation of glucose-lowering pharmacotherapy as the usual diagnostic criterion. The group also made suggestions for active observation of individuals experiencing a remission and discussed further questions and unmet needs regarding predictors and outcomes of remission.

Influence of endocrine multidisciplinary tumor board on patient management and treatment decision making.

BACKGROUND: Multidisciplinary Tumor Boards (MDT) are used to obtain input regarding cancer management. This study assessed the impact of our institutional Endocrine MDT. METHODS: MDT notes on patients with thyroid cancer treated during 2012-2018 were abstracted retrospectively from the electronic medical record. Management change (MC) was prospectively collected by the MDT coordinator. Biannual evaluations reviewed the impact of the MDT as observed by attendees. RESULTS: MC was recommended in 47 (15%) of 286 presentations, with additional imaging being the most frequent (43%). Presentation of recurrences were more likely to result in MC (24% vs. 13% initial, p = 0.03). Overall, 98% of attendees found the conference exceeded educational expectations. About 24% reported intending to use a more evidence/guideline-based approach after attending and this trend increased over time (p = 0.002). CONCLUSION: MDT presentations led to a higher rate of MC particularly in recurrent TC patients and increased evidenced-based practice for attendees.

ENDOCRINOLOGY IN THE TIME OF COVID-19-2021 UPDATES: The management of diabetes insipidus and hyponatraemia.

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counselling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of postoperative SIAD. They should know hyponatraemia symptoms. Hyponatraemia in COVID-19 is common with a prevalence of 20-30% and is mostly due to SIAD or hypovolaemia. It mirrors disease severity and is an early predictor of mortality. Hypernatraemia may also develop in COVID-19 patients, with a prevalence of 3-5%, especially in ICU, and derives from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.

The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy.

Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). Choice of treatment should be based on the assessment of clinical activity and severity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smoking, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments, and selenium (selenium-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight-threatening GO, antithyroid drugs are preferred when managing Graves' hyperthyroidism. In moderate-to-severe and active GO i.v. glucocorticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safety profile, costs and reimbursement, drug availability, long-term effectiveness, and patient choice after extensive counseling, a combination of i.v. methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 g of i.v. methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, higher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplopia. Second-line treatments for moderate-to-severe and active GO include (a) the second course of i.v. methylprednisolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, (b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; (c) orbital radiotherapy combined with oral or i.v. glucocorticoids, (d) teprotumumab; (e) rituximab and (f) tocilizumab. Sight-threatening GO is treated with several high single doses of i.v. methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint, and eyelid surgery) is indicated for inactive residual GO manifestations.

Synacthen Stimulation Test Following Unilateral Adrenalectomy Needs to Be Interpreted With Caution.

Background: Cortisol levels in response to stress are highly variable. Baseline and stimulated cortisol levels are commonly used to determine adrenal function following unilateral adrenalectomy. We report the results of synacthen stimulation testing following unilateral adrenalectomy in a tertiary referral center. Methods: Data were collected retrospectively for 36 patients who underwent synacthen stimulation testing one day post unilateral adrenalectomy. None of the patients had clinical signs of hypercortisolism preoperatively. No patient received pre- or intraoperative steroids. Patients with overt Cushing's syndrome were excluded. Results: The median age was 58 (31-79) years. Preoperatively, 16 (44%) patients had a diagnosis of pheochromocytoma, 12 (33%) patients had primary aldosteronism and 8 (22%) patients had non-functioning adenomas with indeterminate/atypical imaging characteristics necessitating surgery. Preoperative overnight dexamethasone suppression test results revealed that 6 of 29 patients failed to suppress cortisol to <50 nmol/L. Twenty (56%) patients achieved a stimulated cortisol ≥450 nmol/L at 30 minutes and 28 (78%) at 60 minutes. None of the patients developed clinical adrenal insufficiency necessitating steroid replacement. Conclusions: Synacthen stimulation testing following unilateral adrenalectomy using standard stimulated cortisol cut-off values would wrongly label many patients adrenally insufficient and may lead to inappropriate prescriptions of steroids to patients who do not need them.

A Predictive Nomogram for Red Blood Cell Transfusion in Pheochromocytoma Surgery: A Study on Improving the Preoperative Management of Pheochromocytoma.

Purpose: Surgery is the major treatment option for pheochromocytoma but carries potential risks, including hemorrhage and hemodynamic instability. Even with laparoscopic adrenalectomy, intraoperative blood transfusion happens from time to time, but few studies have investigated risk factors. For the first time we develop and validate a nomogram for prediction of red blood cell transfusion in pheochromocytoma surgery. Methods: There were 246 patients in our center and 56 patients in Peking Union Medical College Hospital, who underwent pheochromocytoma surgery, enrolled in the study. We incorporated clinical and radiological risk factors, and presented this with a nomogram. Lasso regression model was used for feature selection. Logistic regression analysis was performed to identify the odd ratios. The performance of the nomogram was assessed with respect to its discrimination, calibration and clinical usefulness. Results: Thirty-two features were reduced to five, which were phenoxybenzamine use, phenoxybenzamine treatment duration, preinduction heart rate, tumor diameter and surgical procedure. The model showed good discrimination (C-index, 0.857; 95% CI, 0.781-0.836) and application in the validation sets also gave good discrimination (internal validation: C-index, 0.831; 95% CI, 0.750-0.822; external validation: C-index, 0.924; 95% CI, 0.766-1.000). Calibration tested with the Hosmer-Lemeshow test yielded a good agreement between prediction and observation (training P=0.358; internal validation P=0.205; external validation P=0.395). Odd ratios of phenoxybenzamine use, phenoxybenzamine treatment duration, preinduction HR, tumor diameter and open surgery were 13.32 (95% CI, 1.48-197.38; P = 0.034), 1.04 (95% CI, 0.99-1.08; P = 0.092), 1.04 (95% CI, 1.01-1.08; P=0.006), 1.03 (95% CI, 1.02-1.06; P<0.001), 17.13 (95% CI, 5.18-78.79; P<0.001), respectively. Decision curve analysis demonstrated the clinical usefulness of the nomogram. Conclusions: This study presents a nomogram that may be used to facilitate the prediction of red blood cell transfusion in pheochromocytoma surgery and help to do the preoperative management more efficiently.

