Adrenal-sparing Surgery Research Articles

Retroperitoneoscopic enucleation adrenalectomy: a viable surgical option for small nonsecreting adrenal tumors with low potential of malignancy.

Laparoscopic total adrenalectomy has become the standard treatment for adrenal mass. Meanwhile, there has been a growing trend toward laparoscopic adrenal-sparing surgery worldwide to avoid the risk and potential complications of adrenal insufficiency. The objectives of this study were to describe a retroperitoneoscopic adrenal tumor enucleation technique, to assess the clinical outcomes of this technique in the treatment of 20-40 mm nonsecreting adrenal tumor (NAT) with low potential of malignancy, and to provide a feasible choice for patients who have preference on resection. This study was a retrospective analysis of 61 patients with low potential of malignancy in 20-40 mm NAT identified at the first imaging examination or during follow-up. All patients were scheduled for planned enucleation adrenalectomy by a single surgeon between July 2016 and December 2020 in Xuanwu Hospital, Beijing, China. In all patients, retroperitoneoscopic surgery was performed via a retroperitoneoscopic process for all the patients. The crucial techniques of enucleation are presented in the video. Safety and feasibility factors of enucleation technique were measured for this study. No blood transfusion or organ injury was registered during the operation. The median operation time was 75 min, and the median blood loss was 35 mL. All operations were successfully performed without open conversion. A total of 58 patients received successful enucleation surgery. Three cases were converted to retroperitoneoscopic total adrenalectomy. In this study, surgical outcomes of retroperitoneoscopic enucleation adrenalectomy as a method to remove adrenal tumors were assessed. This procedure is a feasible and safe technique with the added benefit of preserving the remaining functional adrenal tissue.

FRI188 Exploratory Genomic Analysis From A Brazilian PMAH-Family With ARMC5 Alteration With Insidious Pattern Progression Of The Disease

Abstract Disclosure: H.L. Charchar: None. A.W. Kuhn: None. B.M. Mariani: None. M.Y. Nishi: None. F.L. Ledesma: None. M.C. Zerbini: None. F.Y. Tanno: None. V. Srougi: None. J.L. Chambo: None. M.Q. Almeida: None. B.B. Mendonca: None. M.C. Fragoso: None. Background: The clinical evolution of primary macronodular adrenal hyperplasia (PMAH) is usually slow over many years and is related to the insidious progression of hypercortisolism. The disease presents an autosomal dominant inheritance pattern with incomplete penetrance. Germline heterozygous mutations in the ARMC5 are present in 10% to 55% of the patients. The long-term follow-up of patients harboring germline ARMC5 pathogenic variants with normal evaluation will provide us with important insights regarding the outcomes. Clinical case: A 53-year-old man (index-case) was referred by the cardiologist to our service in October 2012, due to resistant hypertension (HTA), type 2 diabetes mellitus, dyslipidemia, and BMI of 32.4 kg/m2. Hormonal data: low ACTH (<5 pg/mL) and no suppression of cortisol after the overnight DST-1mg (22.7 µg/dL); late-night salivary cortisol, urinary free cortisol, aldosterone/renin ratio and plasma metanephrines were in the normal range. A CT scan showed bilateral enlargement of the adrenals associated with multiple macronodules. He underwent an adrenal-sparing surgery (total adrenalectomy of the left adrenal and partial adrenalectomy of the right adrenal). The macroscopic and histological appearance was consistent with PMAH. Leucocyte DNA genotyping identified the germline heterozygous ARMC5 pathogenic variant in exon 1 c.280del, p.(Ser94Argfs*43). This variant was identified in 3 of the 10 relatives investigated (son#1, daughter#2 and grandson#3). In 2021, the 37-year-old son#1 presented with a BMI of 32.6 kg/m2. Autonomous cortisol secretion was confirmed (cortisol after DST-1mg = 6.7 µg/dL). CT scan showed bilateral enlargement of the adrenals, similar to his father (index-case), with a larger left adrenal. Unilateral left adrenalectomy was performed, and PMAH was histologically confirmed. In 2018, the 21-year-old daugher#2 had normal adrenal function. More recently, in December 2022, she presented with an important weight gain (44kg in 4 years), without any specific signs and symptoms of hypercortisolism. Hormonal investigation showed a possible autonomous cortisol secretion (cortisol after DST-1mg = 2.2 µg/dL); the CT scan demonstrated an adrenal diffusely thickened with several nodules, especially on the left side, as the other relatives. Up to now, she has been using ketoconazole. All of them did not present meningioma of CNS. The grandson#3 with 11-year-old, is asymptomatic so far. Clinical Lesson: PMAH is a heterogenous and underdiagnosed disorder and is more genetically associated than previously thought. Therefore, a careful hormonal-genetic-clinical-radiological study of the relatives of index cases permits the diagnosis of many unsuspected familial-cases, including asymptomatic patients. Surgical or medical treatment should be considered for these patients to avoid progression to a possible overt Cushing syndrome. Presentation: Friday, June 16, 2023

