bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-310 Analysis of the Influence of Glucocorticoid Receptor Gene Polymorphism BCL-1 on Clinical and Psychiatric Manifestations in Brazilian Patients with Cushing’s Disease
Authors: Garcia Erica , Amato Angelica Amorim , Barra Gustavo Barcelos , Naves Luciana Ansaneli , Vilar Lucio , Neves Francisco de Assis Rocha , Azevedo Monalisa Ferreira
Published: May 2020

In Cushing’s disease (CD), the spectrum of clinical manifestations is considerably wide, and the intensity of symptoms does not correlate with the magnitude of cortisol hypersecretion or with pituitary tumor size. Polymorphisms in the gene that encodes the glucocorticoid receptor (GR), an essential regulator of the hypothalamic-pituitary-adrenal axis, have been linked to some psychiatric disorders. Considering that psychiatric manifestations are present in nearly all patients with hypercortisolism, we hypothesized a possible correlation of polymorphisms in the GR gene and clinical and psychiatric manifestations, in CD. To investigate the frequency and clinical implications of the GR gene polymorphism Bcl-1 in patients with CD, we conducted a cross-sectional, case-controlled study. Fifty-three Brazilian patients with CD aged between 12 and 75 years and one hundred healthy controls aged between 42 and 67 years, of both genders, who provided written informed consent, were enrolled. Blood samples were collected from patients for DNA extraction and sequencing for analysis of the GR gene polymorphism Bcl-1. Clinical data (obesity, skin lesions, muscle weakness, hypertension, diabetes, hypokalemia, and sex-related disorders) were obtained through retrospective analysis of medical records, appointment with endocrinologist and with psychiatrist. Mini International Neuropsychiatric Interview, scales self-applicable of anxiety and depression were used to address psychiatric conditions. From the 53 patients studied, 48 were women (90,56%), and 16 patients had macroadenoma (2 of them had tumors larger than 4 cm). Overall frequencies of the Minor Allele for Bcl-1 polymorphism, which corresponds to the risk allele for psychiatric illness in the normal population, did not significantly differ between CD patients (67.92%) and controls (74.00%). Similarly, differences in Minor Allele Frequencies among subgroups of patients presenting with psychiatric and clinical manifestations of CD were not statistically significant. Although data from the literature strongly suggests a correlation between Bcl-1 polymorphism with psychiatric disorders (especially depression) in the normal population, this association was not observed in our cohort of patients with CD. More studies are needed to better clarify a possible role for GR gene polymorphisms as modifiers of the spectrum of psychiatric and clinical manifestations of CD.
SUN-LB24 Clinical Performance of Multiplatform Mutation Panel MicroRNA Risk Classifier in Indeterminate Thyroid Nodules
Authors: Sistrunk J Woody , Shifrin Alexander , Frager Marc , Bardales Ricardo H , Thomas Johnson , Fishman Norman , Goldberg Philip Andrew , Guttler Richard B , Grant Edward
Published: May 2020

Introduction: We evaluated the clinical performance of an expanded mutation panel in combination with microRNA classification (MPTX) for the management of indeterminate thyroid nodules. Methods: MPTX included testing of fine needle aspirates with a combination of ThyGeNEXT® mutation panel for strong and weak driver oncogenic changes and ThyraMIR® microRNA risk classifier. MPTX test status (positive or negative) and MPTX clinical risk classifications (low, moderate, or high risk) were determined blind to patient outcomes. Surgical pathology and clinical follow-up records of patients from multiple centers were used to determine patient outcomes. MPTX performance was assessed by Kaplan Meier analysis for cancer-free survival of patients, with risk of malignancy determined by hazard ratios (HR). Results: Our study included 140 patients with AUS/FLUS or FN/SFN nodules, of which 13% had malignancy. MPTX negative test status and MPTX low risk results conferred a high probability (94%) that patients would remain cancer free. MPTX positive test status (HR 11.2, P<0.001) and MPTX moderate risk results (HR 8.5, P=0.001) were significant risk factors for malignancy, each conferring a 53% probability of malignancy. MPTX high risk results elevated risk of malignancy even more so, conferring a 70% probability of malignancy (HR 38.5, P<0.001). Conclusions: MPTX test status accurately stratifies patients for risk of malignancy. Further classification using MPTX clinical risk categories enhances utility by accurately identifying patients at low, moderate, or high risk of malignancy at the low rate of malignancy encountered when clinically managing patients with indeterminate thyroid nodules.
SAT-LB314 Not That Sweet Honeymoon: A Case of Proinsulinoma
Authors: Maldonado Francisco Javier Lopez , Mayorga León Angel Alfonso , Milan Eduardo Rafael Leon , Chinchillas Carlos Alfonso Morales , Guardado Jesus Alan , Fragoso Maria Elena Marin , Yocupicio Flor Maria , Luareano Karla Itzel , González Alondra Rodríguez
Published: May 2020

Introduction

Proinsulin-secreting tumors (proinsulinomas) are exceedingly rare, characterized by the predominant hypersecretion of proinsulin. We present an unusual case of hypoglycemic syndrome in a 19-year old woman with a proinsulinoma (PI).

