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To compare body composition in patients with autonomous cortisol secretion (ACS), non-functioning adrenal incidentalomas (NFAIs) and controls without adrenal tumours.Cross-sectional study of 3 groups: patients with ACS (cortisol post-dexamethasone suppression test (DST)1.8μg/dL), NFAIs (cortisol post-DST ≤1.8μg/dL) and patients without adrenal tumours (controls). Patients of the three groups were matched according to age (±5 years-old), sex and body mass index (±5kg/m25 patients with ACS, 24 NFAIs and 24 controls were enrolled. Based on CT images, a weak positive correlation between serum cortisol post-DST and subcutaneous fat area (r=0.3, P=0.048) was found. As assessed by bioelectrical impedance, lean mass and bone mass were positively correlated with the excretion of total androgens (r=0.56, P0.001; and r=0.58, P0.001, respectively); and visceral mass was positively correlated with the excretion of glucocorticoid metabolites and total glucocorticoids (r=0.28, P=0.031; and r=0.42, P=0.001, respectively). Based on CT imaging evaluation, a positive correlation was observed between lean mass and androgen metabolites (r=0.30, P=0.036); and between visceral fat area, total fat area, and visceral/total fat area ratio and the excretion of glucocorticoid metabolites (r=0.34, P=0.014; r=0.29, P=0.042; and r=0.31, P=0.170, respectively).The USP observed in adrenal tumours, which consists in a low excretion of androgen metabolites and high excretion of glucocorticoid metabolites, is associated with a lower lean mass and bone mass and higher level of visceral mass in patients with adrenal tumours.

Resumen Introduccion La enfermedad COVID-19 se ha convertido en una prioridad para nuestro sistema sanitario. Los MIR de Endocrinologia y Nutricion (MIR-EyN) se han integrado en los equipos COVID-19. Se ha disenado este estudio con el objetivo de analizar el impacto a nivel formativo, laboral y en la salud de los MIR-EyN. Material y metodos Estudio observacional transversal tipo encuesta via web, dirigida a los MIR-EyN socios de la SEEN, realizado en noviembre de 2020. Se han analizado: variables demograficas, tamano del hospital de formacion en numero de camas, alteracion de las rotaciones, integracion en equipos COVID-19, participacion en teleconsulta, actividad cientifica e impacto sobre la salud fisica y emocional. Resultados Se han obtenido 87 respuestas (27% de los MIR-EyN); 67,8% mujeres, edad media 28,1 ± 1,8 anos, 60% MIR-EyN 4.o ano. El 84% ha participado en equipos COVID-19 y el 93% en las consultas telematicas de su servicio. La mayoria ha visto interrumpidas sus rotaciones. El 97,7% ha participado en reuniones cientificas o congresos virtuales y un tercio de ellos ha colaborado en trabajos cientificos sobre la COVID-19 en relacion con la Endocrinologia y Nutricion. La pandemia ha afectado a su estado de animo mucho o bastante (75,8%) y opinan que ha impactado de forma negativa a su formacion (73,8%). Conclusiones La pandemia por SARS-CoV-2 ha comprometido la formacion, la actividad laboral y la salud de los MIR-EyN. Se han integrado tanto en equipos COVID-19 como en la actividad reestructurada de sus servicios. Sin embargo, han conseguido mantener la formacion en formato virtual y participado en trabajos cientificos.

Diabetes is a rare, but potentially life‐threatening, adverse event of immune checkpoint inhibitors that requires prompt recognition and treatment. It usually occurs in the first 3 months of treatment and is typically related to programmed cell death‐1 antibodies, alone or in combined therapy. It has rarely been described developing after immunotherapy cessation. We present a 51‐year‐old man with metastatic melanoma, who developed acute‐onset diabetes 52 days after combined immunotherapy cessation with nivolumab and ipilimumab, and 25.6 months after receiving the first dose. He presented with acute hyperglycemic symptoms, ketosis, complete insulin depletion and negative autoimmunity, fulfilling the criteria of fulminant type 1 diabetes. The patient had previously developed hypophysitis with isolated adrenocorticotropic hormone deficiency during immunotherapy. We describe a case of late‐onset fulminant type 1 diabetes developing after immunotherapy cessation. Patient education and active follow up after immunotherapy discontinuation are crucial to warrant a timely intervention., We describe a case of immunotherapy‐related type 1 diabetes developing after combined immunotherapy cessation. The patient developed fulminant type 1 diabetes >2 years after the first immunotherapy dose, and had previously developed immune‐related hypophysitis.

