bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-448 Limited Adaptive Response by Deiodinase Enzymes in the Perinatal Hypothyroid Cochlea
Authors: Calderon Maria Uscategui , Sharlin David S
Published: May 2020

Thyroid hormone (TH) is essential for cochlear development and normal auditory function. Considering the importance of TH in mediating cochlear development, understanding the degree to which developing tissues can adapt to perturbations in thyroid hormone signaling is extremely important. The deiodinases (Dio2 and Dio3) are enzymes that tightly control TH availability at the tissue level and have been proposed to function as adaptive mechanisms that maintain tissue TH homeostasis. Dio2 converts thyroxine (T4) to a biologically active ligand triiodothyronine (T3); locally amplifying a T3 signal. Conversely, Dio3 inactivates T3 and T4 by converting these iodothyronines to the inactive metabolites diiodothyronine (T2) and reverse T3 (rT3), respectively. During cochlear development, Dio3 expression is high prenatally while Dio2 expression is low. During the first postnatal week, the expression levels of these enzymes invert, resulting in high expression of Dio2 and low expression of Dio3. Together, the deiodinases control the timing of postnatal cochlear remodeling; suggesting a genetic developmental clock controls TH-mediated cochlear development. Considering the role deiodinases as adaptive mechanisms, it is important to understand whether such a developmental clock can be negated during times of developmental thyroid hormone insufficiency. We hypothesize that the perinatal change in deiodinase expression is controlled by a developmental clock rather than environmental clues and therefore have limited capacity function as compensatory mechanisms in response to low TH during development. To test this, timed-pregnant mice were treated with thyroid gland inhibitors to induced hypothyroidism from gestational day 12.5 until pup sacrifice. A parallel set of untreated timed-pregnant mice served as controls. Cochlea were harvest from control and hypothyroid mice at postnatal (P) ages P1, P5, P10 and P15 for qRT-PCR, and P7 for in situ hybridization. In situ hybridization for Dio2 mRNA demonstrated a striking reduction in Dio2 mRNA in hypothyroid animals compared to euthyroid animals. Additionally, we observed a significant effect of age (p<0.001) and an interaction between age and treatment (p=0.0035) on Dio2 mRNA levels analyzed by qRT-PCR. Specifically, Dio2 mRNA levels were similar or reduced in hypothyroid animals compared to controls at P1, P5, and P10. This finding indicates that Dio2 mRNA at these ages did not respond in manner consistent with compensation. However, at P15, Dio2 mRNA levels were increased in hypothyroid animals compared to controls; a finding that is consistent with a compensatory mechanism. Taken together, our results suggest that developmental programs in tissues may be dominant over potential compensatory mechanisms and that developing tissues may be more susceptible to perturbations in tissue TH levels due to a reduced capacity to compensate.
SAT-243 Lymphocytic Hypophysitis Mimicking Pituitary Apoplexy in a 27-Year-Old Woman
Authors: Brooks Danielle C , Haber Richard S
Published: May 2020

Introduction:

Lymphocytic hypophysitis is an uncommon inflammatory disorder of the pituitary gland. Peripartum women are most often affected, but it can be seen in a wide range of patients. Patients can present with pituitary dysfunction or mass effect symptoms, making it difficult to differentiate from a pituitary adenoma. Pituitary apoplexy is an acute syndrome due to hemorrhage into the pituitary gland causing headache, visual deficits, and hypoadrenalism. We present a case of a woman with a pituitary mass presenting with symptoms mimicking pituitary apoplexy, in whom surgical pathology later revealed lymphocytic hypophysitis without evidence of hemorrhage.

