bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-140 Determining the Undetermined: The Role of Tumor Tissue Staining for Interpretation of Inconclusive Genetic Testing Results in Patients with Pheochromocytomas and Paragangliomas
Authors: Khanna Parul , Berberich Amanda 
Published: May 2020

Abstract
Background:
Paragangliomas and pheochromocytomas are neuroendocrine tumors that can occur in several hereditary tumor syndromes. While these are generally rare, individuals with germline loss of function mutations in the succinate dehydrogenase (SDH) genes are at high risk of developing these tumours, with a penetrance of 70% by age 50. Functional SDHB acts as a tumor suppressor. Consequently, pathogenic mutations in the SDHB gene predispose to familial paraganglioma syndrome type 4, with high incidence of extra adrenal paragangliomas and high rates of metastasis. SDHB mutation carriers are also predisposed to developing tumors in other sites such as renal cell cancer, gastrointestinal stromal tumors and pituitary adenomas. Genetic testing for hereditary syndromes is recommended in patients who present with paragangliomas and pheochromocytomas, especially in those with aggressive tumours or who present at a young age. It is recommended that mutation carriers are monitored with routine clinical and imaging surveillance, and effort is made to identify and screen at-risk family members. In some cases, genetic testing can identify variants that are not clearly pathogenic or benign. In such “variants of undetermined significance”, immunohistochemistry or family history can be a helpful tool in discriminating between SDHB related and non-SDH-related pheochromocytomas and paragangliomas.
Clinical case:
We report on three families who presented with manifestations of paraganglioma syndrome and were found to have Variants of Uncertain Significance (VUSs) in the SDHB gene. Absence of SDHB staining was seen on tumour histopathology in two of the families; staining was not performed in the third. The proband in the third case initially presented at the age of 22 with a cardiac pheochromocytoma. Subsequently, her son was diagnosed with metastatic renal cancer at the age of 37. Genetic test results from both these patients identified a heterozygous VUS in SDHB. The son passed away from complications of his aggressive cancer shortly after diagnosis. Had familial screening and surveillance been initiated sooner in this family, this poor outcome may have been prevented.
Conclusion:
Our case highlights the important diagnostic dilemma that can arise in patients with VUSs in risk genes for hereditary pheochromocytomas and paragangliomas. While universally treating these VUSs as pathogenic would be costly, low-yield and potentially harmful, the incorporation of family history and tumour tissue staining for SDHB should be considered in all individuals with pheochromocytomas and paragangliomas to help guide interpretation of inconclusive genetic testing results, inform subsequent management and help predict risk for inheritance and recurrence.
SAT-341 Hyperparathyroid Crisis Precipitated by Rapid Correction of Symptomatic Hypercalcemia in an Occult Ectopic Parathyroid Adenoma
Authors: Ruiz Vanessa Goyes , Bansal Nidhi 
Published: May 2020

Abstract
Background: Parathyroid adenomas (PA) are typically benign, slow-growing tumors causing gradual increase in parathyroid hormone (PTH) and serum calcium (s.Ca) levels. Hyperparathyroid crisis is a rare and potentially fatal syndrome, which occurs due to rapid elevation of PTH and s.Ca levels (s.Ca &gt;15mg/dL). This can potentiate severe metabolic derangements, manifesting as altered mental status (AMS), renal insufficiency and cardiac arrhythmias. We present a case of hyperparathyroid crisis in the setting of an occult ectopic parathyroid adenoma.