Impact of RET Screening on the Management of Multiple Endocrine Neoplasia Type 2A: 10 Years Experience and Follow-Up in Three Families.

Multiple endocrine neoplasia type 2A (MEN 2A) is mainly caused by germline RET codon C634 mutation and is characterized by Medullary Thyroid Carcinoma (MTC), pheochromocytoma (PHEO), and hyperparathyroidism (HPTH). The early diagnosis and initial normative treatment are helpful for the long-term outcome of MEN2A. Three index cases and their 29 relatives from three families with MEN2A were included in this study. Genetic screening was performed on all participants. Demographic, clinical profiles, tumor histopathologic features, and follow-up records were systematically analyzed. In total, RET C634Y mutation was identified in 10 individuals (10/32, 31.3%). Among them, 5 presented with MTC symptoms, whereas the other 5 did not show apparent clinical manifestation, and all were subjected to thyroidectomy with varying neck dissection. Compared to individuals in the former, the latter benefited greatly from RET screening with significantly younger age at diagnosis of MTC and surgery (18.1 ± 13.8 years vs. 39.0 ± 14.1 years, P =0.045), and lessaggressive MTC behavior (size: 0.74 vs. 2.82 cm, P =0.026; LN+/resected: 20.0% vs. 100.0%, P =0.048) and also lower recurrence rate of MTC (20.0% vs. 100.0%, P =0.048). The PHEO was identified in 6 of the 10 carriers (60.0%), and all had undergone adrenal-sparing surgery. During the 10 years of follow-up, one (16.7%) developed recurrence of PHEO. Integrated RET screening, serum calcitonin, and plasma metanephrine/ normetanephrine levels can facilitate the early diagnosis and standardized MTC/PHEO surgery to improve the prognosis of MEN2A. Laparoscopic adrenal-sparing surgery prior to the bilateral total thyroidectomy is a preferred surgical approach for PHEO.

Operative management and outcomes in children with pheochromocytoma

This study aimed to evaluate management and prognosis in children with pheochromocytoma who were treated at an Egyptian tertiary center. The authors conducted an 8-year retrospective analysis for 17 patients who were presented from January 2013 to January 2021. Clinical criteria, operative details, and follow-up data were assessed. Overall (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method. An event was assigned with the occurrence of recurrence or metachronous disease, or death. Median age at diagnosis was 14 years (range: 6-17.5 years). Ten patients (58.8%) were males and seven (41.2%) were females. Hypertension-related symptoms were the main presentations in 15 patients (88%). None of the included children underwent genetic testing. Sixteen patients (94%) had unilateral tumors (right side: 12), whereas only one was presented with bilateral masses. The median tumor size was 7cm (range: 4-9cm). Metastatic workup did not reveal any metastatic lesions. All patients underwent open adrenalectomy, and clinical manifestations were completely resolved after surgery. Adjuvant therapy was not administered to any patient. There were no deaths or relapses at a median follow-up time of 40 months, whilst two children had metachronous disease after primary resection. Both were managed by adrenal-sparing surgery, and they achieved a second complete remission thereafter. Five-year OS and EFS were 100% and 88%, respectively. Complete surgical resection achieves excellent clinical and survival outcomes for pheochromocytoma in children. Meticulous, long-term follow-up is imperative for early detection of metachronous disease to facilitate adrenal-sparing surgery. Genetic assessment for patients and their families is essential; however, it was not available at our institution.

Robotic approach for partial adrenalectomy.

