ResearchPad - adrenal---tumors https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SAT-LB44 WNT2B Regulates Adrenocortical Progenitor Cell Fate And Zona Glomerulosa Identity In Vivo]]> https://www.researchpad.co/article/elastic_article_8652 Dysregulation of normal adrenal structure and function contributes to a spectrum of diseases from hypoplasia to cancer. Peripheral adrenocortical progenitor cells in the zona glomerulosa (zG) centripetally migrate and differentiate to replenish steroidogenic cells of the zG and the inner cortex over time (1). Both the fate of progenitor cells and aldosterone production by steroidogenic cells in the zG are regulated by Wnt signaling (2,3), but the cell-specific effects of individual Wnt ligands in the adrenal are not fully understood. To further characterize Wnt signaling components crucial for progenitor cell maintenance and zG identity, we analyzed mouse adrenals using single molecule in situ hybridization (smISH), which revealed the previously unknown expression of Wnt2b exclusively in the adrenal capsule. Wnt2b is co-expressed with the Wnt signaling potentiator Rspo3, the loss of which causes zG depletion and reduced adrenal size in mice (4). Therefore, we hypothesized that capsular WNT2B activates Wnt signaling in the underlying cortex to maintain the undifferentiated state of progenitor cells. To define the role of WNT2B in these processes, we generated Wnt2b conditional knockout (cKO) mice by crossing a capsule-specific Gli1-CreERT2 driver (5) and a floxed Wnt2b allele (6). We administered tamoxifen to 6-week-old male mice and assessed the effects of Wnt2b loss 4 weeks later. Gli1-CreERT2 activation significantly decreased Wnt2b expression (P<0.001) and resulted in a lower adrenal to body weight ratio in Wnt2b cKOs compared to controls (P<0.05). Adrenocortical proliferation (Ki67) was significantly decreased in Wnt2b cKO mice (P<0.0001), suggesting that WNT2B may mediate progenitor cell self-renewal. To characterize the effect of WNT2B loss on Wnt signaling, we assessed activation of the primary Wnt effector β-catenin. High β-catenin activity in the zG observed in wild-type mice was disrupted in Wnt2b cKO mice, together with markedly reduced expression of adrenocortical Wnt target genes Axin2 and Wnt4. In addition, Wnt2b loss resulted in downregulation of steroidogenic genes Cyp11b2 (P=0.0139) and Hsd3b6 (P=0.0679). Together, these data suggest that capsule-derived WNT2B activates cortical Wnt signaling to maintain the identity of both undifferentiated progenitor cells and differentiated steroidogenic cells of the zG, which has important implications for adrenal homeostasis and disease, including both primary adrenal failure and neoplasia.

References: (1) King et al., PNAS, 2009 Dec 15;106(50):21185-90. (2) Berthon et al., Hum Mol Genet., 2010 Apr 15;19(8):1561-76. (3) Heikkila et al., Endocrinol., 2002 Nov;143(11):4358-65. (4) Vidal et al., Genes & Dev., 2016 Jun 15;30(12):1389-94. (5) Ahn & Joyner, Cell, 2004 Aug 20;118(4):505-16. (6) Tsukiyama & Yamaguchi, Neurosci Lett., 2012 Mar 14;512(1):48-52.

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<![CDATA[SAT-160 Evaluation of Life Style and Anthropometric Parameters in Patients with Nonfunctional Adrenal Incidentalomas]]> https://www.researchpad.co/article/elastic_article_8539 Introduction

Adrenal lesions that are found incidentally during routine imaging of people who do not have any complaints or physical findings related to adrenal gland are called adrenal incidentaloma (1,2). Incidentalomas appear more frequently with the increasing use of imaging techniques and increasing age. It is unclear why most of these masses emerged. It is controversial whether nonfunctional adrenal incidentalomas (NFAI) increase the risk of cardiovascular disease or metabolic syndrome or are more common in people with these diseases. In this study, we aimed to investigate whether lifestyle and body fat have an impact on the occurrence of NFAI.

Materials and Methods

100 patients with NFAI were included in the study. Control group consisted of 50 healthy and similar age groups. Physical activities of these groups (with the International Physical Activity Questionnaire Short Form), smoking were questioned and anthropometric measurements were made (Height, body weight, body mass index (BMI), neck, hip, waist circumference and body fat mass, fat percentage, total body water, fet free mass with bioimpedance method). Laboratory tests were examined from the patient file.

Results

Female dominance was observed in patients with NFAI. BMI, waist circumference, hip circumference, neck circumference, total body fat percentage and mass and smoking were found to be higher in the patient group compared to the healthy group and a statistically significant difference was found. When a subgroup of patients with similar age and BMI among the patients and the control group were constituted (25-29,99 kg / m2) waist circumference and total fat mass were again significantly higher in the patient group compared to controls. In addition, there was a significant positive correlation between mass size and waist circumference, BMI, neck circumference, cortisol after 1 mg dexamethasone suppression test and a significant negative correlation with ACTH.

Conclusion

The data obtained showed that body adiposity and smoking were higher in patients with NFAI. Also, ıt was shown that although the patients were regarded as nonfunctional, suppressibility of the cortisol decreases as the mass size of the incidentaloma increase.

Resources

1. Turkey Endocrinology and Metabolic Diseases Society of Adrenal and Gonadal Working Group. Adrenal and Gonadal Diseases Guide. 2019, pages 77–84.

2. Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, et al. Management of adrenal incidentalomas: adrenal tumors. 2016; 175 (2): G1-G34.