Clinical Case:

A 27-year-old non-pregnant female presented with severe headaches, nausea, vomiting, and diplopia for four days. A presumed pituitary macroadenoma was diagnosed two years previously during a workup for irregular menses. An emergency evaluation with a CT angiogram of the head showed enhancement at the superior aspect of and surrounding the pituitary gland. MRI of the pituitary revealed an enhancing 17 x 17 mm sellar and suprasellar mass compressing the optic chiasm, without evidence of the normal pituitary posterior bright spot. Visual field testing was normal. She was referred for transsphenoidal resection of the pituitary mass due to persistent headaches, optic chiasm impingement, and suspicion of pituitary apoplexy. Intraoperatively, there was no evidence of hemorrhage. Central diabetes insipidus and hypothyroidism developed in the post-operative period. She was discharged on hydrocortisone replacement therapy (20 mg in the morning, 10 mg in the afternoon). An outpatient random cortisol level of 1.2 mcg/dL (reference: 6.7 - 22.6 mcg/dL) while off hydrocortisone for twenty-four hours confirmed hypocortisolism. Surgical pathology showed moderate lymphocytic infiltrate and focal germinal centers in the adenohypophysis consistent with lymphocytic hypophysitis.

Conclusion:

Although lymphocytic hypophysitis is well-described in the literature, its association with symptoms suggesting pituitary apoplexy has been reported only rarely. This atypical case shows that lymphocytic hypophysitis can present with acute symptoms mimicking pituitary apoplexy. The case highlights the difficulties in recognizing lymphocytic hypophysitis prior to surgery and emphasizes the need to consider the diagnosis in patients presenting with pituitary masses and/or symptoms of pituitary apoplexy.
SUN-643 Potential Contributions of Gut Microbiota-Liver Axis to the Transgenerational Metabolic Reprogramming of Maternal Exercise
Authors: Zhou Liyuan , Xiao Xinhua , Zhang Qian , Li Ming , Yu Miao
Published: May 2020

Background: Early-life overnutrition programs increased risks of metabolic disorders in adulthood. Regular exercise is widely accepted to be an effective measure to maintain metabolic health. However, the transgenerational effects of maternal exercise and the specific mechanism are largely unclear. Aims: Our objective was to investigate whether maternal exercise could alleviate the metabolic disturbances induced by early-life overnutrition in both dams and offspring and to explore the role of gut microbiota-liver axis in mediating the transgenerational metabolic reprogramming. Methods: C57BL/6 females were randomly divided into three groups 3 weeks before mating and during pregnancy: the control group, high-fat group, and high-fat with exercise group (voluntary wheel running training). They received their original diets during lactation. The male offspring had ad libitum access to chow diet from weaning to 24 weeks of age. Glucose tolerance test and serum biochemical parameters were detected. The cecal contents from dams at weaning and 8-week and 24 week of offspring were collected for 16s rDNA sequencing. Hepatic HE staining and transcriptome were performed in adult offspring. Results: The results showed that perinatal high-fat diet resulted in significant glucose intolerance, insulin resistance and lipid profiles disorders in both dams and offspring. Maternal exercise markedly improved insulin sensitivity in dams and metabolic disorders in offspring from young into adulthood, especially the hepatic steatosis. The decrease in harmful bacteria and the persistent enrichment of short chain fatty acid producers from mothers to adult offspring, particularly the genus Odoribacter, were all associated with improvement in metabolism by maternal exercise. In addition, maternal exercise significant upregulated FGF21 and genes involved in the fatty acid oxidation and TCA cycle in adult offspring, which were down-regulated by perinatal high-fat diet and were significantly correlated with the altered microbial species. Conclusion: Overall, maternal exercise could significantly mitigate the detrimental effects of perinatal high-fat diet on metabolism in both dams and male offspring. The continuous alterations in gut microbiota and reprogramming hepatic metabolism might be critical factors in deciphering the transgenerational metabolic benefits of maternal exercise, which provides some novel evidence and targets for combating the metabolic diseases.
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

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

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 >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

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<0.05). Similar results were seen for visual-field defects (LAN 20%, OCT 8%, p<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

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 <65) and normetanephrine 52,3 pg/mL (N<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

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

In the general population renal cysts appear most commonly in patients >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<.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

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

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.
SUN-187 A Case of Adrenal Mass with Elevated ACTH and Cortisol in a Woman with No Cushingoid Features
Authors: Rajiyah Tara , Sam Susan
Published: May 2020

Background

Adrenal incidentalomas can present with subclinical Cushing’s Syndrome (SCS), which is defined as elevated cortisol levels without overt clinical signs or symptoms. Inaccuracies in ACTH levels due to issues with the assay and non-classic presentation of Cushing’s Syndrome (CS) can delay appropriate diagnosis and timely intervention.