Although safe and feasible, partial adrenalectomy is not a widespread procedure. Endorsement of robotic technologies and fluorescence techniques in adrenal surgery might help develop partial adrenalectomy and could avoid unnecessary total adrenalectomies. When performed in selected cases, partial adrenalectomy is associated with good postoperative outcomes comparable with those reported after total adrenalectomy. It has been hypothesized that one of the advantages of the robotic approach in adrenal-sparing surgery is to reduce manipulation of the gland allowing preservation of the vascularization of the residual adrenal, overcoming some limits when performing a laparoscopic conventional approach. A major drawback of the robotic surgery is its cost, but the overcost due to the use of the robotic system could be balanced by the execution of a high number of partial adrenalectomies leading to fewer life-long replacement steroid treatment. Partial adrenalectomy could become the recommended management for small benign and hormonal active adrenal tumors. Indocyanine green fluorescence (IGF) also seems to be a useful technique to help surgeons identify the adrenal gland and to locate small tumors from the normal adrenal tissue in difficult patients. It is likely that the use of a robotic approach associated with IGF may extend indications of partial adrenalectomy in the years to come.

Ganglioneuroma presenting as an adrenal incidentaloma: Feasibility of adrenal-sparing surgery

Adrenal ganglioneuromas (GNs) are very rare tumours that originate from neural crest cells. Most of the time, they are diagnosed incidentally as they are usually non-functional and remain asymptomatic. Nowadays, they are being detected more often due to better availability of imaging facilities such as computed tomography (CT)/magnetic resonance imaging (MRI). Minimally invasive adrenalectomy (laparoscopic or robotic) remains the standard of care for such lesions. Hereby, we report a case of a 15-year-old young girl with right adrenal incidentaloma which was diagnosed on CT with the features suggestive of GN. She underwent robot-assisted excision of the mass with adrenal-sparing surgery. Histopathology revealed benign GN and no adjuvant treatment was required. As GN is not known for recurrence or metastasis, minimal invasive adrenal-sparing surgery should be a preferred modality of choice.

Elevated basal serum levels of calcitonin and simultaneous surgery of MEN2A-specific tumors.

Multiple endocrine neoplasia type 2A (MEN2A) is a rare syndrome caused almost by germline RET mutation, and characterized by medullary thyroid carcinoma (MTC), in combination or not with pheochromocytoma (PHEO), hyperparathyroidism (HPTH), cutaneous lichen amyloidosis (CLA), and Hirschsprung's disease (HD). The basal serum calcitonin (Ctn)/carcinoembryonic antigen (CEA) levels are significantly correlated with the MTC stage. Metachronous surgery of MEN2A-specific tumors is a routine procedure. We aimed to explore the clinical significance of pro-gastrin-releasing peptide (proGRP) in MTC with elevated Ctn and simultaneous surgery of MEN2A-specific tumors. We retrospectively investigated 8 RET mutation carriers of 2 Chinese pedigrees with MEN2A. Clinical profiles, imaging examinations, preoperative and postoperative biochemical data, surgical procedures, and follow-up records were evaluated. Three patients showed levels of elevated Ctn but normal proGRP. Among them, one patient (FAIII-6) in Family A (one for RET C634R mutation), diagnosed with bilateral MTC, left PHEO, bilateral HPTH, and CLA, classified as MEN2A-related CLA subtype, underwent successfully simultaneous adrenal-sparing surgery (ASS), total thyroidectomy (TT), and parathyroidectomy, while TT of the other two patients (FBII-3 and FBIII-7) diagnosed with bilateral MTC in Family B (all for RET C618R mutation) were performed. Unexpectedly, the absence of neck lymph node MTC metastasis was indicated by histopathological examination. Postoperatively, all had consistently "undetectable" or normal levels of Ctn/CEA during follow-up. Patients with normal proGRP, despite high levels of Ctn, might have no regional lymph node MTC metastasis, and neck dissection should be avoided. Moreover, simultaneous surgery for coexistent PHEO and either MTC or HPTH is an approach of choice to use as an alternative treatment pattern. Recognition of MEN2A-related CLA and subsequently early screening of RET mutation may be favorable for timely management of MEN2A-specific tumors.

Adrenal-sparing surgery for a hormonally active tumour - a single-centre experience.

Surgeries that spare the adrenal cortex during adrenalectomy have profound justification. Indications for this type of surgery are fairly strict, and more than 30 years of observations continuously verify the results of the procedure. Of a total of 650 adrenalectomies, 22 (3.4%) were adrenal cortex-sparing surgeries. There were 16 women and six men in this group. In 10 cases, surgery was performed for pheochromocytoma, eight cases involved Conn's syndrome, and in four cases - paragangliomas located in the para-adrenal region. Secretory activity was identified in all cases. Laparoscopic partial adrenalectomy was performed in 20 patients. Conversion to open laparotomy was necessary in two cases. In patients after bilateral resection of pheochromocytoma surgery, glucocorticoids were supplemented for six weeks. No significant surgical complications were observed in this group. Partial adrenalectomy for minor lesions should be a much more commonly utilised treatment method (of choice). Where bilateral adrenalectomy is necessary, a sparing procedure on one side protects patients from the need for hormonal substitution. The remaining part of the adrenal gland undertakes satisfactory secretory function after six weeks at the latest.