We aimed to identify presurgical and surgical risk factors for intraoperative complications in patients with pheochromocytomas. A retrospective study of patients with pheochromocytomas who underwent surgery in ten Spanish hospitals between 2011 and 2021 was performed. One hundred and sixty-two surgeries performed in 159 patients were included. The mean age was 51.6 ± 16.4 years old and 52.8% were women. Median tumour size was 40 mm (range 10–110). Laparoscopic adrenalectomy was performed in 148 patients and open adrenalectomy in 14 patients. Presurgical alpha- and beta-blockade was performed in 95.1% and 51.9% of the surgeries, respectively. 33.3% of the patients (n = 54) had one or more intraoperative complications. The most common complication was the hypertensive crisis in 21.0%, followed by prolonged hypotension in 20.0%, and hemodynamic instability in 10.5%. Patients pre-treated with doxazosin required intraoperative hypotensive treatment more commonly than patients pre-treated with other antihypertensive drugs (51.1% vs 26.5%, P = 0.002). Intraoperative complications were more common in patients with higher levels of urine metanephrine (OR = 1.01 for each 100 μg/24 h, P = 0.026) and normetanephrine (OR = 1.00 for each 100 μg/24 h, P = 0.025), larger tumours (OR = 1.4 for each 10 mm, P < 0.001), presurgical blood pressure > 130/80 mmHg (OR = 2.25, P = 0.027), pre-treated with doxazosin (OR = 2.20, P = 0.023) and who had not received perioperative hydrocortisone (OR = 3.95, P = 0.008). In conclusion, intraoperative complications in pheochromocytoma surgery are common and can be potentially life-threatening. Higher metanephrine and normetanephrine levels, larger tumour size, insufficient blood pressure control before surgery, pre-treatment with doxazosin, and the lack of treatment with perioperative hydrocortisone are associated with higher risk of intraoperative complications.

Purpose: To identify presurgical and surgical risk factors for postsurgical complications in the pheochromocytoma surgery.Methods: A retrospective study of pheochromocytomas submitted to surgery in ten Spanish hospitals between 2011 and 2021. Postoperative complications were classified according to Clavien-Dindo scale.Results: One hundred and sixty-two surgeries (159 patients) were included. Preoperative antihypertensive blockade was performed in 95.1% of the patients, being doxazosin in monotherapy (43.8%) the most frequent regimen. Patients pre-treated with doxazosin required intraoperative hypotensive treatment more frequently (49.4% vs 25.0%, P=0.003) than patients treated with phenoxybenzamine, but no differences in the rate of intraoperative and postsurgical complications were observed. However, patients treated with phenoxybenzamine had a longer hospital stay (12.2±11.16 vs 6.2±6.82, PConclusion: Preoperative medical treatment and postsurgical monitoring of pheochromocytoma should be especially careful in patients with diabetes, cerebrovascular disease, higher levels of plasma glucose and urine free metanephrine and norepinephrine, and with pheochromocytomas >5 cm, due to the higher risk of postsurgical complications.

Chronic cortisol excess induces several alterations on protein, lipid and carbohydrate metabolism resembling those found in the metabolic syndrome. However, patients exposed to prolonged high levels of cortisol in Cushing syndrome (CS) present exceeding cardiometabolic alterations not reflected by conventional biomarkers. Using 3 ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) platforms, we aimed to characterise the serum metabolome of 25 patients with active endogenous CS and 25 control subjects matched by propensity score (sex, BMI, diabetes mellitus type 2 (T2D), high blood pressure (HBP) and dyslipidaemia) to search for potential disease-specific biomarkers and pathways associated to the clinical comorbidities. A total of 93 metabolites were significantly altered in patients with CS. Increased levels of sulfur amino acids (AA), triacylglycerols, glycerophospholipids, ceramides and cholesteryl esters were observed. Contrarily, concentrations of essential and non-essential AA, polyunsaturated fatty acids, conjugated bile acids and second messenger glycerolipids were decreased. Twenty-four-hour urinary free cortisol (24h-UFC) independently determined the concentration of 21 lipids and 4 AA. A metabolic signature composed by 10 AA and 10 lipid metabolites presented an AUC-ROC of 95% for the classification of CS patients. Through differential network analysis, 152 aberrant associations between metabolites involved in the Lands cycle and Kennedy pathway were identified. Our data indicates that chronic hypercortisolemia confers a unique lipidomic signature and several alterations in numerous AA even when compared to patients with similar metabolic comorbidities providing novel insights of the increased cardiometabolic burden of CS. KEY MESSAGES: • Cortisol excess induces metabolic alterations beyond conventional biomarkers. • The hypercortisolism extent determines the concentration of 21 lipids and 5 aa. • Cortisol excess confers a unique metabolic signature of 20 metabolites. • Kennedy and Lands cycle are profoundly disturbed by cortisol excess.

To develop a predictive model of hypertension resolution after adrenalectomy in patients with primary aldosteronism (PA), based on their presurgical characteristics.A retrospective multicenter study of PA patients in follow-up in 20 Spanish tertiary hospitals between 2018 and 2021 was performed (SPAIN-ALDO Register). Clinical response postadrenalectomy was classified according to the primary aldosteronism surgical outcome (PASO) consensus criteria. The predictive model was developed using a multivariate logistic regression model with the estimation of all possible equations.A total of 146 patients (54.8% females; mean age of 51.5 ± 10.9 years) with PA who underwent unilateral adrenalectomy were included. After a mean follow-up of 29.1 ± 30.43 months after surgery, hypertension cure was obtained in 37.7% ( n = 55) of the patients. The predictive model with the highest diagnostic accuracy to predict hypertension cure combined the variables female sex, use of two or fewer antihypertensive medications, hypertension grade 1, without type 2 diabetes and nonobesity. The area under the receiver operating characteristic curve of this model was 0.841 [0.769-0.914]. Based on this model, the group of patients with a higher probability of cure (80.4%) were those without type 2 diabetes, BMI30 kg/m 2 , female sex, hypertension grade 1 and who use two or fewer antihypertensives. Our predictive model offered a slightly higher diagnostic accuracy than Wachtel's (area under the curve [AUC]: 0.809), Utsumi's (AUC: 0.804) and Zarnegar's (AUC: 0.796) models and was similar than the Burello's (AUC: 0.833) model.Female sex, use of two or fewer antihypertensive medications, hypertension grade 1, no type 2 diabetes and nonobesity may predict hypertension cure after adrenalectomy in patients with PA. Our score provides a potential tool to guide preoperative patient counseling.