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<![CDATA[SAT-168 Adrenal Incidentalomas: Impact of Patient Age on Referral Rates for Endocrine Evaluation]]> https://www.researchpad.co/article/elastic_article_7068 It is estimated that the prevalence of adrenal incidentaloma increases with age: ~3% of those aged 50 years, rising to 10% in those >70 years (1). Given the aging population together with increased utilisation of cross-sectional imaging in the UK (eg CT urogram, MR angiogram), we explored the proportion of patients with adrenal incidentaloma by age based on current imaging trends. Furthermore, there is no information currently available on the relationship between age and pattern of endocrine referrals. We extracted data for all CT and MRI scans from Jan 2018-Oct 2019 and used key phrases in radiology reports (eg adrenal adenoma/lesion/mass/nodule/incidentaloma, incidental adrenal, indeterminate adrenal) to identify potential lesions. We also extracted data on patient age and referral patterns as identified by a logged referral or an attendance (new or follow-up) to endocrine clinic 3 months post index scan, stratified by 10 year age groups. Where possible, we excluded false hits (eg no adrenal lesion). Preliminary data showed that, of the 2604 potential lesions identified by CT and MRI scans, 78.7% were on patients aged over 60 years. The numbers of identified lesions gradually increased with age to a peak in the 71-80 year age group after which these declined. Whilst patients younger that 60 years had fewer potential lesions identified, they were more likely to be referred to endocrine services (73 out of 55 patients; 13.2%) than those in the older age group (168 out of 2049; 8.2%; p<0.001). Indeed there was a statistically significant trend towards decreasing referral with age group (Chi-squared test for trend; p<0.001). In conclusion, patients over 60 years have a higher number of potential adrenal incidentalomas. However, this group is less likely to be referred for endocrine evaluation. This is particularly concerning given the large number of scans requested and the higher prevalence of incidentalomas in this age group. This study represents preparatory work on innovations to enhance case detection, particularly in the older age groups (2). 1. Fassnacht M, Arlt W, Bancos I, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline. Eur J Endocrinol. 2016;175:G1-G34 2. Hanna FWF, Issa BG, Lea SC, George C, Golash A, Firn M, Ogunmekan S, Maddock E, Sim J, Xydopoulos G, Fordham R, Fryer AA. Adrenal lesions found incidentally: how to improve clinical and cost-effectiveness. BMJ Open Quality. 2019;In press.

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<![CDATA[SAT-180 Adrenocortical Carcinoma - A Tertiary Center’s Recent 5-Year Experience]]> https://www.researchpad.co/article/elastic_article_6834 BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis. The aim of this study was to characterize patients diagnosed with ACC at a single center between 2014-2019.

METHODS: We retrospectively reviewed data regarding demographics, tumor characteristics and functionality, treatment and survival.

RESULTS: The study cohort included 27 subjects (56% females), followed for 27±10.6 months. The mean age at diagnosis was 49.4±9 years. Co-morbidities at presentation included hypertension (63%), diabetes mellitus (22%) and dyslipidemia (26%). 74.1% of tumors were functioning – of which 85% were cortisol-secreting and 15% androgen-secreting. Aldosterone was secreted additionally in 15%. ENSAT stage at diagnosis was stage 1 in 15%, stage 2 in 35%, stage 3 in 12% and stage 4 in 38%. Eighty-nine % of patients underwent surgery. Treatment with mitotane was initiated in 82% of patients, reaching a mean maximal dose of 3.3 ±0.4 grams/day. Chemotherapy and/or radiation were given in 37% and 22%, respectively. Several patients (14.8%) had a second primary cancer, diagnosed before ACC in 75%. Progression was observed in 48% of patients, with a progression-free survival of 8.3±6.6 months. Thirty-five % of patients died during follow up, time to death was 12.8±0.4 months. Twenty two % of patients survived over 30 months after diagnosis. KI67 above 20% or stage above 2 negatively affected survival.

CONCLUSIONS: ACC remains a rare disease with a poor prognosis. However, it is a heterogeneous disease, with some patients achieving survival of over 30 months after diagnosis. Further characterization of this population may improve our understanding of the biology and treatment of this rare disease.

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<![CDATA[SAT-157 Diagnostic Performance of 18F-fluorodeoxyglucose Positron Emission Tomography in Indeterminate Adrenal Tumors]]> https://www.researchpad.co/article/elastic_article_6684 Evidence on the diagnostic performance of 18F-fluorodeoxyglucose(18FDG) positron emission tomography(PET)/CT imaging of adrenal lesions is limited. We aimed to assess the diagnostic performance of this diagnostic modality in a high risk population for adrenal malignancy using an optimal reference standard. We included 21 patients operated in our clinic during 2019 for whom 8FDG PET was performed before adrenalectomy. 3 patients with pheochromocytoma were later excluded from statistical analysis, they were sent to PET before increased urine metanephrines were received. Unenhanced abdominal CT was performed in all the patients; median size was 4,5 (2.3-10) cm and median radiodensity was 32 (-7 to 43) Hounsfield units (HU). All patients with adrenocortical carcinoma and metastasis to adrenals from other organs had radiodensity of >10 HU. Maximum standardized uptake (SUV max) was higher in malignant lesions when compared to benign lesions (median = 10,9 [5.4-29.6] vs 4.1 [2.6-7.22], respectively, P=.003). Similarly, median SUV max lesion to SUV max liver ratio (ALR) in malignant lesions was higher than in benign lesions (median = 2,18 [1.41-5.53] vs. 1.29 [0.67-2.13], respectively, P=.017).18FDG- PET/CT SUV max lesion > 6.7 diagnosed malignancy with a sensitivity of 83,3%, specificity of 91,7%.

Conclusion: Noncontract CT radiodensity of ≤10 HU excludes malignancy even in a high risk population. For indeterminate adrenal lesions, given a superior specificity, 18FDG PET/CT could be considered as a second stage imaging.

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<![CDATA[SAT-178 Incidence, Patterns of Clinical Presentation, and Outcomes of Patients with Brain Metastasis Due to Adrenocortical Carcinoma]]> https://www.researchpad.co/article/elastic_article_6507 Background: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy, with a heterogeneous but, frequently, dismal prognosis; patients with metastatic ACC have a five-year survival that ranges between 0 and 28%. Metastatic ACC may be present at diagnosis or during follow-up as disease recurrences. The most common sites of metastatic lesions include the liver, lungs, lymph nodes and bones. The brain has only rarely been reported as a site of metastasis in this neoplasia and, to the authors’ knowledge, little is known regarding the incidence, patterns of clinical presentation and disease progression, and outcomes.

Objective: The aim of this report was to describe the clinical characteristics of adult patients with ACC who developed brain metastasis evaluated at a tertiary oncological center (ICESP) from Brazil.

Methods: Retrospective analysis of medical records including evaluation of laboratory and imaging exams and pathologic data (in cases where surgical resection of the metastasis was performed).