Molecular Diagnosis and Treatment of Multiple Endocrine Neoplasia Type 2B in Ethnic Han Chinese.

Multiple endocrine neoplasia type 2B (MEN 2B) is mainly caused by M918T RET germline mutation, and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO) and non-endocrine features. However, the diagnosis and treatment are usually delayed. This study reports 5 Chinese pedigrees with 5 individuals harboring germline RETM918T, and systematically reviewed previous Chinese literature reported. All 5 patients initially presented MTC, but none had biochemically cured postoperatively. 2 also presented bilateral PHEO after adrenal-sparing surgery, 1 needed steroid replacement. Further, a total of 32 MEN 2B patients from literature were clustered with 28 available for analysis. 26 (92.8%) were diagnosed by endocrine-related symptoms; the remaining 2 (7.2%) due to RET testing and oral symptoms, respectively. 25 patients underwent thyroidectomy with/without neck lymph node dissection at the mean age of (23.3 ± 10.4) years. Histopathological examination revealed MTC (100%). Of them, 17 had definite TNM stage, with 1 in stage III and others in IV. Other information of MEN 2B-related symptoms included penetrance of PHEO (60.7%), constipation (32.1%), Hirschsprung disease (25%), alacrima (17.8%), mucosal ganglioneuroma (96.4%) and marfanoid habitus (71.4%). 19 patients were verified harboring RET-M918T (c.2753T>C), of whom 15 (78.9%) were de novo mutation. The other 9 were clinically diagnosed as MEN 2B. The initial diagnosis of MEN 2B is relatively later, and diagnosed by non-endocrine components is extremely lower. Recognition of MEN 2B and its non-endocrine-related components is still the utmost requirement for a Chinese physician. Combined RET screening and serum calcitonin detection can facilitate early diagnosis.

A New Insight into the Surgical Treatment of Primary Macronodular Adrenal Hyperplasia.

PurposeThis prospective study presents the results of a new approach in the treatment of primary macronodular adrenal hyperplasia (PMAH), with simultaneous total adrenalectomy of the larger adrenal gland and partial adrenalectomy of the contralateral adrenal gland (adrenal-sparing surgery).Materials and MethodsWe performed a prospective study including 17 patients with PMAH treated surgically with adrenal-sparing surgery in a tertiary referral hospital, with a median follow-up of 41 months. Clinical, hormonal, and genetic parameters were evaluated before surgery and during follow-up. All patients had at least 1 radiological examination before and after the procedure.ResultsAmong the 17 patients, all but 1 patient had complete hypercortisolism control, and 12 recovered normal adrenal function after surgery. Significant improvement in clinical parameters was observed: weight loss (P = .004); reduction of both systolic (P = .001) and diastolic (P = .001) blood pressure; and reduction in the number of antihypertensive drugs (P < .001). Intra-, peri-, and postoperative complications were not observed.ConclusionAdrenal-sparing surgery is a safe and feasible procedure to treat patients with PMAH, providing a substantial chance of hypercortisolism control without the disadvantages of lifetime corticosteroid replacement.

Minimally Invasive Partial Versus Total Adrenalectomy for the Treatment of Primary Aldosteronism: Results of a Multicenter Series According to the PASO Criteria

