Development of an ontology for laparoscopic transabdominal adrenalectomy via a comprehensive modified Delphi survey and its validation on a multicentric pilot data set for surgical training and future video analysis with machine learning algorithms.

Surgical technique is essential to ensure safe minimally invasive adrenalectomy. Due to the relative rarity of adrenal surgery, it is challenging to ensure adequate exposure in surgical training. Surgical video analysis supports auto-evaluation, expert assessment and could be a target for automatization. The developed ontology was validated by a European expert consensus and is applicable across the surgical techniques encountered in all participating centres, with an exemplary demonstration in bi-centric recordings. Standardization of adrenalectomy video analysis may foster surgical training and enable machine learning training for automated safety alerts.

Emerging Potential of Microwave Ablation for Primary Aldosteronism Resulting From Unilateral Aldosterone-producing Adenoma.

Primary aldosteronism (PA) is the most prevalent form of secondary hypertension and is most commonly caused by an adrenal adenoma or bilateral adrenal hyperplasia. Minimally invasive adrenalectomy is the treatment of choice for unilateral disease. Here, we report the case of a 57-year-old man with previous bladder cancer who was referred for evaluation of resistant hypertension and hypokalemia. Diagnostic workup indicated PA with computed tomography imaging revealing a left adrenal adenoma and adrenal venous sampling lateralizing to the left adrenal. He was therefore referred for a left adrenalectomy using a retroperitoneoscopic approach. However, surgery was complicated by significant perinephritis related to previous bladder cancer immunotherapy and, in view of an identifiable adrenal adenoma, a partial adrenalectomy was performed. Despite histology confirming removal of an adrenal adenoma, he remained hypertensive and hypokalemic with persistent PA. He underwent a computed tomography-guided percutaneous thermal (microwave) ablation of the residual adrenal nodule with immediate biochemical reversal of PA. Six years postprocedure, he remains biochemically and clinically cured from PA. This article presents the details of the case and reviews the literature on long-term outcomes for patients undergoing thermal ablation and adrenalectomy, suggesting that thermal ablation may be a viable alternative for selected patients.

Risk factors for postoperative complications after adrenalectomy for phaeochromocytoma: multicentre cohort study.

BACKGROUND: To determine the incidence and risk factors for postoperative complications and prolonged hospital stay after adrenalectomy for phaeochromocytoma. METHODS: Demographics, perioperative outcomes and complications were evaluated for consecutive patients who underwent adrenalectomy for phaeochromocytoma from 2012 to 2020 in nine high-volume UK centres. Odds ratios were calculated using multivariable models. The primary outcome was postoperative complications according to the Clavien---Dindo classification and secondary outcome was duration of hospital stay. RESULTS: Data were available for 406 patients (female n = 221, 54.4 per cent). Two patients (0.5 per cent) had perioperative death, whilst 148 complications were recorded in 109 (26.8 per cent) patients. On adjusted analysis, the age-adjusted Charlson Co-morbidity Index ≥3 (OR 8.09, 95 per cent c.i. 2.31 to 29.63, P = 0.001), laparoscopic converted to open (OR 10.34, 95 per cent c.i. 3.24 to 36.23, P <0.001), and open surgery (OR 11.69, 95 per cent c.i. 4.52 to 32.55, P <0.001) were independently associated with postoperative complications. Overall, 97 of 430 (22.5 per cent) had a duration of stay ≥5 days and this was associated with an age-adjusted Charlson Co-morbidity Index ≥3 (OR 4.31, 95 per cent c.i. 1.08 to 18.26, P = 0.042), tumour size (OR 1.15, 95 per cent c.i. 1.05 to 1.28, P = 0.006), laparoscopic converted to open (OR 32.11, 95 per cent c.i. 9.2 to 137.77, P <0.001), and open surgery (OR 28.01, 95 per cent c.i. 10.52 to 83.97, P <0.001). CONCLUSION: Adrenalectomy for phaeochromocytoma is associated with a very low mortality rate, whilst postoperative complications are common. Several risk factors, including co-morbidities and operative approach, are independently associated with postoperative complications and/or prolonged hospitalization, and should be considered when counselling patients.

The Impact of Obesity on the Resolution of Hypertension Following Adrenalectomy for Primary Hyperaldosteronism.

