bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-725 Clinical and Genetic Features of Families with Maternally Inherited Central Precocious Puberty
Authors: Tinano Flávia Rezende , Canton Ana Pinheiro Machado , Montenegro Luciana Ribeiro , Leal Andrea de Castro , Ramos Carolina , Piovesan Maiara Ribeiro , Seraphim Carlos Eduardo , de Faria Aline Guimarães , Mendonca Berenice Bilharinho , Brito Vinicius Nahime , Latronico Ana Claudia
Published: May 2020

Context: The clinical recognition of familial central precocious puberty (CPP) has significantly increased in the last years. This fact can be related to the recent descriptions of genetic causes associated with this pediatric condition, such as loss-of-function mutations of two imprinted genes (MKRN3 and DLK1). Inherited defects in both genes cause paternally inherited CPP. However, no genetic abnormality has been described in families with maternally inherited CPP so far.

Objectives: To characterize the clinical and genetic features of several families with maternally inherited CPP.

Setting and Participants: We analyzed clinical and genetic features of children with familial CPP. No brain MRI alterations were detected in the selected patients with CPP. MKRN3 and DLK1 pathogenic mutations were excluded. Whole-exome sequencing was performed in selected cases.

Results: We studied 177 children from 141 families with familial CPP. Paternal inheritance was evidenced in 44 families (31%), whereas 58 (41%) had maternally inheritance. Indeterminate inheritance was detected in the remaining families. Maternally inherited CPP affected mainly female patients (69 girls and two boys). Thelarche occurred at mean age of 6.1 ± 1.9 years in this female group. Most of girls had Tanner 3 (41%) and Tanner 4 (35%) breast development at first evaluation. One boy had additional syndromic features (macrosomia, autism, bilateral eyelid ptosis, high arcade palate, irregular teeth and abnormal gait). The pedigree analysis of patients with maternally inherited CPP revealed the following affected family members: 42 mothers, 10 grandmothers, 11 sisters, 12 aunts, and 11 female cousins. Most of the families (41) had two affected consecutive generations, while eight families had three affected generations. No consanguinity was referred. Ongoing molecular analysis revealed two rare heterozygous variants in the boy with syndromic CPP and three affected family members with precocious menarche (mother, maternally half-sister, and maternally aunt): a frameshift deletion (p.F144fs) in MKKS; and a missense variant (p.P267L) in UGT2B4, which encodes a protein involved in estrogen hydroxylation and it was related to menarche timing in genome-wide association studies.

Conclusions: Maternally inherited CPP was diagnosed mainly in girls, who had thelarche at mean age of 6 years old. Dominant pattern of inheritance was more prevalent, with direct maternal transmission in 72% of the studied families. New candidate genes might be implicated with maternally inherited CPP.
OR23-01 Intrapatient ACTH Variability in Cushing’s Disease: Prognostic Significance
Authors: Alvarez Reinier , Hogan Elizabeth , Wu Tianxia , Stratakis Constantine A , Nieman Lynnette K , Chittiboina Prashant
Published: May 2020

Introduction: In patients with Cushing’s Disease (CD), intrapatient variability of hormone measurements creates significant clinical challenges, therefore multiple measurements are recommended.1 Urinary and salivary cortisol variation has been well described. However, intrapatient variation of adrenocorticotropic hormone (ACTH) in CD remains unknown. In CD patients, ACTH levels are inherently elevated from baseline but the coefficient of diurnal variation is reduced.2Additionally, at each diurnal time point, these exists a significant variation around the mean for the ACTH levels. In this study, we first analyzed the intrapatient variablility of ACTH at each diurnal timepoint in patients with CD. CD is primarily a disorder of ACTH excess, and treatment directed at pituitary adenomas would presumably perturb ACTH levels prior to affecting serum or urine cortisol. We hypothesized that the coefficient of variation at each diurnal time-point can help predict remission from CD following surgery.

Methods: We conducted a retrospective review of patients (n = 645) who had histopathologically confirmed diagnosis of CD from 2005-2019 (NCT NCT00060541). We selected patients that had ≥ 3 plasma ACTH values over a 7 day span prior to surgical or medical intervention. We grouped the ACTH measurements into morning (AM) and midnight (PM) values to account for diurnal variation in ACTH secretion. We then analyzed post-operative hormone measurements performed every 6 hours prior to administration of replacement corticosteroids. Remission was assigned to patients with nadir serum cortisol level ≤5 mcg/dL within ten days post-operatively3,4.

Results: We found 54 patients with multiple PM (n = 27) and AM (n = 41) ACTH measurements within a 7 day span. We found that the median coefficient of variation (CV) of intra-patient variability was 19.7% (N=41) (95% CI:12.5-27.5) for the AM and was 24% (N=27) (95% CI: 9.6-31.8) for the PM. Age, the number of tests, or the length of test period were not correlated with CV or absolute levels of ACTH. The intraclass correlation coefficient (ICC) of the AM data set was 0.59 and the PM data set was 0.79 which demonstrates a good and excellent reliability respectively. We found that that, in general, 30-60% decrease from pre-operative ACTH levels predicted remission from CD. ACTH decrease >50% on POD2 and 3 had 100% specificity and sensitivity in predicting remission. The decrease in ACTH preceded cortisol nadir in 3/10 patients by 24 hours.

