Thyroid cancer under the scope of emerging technologies.

The vast majority of thyroid cancers originate from follicular cells. We outline outstanding issues at each step along the path of cancer patient care, from prevention to post-treatment follow-up and highlight how emerging technologies will help address them in the coming years. Three directions will dominate the coming technological landscape. Genomics will reveal tumoral evolutionary history and shed light on how these cancers arise from the normal epithelium and the genomics alteration driving their progression. Transcriptomics will gain cellular and spatial resolution providing a full account of intra-tumor heterogeneity and opening a window on the microenvironment supporting thyroid tumor growth. Artificial intelligence will set morphological analysis on an objective quantitative ground laying the foundations of a systematic thyroid tumor classification system. It will also integrate into unified representations the molecular and morphological perspectives on thyroid cancer.

Endocrine Surgery Patients' and Providers' Perceptions of Telemedicine in the COVID Era.

BACKGROUND: Telemedicine has become a key modality for health care delivery during the COVID-19 pandemic, including for endocrine surgery. Little data exists on patients' and referring endocrinologists' perspectives of its use. The study aimed to assess and compare endocrine surgery patients' attitudes about telemedicine to that of referring endocrinologists. METHOD: Patients from a regional endocrine surgery practice and referring endocrinologists were sent surveys about their perspectives on telemedicine use. RESULTS: Fifty two patients responded: average age was 58.3 years; 78% were female; 33% were Black. Sixteen referring endocrinologists responded: average age was 52.4 years; 62.5% were female. Nearly all patients (92%) and providers (100%) would try telemedicine or use it again. Providers were more likely than patients to use telemedicine because of COVID-19 (100% versus 70.6%, P = 0.03). Patients were more concerned about the lack of personal connection with telemedicine than providers (60.8% versus 25.0%, P = 0.02). Endocrinologists were more interested in using telemedicine to review abnormal results (81.3% versus 35.3%, P <0.01), and more patients were specifically disinterested in reviewing abnormal results via telemedicine (54.9% versus 6.3%, P = 0.04). Patients were more interested in its use for postoperative visits (47.1% versus 0%, P <0.01). More endocrinologists were specifically disinclined to conduct new consultations with telemedicine (87.5% versus 58.8%, P <0.01). CONCLUSION: Telemedicine is a mutually acceptable method for patients and their referring providers for endocrine surgery delivery, although in-person visits continue to have their place. Telemedicine use may continue to expand after the pandemic as an important point of access for endocrine surgery.

From Pituitary Adenoma to Pituitary Neuroendocrine Tumors: How Molecular Pathways may Impact the Therapeutic Management?

The classification of adeno-pituitary tumor was deeply revised over the last 20 years, in order to better describe the variable and complex biological and clinical behavior of these neoplasia and to identify prognostic markers of aggressiveness and poor prognosis. Recently, the International Pituitary Pathology Club proposed to replace the term "pituitary adenoma" with "pituitary neuroendocrine tumour" (PitNET), to reflect similarities of adeno-pituitary tumours with neuroendocrine neoplasia of other organs, underling better the variable behaviour of adeno-pituitary neoplasia. A definitive consensus was not reached on this issue. In this review, we will describe how molecular and biological marker can predict aggressiveness of PitNETs and impact on therapeutic management of PitNETs.

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.

Function, Failure, and the Future Potential of Tregs in Type 1 Diabetes.

Critical insights into the etiology of type 1 diabetes (T1D) came from genome-wide association studies that unequivocally connected genetic susceptibility to immune cell function. At the top of the susceptibility are genes involved in regulatory T-cell (Treg) function and development. The advances in epigenetic and transcriptional analyses have provided increasing evidence for Treg dysfunction in T1D. These are well supported by functional studies in mouse models and analysis of peripheral blood during T1D. For these reasons, Treg-based therapies are at the forefront of research and development and have a tangible probability to deliver a long-sought-after successful immune-targeted treatment for T1D. The current challenge in the field is whether we can directly assess Treg function at the tissue site or make informative interpretations based on peripheral data. Future studies focused on Treg function in pancreatic lymph nodes and pancreas could provide key insight into the ultimate mechanisms underlying Treg failure in T1D. In this Perspective we will provide an overview of current literature regarding Treg development and function in T1D and how this knowledge has been applied to Treg therapies.