Clinical Case

19-year-old female presented mild neuroglycopenic symptoms (SX) while having sexual intercourse with her husband at their honeymoon. Her condition began with diaphoresis, blurred vision, tremors and anxiety ending in somnolence that appeared exactly during sexual intercourse and disappear with orange juice intake. The SX kept appearing every time she had intercourse during the next month, denying that any other situation triggered them. She was referred to psychiatry where she was diagnosed with erotophobia and treated with fluoxetine and alprazolam. She gained 33 pounds and referred her husband gave her chocolate bars during sexual intercourse so SX wouldn’t appear. 5 months later she presented cognitive deterioration characterized by stupor during intercourse, so she was taken to the emergency department (ED). Arrived the ED with tachycardia (110 bpm), BP 140/90 mmHg, stuporous, diaphoretic, pale and with a 27mg/dl blood glucose (BG). The patient was admitted to the hospital for further evaluation. After 12 hours of insulin fasting test, she began with SX and a 32 mg/dl glycometry was registered, the test was stopped afterwards. Serum labs were obtained: BG 28 mg/dl, insulin 3 (n 3.0-25.0Uiu/ML), C-peptide 0.9 (n 0.8-3.0ng/ml), proinsulin 298 (≤ 18.8 pmol/L). Abdominal CT scan in arterial phase revealed a single round, hypervascular image, located in the pancrea’s body, 1.96 x 1.37 x 1.42 cm and 123 HU. Enucleation of the mass was performed. The histopathological report showed a neuroendocrine neoplasia and chromogranin positive immunohistochemistry in the neoplastic cells. Patient presented complete clinical remission, fluoxetine and alprazolam were discontinued and she lost 35 pounds in the next 6 months.

Conclusion

PI are predominantly benign neuroendocrine tumors that have the potential to cause symptomatic hypoglycemia. The patient’s clinical manifestations were confused with an anxious syndrome and erotophobia, and these cases illustrate that the diagnosis of organic hypoglycemia can be challenging.
MON-059 Acute Hyponatremia Following Computed Tomography Radiocontrast in a Pediatric Patient
Authors: Chiu Harvey Kenn , Bahri Shadfar , Iskander Paul
Published: May 2020

Hyponatremia is a common laboratory finding. Radiocontrast is hyperosmolar and can draw fluid from the intracellular to the extracellular compartment, but radiocontrast-induced hyponatremia is rare, usually noted in the context of renal insufficiency as a consequence of extracellular expansion exceeding diuresis. We describe an unusual case of 3-year old girl with normal renal function who developed significant hyponatremia following computed tomography radiocontrast. The patient had a mediastinal mixed yolk sac/germ cell tumor and mature teratoma. Imaging was performed with a PET/CT, cardiac CT angiogram, and abdominal CT, for which she received Omnipaque radiocontrast 2 cc/kg. Hyponatremia developed 5 days after administration, with a fall from a baseline sodium of 141 mmol/L to an eventual nadir sodium of 123 mmol/L. An assessment using the serum osmolality of 266 mOsm/kg failed to diagnose hyperosmolar effects of the radiocontrast, with an undetectable concurrent vasopressin level of <0.5 pg/mL. 3% NS boluses failed to have an enduring effect. Without a specific enduring intervention, the hyponatremia then resolved 9 days after administration of the radiocontrast, as the sodium levels remained between 134–139 mmol/L over the subsequent 5 days. Recognition of the clinical scenario and time course of events for radiocontrast-induced hyponatremia is essential for a correct diagnosis. Pediatric patients may be particularly susceptible to radiocontrast-induced hyponatremia given the inherently small size, and following administration of radiocontrast in a pediatric patient, significant morbid hyponatremia is a possible sequalae that should suspected especially if suggestive clinical symptoms present.
SAT-689 Amantadine Induced Severe Hypoglycemia in a Patient With Type 1 Diabetes and Multiple Sclerosis
Authors: Mishriky Basem M , Cummings, PharmD Doyle M , Powell James R
Published: May 2020

Introduction: Amantadine is one of the few options commonly used to treat fatigue associated with multiple sclerosis. However, in a previous trial investigating the effect of amantadine on oral glucose tolerance test results, amantadine caused a reduction in plasma glucose and glucagon levels while increasing insulin levels in healthy volunteers [1]. If amantadine can reduce glucagon levels, we hypothesized that it might also cause hypoglycemia in patients with type 1 diabetes.

Case presentation: The patient is a 34-year-old African American male who has a past medical history of type 1 diabetes and multiple sclerosis. His baseline hemoglobin A1c values ranged from 6.9% to 7.6% and his weight was 88 Kg. His insulin glargine dose was 28 units daily while his insulin lispro was 10 units before meals. For almost one year he was followed in clinic and had no episodes of severe hypoglycemia (defined as hypoglycemia requiring assistance from another person).

The patient complained about gait imbalance and fatigue from multiple sclerosis for which he was followed by a neurologist. To treat these symptoms, he was prescribed amantadine 100 mg twice daily. A couple of hours following his first dose of amantadine after eating his usual breakfast (with his sister), the patient was found unconscious by his sister. Emergency Medical Services (EMS) was called and he was found to have a blood glucose of 22 mg/dL. He was admitted to the hospital. During that admission, amantadine was discontinued, and he was discharged on insulin glargine 24 units daily and insulin lispro 10 units with meals.

Discussion: We present a case of suspected amantadine induced severe hypoglycemia. In patients with type 1 diabetes, there is a loss of the pancreatic β-cells while the α-cells are preserved [2, 3]. We hypothesize that if amantadine reduces glucagon production from the α-cells, patients would be prone to severe hypoglycemia, presumably because of the unopposed insulin action. Although it is unlikely that the severe hypoglycemia was secondary to insulin since the patient was on stable doses, it cannot be completely excluded. We recommend caution when prescribing amantadine to patients on insulin therapy particularly within the first two hours after rapid acting insulin administration. More research is needed to explore this possibility.