Conclusion: We found significant intra-patient variability in plasma levels of ACTH at individual diurnal timepoints in CD patients. We also found that the change in ACTH >50% on POD2 or 3 is an excellent predictor of remission from CD.
SAT-136 Hypoxia Effect on Cytokine Production by Breast Cancer Cells
Authors: Avtanski Dimiter , Chen Karin , Satlof Leo , Stoffels Guillaume , Kothapalli Udithi , Ziluck Noah , Lema Maribel , Poretsky Leonid
Published: May 2020

Inflammation is a critical component of tumor initiation and progression. Chronic inflammation triggers molecular events that can promote carcinogenesis, tumor vascularization and metastasis. As inflammatory mediators, cytokines play an important role in the interplay between the tumor cells and tumor microenvironment. Cytokines released by the tumor-associated macrophages modulate cancer cell survival, stemness, invasiveness, and tumor vascularization. Breast cancer cells, however, also produce a variety of cytokines, whose role in cancer development is poorly understood. The aim of our study was to characterize the basal cytokine secretory activity in commonly used human breast cancer cell lines (MDA-MB-231, MCF-7, BT-474, and T-47D). Using MILLIPLEX assay, we measured the expression of 41 cytokines, including interleukins, monokines, interferons and growth factors. We also compared cytokine expression profile of breast cancer cells with those of non-tumorigenic human breast epithelial MCF-10A cells. Further, we investigated whether hypoxia modulates cytokine secretion of breast cancer cells. Using cobalt(II) chloride (CoCl2) to mimic hypoxia, we compared the effect of various treatment doses and intervals on cytokine production in the breast cancer cells. Results demonstrated that CoCl2 affects the release of multiple cytokines in a dose- and concentration-dependent manner, thus highlighting the role of cancer cell-derived cytokines on breast tumor progression. Understanding the molecular actions of cytokines in the tumor microenvironment is important for understanding the mechanism of cancer initiation and progression.
SAT-270 Priapism Secondary to Cabergoline
Authors: Amir Maryam , Flores Monica , Calles-Escandon Jorge
Published: May 2020

Background: Cabergoline and Bromocriptine are ergot derivative long-acting dopamine agonist that are very effective and well tolerated in patients with hyperprolactinemia. A rare and unwanted side effect of Bromocriptine is priapism, which has hardly ever been report in literature and it’s not cited under the medication insert. The underlying mechanism is not totally clear, but it is well known that dopaminergic pathways in the central nervous system are of importance for male sexual behavior and penile erection. Lesser is known about Cabergoline and priapism with only one case report in the literature (1).

Clinical Case: A 65 yr old African American male with a past medical history significant for obesity, essential hypertension, and recent history of frontal headaches was found to have a pituitary macroadenoma. Brain MRI demonstrated 11 x 12 x 9 mm enhancing lesion within the right lateral sella turcica. The lesion extended laterally to abut the right cavernous ICA without vascular encasement or extension into the right temporal skull base. Prolactin level was 276.3 ng/mL (2.1-15.0 ng/mL). He was started on Cabergoline 0.5 mg weekly. 60 days after starting Cabergoline he presented to the ED with a painful penile erection lasting >12 hours. He did not take any Phosphodiesterase (PDE) inhibitors and had no other recent change in medications. He denied any history of sickle cell disease. His most recent dose of Carbergoline was the day prior to the ED visit. He was seen by a Urologist in the ED and confirmed to have a low flow Priapism and underwent aspiration of intracorporal bodies. He was discharged home on pseudoephedrine and pain medications. Carbergoline was discontinued. He has had no further episodes of Priapism since discontinuation of Cabergoline.

Conclusion: The time between drug use and occurrence, absence of other offending medications or precipitating factors and no further priapism episodes once treatment was discontinued suggests a priapism as a rarely reported side effect of Cabergoline. (1)

References:

1.E.de la Pena Zarzuelo, V. Hernandez Canas and C. Llorente Abarca, Department of Urology, Hospital Universitario Fundacion Alcorcon, Madrid, Spain
MON-460 An Extremely Rare Case of Urothelial Carcinoma Metastasizing to the Thyroid Gland
Authors: German Massiell , Singh Abhilasha , Lin Yu Kuei , Sundaresh Vishnu
Published: May 2020

BACKGROUND Metastasis of primary malignancies to the thyroid gland is uncommon, with an overall incidence of 2%. The most common malignancy to metastasize to the thyroid is lung neoplasm (22%) as reported in an autopsy series and renal cell carcinoma (25%) in a clinical series.

CLINICAL CASE A 78 year-old-white male was found to have a thyroid nodule on CT neck performed for surveillance of urothelial carcinoma diagnosed 3 years prior. On retrospective review of CT chest from the previous year, the thyroid nodule had increased in size but didn’t meet criteria for FNAC. Neck/Thyroid US demonstrated a right lobe solid hypoechoic nodule measuring 1.1 x 0.7 x 1.1 cm (longitudinal x anterior-posterior, lateral respectively). Nodule margin was well defined, with no internal vascularity, microcalcifications or abnormal cervical lymph nodes. Seven months later, US reported the nodule to have increased in size to 2.1 x 2.1 x 4.7 cm at which point FNAC was performed. Cytology revealed malignant cells compatible with metastasis from the urothelial carcinoma. Three years prior, his high-grade papillary urothelial carcinoma with extensive infiltration into the muscularis propria had been treated with a partial cystectomy and radiation therapy. Surgical margins and all tested lymph nodes had been negative for neoplasm. The patient underwent right thyroid lobectomy and pathology confirmed high-grade malignant neoplasm consistent with metastatic tumor from the patient’s known urothelial carcinoma.