Results: In the last ten years (2009-2019), fifty-four patients have been treated for ACC at ICESP; all of them with advanced disease (locally advanced disease and metastatic disease). The median age at the time of diagnosis of ACC was 44 (range 24-61 yrs.). No patients presented metastasis at central nervous system (CNS) at the initial diagnosis; however, during follow-up, we identified brain metastasis in six patients (11.1%). The median time between ACC diagnosis and the detection of brain metastasis was 20.8 months (range 5-53 mo.). In all of these six cases, at least three other sites of metastatic involvement were already present when the brain involvement was diagnosed and, therefore, all of them had already been treated with mitotane in association with at least one line of cytotoxic chemotherapy. The number of brain metastasis in each of these six patients varied from one to eight and median size of lesion was 1.7 cm (range 0.5-4.0 cm). Secondary headache and seizure were the main symptoms of presentation and one or two of these symptoms occurred in all but in one patient, in which diagnosis was due to screening with brain MRI. In four patients with stable disease elsewhere, surgical resection of one or two brain metastases was performed. In these cases, SF1-positive immunohistochemistry confirmed the adrenocortical origin of the lesion. The median time between CNS metastasis detection and death was 3.8 months (range 0.4-59.6 mo.), and complications due to brain metastasis were the leading cause of death.

Conclusions: In our institute, brain metastasis occurred in 11.1% of advanced ACC, a prevalence that is higher than previously reported in literature. Despite the relative small number of patients included in this study, we highlight the possibility of brain metastasis in patients with ACC, particularly in cases with a prolonged disease course and multiple systemic treatments.

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<![CDATA[SAT-170 Clinical Course of Adrenal Myelolipoma: A Long-Term Longitudinal Follow-Up Study]]> https://www.researchpad.co/article/elastic_article_6485 Myelolipoma is the second most common adrenal tumor. Yet, systematic approach to these tumors remains poorly defined. Thus, we aimed to describe natural history of myelolipoma and to identify predictors of tumor growth and need for surgery. We conducted a retrospective longitudinal follow-up study of consecutive patients with myelolipoma. A total of 321 myelolipomas (median size, 2.3 cm [range, 0.5-18.0]) were diagnosed in 305 patients at median age of 63 years (25-87). Most myelolipomas were discovered incidentally (86.6%), whereas others were discovered on imaging done for cancer staging (8.8%) or during workup of mass effect symptoms (4.6%). Median duration of follow-up was 54 months (range, 0.03-267). Compared with myelolipomas <6 cm, tumors ≥6 cm were more likely to be right-sided (59% vs 41%, P=0.02), bilateral (21% vs 3%, P <.0001), cause mass effects symptoms (32% vs 0%, P<.0001), have radiographic hemorrhagic changes (14% vs 1%, P<.0001), and undergo adrenalectomy (52% vs 5%, P<.0001). There was no difference in sex or age at diagnosis between the groups. Hemorrhagic changes were noted in 9 (3.0%) patients with median tumor size of 7.0 cm (range, 1.8-18.0). Concomitant adrenal hormone excess was diagnosed in 12/126 (9.5%) patients. Primary aldosteronism was noted in 9 patients: due to concomitant ipsilateral (n=3) or contralateral adrenocortical adenoma (n=3), or bilateral idiopathic adrenal hyperplasia (n=3). Autonomous cortisol excess was noted in 3 patients: due to concomitant contralateral (n=2) or ipsilateral adrenocortical adenoma (n=1). Of 162 patients with ≥6 months of imaging follow-up, tumor size change ranged from -10 to 115 mm (median, 0 mm) and tumor growth rate ranged from -5.6 to 140 mm/year (median, 0 mm/year). Tumor growth ≥1.0 cm (n=26, 16.0%) was associated with larger initial tumor size (3.6 vs 2.3 cm, P=0.02) and hemorrhagic changes on imaging (12% vs 2%, P=0.007), compared with <1 cm size change. Myelolipomas with ≥1.0 cm growth were more likely to undergo adrenalectomy (35% vs 8%, P<.0001). Among 37 (12%) patients that underwent adrenalectomy for myelolipoma, surgical indications included: large tumor size/tumor growth (32%), diagnostic surgery (27%), mass effect symptoms (14%), concomitant ipsilateral tumor leading to hormonal excess (11%), acute hemorrhage (8%), and concomitant resection during non-adrenal surgery (8%). In conclusion, most myelolipomas are discovered incidentally, whereas myelolipomas ≥6 are more likely to cause mass effect symptoms, have radiographic hemorrhagic changes, and more commonly undergo resection. Hormonal excess is rare and is usually attributed to concomitant adrenocortical adenoma or hyperplasia. Tumor growth ≥1.0 cm is associated with larger myelolipoma and presence of hemorrhagic changes. Surgical resection should be considered in symptomatic patients with large tumors, evidence of hemorrhage, or tumor growth.

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<![CDATA[SAT-174 Adrenal Incidentalomas: Prevalence and Referral Patterns in a UK University Hospital Using Real-Life Data]]> https://www.researchpad.co/article/elastic_article_6464 The estimated prevalence of adrenal incidentaloma at abdominal CT scan is 0.5-2% (1). However, from clinical practice, we noticed that incidentalomas are referred from other imaging modalities (eg MRI) and of other sites (eg thorax, spine). We therefore explored the relationship between prevalence rates and (i) imaging modality and (ii) its change over time, in a real world clinical setting from a large UK teaching hospital/trauma centre. We also examined the referral pattern of potential lesions to endocrinology. We extracted data from all radiology reports for all CT and MRI scans from Jan 2018-Oct 2019. We utilised a key phrase search strategy (eg adrenal adenoma/lesion/mass/nodule/incidentaloma, incidental adrenal, indeterminate adrenal). Where possible we excluded false hits (eg no adrenal lesion). These were linked to the referral patterns as identified by a referral logged or an attendance (new or follow-up) to endocrine clinic 3 months post index scan. Preliminary data showed that, from a total of 127878 scans performed, 2604 potential lesions were reported (prevalence 2.0%), comprising 2496/88838 (2.8%) CT scans and 108/39040 (0.3%) MRI scans. The number of scans/month increased in 2019 vs 2018 (6.9% for CT and 12.6% for MRI). Only 9.0% and 15.7% of reported potential lesions detected by CT and MRI, respectively, were referred for endocrine review. Hence, MRI patients were more likely to be referred than those with CT scans (p=0.018). Referral rates were lower in 2019 than 2018 (8.6% vs 14.4%; p less than 0.001). This approach has its limitations but allows efficiently review of large cohorts. Adrenal incidentalomas pose a rising challenge in view of increasing reliance on scanning. Despite a dedicated adrenal multidisciplinary team with a national track record in improving management of incidentalomas (2), the referral rate of potential lesions is worryingly low and not improving, with >90% of cases overlooked. This work is part of on-going innovation to enhance the pick-up rate for these cases whilst addressing the increased endocrine workload in a cost-effective manner. 1. Barzon L, Sonino N, Fallo F, Palu G, Boscaro M. Prevalence and natural history of adrenal incidentalomas. Eur J Endocrinol. 2003;149:273-285. 2. Hanna FWF, Issa BG, Lea SC, George C, Golash A, Firn M, Ogunmekan S, Maddock E, Sim J, Xydopoulos G, Fordham R, Fryer AA. Adrenal lesions found incidentally: how to improve clinical and cost-effectiveness. BMJ Open Quality. 2019;In press.