Case: 75 year old female with a medical history of osteoporosis, hypertension and Parkinson’s disease, presented to our hospital with AMS and one week history of diarrhea. She was recently hospitalized for pneumonia and treated with antibiotics. Biochemical analysis revealed corrected s.Ca 15.4mg/dL (8.2- 9.6mg/dL; 7 days prior s.Ca was 9.7mg/dL), renal insufficiency (Cr 2.26mg/dL; baseline 1.2) with normal serum phosphorus, magnesium, 25-hydroxyvitamin D and alkaline phosphatase. PTH was found to be elevated at 75pg/mL (15-65pg/mL). She was treated with aggressive intravenous hydration and calcitonin 200mg BID for 3 days. Her s.Ca appropriately trended down. However, her PTH level continued to rise: 319pg/mL 12 hours later, 591pg/mL on day 2 and peaked to 1,242pg/mL on day 3. CT angiography neck showed an incidental finding of a heterogeneous, possibly necrotic, soft tissue nodule in the left paraesophageal region. Additional work-up with technetium 99 Sestamibi scan revealed persistent activity in the upper tracheoesophageal groove consistent with an ectopic PA. She underwent parathyroid exploration with excision of an enlarged ectopic left superior parathyroid adenoma, confirmed on histopathological analysis. The remaining parathyroid glands were normal. PTH declined to 34pg/mL postoperatively. Her mental status improved significantly returning to baseline within a few days with normal PTH and s.Ca levels.
Discussion: Secretion of PTH is mediated by s.Ca via the calcium sensing receptors (CaSR). Studies have shown that patients with PA have decreased expression of the CaSR leading to an autonomous rise in PTH secretion and a higher PTH-calcium set point. In our case, the patient initially presented with a mildly elevated PTH level and symptomatic hypercalcemia. The rapid correction of s.Ca levels precipitated a remarkable rise in PTH levels. We postulate that this was caused by a possible upregulation mechanism in calcium sensing by adenomatous parathyroid tissue that is responsive to acute lowering of s.Ca levels, triggering a hyperparathyroid crisis.
Reference: (1) Corbetta S., et al. Calcium-sensing receptor expression and signaling in human parathyroid adenomas and primary hyperplasia. Clinical Endocrinology. 2000; 52(3):339-48.
MON-301 Long-Acting SSA Treatment Patterns in Sweden From 2005 to 2017: A Nationwide Study
Authors: Olsson Daniel S , Granfeldt Daniel , Björstad Åse , Ribeiro-Oliveira Antonio , Jonasson Anna , Whalen John D 
Published: May 2020

Abstract
Background
Acromegaly is a complex disease, primarily treated with pituitary surgery or long-acting somatostatin analogues (LA-SSA). Few studies have examined real-world use of LA-SSA. This analysis evaluated LA-SSA treatment patterns in Sweden for patients with acromegaly.
Methods
Data were obtained from nationwide health care registers. Patients were included if they had diagnosis codes for acromegaly and neoplasm of the pituitary gland between Jul 1, 2005 and Dec 31, 2017, and at least one purchase of LA-SSA (lanreotide [LAN] 60, 90, or 120 mg, or octreotide [OCT] 10, 20, or 30 mg). Cox regression models were used for analyses of persistence and switching.
Results
The analysis included 176 pts treated with LA-SSA in 2005-2017. The cohort was subgrouped on year of initiation of LA-SSA (2005-2011, n=90, 51%; 2012-2017, n=86, 49%). In the first period, 36 pts (40%) initiated LAN while 54 pts (60%) initiated OCT while in the later period, 44 pts (51%) initiated LAN and 42 pts (49%) initiated OCT (p=0.17). No patients initiated pasireotide. Patient characteristics were similar between LAN and OCT initiators, but history of pituitary surgery was more common for LAN as compared to OCT (LAN 62%; OCT 46%, p&lt;0.05). Similar results were seen for visual-field defects (LAN 20%, OCT 8%, p&lt;0.05). Median (95%CI) follow-up was not significantly different [LAN 5.3 (3.7; 6.0) yrs.; OCT 6.4 (4.5; 7.6)].