CONCLUSION We present a rare case of urothelial carcinoma with metastasis to the thyroid gland. While evaluating thyroid nodules in patients with other known malignancies, clinicians should have a lower threshold for FNAC. This will assist with earlier diagnosis of potential metastatic disease and improve clinical outcomes.
SAT-060 Unusual Case of Short Stature and Poor Growth in Childhood
Authors: Patni Nivedita , Heather Fisher G , Scheuerle Angela E
Published: May 2020

Background: Néstor-Guillermo progeria syndrome (NGPS; OMIM 614008) is caused by biallelic pathogenic variants in BANF1 (barrier-to-autointegration factor 1) on chromosome 11q13. It characterized by early onset and slow progression of symptoms including poor growth, lipoatrophy, pseudo-senile facial appearance, and normal cognitive development. Two adult patients have been reported. This is the first reported case of a child with NGPS who presented to endocrine clinic with failure to grow.

Clinical Case: Two year, 8 month old Hispanic female born at 40 weeks gestation with birth weight 3.5 kg. At 1 year, she had short stature, poor weight gain, and thinning hair. There were no developmental concerns. Family history was remarkable for consanguinity. At presentation, her weight was 8.5 kilograms) and height 80 centimeters (both <1st percentile) and head circumference 45.5 centimeters (3rd percentile). Hair was sparse and fine with large areas of scalp alopecia. She had a small face with overhanging brow ridge, flattened midface, narrow nose, small mouth and bilateral lower eyelid ectropion. Fingers were shortened with thickened knuckles, widened fingertips, and distally set nails. Skin was tight throughout, particularly notable on the legs and hands with light discoloration of skin over the hand joints and reticulated dark macules over the lower abdomen. Her cardiac, respiratory, abdominal, genitourinary, neuro and joint examinations were unremarkable. Routine labwork was normal. Her bone age was normal at 2 year and 7 months but there was hypoplasia of the distal phalanges. Full skeletal survey revealed small mandible, thinning of the cranial vault, apparent crowding of the teeth, short stature, acroosteolysis-like changes involving the distal phalanges most evident in the hands, pointed distal phalanx of the great toes, and resorption of the distal clavicles. Her echocardiogram was normal. Sequencing and deletion/duplication analysis of LMNA was not diagnostic. Trio-based whole exome sequencing (WES) was performed after obtaining informed consent. WES revealed homozygosity for a pathogenic missense variant in BANF1 c.34G>A (p.Ala12Thr) inherited from each of the unaffected parents.

Conclusion: Progeria syndromes are unusual but diagnosable causes of failure to grow and can be diagnosed based on clinical suspicion. This patient represents the first child reported with NGPS.
SAT-227 Long-Term Outcomes of Two Siblings with X-Linked Congenital Adrenal Hypoplasia Due to a Mutation in NR0B1 (DAX1) Gene: Reproductive and Neuropsychiatric Aspects
Authors: Pereira Hugo Valente do Couto , Seraphim Carlos Eduardo , Domenice Sorahia , Feitosa Klevia Nunes , Tinano Flávia Rezende , de Faria Aline Guimarães , Freitas Thais Castanheira , Nishi Mirian Yumie , Canton Ana Pinheiro Machado , Brito Vinicius Nahime , Latronico Ana Claudia , Mendonca Berenice Bilharinho
Published: May 2020

Background: X-linked congenital adrenal hypoplasia (CAH) is a rare disease caused by mutations in the NR0B1 (DAX-1) gene. Non-classical manifestations have been described, including late-onset adrenal insufficiency (AI) and gonadotropin-independent precocious puberty (GIPP). We report long-term endocrine and neuropsychiatric outcomes of two siblings with CAH due to mutation in NR0B1.Case report: A 2-yr-old boy was referred due to progressive clinical signs of puberty since 6 months of age. At the age of 3 yr, AI was diagnosed, and the molecular analysis revealed a mutation in the NR0B1 (p.Cys65Leufs*6). Glucocorticoid replacement resulted in reduced testicular volume and decreased testosterone levels. At 11 yr, cyproterone acetate was indicated due to pubertal progression and bone age advancement. At 17 yr the patient had incomplete sexual development and no pubarche. Testosterone levels declined, despite pubertal levels of basal and GnRH-stimulated gonadotropin levels, indicating partial hypogonadotropic hypogonadism. Adult height was 156 cm (SDS: -2.7) within his target height of 161 cm (SDS: -2.1). This patient also presented a psychiatric diagnosis of mood disorder and attention-deficit/hyperactivity disorder (ADHD), and was under methylphenidate, topiramate and sertraline. Both the patient and his mother had SNP array performed, which excluded contiguous gene syndrome. His younger brother also harbored the same mutation in the NR0B1, confirmed shortly after birth. AI was diagnosed with 1 month of age. Cortisone acetate and fludrocortisone were initiated. At 11 months of age, he presented signs of pubertal development with an elevated ACTH and testosterone levels with suppressed gonadotropins, confirming the diagnosis of GIPP. He was treated with cyproterone acetate. At 8 yr, a pubertal response to the GnRH test was detected, and leuprorelin was added. At 9 yr, due to the low growth velocity and advanced bone age, rhGH was started. However, this patient presented a poor compliance and severe obesity (BMI 33 kg/m2). Treatment for GIPP and secondary CPP was stopped at 10 yr, with bone age of 13.5 yr and height of 151 cm (SDS: - 2.3). The diagnosis of ADHD and autism spectrum disorder was made after neuropsychiatric assessment and the patient received treatment with methylphenidate and sertraline. Conclusion: Pubertal development of patients with CAH due to NR0B1 mutations can be heterogeneous. However, the intriguing neuropsychiatric features in two siblings may suggest a role of NR0B1 in neuropsychological development or other still unknown underlying genetic defect.
SAT-002 Does the Age of Women Influence the Evaluation of Ovarian Reserve Through the Determination of Antimullerian Hormone and Follicle Count?
Authors: Maidana Patricia Nieves Amelia , Briones Nancy Bravo , Aparicio Vanesa , Ronconi Delfina , Bonomo Juan Manuel , Jacobsen Dario , Pasqualini Natalia , Singh Lucia , Mesch Viviana , Maggi Liliana
Published: May 2020

INTRODUCTION: Oocyte number and quality are known to decline with age. However, fertility varies significantly even among women of the same age. Given that maternal age has been delayed in recent years, an ovarian biomarker that could reflect follicular activity with precision and accuracy is needed in reproductive medicine.