Clinical Case

A 50-year-old female with a history of an incidentally discovered 3.4 x 1.8 cm adrenal mass was referred for evaluation of hypercortisolism (midnight salivary cortisol 0.17 μg/dL, normal < 0.09 μg/dL) with lack of suppression of both ACTH (19 pg/mL, normal 6-50 pg/mL) and cortisol (13.1 μg/dL, normal 6.0-18.4 μg/dL) on overnight 1-mg dexamethasone suppression test (DST). Pheochromocytoma work up was negative.

Her medical history was remarkable for premature ovarian failure at age 40 and osteoporosis at age 48 (Lumbar spine T-score -3.6, Femoral neck T-score -3.7, Hip T-score -2.7).

She denied alcohol abuse and depression screening was negative. She reported high levels of stress and insomnia. She denied muscle weakness, acne, or change to body habitus. Fasting blood glucose was intermittently as high as 212 mg/dl but HbA1c was 5.5%. She did not have a history of hypertension or glucocorticoid use. Her BMI was 20 kg/m2 and she did not appear Cushingoid. A pitutiary MRI showed no evidence of pituitary lesions or enlargement.

Discussion and Follow up

A non-suppressed ACTH made an adrenal source of cortisol unlikely. The working diagnosis was pseudo-CS secondary to stress, loss of diurnal rhythm due to insomnia, or overlooked depression.

She was taking supplements, including biotin, and was asked to discontinue these for two weeks. Repeat 1-mg DST revealed an elevated cortisol of 9.8 μg/dL with a once again non-suppressed ACTH of 20 pg/mL. Her dexamethasone level was 109 ng/dL (normal after 1 mg dexamethasone 180-950 ng/dL), which may suggest slightly faster metabolism. All ACTH levels were run on Immulite assays, which has recently been suggested to be unreliable (1). When repeated using the Roche Assay, ACTH was low at 1.6 pg/mL. Given suppressed ACTH in conjunction with hypercortisolemia and osteoporosis, an adrenal source of CS was confirmed. Diagnosis was further solidified by a DHEA-S level of 11.4 μg/dL (normal 35.4 - 256 ug/dL). She underwent adrenalectomy and pathology revealed adrenal cortical adenomas.

Conclusion

The correct diagnosis of adrenal CS in this patient was delayed due to erroneously higher ACTH result by the Immulite assay. Similar cases have been reported in the literature with the use of Immulite assays for measurement of ACTH leading to invasive diagnostic procedures and even unnecessary pituitary surgery (1).

1.

Greene LW, Geer EB, Page-Wilson G, Findling JW, Raff H. Assay-Specific Spurious ACTH Results Lead to Misdiagnosis, Unnecessary Testing, and Surgical Misadventure-A Case Series. J Endocr Soc. 2019;3(4):763-72.
OR08-03 Association of Hemoglobin A1c with Early Postpartum Metabolic Syndrome in Women with Gestational Diabetes
Authors: Blair Rachel A , Neves João Sérgio , Nicklas Jacinda M , Skurnik Geraldine , Seely Ellen Wells
Published: May 2020

Background: Women with gestational diabetes (GDM) are at increased risk of metabolic syndrome (MetS), an important risk factor for development of type 2 diabetes (T2DM) and cardiovascular disease. Elevated hemoglobin A1c (HbA1c) is associated with MetS outside of pregnancy and may enhance detection of MetS. It is not known whether HbA1c is associated with MetS in the early postpartum period in women with recent GDM.