References: [1] Diabetes Metab Syndr Obes 2009; 2: 203. [2] Br J Diabetes Vasc Dis 2014; 14: 45. [3] Peptides 2018; 10: 54.
MON-LB131 Perfluoroalkyl Substance Exposure Was Negatively Associated With Cortisone Levels in Pregnancy
Authors: Dreyer Anja Fenger , Jensen Richard Christian , Glintborg Dorte , Schmedes Anne Vibeke , Brandslund Ivan , Nielsen Flemming , Kyhl Henriette Boye , Jensen Tina Kold , Andersen Marianne
Published: May 2020

Introduction: During pregnancy, maternal cortisol levels are increased threefold by third trimester. The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD, isoforms 1 and 2) regulates cortisol levels by the conversion between cortisol and cortisone. Perfluoroalkyl substances (PFAS) are persistent chemicals with suspected endocrine disrupting abilities applied in consumer products. PFAS have been reported to inhibit 11β-HSD1 and 11β-HSD2, which could lead to reduced levels of cortisol and cortisone.

Aim: To investigate a possible effect of early pregnancy PFAS exposure on late pregnancy activity of 11β-HSD1 and 11β-HSD2 assessed by cortisol and cortisone levels in urine and blood samples.

Methods: The study is part of the prospective cohort study, Odense Child Cohort (OCC). A total of 1,826 pregnant women had serum (S) concentrations of five PFAS (Perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA)) measured in first trimester (median gestational week (GW) 11). Diurnal urinary (dU) cortisol and cortisone (n=344), and S-cortisol (n=1,048) were measured in third trimester (median GW 27).

Results: In multiple regression analyses, a two-fold increase in S-PFOS was significantly associated with lower dU-cortisone (β=-9.1%, p<0.05) and higher dU-cortisol/dU-cortisone (dU-C/C) (β=9.3%, p<0.05). The same trend was demonstrated for PFOA, PFHxS, PFNA, and PFDA. In crude models, a doubling in PFOS, PFOA, PFHxS, and PFNA concentrations were associated with a significant increase in S-cortisol, however, these associations became insignificant after adjustment.

Conclusion: Early pregnancy concentrations of maternal S-PFAS were inversely associated with late pregnancy dU-cortisone, indicating reduced activity of 11β-HSD2.
SAT-LB66 X Linked Rickets: Description of 16 Cases in the Adulthood in Argentina
Authors: Schiró Laura María , Núñez Hilda Tatiana Martínez , Rodriguez Patricia , Giacoia Evangelina
Published: May 2020

Introduction. X-linked hypophosphatemic rickets (XLH) is an inherited disorder that results from an inactivating mutation of the PHEX gene. The familiar form comprises most cases. Its incidence is 4.8 per 100000 persons (Haffner D et al., 2019). XLH is characterized by bowed or bent legs, short stature, tooth abscesses, hearing loss, joint pain and impaired mobility, which can alter quality of life.

Aim. To describe clinical characteristics, laboratory and imaging findings of XLH adult patients attending to our hospital; to evaluate physical function and impact on the quality of life; to estimate adherence to conventional treatment.

Methods. A retrospective, observational study from 16 XLH patients medical records was performed. Age, sex, BMI, age at diagnosis, number of fractures, bone deformities, corrective surgeries, biochemical and genetic profile were evaluated. Physical functionality, pain and stiffness were measured with WOMAC (Bellamy N et al., 1988) and PROMIS scale; and QOL with SF36. Adherence to treatment was assessed with the CQR questionnaire. To monitor treatment complications renal ultrasound and brain CT scan were performed.

Results. 16 patients were evaluated, 14 (88%) female, 2 (12%) male, with a mean (☐) age 40.06 years (± 12.4), Age at diagnosis (12%) male, with a mean:12.68 years (SD ± 18.37), BMI ☐:38.5 kg/m2 (13.07), stature ☐:129.9 cm (± 33.9), fractures 8/16 (50%) and skeletal deformities 16/16 (100%), number of corrective surgeries required 15/16 (94%), pseudofractures 13/16 (81%), kyphoscoliosis 8/16 (50%). Laboratory: calcemia ☐:9.5 mg/dl (± 0.37), phosphatemia ☐:2.07 mg/dl (± 0.41), PTH ☐:88.31 pg/ml (± 36.1), 25OHD ☐:26,77 ng/ml (± 11.48), RTP ☐:76.76% (± 11.19), FAO ☐:37.08 (± 26.94), CTX ☐:1646 (± 1119), FGF23 ☐:58.85 pg/ml (± 27.7). Genetic profile: 1/14 had a definitely pathogenic not previously described in the literature mutation. 14/16 (88%) patients showed NOT to adhere to conventional treatment. Application of WOMAC function scale ☐:47.87 (± 25.23); PROMIS ☐:31.5 questionnaire (± 9.23); SF36 ☐:34.95 (± 8.5). Renal ultrasound abnormalities 2/16 (13%) nephrocalcinosis and 3/16 (19%) renal lithiasis; no brain calcifications in the CT were described.