In recent years, two key methods, the concentration of serum antimüllerian hormone (AMH), which reflects the number of small antral follicles and is predictive of ovarian response, and antral follicle count (AFC) performed by ultrasonography, have emerged as preferred methods for assessing ovarian reserve.

AIM: To assess the influence of women’s age in the association between AMH serum level and antral follicle count by ultrasonography in the evaluation of ovarian reserve

SUBJECTS AND METHODS: 49 women between 25 and 45 years old who attended our laboratory with request for AMH and transvaginal ultrasound in early follicular phase were included in the study. In all of them serum AMH was tested using an electrochemiluminescence immunoassay (ECLIA) on a Roche Diagnostic Cobas e801 analyzer. Transvaginal ultrasonography follicle count was performed in both ovaries by Philips affinity 70 on first days of the menstrual cycle. Statistical analysis was performed through SPSS 23 software.

RESULTS: Median and ranges of the variables are the following: AMH: 0.78 (<0.03-9.98) ng/ml and AFC: 6 (1.0-60.0) follicles. AMH and AFC were negatively associated with age (r: -0.302, p< 0.01; r: -0.267 p<0.01, respectively). AMH showed a positive correlation with AFC (r=0.567,p<0.01). We then divided the study population in two subgroups, according to age: Group 1, women <40 years old(n=28) and Group 2, women ≥40 years old (n=21).Considering AMH= 1ng/ml and AFC = 7, the cut-off value used routinely in our institution, we calculated the Kappa coefficient in each group to test the degree of agreement between these two variables, with the following results: Group 1, Kappa= 0.4510, CI 95% [0.1566 – 0.7453], p= 0.0088; Group 2, Kappa= -0.0370, CI 95% [-0.4371 – 0.3630], p=ns.

CONCLUSION: despite the positive correlation found between AMH levels and AFC in the whole group, Kappa values show that in women younger than 40 years serum AMH>1 ng/ml is a good predictor of AFC >7, but this agreement is lost in women above this age, with the cut-off values used in this study. These results must be confirmed with a larger group of women.
SAT-179 Increased Telomere Length in Adrenocortical Tumors Is Associated with Abnormal Expression of Chromatin Remodelling Factors
Authors: Stecchini Monica F , Bueno Ana Carolina , Ramalho Leandra N Z , Ramalho Fernando S , Calado Rodrigo T , Coeli-Lacchini Fernanda B , Campos Mateus R , Aragon Davi C , Moreira Ayrton C , Brandalise Silvia R , Castro Margaret , Yunes Jose A , Antonini Sonir R
Published: May 2020

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

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

Methods: The records of 110 pediatric patients with available ACT samples were reviewed. ATRX, DAXX, TERT and TERC gene expression was assessed by qPCR (n = 100 ACTs; n = 12 normal adrenals). ATRX and DAXX protein expression was assessed by IHC (n = 45 ACTs). Telomere length was assessed by qPCR (n = 64 ACTs). For survival analysis, Kaplan-Meier curves were obtained. For association analysis, simple linear regression models were adjusted.

Results: Most patients were female (70.9%) and harbored germline TP53 mutations (90.2%). Median age at diagnosis was 21.1 months (2.1 – 199). Younger patients (< 3 years) had better survival (p < 0.01), while those with metastasis at diagnosis and carcinomas (classified by the Wieneke score) had worse survival (p < 0.01). ATRX gene expression was decreased (p < 0.01), while DAXX gene expression was increased (p < 0.01) in ACTs, compared to normal adrenals. ATRX gene expression was even lower in the context of the germline TP53 (R337H) mutation (p < 0.01). TERT expression was not detected in ACTs or normal adrenals, and TERC expression was not altered (p = 0.69). ATRX protein expression was lost in the majority of ACTs (95.6%), while DAXX was lost in a minority (21.1%). There was no association between gene or protein expression and disease-free or overall survival. There was a significant association between decreased ATRX and DAXX gene expression and increased telomere length (p < 0.01 and p = 0.03, respectively).

Conclusion: In pediatric ACTs, decreased ATRX and DAXX gene expression was associated with increased telomere length, independently of TERT or TERC expression. In these tumors, ATRX gene expression was decreased and ATRX protein expression was overall lost, while DAXX gene expression was increased and DAXX protein expression was overall retained. No significant association between these alterations and prognosis was found in this cohort. These findings suggest that ATRX and DAXX altered function may be more involved in the pathogenesis of pediatric ACTs than in the prognosis of the affected patients.
MON-902 Etomidate - an Under Utilized but Safe and Efficacious Drug to Treat Acute Severe Cushing’s Syndrome- Case Reports of Ectopic ACTH Syndrome from Neuroendocrine Malignancies
Authors: Cherian Elena Thampy , Naik Sapna , Cillo Marc , Shah Neel L , Gutierrez Absalon Dennis , Guttenberg Katie , Orlander Philip R
Published: May 2020

Background: Intravenous etomidate infusion, in non-hypnotic doses, rapidly lowers cortisol levels by blocking 11-beta hydroxylation of deoxycortisol to inhibit cortisol production. It is an underutilized drug due to concerns of excess sedation and ICU monitoring.