The objective of our study was to determine the prevalence of glycemic disorders (diabetes mellitus and prediabetes) in patients with pheochromocytomas and sympathetic paragangliomas (PPGLs) and identify risk factors for their development and the likelihood of their resolution after surgery. A multicentric retrospective study of patients with PPGLs submitted to surgery between 2000 and 2021 in 17 Spanish hospitals was performed. Diabetes-specific data were collected at diagnosis, in the immediate- and long-term postsurgical follow-up. A total of 229 patients with PPGLs were included (218 with pheochromocytomas and 11 with sympathetic paragangliomas). Before surgery, glycemic disorders were diagnosed in 35.4% of the patients (n = 81): 54 with diabetes and 27 with prediabetes. The variables independently associated with a higher risk of glycemic disorders were sporadic PPGL (odds ratio (OR) = 3.26 (1.14–9.36)) and hypertension (OR = 3.14 (1.09–9.01)). A significant decrease in fasting plasma glucose and HbA1c levels was observed after surgery, in the short-term and long-term follow-up (P < 0.001). After a median follow-up of 48.5 months (range 3.3–168.9), after surgery, 52% of diabetic and 68% of prediabetic patients experienced a complete resolution. Lower body mass index (BMI) (P = 0.001), lower glucose levels (P = 0.047) and shorter duration of diabetes prior to surgery (P = 0.021) were associated with a higher probability of diabetes resolution. In conclusion, glycemic disorders in patients with PPGLs are present in more than a third of them at diagnosis. Sporadic PPGLs and hypertension are risk factors for their development. More than 50% of cases experience a complete resolution of the glycemic disorder after resection of the PPGLs.

To identify alterations in steroid metabolism in patients with nonfunctioning adrenal incidentalomas (NFAIs) through the analysis of their urinary steroid profile (USP).Cross-sectional study with one study group (NFAIs, cortisol post dexamethasone suppression test [DST] ≤ 1.8 µg/dl [49.7 nmol/L]) and 2 control groups: patients with autonomous cortisol secretion (ACS group, cortisol post-DST 1.8 µg/dl (49.7 nmol/L) and patients without adrenal tumours (healthy-adrenal group). Twenty-four-hour urine collections for USP measurement (total and free fraction of 51 24 h-urine specimens) were obtained from 73 participants (24 with NFAIs, 24 without AIs, and 25 with ACS). USP was determined by gas chromatography coupled to mass spectrometry. Patients of the three groups were matched according to sex, age (±5 years-old) and body mass index (±5 kg/mCompared to healthy-adrenal controls, patients with NFAIs had a lower excretion of androgen metabolites (230.5 ± 190.12 vs. 388.7 ± 328.58 µg/24 h, p = .046) and a higher excretion of urinary free cortisol (UFC) (54.3 ± 66.07 vs. 25.4 ± 11.16 µg/24 h, p = .038). UFC was above the reference range in 20.8% of patients in the NFAI, compared to 0% in the healthy-adrenal group (p = .018). Patients with ACS had a higher prevalence of hypertension, dyslipidemia, and diabetes than patients with NFAIs or the control group. A lower excretion of androgen metabolites (218.4 ± 204.24 vs. 231 ± 190 µg/24 h, p = .041) and a nonsignificant higher excretion of glucocorticoid metabolites (2129.6 ± 1195.96 vs. 1550.8 ± 810.03 µg/24 h, p = .180) was found in patients with ACS compared to patients with NFAIs.NFAIs seem to secrete a subtle, yet clinically relevant, excess of glucocorticoids. Future studies are needed to confirm our findings; and to identify metabolic alterations associated with an increased cardiometabolic risk.

Glucocorticoids (GCs) play critical roles in adipose tissue metabolism. Here, we compare in a mouse model the effects of chronic glucocorticoid excess and diet-induced obesity on white adipose tissue mass and distribution, by focusing on visceral adipose tissue (VAT) fatty acid composition changes, the role of de novo lipogenesis (DNL) and the inflammatory state. We used a noninvasive mouse model of hypercortisolism to compare GC-induced effects on adipose tissue with diet-induced obesity [high-fat diet (HFD) 45%] and control mice after 10 wk of treatment. Subcutaneous adipose tissue (SAT) and VAT mass and distribution were measured by nuclear magnetic resonance imaging (NMRI). Fatty acid composition in VAT was analyzed by NMR spectroscopy and gas chromatography. Gene expression of key enzymes involved in DNL was analyzed in liver and VAT. Macrophage infiltration markers and proinflammatory cytokines were measured by gene expression in VAT. HFD or GC treatment induced similar fat mass expansion with comparable distribution between SAT and VAT depots. However, in VAT, GCs induce DNL, higher palmitic acid (PA), macrophage infiltration, and proinflammatory cytokine levels, accompanied by systemic nonesterified fatty acid (NEFA) elevation, hyperinsulinemia, and higher homeostatic model assessment for insulin resistance (HOMA-IR) levels compared with diet-induced obesity. Thus, chronic hypercortisolism induces DNL and fatty acid composition changes toward increased SFA and reduced polyunsaturated fatty acid (PUFA) levels in VAT, promoting macrophage recruitment and proinflammatory cytokines, suggesting a worse cardiometabolic profile even compared with HFD mice.