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<![CDATA[SAT-158 New Data on High Prevalence and Time of Occurrence of New Onset Hypothyroidism Associated with Mitotane Therapy in a Cohort of Adrenocortical Cancer]]> https://www.researchpad.co/article/elastic_article_6416 Context. Mitotane is a steroidogenesis inhibitor and an adrenocorticolytic drug used to treat adrenocortical cancer (ACC). Central hypothyroidism is recognized in mitotane-treated patients and recent data suggested that mitotane could have an inhibitory effect on TSH-secreting cells in the pituitary gland. Moreover, mitotane may lead to induction of thyroid hormone metabolism. Clinical data on hypothyroidism related to mitotane such as prevalence and time of occurrence was described in a limited number of patients.

Objective. To better characterize clinically secondary hypothyroidism in patients with ACC treated with mitotane therapy.

Methods. We reviewed retrospectively paper charts and electronic records from patients with histologically confirmed diagnosis of ACC evaluated at our center from 1995-2019. We analysed the pattern of TSH and thyroid function, but also mitotane timing and levels at baseline and during treatment of patients under mitotane therapy. Thyroid hormone assessment including TSH, FT4 and FT3 was performed at least every 3 months during follow-up.

Results. Our cohort of 104 patients with ACC includes 84 patients that received mitotane therapy. Among them, thyroid function data was incomplete for 39 cases. Complete data was retrieved from 45 patients. Ten out of 45 (22.2%) patients were already known for primary hypothyroidism and were receiving L-T4 replacement before the initiation of mitotane. Two of 45 (4.4%) patients maintained a normal thyroid function during complete follow up (4.5 years) and 33/45 (73.3%) had new onset hypothyroidism requiring levothyroxine treatment. Of these 33 patients, 22 were females and 11 were males, ranging from 22-74 yo with a median of 46 yo. The number of patients with ENSAT stage I, II, III and IV of disease were 1, 8, 11 and 13 respectively. Thyroid profiles were compatible with central hypothyroidism (low T4 with low or inappropriately normal TSH) in 22/33 patients (66.7%). Interestingly, 6/33 patients (18.2%) developed a TSH elevation with a normal lower-limit or low T4 level. The timeline distribution of the occurrence of hypothyroidism was 21.2% (n:7) at <3 months, 15.2% (n:5) between 3-6 months, 21.2% (n:7) between 6-9 months and 15.2% (n:5) between 9-12 months. 9.1% (n:3) occurred within the second year of treatment (between 12-24 months). However, in 5/33 (15.2%) cases, the exact time of new hypothyroidism onset was undetermined.

Conclusion. Mitotane therapy is frequently associated with new onset hypothyroidism with a prevalence of 73% in our cohort of exposed patients and is most likely of central etiology. 72.7% of cases occur in the first year of treatment while 9.1% occur in the second year. This study supports the importance of monitoring thyroid function (including a free T4 level) during the complete course of mitotane therapy.

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<![CDATA[SAT-163 Status at 10 Years: Long-Term Follow-Up for a Phase 2a Study of High-Specific-Activity (HSA) I 131 Iobenguane in Patients (Pts) with Relapsed/Refractory High-Risk Neuroblastoma]]> https://www.researchpad.co/article/elastic_article_6351 Background: Metaiodobenzylguanidine (MIBG; iobenguane), a guanethidine derivative, is a substrate for norepinephrine reuptake transporter which is highly expressed on the surface of neuroblastoma cells. AZEDRA® (HSA I-131 MIBG) has been approved by the FDA for the treatment of pheochromocytoma and paraganglioma, in pts 12 years and older with MIBG avid, unresectable, locally advanced or metastatic PPGL who require systemic anticancer therapy. The aim of this study was to establish the maximum tolerated dose in children with neuroblastoma, with secondary aims of assessing overall response and tumor and organ dosimetry. Here we report current long-term survival and toxicity data. Methods: Eligible pts were 1-30 years old with resistant neuroblastoma. A diagnostic dose of HSA I-131 MIBG was followed by 3 dosimetry scans to assess radiation dose to critical organs and soft-tissue tumors. To prevent prolonged myelosuppression, autologous hematopoietic stem cells were infused 14 days after therapy. Response and toxicity were evaluated on day 60. Dose-limiting toxicity (DLT) was failure to reconstitute neutrophils to greater than 500/µL within 28 days, or platelets to greater than 20,000/µL within 56 days, or grade 3 or 4 nonhematologic toxicity by Common Terminology Criteria for Adverse Events (version 3.0) except for predefined exclusions. Results: First pt was enrolled in June 2008. 15 pts total were evaluable at 12 (n=5), 15 (n=3), and 18 (n=7) mCi/kg. Mean whole-body radiation was 0.23 mGy/MBq, and mean organ doses were 0.92, 0.82, and 1.2 mGy/MBq of MIBG for the liver, lung, and kidney, respectively. Eight pts had 13 soft-tissue lesions with tumor-absorbed doses of 26-378 Gy. MYC-N amplification was present in two of 11 pts with available results. Of the 15 treated pts, 1 had a complete response, 3 had a partial response, 1 had a mixed response and 6 had stable disease. The remaining 4 had progressive disease. Twelve of the 15 evaluable pts received non-protocol therapy after HSA I-131 MIBG, the remaining 3 died due to tumor without further therapy. At 3.6 years of follow-up the overall survival was 26.7% (95% CI, 8.3%-49.6%). As of March 2018, one remaining pt is in long term follow up with an overall survival of 8.4 years. This pt was previously reported to have a secondary malignancy of myelodysplastic syndrome which has been in remission since receiving an allogenic bone marrow transplant in March 2014. Conclusions: HSA I-131 MIBG contributed to long term median survival of two years and was well tolerated. Treatment showed promising activity in the absence of significant nonhematologic toxicity.

