Adrenalectomy for Primary Aldosteronism:Significant Variability in Work-Up Strategies and Low Guideline Adherence in Worldwide Daily Clinical Practice

Background Various diagnostic tests are available to establish the primary aldosteronism (PA) diagnosis and to determine the disease laterality. Combined with the controversies in the literature, unawareness of guidelines and technical demands and high costs of some of these diagnostics, this could lead to significant differences in work-up strategies worldwide. Therefore, we investigated the work-up before surgery for PA in daily clinical practice within a multicenter study. Methods Patients who underwent unilateral adrenalectomy for PA within 16 centers in Europe, Canada, Australia and the USA between 2010 and 2016 were included. We did not exclude patients based on the performed diagnostic tests during work-up to make our data representative for current clinical practice. Adherence to the Endocrine Society Guideline and variables associated with not performing adrenal venous sampling (AVS) were analyzed. Results In total, 435 patients were eligible. An aldosterone-to-renin ratio, confirmatory test, computed tomography (CT), magnetic resonance imaging and AVS were performed in 82.9%, 32.9%, 86.9%, 17.0% and 65.3% of patients, respectively. A complete work-up, as recommended by the guideline, was performed in 13.1% of patients. Bilateral disease or normal adrenal anatomy on CT (OR 16.19; CI 3.50-74.99), smaller tumor size on CT (OR 0.06; CI 0.04-0.08) and presence of hypokalemia (OR 2.00; CI 1.19-3.32) were independently associated with performing AVS. Conclusions This study is the first to examine the daily clinical practice work-up of PA within a worldwide cohort of surgical patients. The results demonstrate significant variability in work-up strategies and low adherence to The Endocrine Society guideline

Validation of the Aldosteronoma Resolution Score Within Current Clinical Practice

Introduction Complete resolution of hypertension after adrenalectomy for primary aldosteronism is far from a certainty. This stresses the importance of adequate preoperative patient counseling. The aldosteronoma resolution score (ARS) is a simple and easy to use prediction model only including four variables

Clinical outcomes after surgery for primary aldosteronism: Evaluation of the PASO-investigators' consensus criteria within a worldwide cohort of patients

Background: In a first step toward standardization, the Primary Aldosteronism Surgical Outcomes investigators introduced consensus criteria defining the clinical outcomes after adrenalectomy for primary aldosteronism. Within this retrospective cohort study, we evaluated the use of these consensus criteria in daily clinical practice in 16 centers in Europe, Canada, Australia, and the United States. Methods: Patients who underwent unilateral adrenalectomy for primary aldosteronism between 2010 and 2016 were included. Patients with missing data regarding preoperative or postoperative blood pressure or their defined daily dose were excluded. According to the Primary Aldosteronism Surgical Outcomes criteria, patients were classified as complete, partial, or absent clinical success. Results: A total of 380 patients were eligible for analysis. Complete, partial, and absent clinical success was achieved in 30%, 48%, and 22%, respectively. Evaluation of the Primary Aldosteronism Surgical Outcomes criteria showed that in 11% and 47% of patients with partial and absent clinical success, this classification was incorrect or debatable (16% of the total cohort). This concept of a "debatable classification of success" was due mainly to the cutoff of >= 20 mmHg used to indicate a clinically relevant change in systolic blood pressure and the use of percentages instead of absolute values to indicate a change in defined daily dose. Conclusion: Although introduction of the Primary Aldosteronism Surgical Outcomes consensus criteria induced substantial advancement in the standardization of postoperative outcomes, our study suggests that there is room for improvement in the concept for success given the observed limitations when the criteria were tested within our international cohort. In line, determining clinical success remains challenging, especially in patients with opposing change in blood pressure and defined daily dose. (C) 2019 Elsevier Inc. All rights reserved

Follow-up of patients with thyroglobulin-antibodies : Rising Tg-Ab trend is a risk factor for recurrence of differentiated thyroid cancer

PURPOSE: Differentiated thyroid cancer is the most common endocrine malignancy. Recurrences (5-20%) are the main reason for follow-up. Thyroglobulin (Tg) has proven to be an excellent disease marker, but thyroglobulin-antibodies (Tg-Ab) may interfere with Tg measurement, leading to over or underestimation. It is proposed that the Tg-Ab trend can be used as a marker for disease recurrence, yet few studies define trend and have a long-term follow-up. The objective of our study was to investigate the value of a well-defined Tg-Ab trend as a surrogate marker for disease recurrence during long-term follow-up. METHODS: We retrospectively studied patients treated at the Nuclear Department of the University Medical Center Utrecht from 1998 to 2010 and the Netherlands Cancer Institute from 2000 to 2009. All patients with Tg-Ab 12 months after treatment were included. The definition of a rise was >50% increase of the Tg-Ab value in a 2 year time period. A decline as >50% decrease of the Tg-Ab value. RESULTS: Twenty-five patients were included. None of the patients with declining or stable Tg-Ab without a concomitant rise in Tg developed a recurrence. Four patients did suffer a recurrence. Three of these patients had a rising Tg-Ab trend, in two of these patients Tg was undetectable. CONCLUSIONS: Tg-Ab trend can be used as a crude surrogate marker for long-term follow-up of Tg-Ab patients. A rising trend in Tg-Ab warrants further investigation to detect recurrent disease. Stable or declining Tg-Ab levels do not seem to reflect a risk for recurrence