BACKGROUND: This study aims to determine the impact of patient obesity on the resolution of hypertension and pill burden post-adrenalectomy for PA. Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension that may be remedied with surgery (unilateral adrenalectomy). Obesity may independently cause hypertension through several mechanisms including activation of the renin-angiotensin-aldosterone pathway. The influence of obesity on the efficacy of adrenalectomy in PA has not been established. METHODS: This is a retrospective analysis of prospectively collected data on patients undergoing adrenalectomy for PA at a single, tertiary-care surgical centre from January 2015 to December 2020. Electronic health records of patients were screened to collect relevant data. The primary outcomes of the study include post-operative blood pressure, the reduction in the number of anti-hypertensive medications and potassium supplementation burden post-adrenalectomy. RESULTS: Fifty-three patients were included in the final analysis. There was a significant reduction in the blood pressure and the number of anti-hypertensive medications in all patients after adrenalectomy (p < 0.001). Of the 34 patients (64.2%) with pre-operative hypokalaemia, all became normokalaemic and were able to stop supplementation. However obese patients required more anti-hypertensive medications to achieve an acceptable blood pressure than overweight or normal BMI patients (p < 0.01). Multivariate logistic regression analysis showed that male gender and BMI were independent predictors of resolution of hypertension (p <0.01). CONCLUSION: Unilateral adrenalectomy improves the management of hypertension and hypokalaemia when present in patients with PA. However, obesity has an independent deleterious impact on improvement in blood pressure post-adrenalectomy for PA.

Resection of an elusive parathyroid adenoma in the aortopulmonary window.

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcaemia and is caused by a single parathyroid adenoma in the neck in 85% or more of patients. National Institute for Health and Care Excellence (NICE) guidelines published in May 2019 advise that preoperative imaging is offered prior to parathyroid surgery for PHPT if it will inform surgical approach. If imaging, typically a neck ultrasound and a second modality that may use ionising radiation, does not identify the adenoma or is discordant, it is advised that surgery is performed by a surgeon with expertise in the management of unlocalised parathyroid disease.The cure rate in such cases is over 96%. Occasionally, however, PHPT cure can be challenging.A woman in her late 40s presented with bilateral renal calculi and was found to have PHPT. Following false positive imaging and three non-curative surgical procedures, removal of a supernumerary ectopic parathyroid adenoma in the aortopulmonary window via sternotomy achieved definitive cure.

Risk factors for postoperative hypotension after adrenalectomy for phaeochromocytoma: derivation of the PACS risk score.

BACKGROUND: Due to the risk of postoperative hypotension (PH), invasive monitoring is recommended for patients who undergo adrenalectomy for phaeochromocytoma. Due to high costs and limited availability of intensive care, our aim was to identify patients at low risk of PH who may not require invasive monitoring. METHODS: Data for patients who underwent adrenalectomy for phaeochromocytoma between 2012 and 2020 were retrospectively collected by nine UK centres, including patient demographics, intraoperative and postoperative haemodynamic parameters. Independent risk factors for PH were analysed and used to develop a clinical risk score. RESULTS: PH developed in 118 of 430 (27.4%) patients. On univariable analysis, female sex (p = 0.007), tumour size (p < 0.001), preoperative catecholamine level (p < 0.001), open surgery (p < 0.001) and epidural analgesia (p = 0.006) were identified as risk factors for PH. On multivariable analysis, female sex (OR 1.85, CI95%, 1.09-3.13, p = 0.02), preoperative catecholamine level (OR: 3.11, CI95%, 1.74-5.55, p < 0.001), open surgery (OR: 3.31, CI95%, 1.57-6.97, p = 0.002) and preoperative mean arterial blood pressure (OR: 0.59, CI95%, 0.48-1.02, p = 0.08) were independently associated with PH, and were incorporated into a clinical risk score (AUROC 0.69, C-statistic 0.69). The risk of PH was 25% and 68% in low and high risk patients, respectively. CONCLUSION: The derived risk score allows stratification of patients at risk of postoperative hypotension after adrenalectomy for phaeochromocytoma. Postoperatively, low risk patients may be managed on a surgical ward, whilst high risk patients should undergo invasive monitoring.

Elevated sphingosine-1-phosphate lyase leads to increased metabolism and reduced survival in adrenocortical carcinoma.