BackgroundDetermination of success after adrenal-sparing surgery for primary aldosteronism (PA) is limited by the lack of standardized definitions of outcomes. ObjectiveTo evaluate the safety and effectiveness of minimally invasive partial adrenalectomy (MIPA) for PA by comparing perioperative and functional outcomes with minimally invasive total adrenalectomy (MITA) according to the Primary Aldosteronism Surgical Outcome (PASO) criteria. Design, setting, and participantsBetween March 2011 and April 2020, a multicenter adrenalectomy dataset was queried for “unilateral adrenal mass, PA, MIPA (n = 29), or MITA (n = 61)”at four participating Institutions. InterventionMITA and MIPA for PA. Outcome measurements and statistical analysisDifferences between continuous variables were assessed with the Wilcoxon rank sum test, while Pearson’s χ2 test was used for categorical data. Complete, partial, and absent clinical success rates were assessed for the overall cohort and compared between groups. Results and limitationsThe median tumor size was significantly higher in the MITA group (4.2 vs 2.7 cm; p = 0.001), while preoperative hypertension rate was significantly higher in the MIPA series (82.8% vs 57.4%, p = 0.01). The median length of hospital stay was increased in the MITA cohort (4 vs 3 d; p = 0.038). Overall, at a median follow-up of 42 mo (interquartile range 27–54 mo), complete, partial, and absent clinical success was observed in 60%, 17.7%, and 22.3% of cases, respectively. The complete clinical success rate was higher in the MIPA group (72.4% vs 54.1%), while a partial clinical success was higher in the MITA series (23% vs 6.8%). The absence of clinical success was comparable between groups (MITA 23% vs MIPA 20.7%). ConclusionsMIPA showed excellent perioperative results with a complete clinical success rate of 72.4%. Owing to the heterogeneity of the PASO criteria in the assessment of partial or absent success, the quest for a univocal definition of satisfactory clinical outcomes in the treatment of PA remains open. Patient summaryWe compared minimally invasive partial adrenalectomy (MIPA) and minimally invasive total adrenalectomy for the treatment of unilateral primary aldosteronism, assessing the outcomes with the Primary Aldosteronism Surgical Outcome (PASO) criteria. MIPA seems to provide comparable perioperative outcomes and midterm clinical success rates.

The feasibility of adrenal-sparing surgery in bilateral adrenal neuroblastoma

PurposeLoss of adrenal function is a major concern in the treatment of children with bilateral adrenal neuroblastoma (BAN). We aimed to evaluate the feasibility of adrenal-sparing surgery in this unique subgroup. MethodRetrospective review of our center's neuroblastoma database was conducted. Patients with synchronous BAN confirmed at surgery were included. Their demographic data and clinical charts were analyzed. ResultsFive patients were confirmed with BAN. Mean age at diagnosis was 0.89 (0.39–1.32) years; male:female ratio was 4:1. They were stratified as stages M (n = 2), MS (n = 1), L1 (n = 1) and L2 (n = 1). MYCN amplification was present in 1 patient (stage M) and was stratified as high-risk group. All patients except one received preoperative chemotherapy. Among the 10 adrenal gland tumors, 2 underwent tumor adrenalectomy (TA) and 8 had adrenal-sparing tumorectomy (AST). After chemotherapy, 3 patients underwent single-stage bilateral AST and 1 patient underwent 2-stage TA-AST. One patient underwent upfront single-stage TA-AST, where lack of preoperative chemotherapy rendered the adrenal gland indistinguishable. The high-risk patient received autologous hematopoietic cell transplantation for consolidation. No patients required adrenal replacement therapy. All patients were alive without evidence of disease with mean follow-up 5.5 (2.6–8.5) years. ConclusionAdrenal-sparing surgery is feasible in patients with BAN. Level of evidenceLevel IV (case series with no comparison group).

MEN2-related pheochromocytoma: current state of knowledge, specific characteristics in MEN2B, and perspectives.

Multiple endocrine neoplasia type 2 (MEN2) is a rare hereditary syndrome due to mutations of the proto-oncogene REarranged during Transfection (RET), defined by the association of medullary thyroid carcinoma (MTC) in almost 100% cases, and pheochromocytoma in roughly 50% (primary hyperparathyroidism can be seen in 10-20% of patients with MEN2A). Early thyroidectomy and the efficacy of novel tyrosine kinase inhibitors modified the natural history of MTC, with possibilities of cure or long-term control. The second main compound, pheochromocytoma, is reported with a variable penetrance, from 10 to 80% cases, depending on the mutation of RET. Pheochromocytoma constitutes the main disease to screen in patients with RET mutations. Pheochromocytoma clinical and biochemical diagnosis, as well as the way to treat it are thus crucial. This review will thus focus on the epidemiological specificities of MEN2-related pheochromocytoma, the genotype/phenotype relationship, the modern imaging modalities necessary to confirm the diagnosis in this hereditary context, as well as the optimal management and the possibilities of adrenal sparing surgery. Additional information will include the natural history of MEN2B-pheochromocytoma, the rare cases of malignant pheochromocytoma, and the factors that could modify the penetrance between individuals carrying the same mutation, especially in the same family.

Adrenal-sparing surgery: current concepts on a theme from the past.