The mean (95%CI) dose interval was not significantly different, 30.5 (28.7; 32.6) days for LAN vs 29.5 (28.5; 30.3) days for OCT. The median (95%CI) duration of 1st-line LA-SSA treatment was 14.4 (10.8; 21.6) months for LAN and 12.0 (7.2; 19.2) months for OCT. Fifty-one pts (64%) discontinued 1st-line LAN while 70 pts (73%) discontinued 1st-line OCT (hazard ratio (HR) LAN vs. OCT 0.80; 95% CI: 0.56-1.15). Due to the use of register data, the reason for therapy change could not be determined. Eight pts (10%) switched LAN to OCT while 29 pts (30%) switched OCT to LAN. Patients initiated on OCT were more likely to switch to LAN than the other way around (HR for switch for 1st-line LAN vs. OCT 0.33; 95% CI 0.15-0.72). Among patients who switched OCT to LAN, 67% of LAN dispensing was 120 mg, 21% 90 mg, and 12% 60 mg. Among patients who switch LAN to OCT, 84% of OCT dispensing was 30 mg, and 16% 20 mg.
Conclusions
There was no significant difference in the number of patients initiated on LAN or OCT despite the later introduction of LAN in Sweden. Patient characteristics were similar but LAN initiators were more likely to have undergone surgery and be diagnosed with visual field defects which could indicate that physicians initiate LAN in patients with more aggressive disease. Extended dose intervals with LAN (dosing every 6-8 w) do not seem to be commonly used in Sweden. In comparison to OCT, patients initiated on LAN were significantly less likely to change LA-SSA therapy.
SAT-201 Adrenal Myelolipoma in a Patient with Sickle Cell Disease
Authors: Alexandre Maria Inês , Gomes Ana Coelho , Cruz Diogo , Bugalho Maria João 
Published: May 2020

Abstract
Background: Adrenal myelolipoma is a rare benign tumor of the adrenal gland, consisting of adipose tissue and hematopoetic elements. It has been reported to be associated with many chronic diseases such as haematological disorders. The majority of the adrenal myelolipomas are diagnosed in the fourth-sixth decades of life, usually as incidental findings. Despite its benign behavior, it may cause difficulties in the differential diagnosis.
Clinical Case: A 33-year-old woman was found to have a right adrenal incidentaloma in a kidney ultrasonography, during work-up for suspected kidney pathology ultimately not confirmed. Her past medical history was significant for sickle cell disease. There was no history of hypertension nor personal or family history of endocrine diseases. The physical examination was unremarkable.
The ultrasonography revealed a mass above the right kidney, measuring 5.5 cm in diameter, markedly heterogeneous and hypoechoic in the center. On CT imaging, one month later, this mass measured 6.2x4.3cm. The absolute contrast washout of 52% was indeterminate for adrenal adenoma. The MRI, twelve months later, showed a well-demarcated and heterogeneous tumor with 8x4.7x4cm, with fat areas, suggesting adrenal myelolipoma, but not excluding the possibility of a malignant lesion, such as liposarcoma. The mass was in contact with the liver although not invading it nor the kidney or inferior vena cava. There was no evidence of metastatic disease. Basal biochemical work-up did not disclose hormonal hypersecretion. The ACTH level was 19.6 pg/ml (N7.2-63.3); free urinary cortisol (24 hours) was 101 μg/24h (N36-137) and the overnight 1 mg dexamethasone suppression test was also normal (0.5 μg/dL). Serum metanephrines were within the normal range: metanephrine 7,8 pg/mL (N &lt;65) and normetanephrine 52,3 pg/mL (N&lt;196). Her remaining laboratory values were within normal values including potassium and sodium values.
Due to the size, rate of growth and atypical features of the mass, right laparoscopic adrenalectomy was performed. The resected adrenal weighed 66.6g and within it there was an intraparenchymal nodule, measuring 7.5 x 3 x 3.5 cm, which on histologic examination proved to be an adrenal myelolipoma.