OBJECTIVE: Adrenocortical carcinomas (ACCs) are invasive tumours arising in the adrenal cortex, and steroidogenic tumours are associated with worse prognostic outcomes. Loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1) cause primary adrenal insufficiency and as a key degradative enzyme in the sphingolipid pathway, SGPL1 also influences the balance of pro-proliferative and pro-apoptotic sphingolipids. We, therefore, hypothesized increased SGPL1 may be linked to increased disease severity in ACC. DESIGN: Analyse SGPL1 expression impact on patient survival and adrenal cancer cell phenotype. We analysed two ACC cohorts with survival and corresponding transcriptomic data, focusing on SGPL1 and sphingolipid pathway genes. In vitro, we generated SGPL1-knockout and overexpressing H295R adrenocortical cells to investigate the role of SGPL1 in cell signalling in ACCs. RESULTS: We found increased expression of several sphingolipid pathway receptors and enzymes, most notably SGPL1 correlated with reduced patient survival in both cohorts. Overexpression of SGPL1 in the H295R cell line increased proliferation and migration while reducing apoptosis, while SGPL1 knockout had the opposite effect. RNA-seq revealed a global increase in the expression of genes in the electron transport chain in overexpressing cells, correlating with increased aerobic respiration and glycolysis. Furthermore, the opposite phenotype was seen in cells lacking SGPL1. We subsequently found the increased proliferation is linked to metabolic substrate availability and increased capacity to use different fuel sources, but particularly glucose, in overexpressing cells. CONCLUSIONS: We, therefore, propose that SGPL1-overexpressing ACC tumours reduce patient survival by increasing fuel usage for anabolism and energy production to facilitate growth and invasion.

Lymph node thyroglobulin in the diagnosis of metastases of thyroid carcinoma with the thyroid in situ: A prospective intraoperative study.

BACKGROUND: The use of thyroglobulin concentration in washout fluid of fine-needle aspiration (FNA-Tg) is a procedure advocated by international guidelines to diagnose metastatic LN in papillary thyroid cancer. With the increasing use of active follow-up or lobectomy alone for low-risk thyroid cancers, the determination of the diagnostic performance of FNA-Tg in the detection of metastatic PTC when the thyroid is in situ is paramount. MATERIALS AND METHODS: Prospective study with measurement of Tg in washout fluid obtained from intraoperative fine needle aspiration (FNA) cytology in order to avoid contamination from thyroid tissue and rigorously isolated punctured nodes. Receiver-operating characteristic (ROC) curve and area under the curve (AUC), optimal threshold to discriminate benign and malignant LN, sensitivity and specificity were provided. RESULTS: a total of 58 lymph nodes from 32 patients were analyzed. ROC analysis defined the optimal cutoff values of FNA-Tg at 60 ng/ml for the diagnosis of malignant LNs in patients with a thyroid in situ. Sensitivity and specificity were 75% (95% confidence interval 57.89-86.75) and 87.5% (95%CI: 69-95.66), respectively. CONCLUSION: Our results support the hypothesis that the Tg-FNA threshold for a safe diagnosis of LN metastasis in PTC is higher in presence of a thyroid gland in situ. The use of lower thresholds could result in false positive results and lead to unnecessary surgery.

Contemporary Multimodality Imaging of Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a disorder characterized by hypercalcemia and an elevated or inappropriately normal parathyroid hormone level. Classic features include bone pain, fractures, renal impairment, nephrolithiasis, and mental disturbance. However, most cases of PHPT are now asymptomatic at diagnosis or associated with nonspecific neurocognitive changes. The most frequent cause of PHPT is a solitary adenoma that secretes parathyroid hormone without the normal suppressive effect of serum calcium. A smaller number of cases can be attributed to multigland disease. Parathyroidectomy is curative and is considered for nearly all affected patients. Although PHPT is primarily a clinical and biochemical diagnosis, imaging is key to the localization of adenomas, which can lie in conventional locations adjacent to the thyroid gland or less commonly at ectopic sites in the neck and mediastinum. In addition, accurate localization facilitates the use of a minimally invasive or targeted surgical approach. Frequently used localization techniques include US, parathyroid scintigraphy, and four-dimensional CT. Second- and third-line modalities such as MRI, PET/CT, and selective venous sampling with or without parathyroid arteriography can increase confidence before surgery. These localization techniques, along with the associated technical aspects, relative advantages, and drawbacks, are described. Local expertise, patient factors, and surgeon preference are important considerations when determining the type and sequence of investigation. A multimodality approach is ultimately desirable, particularly in challenging scenarios such as multigland disease, localization of ectopic adenomas, and persistent or recurrent PHPT. Online supplemental material is available for this article. ©RSNA, 2022.

Management of endocrine surgical disorders during COVID-19 pandemic: expert opinion for non-surgical options.