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<![CDATA[SAT-LB38 Clinical Features, Treatment and Prognosis of Primary Bilateral Macronodular Adrenal Hyperplasia Compared With Unilateral Adrenal Cortisol-Secreting Adenoma: Analysis of 46 Chinese Cases]]> https://www.researchpad.co/article/elastic_article_6289 Objectives: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare condition of Cushing’s syndrome (CS) characterized by benign bilateral enlarged adrenal masses. The aim of this study is to analyze clinical features, individualized treatment and prognosis of PBMAH.

Methods: Clinical data of 46 patients with PBMAH were retrospectively analyzed compared with 205 patients with unilateral adrenal cortisol-secreting adenoma (UAA), including general information, cortisol evaluations, treatments and prognosis.

Results: PBMAH were more frequently found in male, the average age at diagnosis was (52.1±8.7) years; most patients visited hospital due to incidentally findings of bilateral adrenal lesions; had a higher proportion of subclinical CS. The PBMAH cases showed significantly lower levels of basal cortisol, LDDST suppressed cortisol, and HDDST suppressed cortisol than the UAA cases (452.6 ± 183.3 vs. 578.7 ± 166.4 nmol/L, P = 0.003; 394.5 ± 298.9 vs. 549.2 ± 217.7 nmol/L, P= 0.002; 397.3 ± 282.3 vs. 544.3 ± 187.6 nmol/L, P =0.003). Similarly, the PBMAH cases had significantly lower levels of basal 24-h UFC, LDDST suppressed 24-h UFC, and HDDST suppressed 24-h UFC than the UAA patients (1144.4 ± 1048.1 vs. 1674.9 ± 1520.4 nmol/24h, P = 0.032; 1157.3 ± 1483.5 vs. 1940.1 ± 1360.9 nmol/24h, P = 0.003; 1256.4 ± 1767.0 vs. 1969.9 ± 1361.7 nmol/24h, P = 0.011). Compared PBMAH group with UAA group, there were statistically significant differences in the percentage change of cortisol (absolute value after suppressed over the basal value) during LDDST (73.01% ± 39.33% vs. 96.13% ± 31.59%, P =0.001) and during HDDST (73.90% ± 38.53% vs. 96.58% ± 28.79%, P=0.001); and there were statistically significant differences in the percentage change of 24-h UFC during LDDST (90.11% ± 79.60% vs. 134.47% ± 131.26%,P =0.045) and during HDDST (100.05% ± 89.59% vs. 143.75% ± 98.12%, P =0.017). The 24-hour continuous plasma ACTH and cortisol monitoring directly and thoroughly revealed the heterogeneity of hormone secretion of PBMAH cases. Among the 18 PBMAH cases with subclinical CS, 11 only received drug symptomatic treatment; 6 underwent unilateral adrenalectomy on the larger side; 1 not relieved well after unilateral adrenalectomy, then received resection of the contra-side. Among the 28 PBMAH cases with CS, 6 refused surgery because of economic reasons and just received symptomatic drugs treatment with bad prognosis; 15 underwent unilateral adrenalectomy on the larger side; 7 not relieved well after unilateral adrenalectomy, then conducted resection of the contra-side, and at last treated with glucocorticoid replacement obtained good prognosis.

Conclusions: PBMAH is often associated with a relatively low degree of cortisol autonomous secretion. It is necessary to choose a specific therapy plan to alleviate the high cortisol state according to the individualized hypercortisolemia condition.

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<![CDATA[SAT-156 Shorter Hospital Stays Are Not Associated with Increased Readmission or Complication Rates in Patients Undergoing Laparoscopic Adrenalectomies]]> https://www.researchpad.co/article/elastic_article_6210 Background: Traditionally, elective adrenalectomies have been performed as an inpatient procedure. However, the adoption of laparoscopic adrenalectomy as the gold standard has allowed for shorter postoperative stays. Our objective was to assess the safety of same-day discharge for patients undergoing laparoscopic adrenalectomy.

Methods: A retrospective cohort study of patients who underwent laparoscopic adrenalectomy from 2011-2017 was conducted using The American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) database. Demographic data was obtained. Multivariable logistic regression models to assess the association between length of stay and both postoperative complication rates and 30-day readmission rates were regressed on age, sex, race, comorbidities, functional status, postoperative diagnosis, and operative time. Statistical significance was defined as p<.05.

Results: 5,611 unique patients who underwent a laparoscopic adrenalectomy were identified. 1,564 patients had a postoperative diagnosis of a pheochromocytoma (27.9%), 162 with Cushing’s syndrome (2.9%) and 210 (3.7%) had metastatic disease to the adrenal glands. The average postoperative length of stay was 2.4 days (SD=3.9). 93 patients (1.7%) were discharged on the same day as their surgery (POD0). 2,509 (44.7%) were discharged on postoperative day 1 (POD1), 1,558 (27.8%) on postoperative day 2 (POD2), and 1,451 (25.9%) after POD2. Longer hospital stays were predicted by male sex, non-white race, longer operating time, and postoperative complications in regression models.

351 patients (6.26%) experienced a complication postoperatively. Complication rates were 3.23% for patients discharged on POD0, 1.67% for those discharged on POD1, 3.27% for those discharged on POD2, and 17.57% for those discharged after POD2 (p<.01). An increased risk of postoperative complications was also associated with male sex, impaired functional status and the presence of multiple comorbidities in regression models.