Conclusion. We note that the high percentage of patients not adherent to conventional treatment leads to marked impaired physical function with important skeletal deformities, fractures and pseudofractures, bone pain and altered QOL. Early diagnosis, adequate treatment and follow-up by a multidisciplinary team will avoid complications and improve the patient’s quality of life.
MON-LB003 Clinical Case Series of Augmented Fertility in Females After Administration of an Amino Acid Blend That Enhances Release of Human Growth Hormone
Authors: Swelstad Brad B , Blauer Keith Leon , Greenway Frank Lyons , Heaton Amy L , Buster John E
Published: May 2020

Supplementation with adjuvant therapies, including growth hormone (hGH), is commonly used to improve fertility treatment outcomes. hGH is important for normal female fertility; low hGH has been associated with causes of infertility and impaired fertility, including polycystic ovarian syndrome (PCOS), endometriosis, diminished ovarian reserve (DOR), and advanced maternal age. A novel, low dose, orally administered amino acid blend has been previously shown in a double-blind, randomized, placebo-controlled, crossover clinical trial to produce a statistically significant increase in endogenous hGH secretion. In this clinical case series, we report outcomes in 7 women with infertility or impaired fertility and conditions associated with low hGH who administered the amino acid blend during fertility treatment (n=5) or timed intercourse/spontaneous pregnancy (n=2). Medical history included conditions associated with impaired fertility and low hGH: endometriosis (n=3), PCOS (n=2), and poor response to ovarian stimulation/history of failed in vitro fertilization (IVF) (n=3). The amino acid blend (containing 2.9 g of L-lysine, L-arginine, oxo-proline, N-acetyl-L-cysteine, L-glutamine, and schizonepeta) was administered daily on an empty stomach. Outcomes included embryo quality and success of embryo transfer (for IVF) and successful pregnancy/live births. Mean±SD age was 33±5 years (range 27-38) and BMI was 27±7 kg/m2 (range 21-37). Time to pregnancy ranged from 1 week to 9 months (median 3 months) prior to egg retrieval for IVF (n=4), intrauterine insemination (n=1), or timed intercourse/spontaneous pregnancy (n=2). For women with a history of failed IVF (n=3), there was an improvement in oocyte retrieval, a higher fertilization rate, and a greater number of high-quality embryos compared to previous IVF attempts. There were 2 twin pregnancies (both following IVF). All 7 pregnancies resulted in live births. Consistent with previous studies, the amino acid blend was well tolerated; no adverse events were observed. We report a case series of successful pregnancy in 7 women with conditions associated with low hGH including PCOS, endometriosis, and poor response to ovarian stimulation/history of failed IVF who administered the amino acid blend concomitant with fertility treatment or who reported spontaneous pregnancy. This may represent a potential low-risk and cost-effective treatment to improve IVF success and increase pregnancy rates in individuals with infertility or impaired fertility.
SAT-LB55 A Case of Central Hyperthyroidism From a TSH Secreting Pituitary Adenoma
Authors: dela Cruz Almeda Maria Guia Estrella
Published: May 2020

This is a case of a 41 year old Filipino female, with one month history of palpitations, unintentional weight loss and increased frequency of bowel movement. Patient was tachycardic and had a slightly enlarged thyroid on physical exam. There were no cushingoid or acromegalic features. Initial work-up revealed elevated TSH 7.10 U/mL prompting referral to an endocrinologist who had an initial consideration of central hyperthyroidism, MRI was done revealing a pituitary adenoma with dimensions of 7.4 x 11 x 5.8 mm. Prolactin level was at 118.9 ng/mL, gonadotropins (FSH 5 mIU/mL, LH 4.3 IU/L) were within normal range for pre-menopausal non pregnant women and early 24h urine cortisol was within normal at 63.79 nmol/ day. Patient was started on propranolol 40 mg thrice daily and methimazole 20 mg twice a day which prompted slight relief. She was also referred to neurosurgery service for further management. Patient underwent transsphenoidal surgery which was tolerated well. Subsequent clinical course revealed improvement of hyperthyroid symptoms with no evidence of post-operative complications such as hematomas, CSF leak, vision loss, diabetes insipidus or central adrenal insufficiency. Immunohistochemical staining was positive for TSH.

On outpatient follow-up, repeat thyroid function tests were within normal with TSH 1.260 and free T4 15.07 pmol/L. Patient is currently symptom free and off methimazole or propranolol. Future plans include a repeat MRI after 6 months of surgery and hormonal testing to confirm cure.
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
Authors: Zhang Qian , Xiao Haiying , Gu Weijun
Published: May 2020

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.
SUN-LB96 Basal Contralateral Aldosterone Suppression Is Rare in Lateralized Primary Aldosteronism and Can Be Useful in Predicting Surgical Outcome
Authors: Desrochers Marie-Josée , St-Jean Matthieu , Nada El Ghorayeb , Bourdeau Isabelle , So Benny , Therasse Éric , Kline Gregory , Lacroix André
Published: May 2020

Background: Adrenal venous sampling (AVS) is performed to distinguish between unilateral or bilateral source of aldosterone in primary aldosteronism (PA). Unilateral aldosteronomas should lead to suppression of renin and contralateral (CL) aldosterone secretion, assessed by the CL suppression ratio. We recently found that CL aldosterone suppression was relatively rare using the ratio of basal aldosterone concentration of the opposite adrenal vein/periphery (AOPP/AP) in contrast to the traditional cortisol-corrected aldosterone ratio ((A/C)OPP(A/C)P). Pathology studies showed frequent zona glomerulosa (ZG) hyperplasia adjacent to a dominant aldosteronoma, which could also indicate probable ZG hyperplasia in the CL adrenal. The ratio of basal CL suppression could be a usefull parameter to predict cure following unilateral adrenalectomy (UA), but controversy remains in the literature.