GLOBAL ENDOCRINOLOGY: Global perspectives in endocrinology: coverage of iodized salt programs and iodine status in 2020.

Iodine deficiency has multiple adverse effects on growth and development. Diets in many countries cannot provide adequate iodine without iodine fortification of salt. In 2020, 124 countries have legislation for mandatory salt iodization and 21 have legislation allowing voluntary iodization. As a result, 88% of the global population uses iodized salt. For population surveys, the urinary iodine concentration (UIC) should be measured and expressed as the median, in µg/L. The quality of available survey data is high: UIC surveys have been done in 152 out of 194 countries in the past 15 years; in 132 countries, the studies were nationally representative. The number of countries with adequate iodine intake has nearly doubled from 67 in 2003 to 118 in 2020. However, 21 countries remain deficient, while 13 countries have excessive intakes, either due to excess groundwater iodine, or over-iodized salt. Iodine programs are reaching the poorest of the poor: of the 15 poorest countries in the world, 10 are iodine sufficient and only 3 (Burundi, Mozambique and Madagascar) remain mild-to-moderately deficient. Nigeria and India have unstable food systems and millions of malnourished children, but both are iodine-sufficient and population coverage with iodized salt is a remarkable 93% in both. Once entrenched, iodine programs are often surprisingly durable even during national crises, for example, war-torn Afghanistan and Yemen are iodine-sufficient. However, the equity of iodized salt programs within countries remains an important issue. In summary, continued support of iodine programs is needed to sustain these remarkable global achievements, and to reach the remaining iodine-deficient countries.

Best Achievements in Clinical Thyroidology in 2020.

This review highlights the most interesting research in thyroidology conducted in 2020. The publications of interest discussed below dealt with the following topics: thyroid dysfunction, risk of thyroid cancer, molecular diagnostics and new therapeutics for thyroid cancer, and thyroid disease in the coronavirus disease 2019 pandemic era.

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.

MECHANISMS IN ENDOCRINOLOGY: Update on treatments for patients with genetic obesity.

Obesity, defined by an excess of body fat impacting on health, is a complex disease resulting from the interaction between many genetic/epigenetic factors and environmental triggers. For some clinical situations with severe obesity, it has been possible to classify these obesity forms according to the molecular alterations. These include: (i) syndromic obesity, which associates severe early-onset obesity with neurodevelopmental disorders and/or polymalformative syndrome and (ii) non-syndromic monogenic obesity, due to gene variants most often located in the leptin-melanocortin pathway. In addition to severe obesity, patients affected by these diseases display complex somatic conditions, eventually including obesity comorbidities, neuropsychological and psychiatric disorders. These conditions render the clinical management of these patients particularly challenging. Patients' early diagnosis is critical to allow specialized and multidisciplinary care, with a necessary interaction between the health and social sectors. Up to now, the management of genetic obesity was only based, above all, on controlling the patient's environment, which involves limiting access to food, ensuring a reassuring daily eating environment that limits impulsiveness, and the practice of adapted, supported, and supervised physical activity. Bariatric surgery has also been undertaken in genetic obesity cases with uncertain outcomes. The context is rapidly changing, as new innovative therapies are currently being tested both for syndromic and monogenic forms of obesity. This review focuses on care management and new therapeutic opportunities in genetic obesity, including the use of the melanocortin 4 agonist, setmelanotide. The results from ongoing trials will hopefully pave the way to a future precision medicine approach for genetic obesity.

Influence of Nomenclature Changes on Trends in Papillary Thyroid Cancer Incidence in the United States, 2000 to 2017.