Background\ud \ud The association between cortisol secretion and mortality in patients with adrenal incidentalomas is controversial. We aimed to assess all-cause mortality, prevalence of comorbidities, and occurrence of cardiovascular events in uniformly stratified patients with adrenal incidentalomas and cortisol autonomy (defined as non-suppressible serum cortisol on dexamethasone suppression testing).\ud \ud \ud \ud Methods\ud \ud We conducted an international, retrospective, cohort study (NAPACA Outcome) at 30 centres in 16 countries. Eligible patients were aged 18 years or older with an adrenal incidentaloma (diameter ≥1 cm) detected between Jan 1, 1996, and Dec 31, 2015, and availability of a 1 mg dexamethasone suppression test result from the time of the initial diagnosis. Patients with clinically apparent hormone excess, active malignancy, or follow-up of less than 36 months were excluded. Patients were stratified according to the 0800–0900 h serum cortisol values after an overnight 1 mg dexamethasone suppression test; less than 50 nmol/L was classed as non-functioning adenoma, 50–138 nmol/L as possible autonomous cortisol secretion, and greater than 138 nmol/L as autonomous cortisol secretion. The primary endpoint was all-cause mortality. Secondary endpoints were the prevalence of cardiometabolic comorbidities, cardiovascular events, and cause-specific mortality. The primary and secondary endpoints were assessed in all study participants.\ud \ud \ud \ud Findings\ud \ud Of 4374 potentially eligible patients, 3656 (2089 [57·1%] with non-functioning adenoma, 1320 [36·1%] with possible autonomous cortisol secretion, and 247 [6·8%] with autonomous cortisol secretion) were included in the study cohort for mortality analysis (2350 [64·3%] women and 1306 [35·7%] men; median age 61 years [IQR 53–68]; median follow-up 7·0 years [IQR 4·7–10·2]). During follow-up, 352 (9·6%) patients died. All-cause mortality (adjusted for age, sex, comorbidities, and previous cardiovascular events) was significantly increased in patients with possible autonomous cortisol secretion (HR 1·52, 95% CI 1·19–1·94) and autonomous cortisol secretion (1·77, 1·20–2·62) compared with patients with non-functioning adenoma. In women younger than 65 years, autonomous cortisol secretion was associated with higher all-cause mortality than non-functioning adenoma (HR 4·39, 95% CI 1·93–9·96), although this was not observed in men. Cardiometabolic comorbidities were significantly less frequent with non-functioning adenoma than with possible autonomous cortisol secretion and autonomous cortisol secretion (hypertension occurred in 1186 [58·6%] of 2024 patients with non-functioning adenoma, 944 [74·0%] of 1275 with possible autonomous cortisol secretion, and 179 [75·2%] of 238 with autonomous cortisol secretion; dyslipidaemia occurred in 724 [36·2%] of 1999 patients, 547 [43·8%] of 1250, and 123 [51·9%] of 237; and any diabetes occurred in 365 [18·2%] of 2002, 288 [23·0%] of 1250, and 62 [26·7%] of 232; all p values

Background and Objectives11-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide the most relevant clinical features that clinicians dealing with patients presenting with the hallmarks of hypertension due to 11-deoxycorticosterone-producing adrenal lesions should be aware of.Design and MethodsWe report the case of a patient with an 11-deoxycorticosterone-producing adrenal lesion and provide a systematic review of all published cases (PubMed, Web of Science and EMBASE) between 1965 and 2021.ResultsWe identified 46 cases (including ours). Most cases (31, 67%) affected women with a mean age of 42.9 ± 15.2 years and presented with high blood pressure and hypokalemia (average of 2.68 ± 0.62 mmol/L). Median (interquartile range) time from onset of first suggestive symptoms to diagnosis was 24 (55) months. Aldosterone levels were low or in the reference range in 98% of the cases when available. 11-deoxycorticosterone levels were a median of 12.5 (18.9) times above the upper limit of the normal reference range reported in each article and overproduction of more than one hormone was seen in 31 (67%). Carcinoma was the most common histological type (21, 45.7%). Median tumor size was 61.5 (60) mm. Malignant lesions were larger, had higher 11-deoxycorticosterone levels and shorter time of evolution at diagnosis compared to benign lesions.Conclusions11-deoxycorticosterone-producing adrenal lesions are very rare, affecting mostly middle-aged women with a primary aldosteronism-like clinical presentation and carcinoma is the most frequent histological diagnosis. Measuring 11-deoxycorticosterone levels, when low aldosterone levels or in the lower limit of the reference range are present in hypertensive patients, is advisable.Systematic Review RegistrationOpen Science Framework, 10.17605/OSF.IO/NR7UV.