Fluorine-18 fluorocholine PET-CT localizes hyperparathyroidism in patients with inconclusive conventional imaging : a multicenter study from the Netherlands

BACKGROUND: Several reports have shown good performance of fluorine-18 fluorocholine (F-FCH) PET-computed tomography (CT) for parathyroid localization, although overall evidence remains scarce. We collected data from three institutions in the Netherlands and investigated the performance of F-FCH PET-CT as a second-line imaging modality. MATERIALS AND METHODS: We performed a retrospective review of all patients at least 18 years who underwent F-FCH PET-CT for biochemically proven hyperparathyroidism (HPT) and inconclusive ultrasound and sestamibi scintigraphy. Acquisition of PET images was performed 30 min after the administration of 2 MBq/kg F-FCH, together with a low-dose CT. RESULTS: PET-CT scans were performed in 33 (75%) women and 11 (25%) men with a mean age of 58.9 (range 31-80 years). Three patients had multiple endocrine neoplasia type 1, one patient had tertiary HPT because of Alport syndrome and the remaining patients had sporadic primary HPT. F-FCH PET-CT was positive in 34/44 (77.3%) cases. Of the 35 abnormal glands resected in 33 patients, F-FCH PET-CT could successfully localize 33/35 (94.3%), with only one false-positive result [positive predictive value (PPV)=97.1%]. Comparison of the 10 patients with negative PET-CT with the 34 patients with positive PET-CT showed no significant differences in age, sex, ratio of preoperative calcium, use of cinacalcet, history of neck surgery, and concomitant multinodular goiter. CONCLUSION: Our study shows excellent performance of F-FCH PET-CT in patients with HPT and inconclusive conventional imaging. Because of its favorable characteristics with high performance, prospective studies should be initiated to determine whether this new technique may replace conventional sestamibi scintigraphy as a first-line imaging modality

Fluorine-18 fluorocholine PET-CT localizes hyperparathyroidism in patients with inconclusive conventional imaging : a multicenter study from the Netherlands

BACKGROUND: Several reports have shown good performance of fluorine-18 fluorocholine (F-FCH) PET-computed tomography (CT) for parathyroid localization, although overall evidence remains scarce. We collected data from three institutions in the Netherlands and investigated the performance of F-FCH PET-CT as a second-line imaging modality. MATERIALS AND METHODS: We performed a retrospective review of all patients at least 18 years who underwent F-FCH PET-CT for biochemically proven hyperparathyroidism (HPT) and inconclusive ultrasound and sestamibi scintigraphy. Acquisition of PET images was performed 30 min after the administration of 2 MBq/kg F-FCH, together with a low-dose CT. RESULTS: PET-CT scans were performed in 33 (75%) women and 11 (25%) men with a mean age of 58.9 (range 31-80 years). Three patients had multiple endocrine neoplasia type 1, one patient had tertiary HPT because of Alport syndrome and the remaining patients had sporadic primary HPT. F-FCH PET-CT was positive in 34/44 (77.3%) cases. Of the 35 abnormal glands resected in 33 patients, F-FCH PET-CT could successfully localize 33/35 (94.3%), with only one false-positive result [positive predictive value (PPV)=97.1%]. Comparison of the 10 patients with negative PET-CT with the 34 patients with positive PET-CT showed no significant differences in age, sex, ratio of preoperative calcium, use of cinacalcet, history of neck surgery, and concomitant multinodular goiter. CONCLUSION: Our study shows excellent performance of F-FCH PET-CT in patients with HPT and inconclusive conventional imaging. Because of its favorable characteristics with high performance, prospective studies should be initiated to determine whether this new technique may replace conventional sestamibi scintigraphy as a first-line imaging modality

Hemodynamic instability during surgery for pheochromocytoma: comparing the transperitoneal and retroperitoneal approach in a multicenter analysis of 341 patients

Background Intraoperative hemodynamic instability is a major challenge during adrenalectomy for pheochromocytoma. Typically, pheochromocytoma is performed laparoscopically either through the retroperitoneal or transperitoneal approach. We aimed to determine if the operative approach affects intraoperative hemodynamic instability during surgery for pheochromocytoma in a large multicenter multicenter cohort. Methods Retrospective, multicenter analysis of consecutive patients with pheochromocytoma who underwent total unilateral laparoscopic adrenalectomy without conversion were included. Statistical analysis was performed using established intraoperative criteria for intraoperative hemodynamic instability: 1) systolic blood pressure >160 mm Hg; 2) systolic blood pressure > 200 mm Hg; 3) mean arterial pressure <60 mm Hg; 4) systolic blood pressure >160 mm Hg + mean arterial pressure <60 mm Hg; and 5) systolic blood pressure >200 mm Hg + mean arterial pressure <60 mm Hg; and 6) intravenous vasopressor + vasodilator. Results In total, 341 patients met the inclusion criteria, 101 (29.6%) underwent retroperitoneal adrenalectomy and 240 (70.4%) transperitoneal adrenalectomy. Multivariate analysis showed that retroperitoneal adrenalectomy carries greater risk for mean arterial pressure <60 mm Hg (odds ratio 6.255, confidence interval 1.134–34.235, P =.035) compared with transperitoneal adrenalectomy. Overall and cardiovascular morbidity rates were comparable between the 2 approaches. The medical center was a significant independent influencing factor for all 6 intraoperative hemodynamic instability definitions. Conclusion Variability in institutional management of pheochromocytoma intraoperatively has significant impact on all 6 intraoperative hemodynamic instability definitions. Standardization of anesthesia should be considered to reduce this variability