PURPOSE: The COVID-19 pandemic brought unprecedented conditions for overall health care systems by restricting resources for non-COVID-19 patients. As the burden of the disease escalates, routine elective surgeries are being cancelled. The aim of this paper was to provide a guideline for management of endocrine surgical disorders during a pandemic. METHODS: We used Delphi method with a nine-scale Likert scale on two rounds of voting involving 64 experienced eminent surgeons and endocrinologists who had the necessary experience to provide insight on endocrine disorder management. All voting was done by email using a standard questionnaire. RESULTS: Overall, 37 recommendations were voted on. In two rounds, all recommendations reached an agreement and were either endorsed or rejected. Endorsed statements include dietary change in primary hyperparathyroidism, Cinacalcet treatment in secondary hyperparathyroidism, alpha-blocker administration for pheochromocytoma, methimazole ± ß-blocker combination for Graves' disease, and follow-up for fine-needle aspiration results of thyroid nodules indicated as Bethesda 3-4 cytological results and papillary microcarcinoma. CONCLUSION: This survey summarizes expert opinion for the management of endocrine surgical conditions during unprecedented times when access to surgical treatment is severely disrupted. The statements are not applicable in circumstances in which surgical treatment is possible.

Differentiated Thyroid Cancer: A Health Economic Review.

The incidence of differentiated thyroid cancer (DTC) is rising, mainly because of an increased detection of asymptomatic thyroid nodularity revealed by the liberal use of thyroid ultrasound. This review aims to reflect on the health economic considerations associated with the increasing diagnosis and treatment of DTC. Overdiagnosis and the resulting overtreatment have led to more surgical procedures, increasing health care and patients' costs, and a large pool of community-dwelling thyroid cancer follow-up patients. Additionally, the cost of thyroid surgery seems to increase year on year even when inflation is taken into account. The increased healthcare costs and spending have placed significant pressure to identify potential factors associated with these increased costs. Some truly ground-breaking work in health economics has been undertaken, but more cost-effectiveness studies and micro-cost analyses are required to evaluate expenses and guide future solutions.

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.

Posterior Retroperitoneoscopic Versus Laparoscopic Transperitoneal Adrenalectomy: A Systematic Review by an Updated Meta-Analysis.

BACKGROUND: Two main minimal access adrenalectomy techniques are available: laparoscopic transperitoneal (LTA) and posterior retroperitoneoscopic adrenalectomy (PRA). This study aims to compare these approaches in an updated meta-analysis of randomised controlled (RCT) and non-randomised comparative (NRT) trials. METHODS: A systematic search of comparative LTA and PRA studies was performed. Standard demographic and surgical data were recorded. Outcome measures compared included: operative time, estimated blood loss (EBL), conversion to open, post-operative pain, time to oral intake and ambulation, early morbidity, hospital length of stay (HLOS) and mortality. Quality of RCTs and NRTs was assessed using Cochrane and ROBINS-I, respectively, and heterogeneity using the I2 test. Dichotomous and continuous variables were compared using odds ratios and mean/standard difference. Studies were then combined using the Mantel-Haenszel method. Meta-analysis was performed by fixed- and random-effect models. RESULTS: Following exclusions, 12 studies were included in the analysis: 3 RCTs and 9 NRTs. These reported a total of 775 patients: 341 (44%) PRA and 434 (56%) LTA. Demographics were similar except for tumour size which was smaller (by 0.78 cm) in PRA (p = 0.003). Significant differences in outcome were seen in EBL (18 mls less in PRA, p = 0.006), time to oral intake (3.4 h sooner in PRA p = 0.009) and HLOS (shorter in PRA by 0.84 day, p = 0.001). CONCLUSIONS: This analysis demonstrates that while PRA tends to be performed for smaller tumours it allows for less EBL, earlier post-operative oral intake and shorter hospital stays. In appropriately selected patients, it represents an invaluable tool in the endocrine surgeon's armamentarium.

Optimal extent of initial parathyroid resection in patients with multiple endocrine neoplasia syndrome type 1: A meta-analysis.