Objective: We aimed to characterize the prevalence of MetS 4-12 weeks postpartum in women with recent GDM and to determine whether there was an association between HbA1c and MetS.

Methods: Women with GDM as defined by Carpenter-Coustan criteria or clinician diagnosis were enrolled into the Balance After Baby Intervention trial of a web-based intervention to prevent T2DM. They underwent a baseline study visit at 4-12 weeks postpartum. Waist circumference and blood pressure were obtained and a fasting lipid panel, HbA1c and a 75-g, 2 hr OGTT was performed. We defined MetS by NCEP ATP III criteria. We fit a logistic regression model adjusted for age, race/ethnicity, and number of weeks postpartum.

Results: 181 women with GDM were enrolled in the study. Three women were excluded because they did not have fasting lipid measurements. Women were a mean of 8.0 ± 1.8 weeks postpartum at their baseline study visit. 24.2% (n=43) of women had MetS (at least 3 of 5 NCEP ATP III criteria). Of these, 77% met the waist circumference criterion, 37.6% met the HDL criterion, 23.6% met the triglycerides criterion, 16.9% met the fasting glucose criterion and 14.6% met the blood pressure criterion. HbA1c as a continuous variable was not significantly associated with MS (OR for each 0.5% increase: 1.60, 95% CI 0.88-2.91). Elevated HbA1c (prediabetes range ≥5.7 to <6.5%) was also not associated with MetS (OR 0.98, 95% CI 0.46-2.12). A 2 hr blood glucose value of ≥140 mg/dL on OGTT testing was significantly associated with MetS (OR 5.28, 95% CI 2.11-13.22).

Conclusion: Nearly 1 in 4 women with recent GDM had MetS in the early postpartum period. There was no significant association between HbA1c and presence of MetS. However, an elevated 2 hr value on OGTT was significantly associated with MetS, suggesting that women with elevated 2 hr values may require additional monitoring for MetS and may have elevated cardiometabolic risk beyond the risk of development of T2DM.
OR22-02 PTEN Hamartoma Tumor Syndrome in Pediatrics: Triggers for Evaluation and the Value of Surveillance
Authors: Baran Julia , Tsai Steven , Singleton Daniel , Isaza Amber , Brodeur Garrett , MacFarland Suzanne , Zelley Kristin , Mamula Petar , Bauer Andrew Jacob
Published: May 2020

Context: PTEN Hamartoma Tumor Syndrome (PHTS) comprises a collection of rare clinical disorders characterized by germline mutations in the tumor suppressor gene PTEN. Current guidelines recommend screening for thyroid tumors beginning in pediatric age at the time of PHTS diagnosis; however, the benefit of early surveillance has not been well defined. Patients/Objective: We conducted a retrospective, single-site cohort investigation of patients followed at the Children’s Hospital of Philadelphia with diagnosis of PHTS between January 2003 - June 2019. In total, 81 patients under 18 years of age were identified. Clinical features, PTEN mutation codon, thyroid and gastrointestinal (GI) features were extracted from the electronic health record. The aim of the study is to assess genotype-phenotype, the incidence of thyroid and gastrointestinal disease, and to determine whether current recommendations for thyroid surveillance are improving outcomes. Results: The most common clinical feature at presentation was macrocephaly (85%) followed by impaired development (42%), skin/oral lesions (31%), and autistic spectrum disorder (27%). GI polyps were the presenting feature in 5 patients, with 14 of 81 patients ultimately diagnosed secondary to constipation (71%), rectal bleeding (64%), and/or abdominal pain (50%). All polyps were benign. A total of 58 of 81 patients underwent thyroid surveillance, with 30 patients (52%) found to have a nodule(s). Ultimately, 16 patients underwent thyroidectomy, with 31% (5/16) diagnosed with thyroid cancer. All thyroid cancer patients were greater than 10 years of age at diagnosis and all displayed low-invasive behavior (ATA low-risk). Of the patients < 10 years at the time of thyroid ultrasound (US) surveillance, 74% (14/19) had a normal US. The remaining five patients who underwent thyroid surgery all had benign histology. No genotype-phenotype relations were found; however, patients with identical mutations were found to have similar clinical features. Conclusions: Patients with macrocephaly associated with impaired development, skin/oral lesions, thyroid nodules and/or early onset GI polyps should undergo germline testing for PHTS. There does not appear to be a clinical advantage to initiating thyroid US surveillance prior to 10 years of age. Early detection may not improve outcome of thyroid cancer as the majority of thyroid cancers display low-invasive behavior. In PHTS patients with a normal physical exam, thyroid ultrasound surveillance can be delayed until after 10 years of age. Early onset GI polyps may be the presenting diagnosis of PHTS.
SAT-660 Rare Case of Portal Vein Thrombosis Secondary to Acute Pyelonephritis in Type 1 Diabetic Patient
Authors: Alanazi Alanoud , Albaker Waleed Ibrahim , AlSultan Osama , Alabdrabalnabi Fatima , AlSaeed Zahra
Published: May 2020