Adrenal insufficiency represents a debilitating condition which mandates lifelong steroid replacement and which is associated with significant long-term morbidity, due to either inadequate or excessive replacement. The concept of preserving healthy cortical tissue by means of partial adrenalectomy has evolved as a means of avoiding the detrimental consequences of adrenal insufficiency. The advent of advanced technology in adrenal surgery has greatly facilitated the performance of partial adrenalectomy, enabling utilization of this method in an increasing number of endocrine diseases. Hereditary pheochromocytoma, Conn's syndrome, Cushing's syndrome, and non-functional adrenal masses represent the current indications for partial adrenalectomy, although the specific circumstances under which adrenal-sparing surgery should be proposed are still debatable. Partial adrenalectomy can be achieved by all types of minimally invasive surgery. In the absence of randomized, prospective, controlled studies designed to compare laparoscopic, retroperitoneoscopic, and robot-assisted partial adrenalectomy, none of these techniques has as yet been proven to be the gold standard for adrenal-sparing surgery. Apart from indications for surgery, results of surgery, and different types of partial adrenalectomy, controversial topics addressed in this review article include technical aspects such as the volume of residual adrenal tissue needed, ligation of adrenal vein, and means of tumor identification. Discussion of these controversial topics represents an attempt to define the role of partial adrenalectomy in modern adrenal surgery.

SUN-195 Bilateral Aldosterone-Producing Adenomas: A New Subtype of Bilateral Primary Aldosteronism?

Background: Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). PA subtypes include aldosterone-producing adenomas (APA) and bilateral adrenal hyperplasia. To date, few PA patients with bilateral adenomas have been reported, but only one case was well characterized by anatomopathological analysis and clinical outcome after adrenal sparing surgery (1). Clinical case: A 53-year-old woman was referred to investigate resistant HT and hypokalemia. (3.0 mEq/L). PA screening revealed aldosterone (A) of 37.9 ng/dL, renin (R) < 1.6 (4.4-46.1 mUI/L), A/R ratio of 24.8. Confirmatory testing confirmed PA diagnosis: seated saline infusion test (A= 83.3 ng/dL) and intravenous furosemide test (R= 3.1 mUI/L; positive test <13 mUI/L). Hypercortisolism investigation revealed a non-suppressible cortisol after an overnight 1 mg low-dose dexamethasone suppression [cortisol (C)= 2.9 μg/dL and dexamethasone= 701 (˃130 ng/dL)], and normal urinary free cortisol, midnight salivary cortisol, plasma DHEAS and ACTH levels. Computed tomography demonstrated bilateral adrenal nodules without adrenal thickening: 3.5 cm right nodule (pre-contrast density of 7UH density; absolute wash-out of 71%) and 2.5 cm left nodule (pre-contrast density of 8UH density; absolute wash-out of 78%). Sequential adrenal venous (AV) sampling (AVS) under continuous cosyntropin infusion showed a lateralization index of 3.4 (bilateral disease <4). Then, the patient underwent right adrenalectomy and left nodulectomy. In the postoperative period, she presented normalization of K+ levels and complete HT remission. She remained under hydrocortisone replacement for 2 months. After 2 months, biochemical evaluation revealed normal basal cortisol levels (13.3 µg/dL) and biochemical cure of PA (A= 3.1 ng/dL and R= 15.3 mUI/L). Currently, she doesn’t have symptoms of adrenal insufficiency after discontinuation of hydrocortisone. Anatomopathological analysis showed bilateral adenomas (Weiss score of 0) in both sides without adjacent hyperplasia. CYP11B2 immunohistochemistry displayed a strong staining in 50% of cells in the right adenoma and in 30% of cells in the left adenoma. Few aldosterone-producing cell clusters (APCC) were identified in the right zona glomerulosa, which is a frequent finding in normal adrenals. Conclusion: We herein described a very rare case of PA caused by bilateral-producing adenomas, confirmed by AVS and CYP11B2 staining after adrenal sparing surgery.