IntroductionTwenty-four-hour urinary free cortisol (24h-UFC) is the most used test for follow-up decision-making in patients with Cushing syndrome (CS) under medical treatment. However, 24h-UFC determinations by immunoassays (IA) are commonly overestimated because of steroid metabolites’ cross-reaction. It is still uncertain how ketoconazole (KTZ)- and metyrapone (MTP)-induced changes on the urinary steroid metabolites can alter the 24h-UFC*IA determinations’ reliability.Methods24h-UFC was analyzed by IA and gas chromatography-mass spectrometry (GC-MS) in 193 samples (81 before treatment, 73 during KTZ, and 39 during MTP) from 34 CS patients. In addition, urinary steroidome was analyzed by GC-MS on each patient before and during treatment.ResultsBefore treatment, 24h-UFC*IA determinations were overestimated by a factor of 1.75 (95% CI 1.60–1.94) compared to those by GC-MS. However, during KTZ treatment, 24h-UFC*IA results were similar (0.98:1) to those by GC-MS (95% CI, 0.83–1.20). In patients taking MTP, IA bias only decreased 0.55, resulting in persistence of an overestimation factor of 1.33:1 (95% CI, 1.09–1.76). High method agreement between GC-MS and IA before treatment (R2 = 0.954) declined in patients under KTZ (R2 = 0.632) but not in MTP (R2 = 0.917). Upper limit normal (ULN) reductions in patients taking KTZ were 27% larger when using 24h-UFC*IA compared to 24h-UFC*GC-MS, which resulted in higher false efficacy and misleading biochemical classification of 15% of patients. Urinary excretion changes of 22 urinary steroid metabolites explained 86% of the 24h-UFC*IA interference. Larger urinary excretion reductions of 6β-hydroxy-cortisol, 20α-dihydrocortisol, and 18-hydroxy-cortisol in patients with KTZ elucidated the higher 24h-UFC*IA bias decrement compared to MTP-treated patients.ConclusionKTZ and MTP alter the urinary excretion of IA cross-reactive steroid metabolites, thus decreasing the cross-reactive interference of 24h-UFC*IA determinations present before treatment. Consequently, this interference reduction in 24h-UFC*IA leads to loss of method agreement with GC-MS and high risk of overestimating the biochemical impact of KTZ and MTP in controlling CS because of poor reliability of reference ranges and ULN.

To analyze the evolution of the cardiometabolic profile of patients with primary hyperaldosteronism (PA) after the treatment with surgery and with mineralocorticoid receptor antagonists (MRA).Retrospective multicentric study of patients with PA on follow-up in twelve Spanish centers between 2018 and 2020.268 patients with PA treated by surgery (n = 100) or with MRA (n = 168) were included. At baseline, patients treated with surgery were more commonly women (54.6% vs 41.7%, P = 0.042), had a higher prevalence of hypokalemia (72.2% vs 58%, P = 0.022) and lower prevalence of obesity (37.4% vs 51.3%, P = 0.034) than patients treated with MRA. Adrenalectomy resulted in complete biochemical cure in 94.0% and clinical response in 83.0% (complete response in 41.0% and partial response in 42.0%). After a median follow-up of 23.6 (IQR 9.7-53.8) months, the reduction in blood pressure (BP) after treatment was similar between the group of surgery and MRA, but patients surgically treated reduced the number of antihypertensive pills for BP control more than those medically treated (∆antihypertensives: -1.3 ± 1.3 vs 0.0 ± 1.4, P 0.0001) and experienced a higher increased in serum potassium levels (∆serum potassium: 0.9 ± 0.7 vs 0.6 ± 0.8mEq/ml, P = 0.003). However, no differences in the risk of the onset of new renal and cardiometabolic comorbidities was observed between the group of surgery and MRA (HR = 0.9 [0.5-1.5], P = 0.659).In patients with PA, MRA and surgery offer a similar short-term cardiovascular protection, but surgery improves biochemical control and reduces pill burden more commonly than MRA, and lead to hypertension cure or improvement in up to 83% of the patients.

AimThe short-term and long-term efficacy of different thermal percutaneous ablation techniques remains a topical issue. Our group implemented percutaneous laser ablation (LA), a moving-shot technique to increase efficiency and reduce costs and variability of LA by applying multiple lower-intensity energy illuminations (MLIEI) covering the nodular volume (V) through changes in position of a single laser fiber within the thyroid nodule. The aim of the present study was to evaluate the efficacy of the single-fiber LA-MLIEI during a 5-year follow-up and to identify possible predictors of the final outcome.MethodsProspective study: Thirty outpatients (23 women and seven men) with benign symptomatic thyroid nodules were assigned to single-fiber LA-MLIEI, between 2012 and 2015. A single LA session was performed under real-time ultrasound (US) guidance using a 1,064-nm continuous-wave laser at 3 W. A 400-µm optical fiber was inserted through a 21-gauge needle, and 3–10 illuminations were performed per nodule, administering between 400 and 850 J/illumination. The total administered energy was calculated on the initial V of the nodule and the estimated ablation area. US evaluation was performed after LA-MLIEI at 1 week and 1, 3, 6, and 12 months and after that annually up to 5 years. Clinical symptoms, laboratory thyroid function during follow-up, and acute and chronic complications of treatment were registered.ResultsOn follow-up, 67% (n: 20) were responders to single-fiber LA-MLIEI, while 33% (n: 10) were non-responders. The responder group initiated V reduction (ΔV) at 1 month, with remission of symptoms, and presented a 50% ΔV at 3 months of treatment; the maximum response was achieved at 24 months and remained stable until the end of the study. The non-responder group presented a ΔV of less than 50% at 12 months; though a tendency to >50% ΔV was observed at 24–36 months, there was subsequent regrowth, and 40% of this group required surgery. ΔV was positively correlated with the total administered energy/V (J/V) and inversely with nodule V. No severe adverse effects were observed. Thyroid function remained normal in all patients. Remission of symptoms occurred rapidly after 1 month.ConclusionsLA with multiple fractional discharges employing a single fiber in a unique session is a safe and inexpensive technique that allows rapid reduction of thyroid nodules, with a stable response up to 5 years, similarly to what has been reported with the conventional LA. Total nodule volume appears as a predictive factor of the reduction.