290 patients (5.17%) experienced a readmission. Readmission rates were 4.30% for patients discharged on POD0, 3.67% for those discharged on POD1, 4.49% for those discharged on POD2, and 8.55% for those discharged after POD2 (p<.01). Multiple comorbidities, African American race, and post-operative complications were associated with higher readmission rates. Length of hospital stay was not associated with readmission rates in regression models.

Conclusions: Readmission rates were not significantly different for patients discharged on POD0 than POD1 after a laparoscopic adrenalectomy. Readmission rates were higher for patients who had complications or multiple comorbidities. Therefore, low-risk patients with uncomplicated laparoscopic adrenalectomies can be considered for same day discharge to potentially reduce hospital spending and resource utilization.

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<![CDATA[SAT-172 FDG PET/CT in Benign vs. Malignant Adrenocortical Tumors]]> https://www.researchpad.co/article/elastic_article_5970 18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG PET/CT) is frequently used for evaluation of indeterminate adrenal nodules.

The objective of this study was to evaluate the diagnostic performance of FDG PET/CT in distinguishing benign adrenocortical adenomas (ACA) from adrenocortical carcinoma (ACC).

We identified 139 patients in our institution who completed both FDG PET/CT and adrenal biopsy or adrenalectomy from 2001 to 2019 using the institutional Electronic Medical Record Search Engine (EMERSE). Patients with adrenal pathology revealing non-adrenocortical tumors were excluded. The imaging characteristics of ACAs were compared with ACCs.

Sixteen patients with ACAs and 50 patients with ACC were identified; of the latter, 30 were excluded, because FDG PET/CT imaging was completed after adrenalectomy. The average age of the ACC vs. ACA group was 48±14 and 52±17 years, respectively, with a gender composition of 35% and 25% men, respectively. All 20 patients with ACC had FDG avid lesions, defined by imaging report and increased ratio of adrenal tumor maximum standardized uptake value (SUVmax) to hepatic parenchymal average SUV (SUVmean) of greater than 2.5. Among those with ACAs, 11 had positive, 1 had mildly positive, 3 had indeterminate, and 1 had negative FDG PET/CT findings according to the report. Ratio of adrenal SUVmax to hepatic SUVmean was greater in ACC compared to ACA (13.5 versus 1.6, respectively, p = 0.13), but did not reach statistical significance, likely due to the small sample size and unavailability of SUV ratios for all lesions.

Our study identified a large number of ACAs that were deemed FDG avid but without adrenal SUVmax to hepatic SUVmean ratio of greater than 2.5. Although the sensitivity, and therefore the negative predictive value, of FDG PET/CT scan is excellent for the diagnosis of ACC, our data does not allow for the calculation of specificity. This is due to the selection bias inherent in our patient population referred for evaluation of unusual adrenal masses, and the fact that ACAs with negative FDG PET/CT often do not undergo surgery or biopsy, and therefore pathology results are not available. Despite this limitation, our findings show that calculation of the ratio of adrenal SUVmax to hepatic SUVmean, rather than lesion SUVmax alone, helps for characterization of adrenal lesions as malignant vs. benign, and that a negative FDG PET/CT is valuable in excluding ACC.

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<![CDATA[SAT-162 Potential Diagnostic Use of a Steroid Profile in Patients with Poorly Controlled Diabetes Mellitus]]> https://www.researchpad.co/article/elastic_article_5919 Cushing’s syndrome may contribute to insulin resistance and impaired insulin secretion in patients with diabetes mellitus. The prevalence of Cushing’s syndrome in human patients with type II diabetes mellitus has been reported as high as 9.4% (1), and prevalence of diabetes mellitus as a complication of Cushing’s syndrome has been reported as high as 50% (2). In our laboratory, evaluation of steroid profiles (analysis of cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, estradiol, testosterone, and aldosterone at baseline and post-ACTH) in 3,600 dogs over 2 years revealed 2% to 8% of dogs with diabetes mellitus had concurrent hyperadrenocorticism. These steroid profiles in dogs with uncontrolled diabetes mellitus, despite insulin therapy, implicated elevated estradiol, progesterone, and 17-hydroxyprogesterone concentrations, with or without elevated cortisol, as probable contributors to poor control of glycemia. It has been reported that high doses of estradiol can decrease expression of insulin receptors in target tissues (3) and progesterone can decrease GLUT 4 expression in target tissues and modulate beta cell proliferation in the pancreas (4), thereby contributing to insulin resistance and possibly insulin secretion. In human patients, decreasing cortisol concentration in Cushing’s syndrome improves the glycemic state in many, but not all gain normoglycemia (5). It is suspected, that for some human patients, cortisol is not the only steroid involved in hyperglycemia and a steroid profile may be a useful diagnostic tool for investigating other steroids contributing to insulin resistance. References: (1) Nieman, Endocrinol Metab Clin N Am. 2018; 47:259-273. (2) Giordano et al., Eur J Endocrinol. 2014; 170:311-319. (3) Gonzalez et al., Steroids. 2002; 67:993-1005. (4) Branisteanu et al., TRENDS Endocrinol Metab. 2003; 14:54-56. (5) Rogowicz-Frontczak et al., Endokrynol Pol. 2017; 68:334-342.