Background: Portal vein thrombosis (PVT) refers to venous thrombosis that develops within the extrahepatic portal venous system and can extend to the branches of the intrahepatic portal vein or up to splenic veins and superior mesenteric. A few cases have been reported about portal vein thrombosis in non-cirrhotic patient. Asymptomatic or non-specific symptom of portal vein thrombosis may lead to misdiagnosed or delay the diagnosis until the complications develop. We report a case of Portal vein thrombosis in type one diabetes associated with acute pyelonephritis.

Case report: 18 years old female with type one diabetes on insulin pump present with epigastric abdominal pain for three days associated with nausea and vomiting of three days duration. On examination; conscious alert oriented young female looks in pain, vital sign were stable temperature 37oC, heart rate 89 beat per minute, blood pressure 103/72 mmHg, respiratory rate 20 per minute, oxygen saturation 100% and random blood sugar (RBS) 179 mg/dl. Abdominal examination revealed soft and lax abdomen with tenderness in the epigastric area and right renal angle. No sign of rigidity or rebound tenderness. Bowel sound was present. No sign of ascites, splenomegaly or hepatomegaly. Investigations showed; WBC: 10.2, neutrophil 65%, urine analysis WBCs 30-50 per high field microscopy, RBC 5-10, PH 7, negative nitrate and culture did not show any growth. ESR was 48 and CRP was 4.2. Thrombophilic screen was done and all within normal. Computed tomography (CT) reveled reduced enhancement of right kidney likely indicating acute pyelonephritis and portal vein edema with complete occlusion of left branch of portal vein. Local factors and prothrombotic disorders were ruled out. The patient was managed with ciprofloxacin, enoxaparin and warfarin. The patient was symptomatic free and discharge home with a therapeutic range INR.

Conclusion: Portal vein thrombosis is uncommon condition in absence of liver diseases. Few case report liking between sepsis and portal vein thrombosis. Sepsis can create a predisposed environment for hypercoagulability.
MON-195 Genetic Analysis and Clinical Characteristics of Hereditary Paraganglioma and Pheochromocytoma Syndrome in Korean Population
Authors: Choi Heewon , Hong Namki , Shin Saeam , Lee Seung Tae , Choi Jong Rak , Kang Sang Wook , Rhee Yumie
Published: May 2020