Conclusion: Adrenal myelolipomas are usually clinically silent. However, their incidental diagnosis should warrant careful diagnostic study. Although the pathogenesis of these tumors remains unclear, theories include retention of embryonic rests, adrenocortical metaplasia and extramedullary hematopoiesis. In this patient with sickle cell disease, bone marrow elements within the myelolipoma may have grown as a result of the persistent anemia. Particular to this case is the patient’s young age, since most cases reported have occurred during the fourth-sixth decades of life. In addition, the association with sickle cell anemia has only been reported in a few cases.
OR20-02 Maternal Adiponectin Prevents Against Metabolic Dysfunction in Prenatally Androgenized PCOS-Like Mice
Authors: Benrick Anna , Wu Yanling , Stener-Victorin Elisabet , Asterholm Ingrid Wernstedt 
Published: May 2020

Abstract
More than 10% of women worldwide are diagnosed with polycystic ovary syndrome (PCOS), causing reproductive and metabolic disease. Hyperandrogenism is the main characteristic and elevated levels of androgens during pregnancy affect placenta function and fetal programming, which leads to reproductive and metabolic dysfunction in the offspring. Adiponectin secreted from adipose tissue improves whole-body metabolism, but its role during pregnancy is under explored. Adiponectin affects placental nutrient transport during pregnancy allowing for speculation that adiponectin can exert endocrine effects on the developing fetus. This study aims to investigate if, in prenatally androgenized (PNA) mice, adiponectin can prevent metabolic and reproductive dysfunction in female offspring. Adiponectin transgenic (APNtg) and wildtype (wt) female mice were mated with wt males, and received dihydrotestosterone or vehicle injections between gestational days 16.5-18.5 to induce a PCOS-like phenotype. The anogenital distance, a marker of in utero androgen exposure, was measured at 22 days of age, estrus cyclicity was recorded at 6 weeks of age, and metabolic measures were performed at 4 months of age.
APNtg dams gave birth to significantly smaller offspring, independent of genotype, than wt dams. PNA increased f-insulin in all groups but insulin sensitivity was higher in wt mice from APNtg dams compared to wt mice from wt dams. Insulin resistance correlated with subcutaneous and visceral fat mass. PNA increased visceral fat % and adipocyte size in wt offspring from wt dams while wt and APNtg offspring from APNtg dams were protected against this effect. Visceral adipose tissue gene expression was unaltered in PNA wt offspring, regardless of the dam’s genotype, while APNtg offspring, regardless of PNA, had increased expression of adipogenic genes. Anogenital distance was increased in all PNA wt offspring independent of the dam’s genotype. There was, however, no difference between APNtg-vehicle and APNtg-PNA mice, suggesting that adiponectin overexpression protects against this effect. PNA leads to disrupted estrous cycle and fewer ovulations, but this effect was less pronounced in PNA wt mice from APNtg dams. Our data suggests that elevated maternal adiponectin protects the offspring against PNA induced metabolic dysfunction, and to a lesser extent reproductive dysfunction.