BACKGROUND: Hyperparathyroidism is an almost universal feature of multiple endocrine neoplasia type 1 syndrome. We present a systematic review and meta-analysis of the postoperative outcomes of patients undergoing initial operative treatment of primary hyperparathyroidism complicating multiple endocrine neoplasia 1. METHODS: A comprehensive literature search was performed with a priori defined exclusion criteria for studies comparing total parathyroidectomy, subtotal parathyroidectomy, and less than subtotal parathyroidectomy. RESULTS: Twenty-one studies incorporating 1,131 patients (272 undergoing total parathyroidectomy, 510 subtotal parathyroidectomy, and 349 less than subtotal parathyroidectomy) were identified. Pooled results revealed increased risk for long-term hypoparathyroidism in total parathyroidectomy patients (relative risk 1.61; 95% confidence interval, 1.12-2.31; P = .009) versus those undergoing subtotal parathyroidectomy. In the less than subtotal parathyroidectomy or subtotal parathyroidectomy comparison group, a greater risk for recurrence of hyperparathyroidism (relative risk 1.37; 95% confidence interval, 1.05-1.79; P = .02), persistence of hyperparathyroidism (relative risk 2.26; 95% confidence interval, 1.49-3.41; P = .0001), and reoperation for hyperparathyroidism (relative risk 2.48; 95% confidence interval, 1.65-3.73; P < .0001) was noted for less than subtotal parathyroidectomy patients, albeit with lesser risk for long-term for hypoparathyroidism (relative risk 0.47; 95% confidence interval, 0.29-0.75; P = .002). CONCLUSION: Subtotal parathyroidectomy compares favorably to total parathyroidectomy, exhibiting similar recurrence and persistence rates with a decreased propensity for long-term postoperative hypoparathyroidism. The benefit of the decreased risk of hypoparathyroidism in less than subtotal parathyroidectomy is negated by the increase in the risk for recurrence, persistence, and reoperation. Future studies evaluating the performance of less than subtotal parathyroidectomy in specific multiple endocrine neoplasia 1 phenotypes should be pursued in an effort to delineate a patient-tailored, operative approach that optimizes long-term outcomes.

Near-infrared autofluorescence in thyroid and parathyroid surgery.

Contrast-free autofluorescence (AF) of the parathyroid glands (PTGs) and thyroid tissue occurs in the near-infrared (NIR) spectrum on excitation by light in the upper range of the visible spectrum or lower NIR spectrum. In vivo, PTGs autofluoresce more brightly than thyroid (by a factor of 2-20 times) and appear as a bright spot against surrounding thyroid, muscle or fat on a processed image which is generated in real-time. NIR-AF of PTGs was first described in 2009 although NIR-AF had previously been used in several other clinical applications. Since then there has been a great amount of interest in the use of NIR-AF in thyroid and parathyroid surgery with over 25 published reports of the utilisation of both self-built and proprietary NIR-AF devices in neck endocrine surgery. All of these reports have confirmed the feasibility of NIR-AF intraoperatively and its ability to detect PTGs, although the reported accuracy varies from 90-100%. Reports of the effect of NIR-AF on relevant clinical endpoints i.e., post-operative hypoparathyroidism in thyroidectomy and persistent disease in parathyroidectomy are however scant. There has been one multicentre clinical trial of NIR-AF in thyroidectomy but this did not report clinical outcomes and two single-centre, non-randomised studies which did report post-operative hypoparathyroidism but with differing results: one showing no benefit in 106 NIR-AF vs. 163 controls and one, a reduction of early hypocalcaemia from 20% to 5% in 93 NIR-AF patients vs. 420 controls. There were only 2 cases of permanent hypoparathyroidism across both studies and therefore no significant observable difference in this key outcome variable. In parathyroidectomy, possible variability of the AF signal due to composition of a PTG adenoma, secondary/tertiary disease and MEN1 as well as depth-penetration preventing detection of sub-surface PTGs would imply that NIR-AF in its current form is not well-placed to improve cure-rates in hyperparathyroidism, which may already be as high as 98%. Thus far, no study has addressed this. Despite the promising results of NIR-AF, the absence of data demonstrating an improvement in outcomes and the cost of its use currently limit its use in routine clinical practice, especially in a publicly funded healthcare system with budgetary constraints. However, it can be utilised in research settings and this should be undertaken within the context of well-designed and conducted randomised, multi-centre, appropriately powered studies, which will assist in establishing its role in neck endocrine surgery.

A rare cause of severe Cushing's syndrome.