Clinical Case 1: A 44 year-old female with HTN, diabetes, and recently diagnosed pancreatic neuroendocrine tumor with liver metastases presented with altered mentation. Labs showed severe hypokalemia, metabolic alkalosis, serum AM cortisol >60.2 ug/dL (n 6.7-22.6 ug/dL), ACTH of 698.1 pg/mL (n 7.2-63.3 pg/mL), 24-hour urine free cortisol (UFC) of 5791 ug/24hr (n 5-64 ug/24hr), midnight salivary cortisol of 8.04 ug/dL (n <0.01-0.09), and abnormal low dose (LDDST) and high dose (HDDST) dexamethasone suppression tests each with cortisol >60.2 ug/dL. She developed worsening psychosis, likely secondary to hypercortisolism. After ICU transfer, etomidate infusion was initiated at 2.5 mg/hr and titrated upward, leading to rapid drop in cortisol levels and concomitant improvement in mentation. No respiratory or airway difficulties developed. Ketoconazole and metyrapone were started and etomidate was weaned off. Steroids were added once cortisol levels fell below 10 ug/dL as part of “block and replace.” The patient eventually underwent bilateral adrenalectomy with improvement in hemodynamic and blood glucose parameters. She was discharged on physiologic replacement doses of hydrocortisone and fludrocortisone, with no reported issues two months later.

Clinical Case 2: A 51 year-old man with one month of hematochezia presented with hypertension, severe hypokalemia, metabolic alkalosis, and QTc prolongation. Colonoscopy was unremarkable; however, labs revealed a cortisol of 43.1 ug/dL, ACTH of 83.6 pg/mL, and 24-hour UFC of 7,494 ug/L, with an abnormally elevated LDDST. Imaging showed a pancreatic mass and multiple hypodense liver lesions. The overall presentation was suggestive of ectopic ACTH syndrome due to metastatic neuroendocrine carcinoma, which was confirmed on biopsy. Chemotherapy, ketoconazole, and metyrapone inadequately lowered cortisol. Etomidate drip was initiated at 3 mg/hr in the ICU, with rapid reduction in cortisol levels to <20 ug/dL without respiratory compromise. Attempts to wean off etomidate were unsuccessful and the patient underwent bilateral adrenalectomy. The surgery was compromised due to extensive liver and pancreatic enlargement, and follow up imaging revealed incomplete resection. 8am cortisol level (off etomidate) was >60.0 ug/dL. Metyrapone and ketoconazole were resumed and hydrocortisone was later initiated for “block and replace”. The patient remains in critical condition.

Conclusion: Etomidate-in non- hypnotic doses is useful for the rapid lowering of cortisol levels.
SUN-181 A Case of Metastatic Merkel Cell Carcinoma Within a Cortisol-Producing Adrenal Adenoma
Authors: Maier Adrienne , Kerut Sarah Elizabeth , Subauste Jose S , Curry Stephen
Published: May 2020

Introduction:

Metastasis within another tumor is rare, and exceedingly more rare within a functional adrenal adenoma. Merkel cell carcinoma (MCC) is an aggressive and rare neuroendocrine carcinoma of the skin. We present a patient with history of MCC who presented with an adrenal mass, found to be metastatic MCC within a cortisol-producing adrenal adenoma.

Case description:

54 year old male with a history of type 2 diabetes, hypertension, MCC of right thigh, presented for adrenal mass. He was initially evaluated in the ER for severe abdominal pain for 4 days. He had a CT abdomen done, which showed 6cm right adrenal mass with extensive fat and soft tissue component within it. Hounsfield units within solid area measured up to 47 units, and surrounding area measured -3 Hounsfield units.

His history was significant for MCC of right thigh, type 2 diabetes, HTN, obesity and OSA. Pathology from MCC resection showed no evidence of invasion and clear margins, but he did have microscopic focus on inguinal lymph node biopsy. His PET scan was negative except for low uptake in a 6cm right adrenal lesion that was considered benign-appearing. He completed radiation therapy to right thigh and groin.

Physical exam was notably negative for any cushingoid features. Aldosterone, renin and plasma metanephrines were normal. Cortisol after dexamethasone suppression test was elevated, and ACTH and DHEAS were low, raising suspicion of Cushing’s syndrome. He had right adrenalectomy and was then started on steroid replacement. Pathology showed adrenocortical adenoma with a 2cm well-circumscribed mass within the adenoma positive for metastatic MCC with lymphovascular invasion. ACTH stimulation testing was performed at follow up after holding hydrocortisone for over 24 hours, and was consistent with suppression of glucocorticoid axis in the contralateral adrenal gland.

Discussion:

MCC and metastasis within a functional adrenal tumor are both rare occurrences. Our patient had positive regional lymph node involvement at the time of diagnosis, and although the initial PET scan was interpreted as showing an benign adrenal adenoma, it is likely that this represented distant metastasis. Labs indicated that the surrounding adenoma was likely cortisol-producing. To our knowledge, this is the first case reported of metastatic MCC within a functional adrenal adenoma.

References:

Baek, SH, et al. “Merkel cell carcinoma of the Axilla and Adrenal Gland: A Case Report with Imaging and Pathologic Findings.” Case Reports in Medicine. Volume 2015, Article ID 931238.

Dongyan, L., S. Kumar. “An exceedingly rare adrenal collision tumor: adrenal adenoma-metastatic breast cancer-myelolipoma.” Journal of Community Hospital Internal Medicine Perspectives, 2017. Vol. 7, No. 4, 241-244.