Contemporary Trends in Adrenal Sparing Surgery

Contemporary Trends in Adrenal Sparing Surgery

V10-02 ROBOTIC BILATERAL PARTIAL ADRENALECTOMY FOR PHEOCHROMOCYTOMA

You have accessJournal of UrologyAdrenal Surgery & Kidney Cancer II (Advanced Kidney Cancer & Vascular Reconstruction) (V10)1 Apr 2020V10-02 ROBOTIC BILATERAL PARTIAL ADRENALECTOMY FOR PHEOCHROMOCYTOMA Jeremy Archer*, Jonathan Pavlinec, Shavano Stedman, Tejal Patel, Sara Falzarano, and Li-Ming Su Jeremy Archer*Jeremy Archer* More articles by this author , Jonathan PavlinecJonathan Pavlinec More articles by this author , Shavano StedmanShavano Stedman More articles by this author , Tejal PatelTejal Patel More articles by this author , Sara FalzaranoSara Falzarano More articles by this author , and Li-Ming SuLi-Ming Su More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000935.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with multiple endocrine neoplasia type 2 (MEN2) and von Hippel-Lindau disease (VHL) are risk of bilateral adrenal pheochromocytomas. Total adrenalectomy was historically the standard of care for patients with hereditary syndromes, but this leads to lifelong steroid supplementation. Adrenal-sparing surgery has been described in the treatment of adrenal incidentaloma, aldosteronoma, isolated metastasis, and the hereditary pheochromocytomas of MEN2 and VHL. Synchronous bilateral laparoscopic partial adrenalectomy with intraoperative ultrasonography has been described for pheochromocytomas as safe and technically feasible, but the majority of bilateral lesions have been treated by staged operations. We report our experience of synchronous bilateral robotic partial adrenalectomy for multifocal bilateral adrenal pheochromocytomas. METHODS: A 36-year-old female with marfanoid habitus and biopsy-proven medullary thyroid cancer was found to have bilateral adrenal masses on staging workup. Laboratory results showed elevated serum metanephrines, and she was started on alpha blockade with phenoxybenzamine. Imaging revealed a 3 cm right adrenal mass with a separate area of 1 cm irregularity and a 2 cm left adrenal lesion. Bilateral robotic partial adrenalectomies were successfully performed using a 4-arm technique with the daVinci Xi robotic platform (Intuitive, Sunnyvale CA) and a 12mm assistant trocar at the umbilicus. The patient was positioned in full-flank positioning for each side with docking from the same side of the room. The midline subxiphoid robotic 8mm and the 12mm assistant trocars were used for both portions of the operation. RESULTS: Enucleation of the tumors was performed with a total operative time of 330 minutes and estimated blood loss of 50mL. Pathology revealed three pheochromocytomas, and the patient was started post-operatively on a steroid taper. She was referred for genetic counseling given suspicion for MEN2B syndrome. CONCLUSIONS: Bilateral adrenal-sparing surgery for pheochromocytoma is safe and feasible and may be achieved using a robotic 4-arm technique with linear trocar configuration with repositioning. This approach in patients with genetic predisposition to synchronous adrenal lesions may preclude or delay the need for lifelong steroid supplementation. Source of Funding: N/A © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e931-e931 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jeremy Archer* More articles by this author Jonathan Pavlinec More articles by this author Shavano Stedman More articles by this author Tejal Patel More articles by this author Sara Falzarano More articles by this author Li-Ming Su More articles by this author Expand All Advertisement PDF downloadLoading ...

SUN-382 Heterogeneous Clinical Presentation In Familial Cases Of Primary Macronodular Adrenal Hyperplasia (PMAH): The Influence Of Somatic Event Of ARMC5.

Background: PMAH is a cause of adrenal hypercortisolism and it is a genetic disease linked to ARMC5 gene in most cases. Heterogenous phenotypes due to cortisol secretion and also due to different germline mutations in the ARMC5 have been described in around the world. The diversity of the molecular second hits in adrenal nodules may be able to justify different clinical outcome in the same family. We report two sisters with the same germline mutation and different clinical outcome. Case: A 45-year-old female patient presented with clinical evidence of hypercortisolism. Metabolic syndrome has been evidenced since the age of 35. Hormonal data confirmed an autonomous cortisol secretion. Abdominal CT revealed a bilateral enlargement of adrenal glands with multiples nodules (up to 2 cm, with 10 Housfield Units). 18F-FDG-PET/CT identified a slight SUV (left SUV 3.4 and right SUV 2.7). A heterozygous germline pathogenic variant of ARMC5 was identified at exon 1: c.165_166insG, p.Ile58Asnfs*45 at BTB (POZ) domain associated with a somatic LOH of the germline mutation. In 2013, the patient underwent Adrenal Sparing Surgery (ASS). She presented an excellent control of metabolic syndrome associated with adrenal insufficiency (AI) for 12 months. After 2 years a clinical recurrence of hypercortisolism was observed and confirmed by laboratory data. A new abdominal 18F-FDG-PET/CT and CT showed an increase of SUV and enlargement of the right residual adrenal gland (SUV - 3.4). The patient was submitted to a partial right adrenalectomy. Interesting, she did not present total or partial AI after the second surgical procedure. Inversely, her sister (46 years of age), with classical Cushing´s syndrome and carrier of same germline mutation (with similar hormonal data and SUV of 18F-FDG-PET/CT), presented a long-term remission of hypercortisolism after ASS. The analysis of somatic mutation of ARMC5 revealed a new event c.2082_2088delCCCGCTC, p.Pro695Serfs*20 in heterozygous status at exon 6. Analysis of PMAH sections HE stained showed a different pattern in the proportion and distribution of clusters of compact cells (60%) relative to clear spongiocytic cells. Her sister presented 13% of compact cells, similar to the PMAH pattern. Discussion: The macronodules of PMAH are composed of clear spongiocytic cells which preferentially express 3βHSD steroidogenic enzyme, and small or compact cells, which differentially express CYP17A1 steroidogenic enzyme and are located in dispersed clusters among the clear cells. CYP17A1 has both 17α-hydroxylase activity and 17,20-lyase activity. Conclusion: The somatic events of ARMC5 should be considered and could be involved in heterogeneous cortisol secretion and clinical presentation in familial cases with different outcome. Further familial cohorts and functional studies should increase our understanding of this challenged adrenal disorder.