SUMMARY: Ectopic adrenocorticotropic hormone (ACTH) production is an uncommon cause of Cushing's syndrome and, rarely, the source can be a phaeochromocytoma. A 55-year-old man presented following an episode of presumed gastroenteritis with vomiting and general malaise. Further episodes of diarrhoea, joint pains and palpitations followed. On examination, he was hypertensive with no clinical features to suggest hypercortisolaemia. He was subsequently found to have raised plasma normetanephrines of 3.98 nmol/L (NR <0.71) and metanephrines of 0.69 nmol/L (NR <0.36). An adrenal CT showed a 3.8 cm right adrenal nodule, which was not MIBG-avid but was clinically and biochemically consistent with a phaeochromocytoma. He was started on alpha blockade and referred for right adrenalectomy. Four weeks later, on the day of admission for adrenalectomy, profound hypokalaemia was noted (serum potassium 2.0 mmol/L) with non-specific ST-segment ECG changes. He was also diagnosed with new-onset diabetes mellitus (capillary blood glucose of 28 mmol/L). He reported to have gained weight and his skin had become darker over the course of the last 4 weeks. Given these findings, he underwent overnight dexamethasone suppression testing, which showed a non-suppressed serum cortisol of 1099 nmol/L. Baseline serum ACTH was 273 ng/L. A preliminary diagnosis of ectopic ACTH secretion from the known right-sided phaeochromocytoma was made and he was started on metyrapone and insulin. Surgery was postponed for 4 weeks. Following uncomplicated laparoscopic adrenalectomy, the patient recovered with full resolution of symptoms. LEARNING POINTS: Phaeochromocytomas are a rare source of ectopic ACTH secretion. A high clinical index of suspicion is therefore required to make the diagnosis. Ectopic ACTH secretion from a phaeochromocytoma can rapidly progress to severe Cushing's syndrome, thus complicating tumour removal. Removal of the primary tumour often leads to full recovery. The limited literature suggests that the presence of ectopic Cushing's syndrome does not appear to have any long-term prognostic implications.

Correlating the Bethesda System for Reporting Thyroid Cytopathology with Histology and Extent of Surgery: A Review of 21,746 Patients from Four Endocrine Surgery Registries Across Two Continents.

BACKGROUND: The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category. METHODS: Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed. RESULTS: Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31-35 years (52.1%, 95% confidence interval (CI) 37.9-66.2%), aged 36-40 years (55.9%, 95% CI 39.2-72.6%) and aged 41-45 years (46.9%, 95% CI 33-60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males. CONCLUSIONS: These data demonstrate that Bethesda categories 1-4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC.

Association Between hsa-miR-30e Polymorphisms and Sporadic Primary Hyperparathyroidism Risk.

BACKGROUND/AIM: Almost 15% of patients with sporadic primary hyperparathyroidism (sPHPT) present with multiple gland disease (MGD). The aim of this study was to investigate the potential role of two polymorphisms of the hsa-miR-30e, in sPHPT tumorigenesis. PATIENTS AND METHODS: One-hundred twenty sPHPT patients, 77 presenting a single adenoma and 43 with MGD, and 54 healthy controls were genotyped. The SNPs were identified using the allele-specific PCR methodology, while the hsa-miR-30e expression was analyzed by real-time quantitative reverse transcriptase PCR. RESULTS: Hsa-miR-30e expression was found to be significantly higher in patients with MGD compared to patients with single adenomas (p=0.0019), but no differences were found regarding specific genotype carriers. The genotype frequencies for ss178077483 and rs7556088 were significantly different between patients and healthy controls. CONCLUSION: Although the polymorphisms cannot be used as biomarkers for the differential diagnosis of MGD, hsa-miR-30e expression could potentially serve as a biomarker for this purpose.

DLK1/PREF1 marks a novel cell population in the human adrenal cortex.

The adrenal cortex governs fundamental metabolic processes though synthesis of glucocorticoid, mineralocorticoids and androgens. Studies in rodents have demonstrated that the cortex undergoes a self-renewal process and that capsular/subcapsular stem/progenitor cell pools differentiate towards functional steroidogenic cells supporting the dynamic centripetal streaming of adrenocortical cells throughout life. We previously demonstrated that the Notch atypical ligand Delta-like homologue 1 (DLK1)/preadipocyte factor 1 (PREF1) is expressed in subcapsular Sf1 and Shh-positive, CYP11B1-negative and CYP11B2-partially positive cortical progenitor cells in rat adrenals, and that secreted DLK1 can modulate GLI1 expression in H295R cells. Here we show that the human adrenal cortex remodels with age to generate clusters of relatively undifferentiated cells expressing DLK1. These clusters (named DLK1-expressing cell clusters or DCCs) increased with age in size and were found to be different entities to aldosterone-producing cell clusters, another well-characterized and age-dependent cluster structure. DLK1 was markedly overexpressed in adrenocortical carcinomas but not in aldosterone-producing adenomas. Thus, this data identifies a novel cell population in the human adrenal cortex and might suggest a yet-to be identified role of DLK1 in the pathogenesis of adrenocortical carcinoma in humans.