Martin, JT, et al. “Metastatic adenocarcinoma within a functioning adrenal adenoma: a case report.” Cases Journal 2009, 2:7965.
MON-607 Very Low-Calorie Ketogenic Diet Modifies Visceral Adipose Tissue Distribution and Taxonomic Composition of Gut Microbiota in Obese Patients with Insulin Resistance Depending on Protein Source
Authors: Basciani Sabrina , Camajani Elisabetta , Contini Savina , Persichetti Agnese , Mariani Stefania , Lubrano Carla , Watanabe Mikiko , Faro Maria , Bernardo Settimia Di , Vari Michaela , Risi Renata , Strigari Lidia , Gnessi Lucio
Published: May 2020

Background. Short-term interventions based on very low-calorie ketogenic diets (VLCKDs) and meal replacements may be prescribed to selected overweight or obese patients. Few, inconsistent data are available on protein intake from various sources on body weight, composition of gut microbiota and metabolic outcomes in these patients.

Aim. To compare efficacy, safety and effect on microbiota composition of short-term isocaloric very low-calorie ketogenic diets encompassing whey, vegetable or animal proteins, in obese patients with insulin resistance.

Materials and Methods. 48 obese patients (19 males and 29 females) with HOMA-index ≥ 2.5, age mean: 55.2 years (range: 45-73), BMI mean 35.9 kg/m2 (range: 30.2 - 46.4) were randomly assigned to three isocaloric VLCKD regimens (≤800 kcal/day) containing either whey, plant or animal proteins for 45 days, with assessments of anthropometric indexes, blood and urine chemistry, body composition, muscle strength, taxonomic composition of the gut microbiome.

Results. A significant reduction of body weight, BMI, blood pressure, waist circumference, HOMA index, insulin, total and LDL cholesterol was observed in all the patients, regardless the dietary protein source. Patients fed with whey proteins and vegetable proteins had a more pronounced decrease of visceral adipose tissue (VAT) compared with the group fed with animal proteins. The markers of renal function slightly worsened in the group fed with animal proteins. A decrease in relative abundance of Firmicutes and an increase of Bacteroidetes was observed after VLCKDs. This pattern was less pronounced in patients consuming animal proteins.

Conclusions. VLCKDs lead to significant weight loss and a striking improvement of the metabolic parameters over a short period of time. VLCKDs based on whey or vegetable proteins induce a larger reduction of VAT, have a safer profile and determine a healthier microbiota composition compared to those containing animal proteins.
MON-354 Hypocalcemia: Hypoparathyroidism or Calcium Chelation in a Transfusion-Dependent Patient?
Authors: Tran Anh , Chao Jing , Tylee Tracy Susan
Published: May 2020

Transfusion-associated hemochromatosis (TAH) can result in multiple endocrinopathies. Timely diagnosis and treatment can prevent life-threatening consequences. Here we report a misdiagnosed case of a transfusion-dependent 32 yo female with severe hypocalcemia.

CASE DESCRIPTION

Patient is a 32 yo female with Diamond-Blackfan anemia requiring chronic blood transfusions every 2-3 weeks. She has a history of non-compliance with iron chelation therapy, and as a child was diagnosed with TAH complicated by pancreatic diabetes, GH deficiency, hypogonadotropic hypogonadism, and primary hypothyroidism. In 2014, patient was evaluated for bilateral calf pain and found to have low calcium (6.9mg/dL) and elevated phosphorus (6.4mg/dL). She was started on calcium carbonate and calcitriol, but subsequently lost to endocrine follow up. During that time, calcitriol was discontinued, and she was treated with calcium alone for presumed hypocalcemia due to transfusion-related calcium chelation.

In 8/2019, patient was seen in the ED for symptomatic hypocalcemia (Ca 6.2mg/dL, PTH 3pg/mL, vitamin D 25-OH 43.5ng/mL and ferritin 1147ng/mL). She was not taking medications for her other endocrinopathies at that time, with TSH 104, estradiol <30, FSH <1, IGF-1 11. MRI confirmed no pituitary abnormality. She was evaluated by Endocrinology and diagnosed with hypoparathyroidism. She was started on calcium carbonate and calcitriol with stabilization of calcium levels, restarted on levothyroxine and discussion of estrogen replacement was started. She is not currently requiring insulin for treatment of her diabetes.

DISCUSSION

Patients with TAH develop organ damage from iron deposition in a pattern similar to hereditary hemochromatosis, with preferential deposition in the gonadotrophs and lactotrophs leading to hypogonadism and hypoprolactinemia. Primary hypothyroidism, GH deficiency and primary hypoparathyroidism are rare by comparison. Our patient is unique in her wide range of endocrinopathies.

More importantly, this case highlights that failure to recognize these endocrinopathies can lead to inappropriate management and increased morbidity to patients. Despite frequent contact with the health care system for management of her anemia, her endocrine labs were not consistently monitored, leading to the false diagnosis of calcium chelation for her hypocalcemia and treatment with calcium replacement alone. A correct diagnosis of primary hypoparathyroidism due to iron deposition ensured proper treatment with both calcium and calcitriol in this patient’s case.

CONCLUSION

Hypocalcemia associated with transfusion may be due to TAH or calcium chelation. It is important to recognize the rare case of primary hypoparathyroidism when present, in addition to other endocrinopathies, to ensure patients receive appropriate treatment.
SAT-563 The Unsuppressed Plasma Renin Activity May Not Enough for Management of Non-Surgically Treated Primary Aldosteronism
Authors: Ichijo Takamasa , Hayasaka Moe , Suzuki Takayuki , Suzuki Ayako , Saito Manabu , Hijikata Mai , Yamashita Kaoru , Ikehara Kayoko , Higa Mariko
Published: May 2020

It is well known the primary aldosteronism (PA) is most common endocrinological hypertension and accounted for 10% among all hypertension population, and it develops cardiovascular disease more frequently than blood pressure matched essential hypertension. Those patients with bilateral hyperaldosteronism, called idiopathic hyperaldosteronism (IHA), or unwilling for surgical treatment are treated by mineralcorticoid receptor antagonists (MRAs). Although it had been unclear how titrate MRAs to prevent atherosclerotic cardiovascular events, a managemental target for those patients was recently reported as plasma renin activity (PRA) ≥ 1.0 ng/ml/hr to prevent cardiovascular events (Hundemer GL, et. al. Lancet Diabetes Endocrinol. 2018 Jan;6(1):51-59).