Objectives:

1. To evaluate the prevalence of basal CL suppression using the AOPP/AP ratio as compared to the (A/C)OPP/(A/C)P ratio at previously established cut-offs.

2. To determine the best cut-off to predict clinical and biochemical surgical cure in two Canadian referral centers.

3. To compare the accuracy of the AOPP/AP ratio to the basal lateralization ratio (LR) and the post-ACTH LR in predicting the surgical outcome.

Methods: 330 patients with PA and successful bilateral simultaneous basal and post-ACTH stimulated AVS (selectivity index >2 basally and >5 post-ACTH) were included; 124 patients found to be lateralized underwent UA. The follow-up data were evaluated for clinical and biochemical cure at 3 and 12 months using the PASO criteria.

Results: Using AOPP/AP and (A/C)OPP/(A/C)P at the cut-off of 1, the prevalence of CL suppression is 6% and 45%, respectively. The median CL suppression ratio is 2.3 (1.3-5.1) in lateralized cases of PA using AOPP/AP. Using ROC curves, the AOPP/AP ratio is associated with clinical cure at 3 and 12 months and biochemical cure at 12 months. (A/C)OPP/(A/C)P is associated with biochemical cure only. The cut-offs for AOPP/AP offering the best sensitivity and specificity for clinical and biochemical cures at 12 months are 2.15 (Se 63% and Sp 71%) and 6.15 (Se 84% and Sp 77%), respectively. Basal LR and post-ACTH LR are associated with clinical cure but only the post-ACTH LR is associated with biochemical cure.

Conclusions: Basal CL suppression defined by the AOPP/AP ratio is rare and incomplete compared to the traditional (A/C)OPP/(A/C)P ratio in lateralized cases of PA. This may reflect the frequent micronodular hyperplasia adjacent to dominant aldosteronomas and possibly in the CL adrenal. Basal CL aldosterone suppression may predict clinical postoperative outcome, but with modest accuracy.
SUN-737 Induction of the Pro-Diabetic Gene DPP4 by Glucocorticoids: New Evidence of Pro-Inflammatory Effects in Macrophages
Authors: Diaz-Jimenez David , Petrillo Maria-Grazie , Busada Jonathan T , Cidlowski John A
Published: May 2020

Glucocorticoids are potent endogenous anti-inflammatory molecules, with its receptor (GR) expressed in nearly all immune cells. Macrophages are heterogeneous cells having a central role in both tissue homeostasis and inflammation. Paradoxically glucocorticoids have a limited efficacy controlling these processes and inflammation resolution of macrophage-related diseases, such as type 2 diabetes, atherosclerosis and rheumatoid arthritis. To address this issue, we explored new glucocorticoid target genes in macrophages with potential clinical and therapeutic implications for these diseases. Analysis of genomic platforms identified the pro-diabetic exopeptidase dipeptidyl peptidase 4 (DPP4) as a novel glucocorticoid-responsive gene. GR directly induces its expression by binding to two glucocorticoid-responsive elements within the DPP4 promoter. Unexpectedly, DPP4 mediated the glucocorticoid-induced spontaneous macrophage migration. These actions were blocked by both GR and DPP4 siRNA knockdowns. Furthermore, two DPP4 inhibitors, Sitagliptin and Linagliptin, used clinically for the treatment of diabetes inhibited glucocorticoid-induced mobility of macrophages. DPP4 induction by glucocorticoids was also observed in murine peritoneal macrophages and pro-inflammatory M1 polarized macrophages and was associated with an increase in their migratory properties. Provocatively, DPP4 has been shown to be involved in the inflammatory macrophage profile associated with type 2 diabetes, obesity and atherosclerosis. Since macrophages require efficient cell movement for all their functions, such as sensing of Pattern Associated Molecular Patterns (PAMPs), phagocytosis and the antigen presentation, the DPP4 induction by glucocorticoids could potentiate the macrophage infiltration and their activation in chronic inflammatory tissues and diabetes.
MON-LB036 Uncommon Findings in Beckwith-Wiedemann Syndrome
Authors: Martins Jéssica M E S , Garcia Tamires S , Lee Juliana S , Cechinel Edson , Simoni Genoir , Nascimento Marilza Leal , Da Silva Paulo Cesar Alves
Published: May 2020

Introduction: Beckwith-Wiedemann syndrome (BWS) is characterized by variable phenotypes that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia, hemihypertrophy and predisposition to embryonal tumours.

Some features are more specific, including adrenal cytomegaly. BWS increases risk for several tumors, including adrenocortical tumor (ACT). Some protocols recommend screening with adrenal ultrasonography and serum DHEAS every 4–6 months.

Case report: A 1-month-old male, preterm (34 weeks 4 days), large for gestational age (weight 3670g), presented with macrosomia, macroglossia, umbilical hernia and auricular pits, with clinical diagnosis of BWS. In newborn screening 17 alpha hydroxyprogesterone (17OHP): 70,15 ng/mL (<15ng/mL) and 66,32 ng/mL in second sample. Presented basal cortisol 11.4 mcg/L (6,70 a 22,60 µg/dL), normal electrolytes, dehydroepiandrosterone sulphate (DHEAS) > 1000 mcg/dL (30,0 - 250,0 mcg/dL), testosterone 637 ng/dL (60-400 ng/dL), leading to ACT suspicion. No suppression of cortisol (2,8 mcg/dL) after dexamethasone 10 mcg/kg. Urinary metanephrines were normal, plasmatic normetanephrine 554 pg/mL (<196 pg/mL) and plasmatic norepinephrine 2094 pg/mL (< 420 pg/mL). Abdominal CT showed increased adrenal glands, with normal contrast uptake. MRI and PET/CT DOTA-68Ga did not identify tumors. Eight months later: 17OHP 0,88 ng/mL (0,8-5ng/mL), DHEAS 37 mcg/dL (<30,0 mcg/dL), testosterone 13 ng/mL (< 30 ng/dL), normal urinary metanephrines and plasmatic catecholamines.