Clinical Outcomes after Unilateral Adrenalectomy for Primary Aldosteronism

Importance: In addition to biochemical cure, clinical benefits after surgery for primary aldosteronism depend on the magnitude of decrease in blood pressure (BP) and use of antihypertensive medications with a subsequent decreased risk of cardiovascular and/or cerebrovascular morbidity and drug-induced adverse effects. Objective: To evaluate the change in BP and use of antihypertensive medications within an international cohort of patients who recently underwent surgery for primary aldosteronism. Design, Setting, and Participants: A cohort study was conducted across 16 referral medical centers in Europe, the United States, Canada, and Australia. Patients who underwent unilateral adrenalectomy for primary aldosteronism between January 2010 and December 2016 were included. Data analysis was performed from August 2017 to June 2018. Unilateral disease was confirmed using computed tomography, magnetic resonance imaging, and/or adrenal venous sampling. Patients with missing or incomplete preoperative or follow-up data regarding BP or corresponding number of antihypertensive medications were excluded. Main Outcomes and Measures: Clinical success was defined based on postoperative BP and number of antihypertensive medications. Cure was defined as normotension without antihypertensive medications, and clear improvement as normotension with lower or equal use of antihypertensive medications. In patients with preoperative normotensivity, improvement was defined as postoperative normotension with lower antihypertensive use. All other patients were stratified as no clear success because the benefits of surgery were less obvious, mainly owing to postoperative, persistent hypertension. Clinical outcomes were assessed at follow-up closest to 6 months after surgery. Results: On the basis of inclusion and exclusion criteria, a total of 435 patients (84.6%) from a cohort of 514 patients who underwent unilateral adrenalectomy were eligible. Of these patients, 186 (42.3%) were women; mean (SD) age at the time of surgery was 50.7 (11.4) years. Cure was achieved in 118 patients (27.1%), clear improvement in 135 (31.0%), and no clear success in 182 (41.8%). In the subgroup classified as no clear success, 166 patients (91.2%) had postoperative hypertension. However, within this subgroup, the mean (SD) systolic and diastolic BP decreased significantly by 9 (22) mm Hg (P <.001) and 3 (15) mm Hg (P =.04), respectively. Also, the number of antihypertensive medications used decreased from 3 (range, 0-7) to 2 (range, 0-6) (P <.001). Moreover, in 75 of 182 patients (41.2%) within this subgroup, the decrease in systolic BP was 10 mm Hg or greater. Conclusions and Relevance: In this study, for most patients, adrenalectomy was associated with a postoperative normotensive state and reduction of antihypertensive medications. Furthermore, a significant proportion of patients with postoperative, persistent hypertension may benefit from adrenalectomy given the observed clinically relevant and significant reduction of BP and antihypertensive medications.

Clinical outcomes after surgery for primary aldosteronism: Evaluation of the PASO-investigators’ consensus criteria within a worldwide cohort of patients

Background: In a first step toward standardization, the Primary Aldosteronism Surgical Outcomes investigators introduced consensus criteria defining the clinical outcomes after adrenalectomy for primary aldosteronism. Within this retrospective cohort study, we evaluated the use of these consensus criteria in daily clinical practice in 16 centers in Europe, Canada, Australia, and the United States. Methods: Patients who underwent unilateral adrenalectomy for primary aldosteronism between 2010 and 2016 were included. Patients with missing data regarding preoperative or postoperative blood pressure or their defined daily dose were excluded. According to the Primary Aldosteronism Surgical Outcomes criteria, patients were classified as complete, partial, or absent clinical success. Results: A total of 380 patients were eligible for analysis. Complete, partial, and absent clinical success was achieved in 30%, 48%, and 22%, respectively. Evaluation of the Primary Aldosteronism Surgical Outcomes criteria showed that in 11% and 47% of patients with partial and absent clinical success, this classification was incorrect or debatable (16% of the total cohort). This concept of a “debatable classification of success” was due mainly to the cutoff of ≥20 mmHg used to indicate a clinically relevant change in systolic blood pressure and the use of percentages instead of absolute values to indicate a change in defined daily dose. Conclusion: Although introduction of the Primary Aldosteronism Surgical Outcomes consensus criteria induced substantial advancement in the standardization of postoperative outcomes, our study suggests that there is room for improvement in the concept for success given the observed limitations when the criteria were tested within our international cohort. In line, determining clinical success remains challenging, especially in patients with opposing change in blood pressure and defined daily dose