Thus, we investigated 77 cases of adrenal venous sampling performed patients with PA and followed up for 3 years in our hospital since 2007, including 24 males and 53 females, and their mean age was 56.3 ± 12.5 years old. All patients underwent AVS and showed bilateral hyperaldosteronism and treated with MRAs and followed up more than 3 years. We collected blood pressure, serum sodium and potassium concentration, estimated glomerular filtration ratio (eGFR), PRA, plasma aldosterone concentration (PAC), atherosclerotic parameter, such as mean intima media thickness (IMT), brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). We evaluated the relationship of those patients’ PRA and aldosterone to renin ratio (ARR) with eGFR, IMT, baPWV, and ABI. The change of mean IMT after 3 year-follow up were 0.03 ± 0.11 mm vs. 0.06 ± 0.09 mm for well controlled (PRA ≥ 1.0 ng/ml/hr) and poorly controlled (PRA < 1.0 ng/ml/hr), respectively, and no significant difference between them. In the other hand, the change of mean IMT after 3 year-follow up showed 0.03 ± 0.10 mm vs. 0.08 ± 0.10 mm for well controlled (PRA ≥ 1.0 ng/ml/hr and ARR <20) and poorly controlled (PRA < 1.0 ng/ml/hr or ARR ≥ 20), respectively, and the mean IMT increase was significantly lower in this group.

The mean IMT increase showed significantly lower only with PRA ≥ 1.0 ng/ml/hr and ARR <20 rather than PRA ≥ 1.0 ng/ml/hr alone.

In our results, both PRA ≥ 1.0 ng/ml/hr and ARR<20 are important to prevent or improve atherosclerosis, rather than only PRA ≥ 1.0 ng/ml/hr and should be titrated MRAs to achieve this target.

In conclusion, our result revealed the titration of MRAs is important to prevent atherosclerotic cardiovascular event and not only PRA ≥ 1.0 ng/ml/hr, but both PRA and ARR <20 should be achieved.
SAT-749 Defining The Role Of Androgens In Hernia Associated Skeletal Muscle Fibrosis
Authors: Taylor Matthew Joseph , Zhao Hong , Potluri Tanvi , Bulun Serdar Ekrem
Published: May 2020

Introduction: Inguinal hernia is a highly prevalent condition occurring in 27% of adult men in their lifetime. The recurrence rate of hernia is 5-20%, resulting in a substantial cost burden in surgical repair procedures. Until recently, the mechanisms leading to the lower abdominal muscle (LAM) weakening characteristic of hernia were unknown. Our group developed the first mouse model of inguinal hernia through expression of the human aromatase enzyme in male mice (AromHum). Aromatase converts androgens to estrogens, and is expressed in the skeletal muscle in humans, but not mice. We found that locally formed estrogen from aromatase activity in LAM and decreased circulating testosterone levels are associated with muscle atrophy and fibrosis resulting in hernia. However, it is unclear how decreasing androgen levels might affect muscle fibrosis, and defining this potential mechanism could impact hernia treatment. We hypothesized that low androgen levels promote muscle fibroblast proliferation and fibrosis, and that androgen treatment would prevent hernia progression in AromHum mice.

Methods: Arom Hum mice (3 weeks old) were treated with high-dose dihydrotestosterone (DHT) via injection for 7.5 weeks with hernia volume continuously recorded (n=5/group). Primary fibroblasts were isolated from LAM from WT and AromHum mice (n=5/genotype). Cells were treated for 24 hours with increasing doses (0.001, 0.01, 0.1, 1, 5, 10 and 100 nM) of R1881, a synthetic androgen, and compared to untreated cells by western blot.

Results: Hernia volume was significantly decreased in AromHum mice treated with DHT compared to vehicle-treated mice, and volume remained consistently suppressed after DHT treatment (p < 0.005). In both primary fibroblast lines, R1881 treatment increased AR levels in a dose dependent manner, indicating that the treatment was effective. Preliminary data indicated that low doses of R1881 (0.001 and 0.01 nM) increased PCNA levels in LAM WT and LAM AromHum fibroblasts. Densitometry normalized to GAPDH showed 80% and 60% increases for 0.001 nM and 0.01 nM respectively in LAM WT fibroblasts, and 20% and 30% increases at these doses in LAM AromHum fibroblasts. Higher doses of R1881 decreased PCNA levels in LAM AromHum fibroblasts by 40% (10 nM) and 30% (100 nM), whereas a 25% decrease was detected in LAM WT fibroblasts at 100 nM.