Conclusion: In this case congenital adrenal hyperplasia was ruled out and ACT was suspected. Imaging did not identify tumors and biochemical findings (hypercortisolism and high androgens levels) had progressive improvement. Bilateral adrenal hyperplasia may be present in BWS as a result of fetal adrenal gland delay maturation. Permanent adrenal cortex cytomegaly may be responsible for hypercortisolism. Transient cortex persistence can lead to androgens elevation and produces large amounts of DHEA, that could explain DHEAS elevation similar to that in ACT.

Bilateral adrenal hyperplasia is described as a feature of BWS, but, to our knowledge, there is no similar case in literature with these biochemical findings.

References:

1)

Beckwith JB. Extreme cytomegaly of the adrenal fetal cortex, omphalocele, hyperplasia of kidneys and pancreas, and Leydig-cell hyperplasia: Another syndrome. West Soc Pediatr Res. 1963; 11

2)

Carney JA, Ho J, Kitsuda K, et al. Massive neonatal adrenal enlargement due to cytomegaly, persistence of the transient cortex, and hyperplasia of the permanent cortex: findings in Cushing syndrome associated with hemihypertrophy. Am J Surg Pathol. 2012
SAT-226 Lifestyle Modifications or Adrenalectomy? Pheochromocytoma Presenting with New Onset Diabetes Mellitus
Authors: Sosa-Pagan Max , Sarmiento-Ramon Juan Camilo , Panunti Brandy Ann
Published: May 2020

Introduction

When clinicians think of pheochromocytomas, diabetes might not be the first thing that comes to mind. Pheochromocytomas elicit deterioration in glucose tolerance in 20% to 40% of affected individuals. Size of the pheochromocytoma could be an independent risk factor for developing diabetes, as larger pheochromocytomas often present with diabetes mellitus in 23% to 33% of patients with symptomatic pheochromocytomas. Evidence suggests that pheochromocytoma proposes a risk for development of diabetes. There is no consensus or recommendations on which patients with new onset diabetes should be screened for pheochromocytoma or how to manage hyperglycemia in these patients.

Clinical Case

42 YO F with PMH of HTN presented to primary care clinic c/o polyuria, fatigue, 25-pound weight loss, epigastric pain and worsening hypertension over 3 months. Initial work up showed a HbA1C of 9%. The patient was diagnosed with type 2 diabetes mellitus and started on Metformin 1g BID with no improvement of glucose levels or symptoms. As part of initial work up for suspicion of pancreatic malignancy patient had an abdominal CT scan showing a 5.6 x 4.8 cm well-circumscribed left adrenal mass. Patient was referred for endocrine evaluation. Initial workup showed negative GAD Ab, normal 1mg Dexamethasone suppression test, normal aldosterone/renin ratio, elevated Free Normetanephrine of 17,921 pg/mL and elevated chromogranin A of 3,427 ng/mL. Based on biochemical evidence of catecholamine excess and left adrenal mass on imaging, patient was diagnosed with Pheochromocytoma. MIBG showed no evidence of metastatic disease. She was started on insulin therapy, Doxazosin 1mg BID which was titrated to 2mg BID and Amlodipine 5mg was increased to 10mg daily. Pt was referred to surgery for adrenalectomy. On pre-op evaluation patient had significant improvement of glucose levels and symptoms. Propranolol 20mg BID was started for BP optimization. A laparoscopic left adrenalectomy was performed without complications. Patient did not require anti-hypertensive medications or insulin during hospitalization and was discharged on metformin 500mg daily with no anti-hypertensive medications. At one-month Post-adrenalectomy follow up patient had normal BP of 116/72 mmHg and A1C of 5.4% with normal glucose logs indicating resolution of diabetes and HTN post adrenalectomy.

Conclusion

Diabetes is a multifactorial disease that has direct impact on patient’s quality of life, morbidity and mortality. It is important to consider pheochromocytoma as a risk factor for development of diabetes, especially in young patients with atypical presentation, uncontrolled hypertension or without evidence of antibodies or insulin resistance. Screening and early diagnosis of pheochromocytoma could mean significant reduction on long term diabetes complications as diabetes seems to improve or even resolve after adrenalectomy.
OR11-01 Using Kisspeptin to Predict Pubertal Outcomes for Youth With Pubertal Delay
Authors: Chan Yee-Ming , Lippincott Margaret Flynn , Barroso Priscila Sales , Alleyn Cielo , Brodsky Jill , Granados Hector , Roberts Stephanie , Sandler Courtney Nagel , Srivatsa Abhinash , Seminara Stephanie Beth
Published: May 2020