Pheochromocytoma (PCC) and paragangliomas (PGL), rare neuroendocrine tumor originating from the chromaffin cells together referred as PPGL, are acknowledged to be more than 40% hereditary, related to germline mutations of susceptibility gene. With the advancement of genetic analysis technique, including next-generation sequencing (NGS), there has been attempts to classify PPGL into molecular clusters - Pseudohypoxic, Wnt signaling, and Kinase signaling PPGL. With NGS being applied to clinical setting only recently in Korea, we aimed to review the result of genetic analysis, including NGS, and investigate its association with clinical characteristics in Korean PPGL patients. We reviewed medical records of patients with PPGL in Severance hospital enrolled between January of 2006 to October of 2019. We gathered clinical phenotype by reviewing medical records of the patients who underwent targeted NGS from March of 2017 to October of 2019 using Severance hospital’s endocrine panel or who had known germline mutations of related genes. Family gene analysis was recommended for family members of patients with significant gene mutations. Among 78 patients with PPGL, 58 patients underwent targeted NGS results or had prediagnosed mutations. Thirty-three patients (62.1%) had clinically significant germline mutation. In patients with hereditary PPGL, there were higher likelihood of family history and presence of other tumors. There were significant differences in the type of PPGLs, percentage of family history, metastasis rate and the presence of other tumors among 3 molecular clusters - pseudohypoxic TCA cycle-related, pseudohypoxic VHL/EPAS1-related and kinase-signaling group. Twenty-seven different germline mutations from 11 genes (SDHB, RET, VHL, EPAS1, NF1, KIF1B, MAX, SDHA, SDHC, SDHD, and TMEM127) were found, SDHB mutation being the most common. Four of them were novel mutations; EPAS1 c.1250G>A (p.Gly417Glu), NF1 c.6215delA (p.His2072LeufsTer10), NF1 c.6777del (p.Gly2260fs), and SDHC exon 2-6 duplication. In conclusion, we report the prevalence of germline mutations in Korean PPGL patients, and the rate of hereditary PPGL is estimated to be as high as 62.1%. NGS is a good and accessible tool for genetic analysis in patients with PPGLs, and further research on molecular classification will lead to precision medicine.
SUN-073 Urine Steroid Profile of Girls with Premature Adrenarche
Authors: Sommer Grit , Janner Marco , Groessl Michael , Flueck Christa E
Published: May 2020

Background: Adrenarche describes the development of the human adrenal cortex when the zona reticularis increases the synthesis of C19 steroids (DHEA/-S). Girls with premature adrenarche have a higher risk to develop adverse outcomes including polycystic ovary syndrome and metabolic syndrome later in life. The role of novel biosynthetic pathways of androgen production in health and disease remains largely unsolved.

Objective: This study aimed to compare the urinary steroid metabolome between girls with premature adrenarche and healthy girls with focus on metabolites originating of novel, alternate androgen pathways.

Methods: In 23 girls with premature adrenarche (median age 7 years) and 22 healthy, age-matched girls, we measured 39 steroid metabolites comprising progesterones, corticosterones, aldosterone, androgens, estrogens and glucocorticoids in the urine collected over 24 h by gas chromatography mass spectrometry. We compared metabolites and metabolite ratios between both groups of girls using Mann-Whitney tests with Bonferroni correction to account for multiple testing.

Results: Girls with premature adrenarche were heavier than healthy girls (median weight 26.2 kg vs. 21.5 kg, p=0.003) and had a higher BMI SDS (0.8 vs -0.3, p=0.013). Gestational age and birth weight was similar between groups. Overall androgen excretion was different between groups, in particular amounts of androsterone, etiocholanolone, androstanediol, dehydroepiandrosterone, androstenediol, androstenetriol and pregnenetriol were higher in girls with premature adrenarche than in healthy girls (p<0.05). Some of these metabolites originate from alternate androgen pathways, e.g. androsterone. We found no differences in progesterones, corticosterones, aldosterone, estrogens and glucocorticoids, except for 20β-dihydrocortisone, which was higher in girls with premature adrenarche. Activities of 17βHSD and of 17,20-lyase via the Δ4pathway were higher in girls with premature adrenarche than in healthy girls.

Conclusions: Girls with premature adrenarche produce more androgens than healthy girls of similar age. The urinary steroid signature of adrenarche includes metabolites of alternate pathways. Androstanediol seems a marker of adrenarche. Future studies should assess whether the steroid signature of adrenarche is just appearing earlier in girls with premature adrenarche or earlier and different compared to adrenarche at normal timing.