Conclusion: These data suggest that low androgen doses increase LAM fibroblast proliferation, which possibly contributes to hernia formation. Androgen treatment at higher doses can partially block the progression of hernia in vivo. However, it is unclear whether and how androgen deficiency in combination with excess estrogen affects fibroblast proliferation and hernia formation. Additional research is required to determine if androgen supplementation in sufficient doses is a potential therapeutic for inguinal hernia and other muscle weakness diseases.
SAT-142 Periodic Cushing Syndrome in a Patient with an Intestinal Neuroendocrine Tumor (NET). A Novel Case Report
Authors: Papadopoulou-Marketou Nektaria , Typhoxylou Ern , Kounadi Th , George Piaditis , Chrousos George P , Kaltsas Grigorios , Linos Dimitrios
Published: May 2020

Introduction A major diagnostic enigma regarding ACTH-dependent Cushing syndrome is the distinction between the source of ACTH, which may have either a pituitary or ectopic origin. We present the first described patient with cyclic Cushing syndrome caused by an intestinal neuroendocrine tumour (NET) detected by 68GA-DOTATATE PET-CT, despite functional tests that were indicative of pituitary Cushing disease. Clinical Case A 53-year old man was admitted to outpatient clinic because of muscle weakness. His phenotype and clinical findings (progressively worsening upper and lower limb weakness, emotional disturbances, easy bruising, a Buffalo hump, prediabetes and leucocytosis) led to the diagnosis of Cushing syndrome. Initial laboratory tests established the diagnosis with an abnormal diurnal cortisol and ACTH secretion (night cortisol F: 22.1μg / dl), absence of suppression with dexamethasone 1mg and increased free urinary free cortisol 24h (243.5μg /24h). Abdominal CT scanning revealed a left-sided adrenal adrenocortical adenoma 1.5 mm in max diameter. Pituitary MRI and somatostatin scintigraphy were normal. Low dexamethasone suppression test was indicative of Cushing (F: 14μg / dl) followed by a combined CRH stimulation test during bilateral inferior petrosal sinus sampling. Pituitary / peripheral ACTH ratio pre-infusion of CRH and 3 min after CRH infusion was compatible with right-sided pituitary origin of ACTH hypersecretion. Pending the results of the laboratory, the patient showed a remission of his symptoms along with a laboratory-confirmed recession of active hypercortisolaemia (LDDST test), and this led to the suspicion of periodic Cushing syndrome. The patient was followed with clinical and laboratory examinations weekly, with recurrence of symptoms 2 months later followed by a new remission 3 months later. A PETGA CT SCAN with 68GA-HA-DOTATATE was performed, which showed an increased uptake of the radioisotope in the small intestine. A surgical excision of the affected small bowel region was performed according to the guidelines for intestinal NETs. Histology confirmed the existence of a well-differentiated neuroendocrine neoplasm of the small intestine of 1.1 cm diameter, grade 1 (WHO 2010). Immunophenotype was positive for serotonin and ACTH. Postoperatively, the patient showed a complete remission of symptomatology and regression of hypercortisolaemia over a 18-month period. Follow-up abdominal MRI and 68GA-HA-DOTATATE revealed no pathological findings. Conclusion: Our patient is the first case of ectopic Cushing disease caused by intestinal NET. The differential diagnosis between pituitary and ectopic Cushing syndrome due to ACTH or CRH hypersecretion is not easy and frequently complicated by the periodicity of the disease. In patients with no visible pituitary lesions on MRI we suggest further investigation for ectopic ACTH- driven Cushing syndrome.
SAT-678 New Onset Type 1 Diabetes and Immune Thrombocytopenic Purpura in an Adolescent Male: A Case Report
Authors: Gonzalez-Garcia Zoe Milagros
Published: May 2020

INTRODUCTION:

Type 1 diabetes mellitus (T1D) is an autoimmune condition caused by anti-pancreatic antibodies which attack and destroy the insulin-producing beta cells. Similarly, in immune thrombocytopenic purpura (ITP), anti-platelet antibodies destroy platelets, causing low platelet counts which can lead to petechiae and bleeding. Common autoimmune conditions seen in children with T1D include thyroid and celiac disease. Previous case reports discussed ITP in children with known T1D. Our patient presented with new onset T1D and diabetic ketoacidosis (DKA) in addition to new onset ITP.

CLINICAL CASE:

The patient is a 12 year old previously healthy male with a several week history of polyuria, polydipsia and nocturia, in addition to fatigue and lack of weight gain in the previous two years. Initial labs confirmed diagnosis of T1D with hemoglobin A1c of 12.9% and serum glucose of 460 mg/dL, in addition to DKA, with bicarbonate of 13 mmol/L, pH of 7.30, elevated anion gap and beta-hydroxybutyrate. Due to the presence of DKA, the patient was started on an insulin drip. Thyroid labs showed hyperthyroidism, with TSH- <0.02 (0.5-4.5 mIU/L) and free T4- 2.84 (0.7-1.68 ng/dL), so he was started on methimazole 20 mg daily. Confirmatory pancreatic antibodies and thyroid antibodies were sent. CBC showed thrombocytopenia with initial platelet count of 41,000, hemoglobin of 16.9 g/dL, and white blood cells of 5.05. Follow up platelets continued low at 37,000, so he was seen by a hematologist, which confirmed the Diagnosisx of ITP. Patient had a history of easy bruising in arms and legs, one episode of epistaxis and minimal bleeding after brushing teeth, with negative history of hematuria. Follow up labs resulted in negative thyroid antibodies (TPO Ab, TSI and thyroglobulin Ab) with normalization of labsthyroid function tests, so the methimazole was discontinued. Patient is being followed by Hematologya hematologist, and pancreatic antibodies were done, which were negative. Hematology concurred with diagnosis of ITP despite negative antibodies due to diagnosis of T1D. First line therapy for ITP is IVIG and steroids, however due to national shortage of IVIG and risk for worsening hyperglycemia with steroids, these were avoided. Instead, patient was started on Eltrombopag daily for treatment of his ITP. Platelet count has improved on eltrombopag, with latest range of 126-146,000. Latest hemoglobin A1c is of 6.2%.

CONCLUSION:

In the case of new onset type 1 diabetes mellitusT1D, it is’s important to keep in mind that ITP is another autoimmune condition that can present in these patientspresent. In addition to IVIG and steroids, Eltrombopag is a good ttreatment option that does not interfere with glycemic control. More research is needed to measure the frequency of ITP among patients with type 1 diabetes.