Background: The management of youth presenting with delayed puberty is challenging because it can be difficult to predict which children will eventually progress through puberty and which children will not. We have previously shown that exogenous administration of the neuropeptide kisspeptin, which stimulates GnRH release, can be used to probe the integrity of the reproductive endocrine axis. We hypothesized that responses to kisspeptin could predict outcomes for individuals with pubertal delay. Methods: We conducted a longitudinal study of 16 children (3 girls and 13 boys) with delayed or stalled puberty who had undergone stimulation testing with kisspeptin and GnRH. Participants were followed with serial physical examinations and laboratory studies every six months for evidence of progression through puberty. Inhibin B was measured in boys. A subset of participants underwent exome sequencing. Results: “Kisspeptin responders” who had responded to kisspeptin with a rise in LH of 0.8 mIU/mL or greater all subsequently progressed through puberty (n = 8). In contrast, “kisspeptin nonresponders” who had exhibited LH responses to kisspeptin ≤0.4 mIU/mL all reached age 18 years without developing physical signs of puberty (n = 8). Thus, responses to kisspeptin accurately predicted later pubertal outcomes (p = 0.0002), with sensitivity and specificity of 100% (95% CI 74-100%). Moreover, the kisspeptin-stimulation test outperformed overnight LH measurements, GnRH-stimulated LH, inhibin B, and genetic testing in predicting pubertal outcomes. Conclusion: The kisspeptin-stimulation test can be used to reveal future reproductive endocrine potential in prepubertal children and is a promising novel tool for predicting pubertal outcomes for children with delayed puberty. Trial registration: ClinicalTrials.gov NCT01438034
SUN-LB95 Developing a Highly Equivalent Non-Competitive Chemiluminescence Immunoassay Aldosterone Measurement to LC/MS
Authors: Satoh Fumitoshi , Ono Yoshikiyo , Omata Kei , Tezuka Yuta , Yamanami Hiroaki , Morimoto Ryo , Kojima Satoshi , Sasano Hironobu
Published: May 2020

Background Measurement of plasma aldosterone and renin concentration, or activity, is useful for selecting antihypertensive agents anddetecting hyperaldosteronism in hypertensive patients. However, it takes several days to get results even if measured by inaccurateradioimmunoassay, or we must accept high-cost LC/MS, and development of a more rapid and accurate substitute has been long hoped. We havedeveloped a novel, fully-automated, high-quantitative noncompetitive chemiluminescence immunoassay (NC-CLEIA) for detecting aldosterone inserum and plasma, and its performance is evaluated as compared to LC/MS measurement. Methods Recently a unique anti-metatype antibody,which recognizes the immunocomplex of aldosterone and its monoclonal antibody, was established. Using this antibody for sensing permittedthe construction of non-competitive assay for the detection of aldosterone. The reaction protocol of novel aldosterone assay is the following. Inthe 1st reaction, aldosterone in patient’s sample is captured on anti-body coated magnetic particles. Alkaline phosphatase-conjugated antimetatypeantibody is added and incubated as 2nd reaction following a wash. Then substrate solution is added after washing immunocomplex.The resulting reaction signals are proportional to the amount of aldosterone in the sample allowing quantitative determination of in serum orplasma sample. The overall reaction is completed within 30 min. Results Limit of blank (LoB), limit of detection (LoD) and limit of quantitation(LoQ) of our NC-CLEIA aldosterone assay were 0.09 ng/dL, 0.21 ng/dL and 0.57 ng/dL, respectively. NC-CLEIA aldosterone measurements werelinearly well correlated with LC/MS aldosterone measurements (N = 130, y = 1.027x - 0.23 ng/dL, Spearman’s ρ = 0.996, P< 0.0001). Bland-Altmanplot analysis between NC-CLEIA and LC-MS/MS of aldosterone revealed a bias of 0.40 ng/dL with the limits of agreement of -4.60 and 5.41 ng/dLwith 95% confidence interval. Conclusion Our novel NC-CLEIA aldosterone assay was well-correlated and had only a very low bias with LC-MS/MSmethod and also was able to accurately quantify low level samples even in essential hypertension patients. This aldosterone assay can be a most equivalent to LC-MS/MS measurement with a low cost of 12 $ and a short measuring time of 30 minutes.
SAT-LB96 Chronic Kidney Disease Incidence and Cardiorespiratory Fitness Association in Patients With Diabetes And/Or Hypertension
Authors: Powell Joseph , Nylen Eric S , Myers Jonathan , Karasik Pamela , Moore Hans , Faselis Charles , Patel Samir , Samuel Imannuel , Kokkinos Peter
Published: May 2020

Introduction: Type 2 diabetes mellitus (T2DM) and hypertension (HTN) are considered strong risk factors for developing chronic kidney disease (CKD). Increased cardiorespiratory fitness (CRF) is associated with lower CKD risk. However, the CRF-CKD association in patients with T2DM and/or HTN has not been assessed.Methods: We identified 9,751 patients (age 58.6 + 10.1 years) with T2DM (N=1,444) or HTN (n=5,031) or both (n=3,276) prior to a maximal standardized exercise treadmill test (ETT) and no evidence of ischemia as indicated by the ETT. We established four CRF categories based on age-adjusted peak metabolic equivalents (METs) achieved: Least-Fit (4.6±1.2 METs; n=2,231); Low-Fit Fit (6.4±1.1 METs; n=2,693); Moderate-Fit (8.0±1.0 METs; n=2,432); and High-Fit (10.8±2.1 METs; n=2,395). We performed multivariable Cox Regression analyses to access the risk of CKD according to fitness. The models were adjusted for age, body mass index (BMI), traditional risk factors and medications. Results: During the median follow-up of 12.4 years, 1,118 patients developed CKD, accounting for 9.1 events/ 1,000 person-years of observation. The association between CRF and CKD was inverse and graded. The risk of CKD was 21% lower (Hazard Ratio [HR] 0.79; 95% confidence interval [CI] 0.77-0.81). When CRF categories were considered, the CKD risk was 44% lower for Moderate-Fit patients (HR 0.56; 95% CI 0.48-0.67) and 80% lower for High-Fit (HR 0.20; 95% CI 0.15-0.25). Similar findings were noted in patients with both T2DM and HTN. Conclusions: We noted an inverse and dose-response association between CRF and CKD incidence. The risk was attenuated significantly beyond a mean peak MET level of 8.0±1.0, suggesting that moderate increases in exercise capacity confers favorable health benefits in patients at high risk of developing CKD.
MON-LB59 Radiofrequency Ablation as a Primary Therapy for Benign Functioning Insulinoma
Authors: Alyusuf Ebtihal Y , Ekhzaimy Aishah Ali , Alomair Basil
Published: May 2020