To evaluate the indication and the resources for the screening/diagnosis of primary aldosteronism (PA) in Endocrinology units in Spain.An anonymous 2-phase (2020/2021) online survey was conducted by the AdrenoSEEN group among SEEN members with data about screening, confirmation tests, availability of catheterisation and the treatment of PA.Eighty-eight (88) specialists completed the survey. Plasma aldosterone concentration and plasma renin activity were available at all centres; urinary aldosterone was available in 55% of them. The most frequent indications for determining the aldosterone/renin ratio (ARR) were adrenal incidentaloma (82.6%), hypertension with hypokalaemia (82.6%), hypertension in patients40 years (79.1%) and a family history of PA (77.9%). 61% and 18% of the respondents used an ARR cut-off value of PA of ≥30 and 20ng/dl per ng/mL/, respectively. The intravenous saline loading test was the most commonly used confirmatory test (66.3%), followed by the captopril challenge test (24.4%), with the 25mg dose used more than the 50mg dose (65% versus 35%). 67.4% of the participants confirmed the availability of adrenal vein catheterization (AVC). 41% of this subgroup perform it with a continuous infusion versus 30.5% with an ACTH (1-24) bolus, whereas 70.3% employ sequential adrenal vein catheterization. 48% of the participants reported an AVC success50%. Total laparoscopic adrenalectomy was the treatment of choice (90.6%), performed by specialists in General and Digestive Surgery specialising in endocrinological pathology.PA screening and diagnostic tests are extensively available to Spanish endocrinologists. However, there is a major variability in their use and in the cut-off points of the diagnostic methods. The AVS procedure remains poorly standardised and is far from delivering optimal performance. Greater standardisation in the study and diagnosis of PA is called for.

Transgender men and women represent about 0.6 -1.1%% of the general population. Gender affirming hormone therapy (GAHT) helps ameliorate gender dysphoria and promote well-being. However, these treatments’ cardiovascular (CV) effects are difficult to evaluate due to the limited number of extensive longitudinal studies focused on CV outcomes in this population. Furthermore, these studies are mainly observational and difficult to interpret due to a variety of hormone regimens and observation periods, together with possible bias by confounding factors (comorbidities, estrogen types, smoking, alcohol abuse, HIV infection). In addition, the introduction of GAHT at increasingly earlier ages, even before the full development of the secondary sexual characteristics, could lead to long-term changes in CV risk compared to current data.This review examines the impact of GAHT in the transgender population on CV outcomes and surrogate markers of CV health. Furthermore, we review available data on changes in DNA methylation or RNA transcription induced by GAHT that may translate into changes in metabolic parameters that could increase CV risk.

Determination of cortisol levels in the urine (24 hours urine free cortisol), saliva (late-night), or serum (total cortisol after dexamethasone suppression) is recommended to screen for Cushing's syndrome (CS). This review focuses on the differences between the frequently used cortisol-antibody immunoassay-based methods and the highly specific mass-spectrometry-based methods that are progressively being employed in clinical laboratories for CS screening. The particular characteristics of cortisol metabolism and the lack of specificity of the immunoassays cause marked differences between both methods that are in turn highly dependent on the biological matrix, in which the cortisol is measured. Understanding the origin of these differences is essential for the interpretation of these results. Although cross-reactivity with endogenous steroids leads to grossly inaccurate results of immunoassay measurements of cortisol in the saliva and urine, preliminary evidence suggests that the clinical sensitivity of CS screening using immunoassays may be similar to CS screening using mass spectrometry. However, mass spectrometry offers more accurate results and considerably reduced variation across laboratories, while avoiding false-positive results. Moreover, mass spectrometry can overcome some common diagnostic challenges, such as identification of exogenous corticosteroids or simultaneous assessment of appropriate dexamethasone levels in suppression tests. Further, comprehensive mass spectrometry-based profiling of several steroid metabolites may be useful for discriminating among different subtypes of CS. Finally, this review discusses the main preanalytical factors that could cause variations in cortisol measurements and their influence on the reliability of the results.

Acute adrenal insufficiency (AAI) is a potentially fatal medical emergency whose prevention and treatment should be known by all medical professionals. AAI is an underdiagnosed condition because of its non-specific symptoms, but its diagnosis and early treatment with glucocorticoids is vital. It may be triggered by a de novo deficiency in cortisol synthesis or occur secondarily to omission of hormone replacement therapy (corticosteroids) or inadequate adjustment of the dose required in stress situations in patients previously diagnosed with adrenal insufficiency. AAI prevention significantly decreases death from cardiovascular diseases and infections in patients with adrenal insufficiency, and also improves their quality of life. Adequate education of patients, relatives, and all healthcare professionals is therefore essential. Therefore, the Adrenal Disorders Group of the Neuroendocrinology Area of the Spanish Society of Endocrinology and Nutrition (SEEN) has prepared, at the proposal of the SEEN's board, a guideline for optimal management of acute adrenal insufficiency. The guideline is intended to provide practical recommendations for all healthcare professionals who may be involved in the diagnosis, treatment, and prevention of AAI. It is also intended to provide patients and their families with action guidelines for AAI management and prevention.