SUN-713 Prevalence of Renal Cysts in Patients with Carney Complex
Authors: Kamilaris Crystal Dawn Chrysavgi , Gkirgkinoudis Athanasios , Tatsi Christina , Pitsava Georgia , Sinaii Ninet , Hannah-Shmouni Fady , Stratakis Constantine A 
Published: May 2020

Abstract
In the general population renal cysts appear most commonly in patients &gt;50 y and in men. Among published studies, the prevalence of renal cysts detected by MRI was 27%, detected by CT was 20-41%, and detected by US was 4-17% (Mensel, et al., 2018; Choi, et al., 2016). In these studies, the male to female ratio in patients with renal cysts ranged from 1.4:1 to 2.93:1. Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia and lentiginosis syndrome predominantly caused by aberrant cAMP-protein kinase A (PKA) signaling mostly (but not always) due to germline inactivating defects in PRKAR1A which encodes the regulatory subunit type 1α of PKA. In a small retrospective study, 5 of 9 subjects with CNC had renal cysts on MRI or CT (Ye, et al., 2017). This same study evaluated the development of renal cysts in kidney-specific Prkar1a knockout mice, where all mice developed a renal cystic phenotype. To determine the prevalence of renal cysts, we performed a retrospective cohort study of patients with CNC evaluated at our institution between 1984 and 2019 who underwent renal imaging with MRI, CT, and/or US. We hypothesized that CNC leads to renal formation of cysts in humans, with increased number of renal cysts and earlier age at detection. 117 patients with CNC (69 female [59%], 48 male [41%]) were evaluated with renal imaging (56% MRI, 41% CT, 3% US). Of these, 39 (33%) patients had renal cysts that were first detected on imaging between the ages of 13 and 58 y (mean age at diagnosis 37.1 ±12.7 y; 5 [13%] 12-19 y, 5 [13%] 20-29 y, 10 [26%] 30-39 y, 11 [28%] 40-49 y, and 8 [21%] 50-59 y). The mean number of cysts was 1.3 ±0.7, and mean dominant cyst size was 1.2 ±0.9 cm. Average creatinine at diagnosis was 0.8 ±0.2 mg/dl. Of the patients with renal cysts, 22 were female (56% of patients with renal cysts, 32% of females with CNC that underwent renal imaging) and 17 were male (44% of patients with renal cysts, 35% of males with CNC that underwent renal imaging). There was no difference in the prevalence of renal cysts between males and females (35% vs 32%, p=.70, for a 1.1:1 ratio). Age, number, and dominant cyst size were also not different between sexes (p=.51, p=.84, and p=.26, respectively). However, creatinine levels were higher in males (0.9 ±0.1 vs 0.7 ±0.1, p&lt;.001). All 39 patients with renal cysts had defects in PRKAR1A as compared to 73 of 78 (94%) patients with CNC that did not have renal cysts on imaging (p=.17). In conclusion, our data demonstrate that there is a high prevalence of renal cysts in patients with CNC with both males and females being affected equally, in contrast to the majority of previously reported population studies. They also suggest that renal cysts may develop in patients with CNC at a younger age. These results can be further validated by comparison to a cohort of healthy controls.
SUN-190 Metastatic Adrenocortical Carcinoma in Remission After a Single Dose of Gemcitabine
Authors: Go Muriel Tania L , Hor Tiffany K , Soriano Paolo K 
Published: May 2020

Abstract
Background
Adrenocortical carcinoma (ACC) is a rare tumor with an incidence of one per million population per year. Overall prognosis is poor especially in the presence of distant metastasis where five-year survival rate is 10%. Aside from chemotherapy along with mitotane, second-line regimens are not well-established, and therapeutic options remain limited. Here we present a case of metastatic ACC with rapid and complete remission after salvage therapy with gemcitabine (GEM).
Clinical Case
A 28-year-old man presented with night sweats, 10-lb weight loss and abdominal pain for three months. An abdominal CT showed a 13x14 cm complex mass partially effacing the inferior vena cava (IVC) and a chest CT showed multiple pulmonary micronodules. Biochemical evaluation was unremarkable, confirming a non-functioning adrenal tumor.
The patient underwent right adrenalectomy, hepatectomy, right diaphragm resection and cavotomy of IVC. Pathology confirmed ACC with extra-adrenal and vascular invasion. He then underwent adjuvant intensity-modulated radiation therapy with no evidence of disease on imaging thereafter. However, he was lost to follow-up for six months and returned with new enlarging pulmonary nodules.
He was started on chemotherapy (cisplatin, etoposide, adriamycin) with mitotane which were discontinued after two months, due to intractable vomiting despite high dose glucocorticoids and anti-emetics. He was then enrolled in a clinical trial using immunotherapy with nivolumab and ipilimumab which led to a significant decrease in the size of pulmonary metastases. His clinical course was complicated by the development of type 1 diabetes mellitus and proliferative glomerulonephritis related to immunotherapy.