Glucocorticoid use in patients with adrenal insufficiency following administration of the COVID-19 vaccine: a pituitary society statement.

PURPOSE: Side effects of the coronavirus disease 2019 (COVID-19) vaccines include pain at the injection site, fatigue, headache, myalgias, arthralgias, chills, and fever, all of which can be early indicators of an increased need for glucocorticoid replacement in patients with adrenal insufficiency. The Pituitary Society surveyed its membership to understand planned approaches to glucocorticoid management in patients with adrenal insufficiency who will receive a COVID-19 vaccine. METHODS: Members were asked to complete up to 3 questions regarding their planned approach for use of glucocorticoid replacement in patients with proven adrenal insufficiency. RESULTS: Surveys were sent to 273 members and 103 responded. Thirty-six percent plan to recommend that patients automatically increase glucocorticoid dosage with administration of the first vaccine injection. Of these, 84% plan to increase glucocorticoid dose on the day of vaccination, and 49% plan to increase glucocorticoid dose prior to vaccination. Of the 64% who do not plan to recommend automatic glucocorticoid dose increase with vaccine administration, 88% plan to increase the dose if the patient develops a fever, and 47% plan to increase the dose if myalgias and arthralgias occur. CONCLUSIONS: Most clinicians plan to maintain the current glucocorticoid dose with vaccine administration. The vast majority plan and to increase glucocorticoid dose in case of fever, and just under half in case of arthralgias and myalgias. These survey results offer suggested management guidance for glucocorticoid management in patients with adrenal insufficiency.

Discrepancies in the Recommended Management of Adrenal Incidentalomas by Various Guidelines.

PURPOSE: Adrenal incidentalomas are being discovered with increasing frequency, and their discovery poses a challenge to clinicians. Despite the 2002 National Institutes of Health consensus statement, there are still discrepancies in the most recent guidelines from organizations representing endocrinology, endocrine surgery, urology and radiology. We review recent guidelines across the specialties involved in diagnosing and treating adrenal incidentalomas, and discuss points of agreement as well as controversy among guidelines. MATERIALS AND METHODS: PubMed®, Scopus®, Embase™ and Web of Science™ databases were searched systematically in November 2019 in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement to identify the most recently updated committee produced clinical guidelines in each of the 4 specialties. Five articles met the inclusion criteria. RESULTS: There is little debate among the reviewed guidelines as to the initial evaluation of an adrenal incidentaloma. All patients with a newly discovered adrenal incidentaloma should receive an unenhanced computerized tomogram and hormone screen. The most significant points of divergence among the guidelines regard reimaging an initially benign appearing mass, repeat hormone testing and management of an adrenal incidentaloma that is not easily characterized as benign or malignant on computerized tomography. The guidelines range from actively recommending against any repeat imaging and hormone screening to recommending a repeat scan as early as in 3 to 6 months and annual hormonal screening for several years. CONCLUSIONS: After reviewing the guidelines and the evidence used to support them we posit that best practices lie at their convergence and have presented our management recommendations on how to navigate the guidelines when they are discrepant.

AHNS endocrine surgery section consensus statement on nasopharyngolaryngoscopy and clinic reopening during COVID-19: How to get back to optimal safe care.

This article provides best practice guidelines regarding nasopharyngolaryngoscopy and OHNS clinic reopening during the COVID-19 pandemic. The aim is to provide evidence-based recommendations defining the risks of COVID-19 in clinic, the importance of pre-visit screening in addition to testing, along with ways to adhere to CDC guidelines for environmental, source, and engineering controls.

ENSAT registry-based randomized clinical trials for adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.

Medical management of adrenocortical carcinoma: Current recommendations, new therapeutic options and future perspectives.

Adrenocortical carcinoma is a rare malignant tumor of poor prognosis, frequently requiring additional treatments after initial surgery. Due to its adrenolytic action, mitotane has become the first-line medical treatment in patients with aggressive adrenocortical carcinoma. Over the last 2years, apart from the classical chemotherapy based on etoposide and platinum salts, several studies reported the use of drugs such as temozolomide, tyrosine kinase inhibitors or immunotherapy, with more or less convincing results. The aim of this review is to give further insights in the use of these drugs, and to describe potential therapeutic perspectives based on recent pangenomic studies, for the future management of these still difficult to treat tumors.