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<![CDATA[SAT-167 Dehydroepiandrosterone Sulfate (DHEAS) Levels Predict Weight Gain in Women with Anorexia Nervosa]]> https://www.researchpad.co/article/N29df35b7-3bca-4a83-8780-206316ac0d8e 18.5 kg/m2) are serious disorders characterized by undernutrition and complicated by endocrine dysregulation. Predictors of recovery, including serum biomarkers, are lacking. Prior studies have suggested that higher urinary free cortisol (UFC) may predict weight gain in women with AN, but 24-hour urine collections are not feasible in a real-world setting. Like cortisol, the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfated form DHEAS, which has a longer half-life, are stimulated by ACTH. We hypothesized that DHEAS levels would correlate with UFC and be a predictor of weight gain in women with AN.Methods: We prospectively studied 34 women with AN and atypical AN, mean age 27.4 ± 7.7 years (mean ± SD), who received placebo in a randomized trial. AN and atypical AN were diagnosed by SCID. Baseline DHEAS and 24-hour UFC were measured by LC-MS/MS (Endocrine Sciences, Calabasas Hills, CA). Weight and body composition were assessed at baseline and 6 months later by DXA and cross-sectional abdominal CT at L4.Results: At baseline, mean weight was 51.3 ± 4.9 kg. Of the 18 subjects who gained weight (range 0.1–10.3 kg), 28% were eumenorrheic, 39% amenorrheic, and 33% on oral contraceptives at baseline; baseline reproductive status was similar for subjects who did not subsequently gain weight. In the group as a whole, mean baseline DHEAS level was 173 ± 70 µg/dL (0.7 ± 0.3 times the mean normal range for age) and mean baseline UFC for subjects who completed testing (n=15) was 20 ± 18 µg/24h (normal range 0–50 µg/24h). Higher DHEAS levels at baseline predicted weight gain over 6 months (r=0.61, p<0.001), which remained significant after controlling for age, baseline BMI, OCP use, and SSRI/SNRI use (p<0.001); none of these covariates were predictors of weight gain. Baseline DHEAS levels predicted an increase in fat mass (r=0.40, p=0.03) and appendicular lean mass (r=0.38, p=0.04) by DXA, and abdominal fat by CT (r=0.60, p<0.001); the associations remained significant after controlling for the above factors. UFC did not predict change in weight (r=0.37, p=0.17) or body composition. DHEAS levels were positively associated with UFC (r=0.61, p=0.02).Conclusion: In women with AN, higher DHEAS levels are a predictor of weight gain and increases in fat mass, skeletal muscle mass, and abdominal fat. Serum DHEAS correlates with UFC, a predictor of weight gain in prior studies. DHEAS may be a more practical biomarker of recovery, as 24-hour urine collections are challenging. Further studies are needed to determine whether higher DHEAS levels are a marker of global adrenal stress response and a reflection of higher cortisol levels, which may stimulate weight gain, or an independent predictor of weight gain in AN and atypical AN, perhaps through neuromodulation. ]]> <![CDATA[SAT-LB36 Distinct Vitamin D Receptor DNA Methylation Profiles Are Associated With the Outcome of Pediatric Patients With Adrenocortical Tumors]]> https://www.researchpad.co/article/N5314e9f4-19a9-48e2-a0a3-12b9cf833a71 =4), were not carriers of somatic Beta-catenin activating mutations, or died. Although cluster C2 patients (n=21) presented intermediary disease features, only 2 patients died and the overall outcome was positive. Instead, the C3 cluster concentrated patients (n=18) with non-localized/metastatic disease (IPACTR stages I/II vs. III/IV; p=0.004), post-surgical metastasis/recurrence (p=0.009), and patients who needed adjuvant chemotherapy (p=0.005). Moreover, C3 patients had lower overall and disease-free survival rates (log-rank: p=0.001 and p=0.014, respectively). VDR methylation was not associated with sex, clinical presentation, P53 mutations, nor with tumor VDR mRNA expression or nuclear immunoreactivity. Conclusions: Three VDR methylation profiles were associated with distinct pACT clinical features and outcome. High VDR methylation was associated with worst outcome. Fully functioning VDR may play a beneficial role against pediatric adrenocortical tumorigenesis. This finding highlights the potential of targeting VDR as an adjuvant therapeutic target. ]]> <![CDATA[SAT-LB41 Surgery Outcomes for Patients With Primary Aldosteronism Who Show Normal-Appearing Adrenals on Computed Tomography but Unilateral Disease on Adrenal Venous Sampling]]> https://www.researchpad.co/article/N51ea3fb0-6732-48aa-a69b-28aa643e918c 2 and unilateral aldosterone overproduction was confirmed by lateralized index ≥2. Among the group with normal appearing-adrenals on CT, we examined preoperative clinical characteristics between those with unilateral disease on AVS and those with bilateral disease on AVS. In addition, we compared surgical outcomes of CT-negative and AVS-unilateral group with those of CT-unilateral and AVS-ipsilateral group (patients with unilateral lesions on CT and ipsilateral disease on AVS). The Surgical outcomes for unilateral PA were evaluated according to the criteria of the Primary Aldosteronism Surgical Outcome study. Results: The success rate of AVS in patients with normal-appearing adrenals on CT was 88% (167/190). Furthermore, the discordance rate between CT and AVS in patients with normal-appearing adrenals on CT was 36% (60/167). There were no significant differences in preoperative clinical characteristics between the CT-negative and AVS-unilateral group (n=60) and the CT-negative and AVS-bilateral group (n=107). After surgery, the CT-negative and AVS-unilateral group (n=14) had a lower complete biochemical success rate than the CT-unilateral and AVS-ipsilateral group (n=30) (43% vs. 80%, p=0.02), but clinical and biochemical benefits (the complete and partial success combined) were not significantly different between them (71% vs. 93% (p=0.07) and 71% vs. 90% (p=0.13), respectively). Conclusion: The clinical features of CT-negative and AVS-unilateral group were significantly similar to those of CT-negative and AVS-bilateral group. They benefited from surgery, and AVS should be performed for patients who pursue surgical management when the CT findings suggest normal-appearing adrenals. ]]> <![CDATA[SAT-179 Increased Telomere Length in Adrenocortical Tumors Is Associated with Abnormal Expression of Chromatin Remodelling Factors]]> https://www.researchpad.co/article/N65c67f1e-bc3f-4119-86ba-45ddaf784ec2

Abstract

: The pathogenesis of adrenocortical tumors (ACTs) in the pediatric population is partially known, and few prognostic factors have been identified in this age group. Recently, ATRX and DAXX have been implicated in the pathogenesis and prognosis of a variety of cancers. Their altered function has been shown to affect telomere length through a telomerase-independent mechanism.

: To investigate

and

gene expression, ATRX and DAXX protein expression, and telomere length, as well as their clinical significance, in ACT samples from pediatric patients.

: The records of 110 pediatric patients with available ACT samples were reviewed.

,

,

and

gene expression was assessed by qPCR (n = 100 ACTs; n = 12 normal adrenals). ATRX and DAXX protein expression was assessed by IHC (n = 45 ACTs). Telomere length was assessed by qPCR (n = 64 ACTs). For survival analysis, Kaplan-Meier curves were obtained. For association analysis, simple linear regression models were adjusted.