After one year of immunotherapy, repeat imaging showed disease progression with new pulmonary nodules. These agents were discontinued, and he was then given a single dose of GEM. Subsequent imaging with CT chest, abdomen and pelvis three months later showed complete response with resolution of lung nodules. He has no evidence of disease one year post therapy and continues to undergo active surveillance.
Discussion
GEM-based chemotherapy has shown to be a modestly active regimen based on a multicenter study which demonstrated a partial response or stable disease in 4.9% and 25% of cases, respectively, with a median duration of 26 weeks. Median progression-free survival is 12 weeks (range 1 to 94). From the available data, GEM remains an important option for salvage therapy however, to date, there are no reliable predictive biomarkers to potentially identify responsive patients.
Conclusion
This is an extremely rare case of metastatic ACC achieving complete response after definitive surgery and a single dose of gemcitabine, despite failing first-line chemotherapy and immunotherapy. The unusual positive response may lead to the consideration of its use as a second line regimen.
MON-336 Presumed Parathyroid Infarction Leading to Remission of Primary Hyperparathyroidism: A Rare Clinical Occurrence
Authors: Nguyen Tiffany , Narla Radhika Rao 
Published: May 2020

Abstract
Background: Infarction of a parathyroid adenoma, also known as ‘parathyroid auto-infarction’ or ‘parathyroid apoplexy,’ is a rare condition that can present and lead to acute and dramatic reduction of calcium (Ca2+) and parathyroid hormone (PTH) levels and spontaneous remission of primary hyperparathyroidism (PHPT). Some patients may experience neck pain, dysphagia, hoarseness, anterior neck swelling or ecchymoses, while others are asymptomatic. Ultrasound can show the lesion getting larger due to hemorrhage, but weeks to months later, there can be a size decrease of the adenoma due to loss of blood supply and necrosis. Sestamibi scans can also show non-localization on serial exams. Few case reports have evidence of infarction on pathology.
Clinical Case: A 38 year old man with no significant past medical history presented after a pedestrian-motor vehicle accident with polytrauma, including a cervical spine injury requiring tracheostomy and immobilization of his neck. Over the first week of his hospitalization, his Ca2+ rose as high as 14.0 mg/dL (8.9-10.2 mg/dL). Concurrent PTH level was 233 pg/mL (12-88 pg/mL) and 25-OH vitamin D level was 14.8 ng/mL (20.1-50.0 ng/mL). A neck ultrasound showed a hypoechoic nodule measuring 1.4 x 1.2 x 1.6 cm posterior to the superior aspect right thyroid lobe. A sestamibi scan with SPECT-CT showed a persistent focal activity in the region of right thyroid bed. He was treated with aggressive intravenous (IV) hydration, 7 doses of intranasal calcitonin 500 units, multiple doses of furosemide 40-80 mg IV, pamidronic acid 90 mg IV, and eventually transitioned to cinacalcet 30 mg twice daily. Due to his C-spine injury, parathyroid surgery was deferred.
Four months later, the patient developed acute muscle spasms. He denied anterior neck pain, dysphagia, bruising, or swelling. Ca2+ level was checked and found to be 7.0 mg/dL. Cinacalcet was decreased, and eventually had to be discontinued. His serial Ca2+ and PTH levels normalized to 9.8 mg/dL and 55 pg/mL, respectively. A repeat 25-OH vitamin D level was replete at 31.1 ng/mL. A follow up ultrasound redemonstrated a slightly ill-defined hypoechoic nodule, now only measuring 0.9 x 0.9 x 1.4 cm along the the right thyroid. A sestamibi scan was also obtained and did not localize any lesion.
The biochemical and imaging findings were most consistent with a parathyroid infarction resulting in spontaneous remission of PHPT. Now one year following his initial presentation, he remains normocalcemic.
Clinical Lesson: The differential diagnosis for a sudden remission of PTH-dependent hypercalcemia is limited. Parathyroid infarction is a rare condition with paucity of data regarding follow up, but these patients likely need to remain under close long term clinical and biochemical surveillance as recurrence has been documented in the literature.