Analysis of characteristics of pedigrees with von Hippel-Lindau disease

Objective To discuss the clinical characteristics of von Hippel-Lindau (VHL) syndrome and the significance of genetic test for this disease. Methods Patients with VHL disease from 3 different families were reviewed from August 1985 to October 2017. The study was including clinical family survey and VHL-gene test on phylogenetic level. Totally 21 family members from 3 families were investigated, consisting of 14 males and 7 females with average age of 48.6 (5-70)years when analyzed. There were 8 patients with VHL disease comprising 5 males and 3 females with average onset age of 31.5 (9-67) years. Results The proband of pedigree one (VHL-ⅡC) was diagnosed as pheochromocytoma (PHEO) of right adrenal gland at 18 years old and underwent adrenalectomy, and her son was diagnosed with PHEO of bilateral adrenal glands with diagnostic age of 9 years old and received bilateral adrenalectomy sequentially. Her niece was diagnosed as PHEO of bilateral adrenal glands at 28 years old and received bilateral adrenal-sparing surgery simultaneously. Genetic analysis revealed a heterozygous mutation located at the third exon of the VHL gene (c.482G>A). The proband of pedigree two (VHL-ⅡB) was diagnosed as right PHEO, bilateral multiple renal clear cell carcinoma (RCC), multiple pancreatic cysts and bilateral epididymal cystadenoma, and he received right adrenalectomy, right partial nephrectomy at 25 years old and delayed cystadenoma excision. His younger brother was also diagnosed as bilateral, pancreatic multiple cysts and bilateral epididymal nodules at 27 years old, and underwent right radical nephrectomy. Genetic analysis revealed a heterozygous mutation located at the first exon of the VHL gene (c.233A>G). The proband of pedigree three (VHL-ⅡB) was diagnosed with central nerve system hemangioblastomas (CNS-HB) at 35 years old and received external beam radiotherapy. His elder sister was diagnosed as CNS-HB at 43 years old and received surgery. His father was diagnosed as right PHEO, bilateral RCC, bilateral multiple renal and pancreatic cysts and pancreatic neuroendocrine tumors at 67 years old. He received right adrenalectomy and partial nephrectomy. Genetic analysis showed a heterozygous mutation located at the third exon of the VHL gene(c.500G>A). In addition, two cases (F2-Ⅲ 1 and F3-Ⅳ1) were found to be asymptomatic VHL gene carriers by genetic screening. 8 patients were followed up for an average of 9.8 (2-32) years. The symptoms were stable and no local recurrence or distant metastasis was found after operation. In this study, no CNS-HB was found in patients within family 1 and family 2, and RCC in 3 patients within family 2 and family 3 were low grade. Conclusions The clinical manifestations of VHL disease are diverse. RCC and CNS-HB are not present in all patients with the disease. PHEO is the only manifestation in patients with VHL-ⅡC. It is necessary to inform the members of VHL syndrome family for genetic test. Genetic test combined with clinical screening can facilitate differential diagnosis for VHL syndrome and other hereditary urological diseases. Key words: von Hippel-Lindau disease; Pedigree investigation; Gene; Diagnosis; Treatment

Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study

Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year. None.