Acute adrenal insufficiency (AAI) is a potentially fatal medical emergency whose prevention and treatment should be known by all medical professionals. AAI is an underdiagnosed condition because of its non-specific symptoms, but its diagnosis and early treatment with glucocorticoids is vital. It may be triggered by a de novo deficiency in cortisol synthesis or occur secondarily to omission of hormone replacement therapy (corticosteroids) or inadequate adjustment of the dose required in stress situations in patients previously diagnosed with adrenal insufficiency. AAI prevention significantly decreases death from cardiovascular diseases and infections in patients with adrenal insufficiency, and also improves their quality of life. Adequate education of patients, relatives, and all healthcare professionals is therefore essential. Therefore, the Adrenal Disorders Group of the Neuroendocrinology Area of the Spanish Society of Endocrinology and Nutrition (SEEN) has prepared, at the proposal of the SEEN's board, a guideline for optimal management of acute adrenal insufficiency. The guideline is intended to provide practical recommendations for all healthcare professionals who may be involved in the diagnosis, treatment, and prevention of AAI. It is also intended to provide patients and their families with action guidelines for AAI management and prevention.

Excessive and prolonged glucocorticoid (GC) exposure, resulting from either prescribed or endogenous hypercortisolism, is associated with a high cardiovascular and metabolic burden (Cushing’s syndrome). Although previous studies in humans and mice have reported heterogeneous data about the persistence of metabolic syndrome features after remission of hypercortisolism, there is still controversy as to whether this is due to the deleterious changes induced by GCs during active disease or the result of various other factors interfering in the recovery period. In order to study metabolic effects after remission, we used a reversible mouse model of corticosterone (CORT) (100 µg/mL) administration in drinking water for 5 weeks, followed by a 10-week recovery period. We compared CORT-induced effects at these time points with a high-fat diet-treated group (HFD 45%) and a vehicle group (VEH). Plasma CORT, 11β-HSD activity, food intake, glucose levels, interscapular brown adiposity, hepatic triglycerides and muscle mass were found altered during CORT treatment but normalized after recovery. Although hyperinsulinemia and insulin resistance were increased during CORT and HFD treatment, insulin homeostasis remained altered following the recovery period only in CORT-treated mice. Subcutaneous and visceral adipose tissues (SAT and VAT) were enlarged during HFD and CORT treatment as measured by MRI. However, increased muscle lipid content, adiposity and macrophage infiltration in VAT were only present in the CORT group following recovery. Taken together, CORT-induced insulin alterations were more potent than HFD-induced ones during the same period of treatment, and also more persistent long term. Moreover, we demonstrated that CORT treatment induces more long-lasting VAT enlargement than HFD.

Purpose Gender affirming hormone therapy (HT) in transgender men both improves and impairs several surrogate cardiovascular risk markers. However, few prospective works with long follow-up and control group are available. In this context, this work aimed to assess the changes in the metabolic and cardiovascular risk pattern after 12 months of HT in transgender men. Furthermore, we aimed to investigate early effects on target tissues that may reflect an initial vascular damage. Methods Prospective observational study, including 20 transgender men, attended in the Gender Identity Unit (UIG) of the Hospital Clinic from July 2013 to November 2015. Anthropometric and body composition by dual-energy X-ray absorptiometry (DXA), hormonal, metabolic and coagulation parameters, endothelial dysfunction by flow-mediated dilation (FMD) and intima–media thickness (IMT) by carotid ultrasound, were assessed at baseline, at 6 and 12 months of HT. Results We observed an impairment of lipid profile, and increase of homocysteine and leucocytes count, as well as changes in body composition with increased total lean mass together with decreased total fat mass. In addition, higher mean-maximum common IMT was observed after 12 months of HT. Conclusion Our work shows changes in metabolic and inflammatory parameters after HT after short-medium follow-up, which could increase cardiovascular risk in this setting, together with initial evidence of vascular changes.

Introducción: La enfermedad COVID-19 se ha convertido en una prioridad para nuestro sistema sanitario. Los MIR de Endocrinología y Nutrición (MIR-EyN) se han integrado en los equipos COVID-19. Se ha diseñado este estudio con el objetivo de analizar el impacto a nivel formativo, laboral y en la salud de MIR-EyN. Material y métodos: Estudio observacional transversal tipo encuesta vía web, dirigida a MIR-EyN socios SEEN, realizado en noviembre 2020. Se han analizado: variables demográficas, tamaño del hospital de formación en número de camas, alteración de las rotaciones, integración en equipos COVID-19, participación en teleconsulta, actividad científica e impacto sobre la salud física y emocional. Resultados: Se han obtenido 87 respuestas (27% de los MIR-EyN), 67,8% mujeres, 28,1 ± 1,8 años, 60% MIR-EyN 4º año. El 84% ha participado en equipos COVID-19 y el 93% en las consultas telemáticas de su servicio. La mayoría han visto interrumpidas sus rotaciones. El 97,7% ha participado en reuniones científicas o congresos virtuales y un tercio de ellos ha colaborado en trabajos científicos sobre la COVID-19 en relación a la Endocrinología y Nutrición. La pandemia ha afectado a su estado de ánimo mucho o bastante (75,8%) y opinan que ha impactado de forma negativa a su formación (73,8%). Conclusiones: La pandemia por SARS-CoV-2 ha comprometido la formación, la actividad laboral y la salud de los MIR-EyN. Se han integrado tanto en equipos COVID-19 como en la actividad reestructurada de sus servicios. Sin embargo, han conseguido mantener la formación en formato virtual y participado en trabajos científicos.