CONTEXT: US papillary thyroid carcinoma (PTC) incidence recently declined for the first time in decades, for reasons that remain unclear. OBJECTIVE: This work aims to evaluate PTC incidence trends, including by histologic subtype and size, and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). DESIGN: This descriptive study uses US Surveillance, Epidemiology, and End Results-18 cancer registry data (2000-2017). PATIENTS: Participants included individuals diagnosed with PTC (2000-2017) or NIFTP (2016-2017). RESULTS: During 2000 to 2015, PTC incidence increased an average 7.3% per year, (95% CI, 6.9% to 7.8%) during 2000 to 2009, and 3.7% per year (95% CI, 0.2% to 7.3%) during 2009 to 2012, before stabilizing in 2012 to 2015 (annual percentage change [APC] = 1.4% per year, 95% CI, -1.8% to 4.7%) and declining in 2015 to 2017 (APC = -4.6% per year, 95% CI, -7.6% to -1.4%). The recent declines were observed for all sizes of PTC at diagnosis. Incidence of follicular variant of PTC (FVPTC) sharply declined in 2015 to 2017, overall (APC = -21.1% per year; 95% CI, -26.5% to -15.2%) and for all tumor sizes. Observed increases in encapsulated papillary carcinoma (classical PTC subtype) and NIFTP each accounted for 10% of the decline in FVPTC. Classical PTC incidence continuously increased (2000-2009, APC = 8.7% per year, 95% CI, 8.1% to 9.4%; 2009-2017, APC = 1.0% per year, 95% CI, 0.4% to 1.5%), overall and for all sizes except smaller than 1 cm, as did incidence of other PTC variants combined (2000-2017, APC = 5.9% per year, 95% CI, 4.0% to 7.9%). CONCLUSION: The reasons underlying PTC incidence trends were multifactorial. Sharp declines in FVPTC incidence during 2015 to 2017 coincided with clinical practice and diagnostic coding changes, including reclassification of noninvasive encapsulated FVPTC from a malignant to in situ neoplasm (NIFTP). Observed increases in NIFTP accounted for 10% of the decline in FVPTC.

Recent advances in the management of pheochromocytoma and paraganglioma.

Pheochromocytomas and paragangliomas (PPGLs) are rare tumors that cause refractory hypertension and hypertensive crisis. Although metastatic disease accounts for 30% of PPGLs, the diagnosis of malignancy is difficult without the presence of metastatic lesions. Here, we review several advancements in the diagnosis and treatment of PPGL. A nationwide epidemiological survey in Japan revealed that the annual number of patients with PPGL was 3000, which was higher than that reported previously. While plasma and urine fractionated metanephrines are recommended for use in specific biochemical testing for diagnosis, creatinine-corrected fractionated metanephrines in spot urine samples that had been widely used in Japan as a convenient screening test were shown to be as useful as 24-h urine fractionated metanephrines. Regarding imaging studies, a more specific functional imaging for PPGLs, 68Ga DOTATATE, was newly developed. 68Ga DOTATATE provides a clear image with high sensitivity and specificity. Currently, PASS or GAPP histological scores and SDHB immunostaining are clinically used to attempt to discriminate benign from malignant tumors. However, since this distinguishing process remains difficult, all cases were classified as malignant with the possibility of metastasis in the WHO classification of endocrine tumors updated in 2017. Approximately 60% of PPGLs have germline mutations in PPGL-related genes. Currently, the genes are classified into two clusters based on their mechanism for the etiology of tumorigenesis. Based on the possible mechanisms of tumor development associated with gene mutations, several molecular target drugs are under evaluation to explore more promising treatments for malignant PPGL.

Advances in the Imaging of Pituitary Tumors.

In most patients with pituitary adenomas magnetic resonance imaging (MRI) is essential to guide effective decision-making. T1- and T2-weighted sequences allow the majority of adenomas to be readily identified. Supplementary MR sequences (e.g. FLAIR; MR angiography) may also help inform surgery. However, in some patients MRI findings are 'negative' or equivocal (e.g. with failure to reliably identify a microadenoma or to distinguish postoperative change from residual/recurrent disease). Molecular imaging [e.g. 11C-methionine PET/CT coregistered with volumetric MRI (Met-PET/MRCR)] may allow accurate localisation of the site of de novo or persistent disease to guide definitive treatment (e.g. surgery or radiosurgery).

World Health Ozganization 2017 Classification of Pituitary Tumors.

The 2017 (fourth edition) World Health Organization Classification of Endocrine Tumors has recommended major changes in classification of tumors of the pituitary gland and region. In addition to the accurate tumor subtyping, assessment of the tumor proliferative potential (mitotic and/or Ki-67 index) and other clinical parameters such as tumor invasion is strongly recommended in individual cases for consideration of clinically aggressive adenomas. It is expected that this new WHO classification will establish more uniform biologically and clinically groups of pituitary tumors and contribute to understanding of clinical outcomes for patients harboring pituitary tumors.