Background Insulinomas are rare life-threatening pancreatic neuroendocrine tumors. Surgical removal continues to be the treatment of choice for such benign cases with a high cure rate. However, surgery is associated with a considerable risk of morbidity and mortality.Here we describe a case of benign solitary insulinoma successfully treated with RFA in a patient who strongly refused surgery. Case Description A 56-year- old non- diabetic, male is known to have hypertension and lymphoma diagnosed at age of 20 years, in remission. He presented with recurrent episodes of transient ischemic attack and stroke over the last three years. A change in his cognitive function, behavior, and memory was noticed. During his hospital stay for the second episode of stroke, he was found to have hypoglycemia which was asymptomatic. Insulinoma was confirmed based on the followings: low plasma glucose level of 2.04 mmol/l (4.0- 5.6), inappropriately elevated plasma f insulin and C-peptide 68.9 mU/l (3-13) and 4.08 ug/l (1.0-3.1); respectively. Sulfonylurea screening test was negative. MRI of the abdomen showed a 3.2x2.5 cm, well-circumscribed hypervascular lesion at the uncinate process of the pancreas, which is compatible with neuroendocrine tumor. Treatment modalities have been explained to the patient who was fully informed about the risk and benefit of each treatment option. However, he strongly refused surgery. Meanwhile, he was admitted with a third attack of stroke with concurrent hypoglycemia. In view of his refusal of the surgical treatment and due to his recent stroke and high-risk status for surgery, the option of radiofrequency ablation was decided. RFA of the pancreatic tumor using 40.75 GY fractions was carried out with a favorable outcome. The patient achieved biochemical normalization and remains euglycemic during his follow up. Reversal of his cognitive, behavioral, and memory changes was recognized. CT abdomen during a follow-up of 2 months after radiation showed a mild regression of the size of the tumor with no evidence of new lesions or distance metastasis. He remained under close follow up at the neuroendocrine clinic.

Conclusion This case shows a treatment challenge which required the use of an alternative treatment option other than the standard of care in managing a case of benign insulinoma. Successful treatment was achieved in our case with the use of RFA rather than surgery. This report highlights the evolving evidence of nonsurgical RFA being a potential safe, feasible therapeutic modality option or even an alternative to surgery in selected cases of benign insulinoma. Because of the rarity of this tumor and low rate of therapeutic application of RFA in similar cases, the role of RFA had not been extensively studied. Large studies are needed to evaluate the long-term outcomes of RFA in this setting.
MON-LB52 Evaluation of Arterial Stiffness in Acromegaly Patients
Authors: alagüney sevil , Yorulmaz Goknur , Kalkan Toygar Ahmet , Mert Kadir Ugur , Dural Muhammet , Akalin Aysen , Efe Belgin , Kebapci Nur
Published: May 2020

Acromegaly is associated with increased morbidity and mortality primarily attributed to cardiovascular and cerebrovascular diseases, thus demonstrating the negative arterial impact of chronic GH and IGF-1 excess. There are limited and conflicting data regarding coronary artery disease (CAD) in acromegaly that consists mainly of heterogeneous cohorts and pathological reviews of old case series. Increased arterial stiffness is associated with an increased risk of cardiovascular events such as myocardial infarction. Arterial stiffness may measured from pulse wave velocity(PWV). In this study we aimed to evaluate the association between pulse wave velocity and aortic augmentation index in acromegalic patients. Methods: Our study population consists of a consecutive subset of 32 acromegalic patients and 19 control. Acromegalic patients IGF 1 levels were noted. All patients BMI, age, blood pressure, gender also were noted. Also pulse pressure, central blood pressures were measured by non-invasive central blood pressure measurement device (SphygmoCor). Pulse wave velocity and aortic augmentation index were measured by the same device. Results: A total of 32 acromegalic patients and 19 control were enrolled in the study. Body mass index and gender were not significantly different between the groups. Aortic augmentation index (5 vs. 6, p =0,685) variables weren’t significantly different in the study. Systolic and diastolic blood pressures were significantly high in the acromegalic group. (130/82 vs. 120/70) PWV was significantly high in the acromegalic group. (13 vs 11,5 p=0,002)Conclusions: Our study results suggest that acromegaly patients have worse arterial stiffness due to increased pulse wave velocity. Acromegaly is associated with increased morbidity and mortality primarily attributed to cardiovascular problems. We thought that it may be a guiding method in disease management since it can be an early marker of cardiovascular risk.Keywords: acromegaly, pulse wave velocity, aortic augmentation index