Context Chronic glucocorticoid (GC) overexposure, resulting from endogenous Cushing’s syndrome (CS) or exogenous GC therapy, causes several adverse outcomes, including persistent central fat accumulation associated with a low-grade inflammation. However, no previous multiomics studies in visceral adipose tissue (VAT) from patients exposed to high levels of unsuppressed GC during active CS or after remission are available yet. Objective To determine the persistent VAT transcriptomic alterations and epigenetic fingerprints induced by chronic hypercortisolism. Methods We employed a translational approach combining high-throughput data on endogenous CS patients and a reversible CS mouse model. We performed RNA sequencing and chromatin immunoprecipitation sequencing on histone modifications (H3K4me3, H3K27ac, and H3K27me3) to identify persistent transcriptional and epigenetic signatures in VAT produced during active CS and maintained after remission. Results VAT dysfunction was associated with low-grade proinflammatory status, macrophage infiltration, and extracellular matrix remodeling. Most notably, chronic hypercortisolism caused a persistent circadian rhythm disruption in VAT through core clock genes modulation. Importantly, changes in the levels of 2 histone modifications associated to gene transcriptional activation (H3K4me3 and H3K27ac) correlated with the observed differences in gene expression during active CS and after CS remission. Conclusion We identified for the first time the persistent transcriptional and epigenetic signatures induced by hypercortisolism in VAT, providing a novel integrated view of molecular components driving the long-term VAT impairment associated with CS.

We present the LUCA device, a multi-modal platform combining eight-wavelength near infrared time resolved spectroscopy, sixteen-channel diffuse correlation spectroscopy and a clinical ultrasound in a single device. By simultaneously measuring the tissue hemodynamics and performing ultrasound imaging, this platform aims to tackle the low specificity and sensitivity of the current thyroid cancer diagnosis techniques, improving the screening of thyroid nodules. Here, we show a detailed description of the device, components and modules. Furthermore, we show the device tests performed through well established protocols for phantom validation, and the performance assessment for in vivo. The characterization tests demonstrate that LUCA device is capable of performing high quality measurements, with a precision in determining in vivo tissue optical and dynamic properties of better than 3%, and a reproducibility of better than 10% after ultrasound-guided probe repositioning, even with low photon count-rates, making it suitable for a wide variety of clinical applications.

To review the literature assessing the diagnostic performance of urinary steroid profiling (USP) by high-performance liquid chromatography (LC–MS) or gas chromatography (GC) coupled to mass spectrometry (MS) in the evaluation of adrenal lesions, both in terms of functionality and malignancy. The evaluation of adrenal incidentalomas (AI) aims to rule out malignancy and hormone excess. Current diagnostic protocols have several limitations and include time consuming and relatively complicated multi-step processes in most cases. On the contrary, USP by LC–MS/MS or LC-GC/MS offer an easy, comprehensive and non-invasive assessment of adrenal steroid secretion. USP complements current workups used in the evaluation of AIs by improving our ability to identify malignancy and/or autonomous hormone secretion. Urine steroid profiling by LC–MS/MS and GC–MS allows a thorough, non-invasive, assessment of adrenal steroidogenesis as a whole which complement the current evaluation of AIs, and holds a promising role in the diagnosis of autonomous cortisol secretion, primary aldosteronism, and adrenal malignancy.

Objective. Several smaller studies on adrenal incidentalomas (AI) suggested an association between autonomous cortisol secretion (ACS) and mortality (Di Dalmazi Lancet Diabetes Endocrinol 2014, Debono J Clin Endocrinol Metab 2014, Patrova Endocrine 2017). However, a recent meta-analysis (9 studies, 1356 patients) could not confirm these findings (Elhassan Ann Intern Med 2019). Aim. To investigate the effects of ACS on mortality, prevalence of cardiovascular (CV) risk factors, and (CV) morbidity, in a representative cohort of AI. Design. Retrospective observational study conducted at 27 ENS@T centers from 15 countries. Methods. Inclusion criteria: AI diagnosed 1996-2015, 1 mg dexamethasone suppression test, follow-up (FU) of ≥36 months, known survival status. Exclusion criteria: clinically relevant adrenal hormone excess (i.e. Cushing’s syndrome, pheochromocytoma, primary hyperaldosteronism), known malignancy. Patient stratification: serum cortisol after dexamethasone (>5 µg/dl, ACS; 1.9-5 µg/dl, possible ACS (PACS); ≤1.8 µg/dl, non-functioning adenoma (NFA)). Definition of CV events (CVE): hospitalization due to myocardial infarction and related interventions (PTCA, surgical bypass), stroke, deep vein thrombosis, pulmonary embolism. Results. 3640 patients (57% NFA, 36% PACS, 7% ACS) were considered eligible: 64% females; median age 61 years (range 18-91); median FU 84 months (36-277) (distribution between subgroups n.s.). 352 patients died during FU. Age- and sex adjusted overall survival was significantly reduced in patients with PACS (HR 1.55; 95%CI 1.24-1.94) and ACS (1.84; 1.29-2.61). Prevalence of CV risk factors were significantly higher in PACS and ACS than in NFA (hypertension: 72, 73, 57%, p