: Most patients were female (70.9%) and harbored germline

mutations (90.2%). Median age at diagnosis was 21.1 months (2.1 – 199). Younger patients (< 3 years) had better survival (p < 0.01), while those with metastasis at diagnosis and carcinomas (classified by the Wieneke score) had worse survival (p < 0.01).

gene expression was decreased (

< 0.01), while

gene expression was increased (

< 0.01) in ACTs, compared to normal adrenals.

gene expression was even lower in the context of the germline

(R337H) mutation (

< 0.01).

expression was not detected in ACTs or normal adrenals, and

expression was not altered (p = 0.69). ATRX protein expression was lost in the majority of ACTs (95.6%), while DAXX was lost in a minority (21.1%). There was no association between gene or protein expression and disease-free or overall survival. There was a significant association between decreased

and

gene expression and increased telomere length (

< 0.01 and

= 0.03, respectively).

: In pediatric ACTs, decreased

and

gene expression was associated with increased telomere length, independently of

or

expression. In these tumors,

gene expression was decreased and ATRX protein expression was overall lost, while

gene expression was increased and DAXX protein expression was overall retained. No significant association between these alterations and prognosis was found in this cohort. These findings suggest that ATRX and DAXX altered function may be more involved in the pathogenesis of pediatric ACTs than in the prognosis of the affected patients.

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<![CDATA[SAT-166 Advantage and Trustworthy of Cortisol and Dexamethasone Evaluation in Different Biological Matrices in Patients with Adrenal Masses]]> https://www.researchpad.co/article/N494b3e6f-47a5-4655-9827-f7d4d5ae8fae

Abstract

Biochemical function of adrenal masses is currently based on 1mg post-overnight dexamethasone suppression test (pDST). Several approaches are recently developed, in order to reduce false positive/negative samples, only in retrospective series. They are based on the correlation of some different parameters, i.e. late-night salivary cortisol (LNSC)

serum and salivary cortisol pDST; LNSC

serum and salivary cortisol and serum dexamethasone pDST; LNSC and cortisone

serum cortisol and salivary cortisol and cortisone pDST. Although these findings offer a better diagnostic performance, several conditions are still disappointed. No information is traceable about the harvest time of diurnal salivary and serum samples and no study include neither the levels of salivary nor urinary dexamethasone pDST. Aim of our study is to combine all these strategies in order to avoid the underestimated biases and obtain more precise information about the true “cortisol condition” of the patients.

To reach this purpose we assess both cortisol and dexamethasone concentrations in several samples: saliva at 11PM before the drug administration, diurnal saliva and serum at 8AM and also the urine collection from 11PM to 8AM. Analytes levels are measured using a validated liquid chromatography-tandem mass spectrometry method. In this study we included 20 subjects without morphological adrenal alteration (MRI assessment), dyslipidemia, hypertension and impaired glucose tolerance (healthy controls) and 20 patients with adrenal incidentaloma showing different cortisol levels ranging from normal to ACTH-independent hypercortisolism. In both series, LNSC were similar to salivary cortisol pDST, even if they were greater in the patients with adrenal incidentalomas and subclinical cortisol secretion. Serum dexamethasone levels were in reference ranges, while salivary and urinary dexamethasone found in these matrices require additional sample numbers in order to establish appropriate cut-offs. Our preliminary results suggest that the combination of these findings could represent an improvement to assess the individual cortisol status.

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<![CDATA[SAT-169 Adrenocortical Cancer Is Diagnosed at Large Size and Advanced Stage in a Canadian Referral Center; Focus on Modes of Presentation Depending on Stages]]> https://www.researchpad.co/article/N00f14636-c27c-4907-b834-4a60823b3c99 5 cm (stage II). Advanced disease is confirmed if there is tumoral invasion, either locally in the surrounding tissues/nodes (stage III) or in other organs/vascular structures (stage IV). Objective: To describe patient characteristics, staging and modes of presentation at initial diagnosis in our cohort of ACC patients. Methods: We retrospectively reviewed paper and electronic charts of patients with pathology-confirmed ACCs who were treated at our referral center from 1995 to May 2019. Results: One hundred four patients were diagnosed with ACC: 28 were men (26.9%) and 76 (73.1%) were women and median age was 51 years. The overall modes of presentation were hormonal hypersecretion (40.4%), mass-related symptoms (36.5%), incidentalomas (17.3%) and unknown (1.9%). Hormonal profile was available for 71 tumors: 67,6 % were secreting [androgen and cortisol co-secretion (39.4%), cortisol only (28.2%)] and 18,3% were non-secreting. At initial diagnosis, sixty-four patients (61.5%) had tumors >10 cm including 32.7% between 10-14.9 cm (n:34), 19.2% were 15-20 cm (n:20) and 9.6% were >20cm (n:10). Initial ENSAT stages were I (6.7%), II (17.3%), III (28.8%) and IV (44.2%) and unknown (2,9%). The age repartition was similar for most patients (median ~50 yo) regardless of disease stage or tumor size except in the subgroup of very large tumors (>20 cm) for which the median age was 40 yo. The mode of presentation at initial diagnosis varied at various stages. Incidentaloma was a frequent mode of presentation of earlier ACC stages; Stage 1: 3/7 (42,9%), stage II: 7/18 (38,9%), stage III: 4/30 (13,3%) and stage IV: 4/46 (8,7%). Hormonal excess symptoms led to ACC diagnosis less frequently in early stages (stages I and II) (24%) than in later stages (stage III and IV) (47,3%), while the hormonal work up showed high prevalence of secreting tumors in both groups (58,8% and 88,7%). Mass-related initial symptoms were similar in both groups 36% vs 39%. Conclusions: In our cohort, 61.5% of ACC tumors were larger than 10 cm at initial diagnosis. Seventy-three percent of ACC patients had an advanced ENSAT stage III or IV disease which is associated with a 5 years survival of less than 50%. Incidentalomas is a frequent mode of presentation in stages I and II, while clinical hormonal excess symptoms were more frequent in later stages III and IV. Early stage diagnosis presents a difficult challenge in ACC and new biomarkers are needed to improve the odds against this deadly cancer. ]]>